Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment

PurposeCholine derivatives labelled with positron emitters are successfully used for PET imaging of prostate cancer patients. Since little is known about uptake mechanisms, the aim of this study was to characterize choline uptake in prostate cancer cells, also following anti-androgen treatment or chemotherapy.

Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine

It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC 531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 g TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.

Oral and Pharyngeal Cancer Control and Early Detection

Sixty-four standardized continuing education courses were given for dentists throughout the ten public health districts of the USA to determine if certain behaviors regarding oral and pharyngeal cancer (OPC) control could be modified. Questionnaires were obtained at baseline and at 6 months along with matched control groups. One thousand eight hundred two general dentists participated at baseline and 988 at a 6-month questionnaire follow-up. Analysis of the data indicated that continuing education courses had a positive influence on participants’ oral cancer attitudes, knowledge, and behavior that potentially could make a difference on prevention, early detection, and ultimately OPC control.

Proteomics, pathway array and signaling network-based medicine in cancer

Cancer is a multifaceted disease that results from dysregulated normal cellular signaling networks caused by genetic, genomic and epigenetic alterations at cell or tissue levels. Uncovering the underlying protein signaling network changes, including cell cycle gene networks in cancer, aids in understanding the molecular mechanism of carcinogenesis and identifies the characteristic signaling network signatures unique for different cancers and specific cancer subtypes. The identified signatures can be used for cancer diagnosis, prognosis, and personalized treatment. During the past several decades, the available technology to study signaling networks has significantly evolved to include such platforms as genomic microarray (expression array, SNP array, CGH array, etc.) and proteomic analysis, which globally assesses genetic, epigenetic, and proteomic alterations in cancer. In this review, we compared Pathway Array analysis with other proteomic approaches in analyzing protein network involved in cancer and its utility serving as cancer biomarkers in diagnosis, prognosis and therapeutic target identification. With the advent of bioinformatics, constructing high complexity signaling networks is possible. As the use of signaling network-based cancer diagnosis, prognosis and treatment is anticipated in the near future, medical and scientific communities should be prepared to apply these techniques to further enhance personalized medicine.

Molecular Breast Cancer Subtypes in Premenopausal African-American Women, Tumor Biologic Factors and Clinical Outcome

IntroductionBreast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women.

Emergency surgery for recurrent intraabdominal cancer

BackgroundRecurrent abdominal cancer can manifest in many ways but there are certain situations that are a great challenge to clinicians. Emergency presentation is one such situation. Surgeons are faced with a therapeutic dilemma that on the one hand most of these patients have a limited life expectancy, and on the other surgical procedures are unavoidable. We reviewed our experience of recurrent abdominal cancers presenting with acute abdominal symptoms requiring emergency.

Long-Term Morbidity Following Axillary Dissection in Breast Cancer Patients – Clinical Assessment, Significance for Life Quality and the Impact of Demographic, Oncologic and Therapeutic Factors

Objective. This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors.Material and methods: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated. The subjective assessment of the degree of symptom intensity was compared with objective measurements. The extent of surgery (number of resected nodes, level of dissection) as well as the influence of demographic, oncologic and adjuvant measures (age, time interval, number of involved nodes, chemotherapy) were evaluated.

Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients

PurposeThe aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose.

Radiosurgery for brain metastasis from advanced gastric cancer

PurposeWe retrospectively evaluated the survival of patients with brain metastases from advanced gastric cancer (AGC) after radiosurgery (RS).

Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer

BackgroundMatrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in biopsy tissues of gastric cancer, and the correlation between their expression and clinicopathological parameters.

Multi-institutional study of risk factors of liver metastasis from colorectal cancer: correlation with CD10 expression

BackgroundThe risk factors for liver metastasis from colorectal cancer are still unclear. We therefore evaluated the relationships between various clinicopathological factors, including CD10 expression, liver metastasis, and survival, in patients with colorectal cancer.

The Role of a Clinician-Led Reflective Interview on Improving Self-Efficacy in Breast Cancer Survivors: A Pilot Study

Breast cancer survivors experience a wide range of survivorship issues that are not always adequately addressed. This study is an assessment of the Survivorship Consult (SC), a one-to-one clinician-led reflective interview used to capture a comprehensive summary of the survivor experience, to determine its impact on self-efficacy and the perceived likelihood that it initiates behavior change. Using a pre-test/post-test design, data were collected from participants (N = 40) using validated instruments and opened-ended questions to evaluate the SC. Participants found the SC to be a useful tool for planning and goal setting and improved self-efficacy as measured by the Cancer Behavior Inventory with an increase of 2.0 (p = 0.03). The SC demonstrates promise in improving the ability and confidence of breast cancer survivors to manage their care, but further research is required to understand the optimal implementation of this intervention and its impact on the delivery of survivorship services.

Successful immunological treatment of gallbladder cancer in India—Case report

Gallbladder cancer has a poor outcome because of its anatomy and location. Often, the diagnosis is made very late due to its silent course. Post-operated cases do respond to chemotherapy but the survival is counted in months and the quality of life is further hampered due to toxicity of drugs. Immunotherapy holds good promise in non-responding cancers treated by conventional chemotherapeutic agents. Among various therapies, dendritic cell therapy is growing at rapid pace due to its acceptable rationale. It has been utilized in treating successfully resected stage III (T2, N1, M0) gallbladder cancer in one of our patients. A 48 years old lady treated with this therapy is free of metastasis with ten doses of autologous dendritic cell vaccine constructed by utilizing resected tumor lysate antigen. She has received ten doses of therapy in 14 months of her treatment. This therapy has proven to be safe and without apparent side effects. The positive clinical response obtained supports that autologous dendritic cell-based immunotherapy is a promising therapeutic approach for refractory gallbladder cancers. Key wordsGallbladder-Cancer-Dendritic cell-Immunotherapy CLC numberR735.8 Project partly supported by grant from Amim Cancer Trust and Patient’s Co-Operation, India

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

ObjectiveTo study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer (NSCLC).

Overcoming endocrine resistance in breast cancer—are signal transduction inhibitors the answer?

Endocrine therapy is probably the most important systemic therapy for hormone receptor positive breast cancer. Hormonal manipulation was the first targeted treatment employed in breast cancer therapy even before the role of the estrogen (ER) and progesterone receptors (PR) had been elucidated. Unfortunately, a substantial proportion of patients, despite being ER and/or PR positive, are either primarily resistant to hormone therapies or will develop hormone resistance during the course of their disease. Signaling through complex growth factor receptor pathways, which activate the ER are emerging as important causes of endocrine resistance. Targeted therapies, such as signal transduction inhibitors (STIs), are being explored as agents to be able to potentially overcome this crosstalk and thus, resistance to hormone treatment. This article reviews the biology of the ER, the proposed mechanisms of endocrine resistance, and ongoing clinical trials with STIs in combination with hormonal manipulation as a means to overcome endocrine resistance. KeywordsEndocrine resistance-Signal transduction inhibitor-Estrogen receptor

RAS Inhibitors in Hematologic Cancers: Biologic Considerations and Clinical Applications

As the molecular mechanisms responsible for the development and propagation of cancer are becoming elucidated, therapy is emerging. Recently, several investigators have described inhibitors of the Ras protein. This molecule has been targeted because RAS is one of the most commonly mutated oncogenes in human neoplasia. In this review, we will discuss the role of Ras in the pathogenesis of hematologic neoplasms, and the biology behind the development of novel compounds which specifically suppress Ras function.hematologic cancers-RAS inhibitors

Validation of a Questionnaire to Assess Self-Reported Colorectal Cancer Screening Status Using Face-to-Face Administration

Purpose The aim of this study was to assess the accuracy of a National Cancer Institute (NCI)-developed colorectal cancer screening questionnaire. Methods We conducted 36 cognitive interviews and made iterative changes to the questionnaire to improve comprehension. The revised questionnaire was administered face-to-face to 201 participants. The primary outcome was agreement between questionnaire responses and medical records for whether or not a participant was up-to-date for any colorectal cancer screening test. Results Comprehension of descriptions and questions was generally good; however, the barium enema description required several revisions. The sensitivity of the questionnaire for up-to-date screening status was 94%, specificity 63%, and concordance 88%. Conclusions The modified questionnaire was highly sensitive for determining if a person was up-to-date for any colorectal cancer screening test, although the specificity was low. Given the difficulty of obtaining all relevant records, self-report using this questionnaire is a reasonable option for identifying people who have undergone testing. KeywordsColorectal neoplasms-Mass screening-Validation studies-Questionnaires

Preoperative transcatheter arterial chemo-embolization for locally advanced breast cancer —Application of new thrombotic materials—

The anticancer drugs, Adriamycin and Mitomycin were individually immobilized on absorbable gelatin materials, together with a blood clotting factor, Factor XIII and thrombin, using a special technique. The materials were applied as thrombotic agents in preoperative therapeutic transcatheter arterial embolization for patients with locally advanced breast cancer. This approach to preoperative management proved to be superior to intra-arterial infusion therapy currently applied in various clinics. Key wordsblood clotting factor XIII-transcatheter arterial chemoembolization (TACE)-(locally advanced) breast cancer

Pathological features of rectal cancer after preoperative radiochemotherapy

The standard therapy for rectal carcinoma is surgical, however, preoperative radiochemotherapy will play an increasing role especially in locally advanced disease. To estimate the prognosis and the effect of radiochemotherapy the postradiochemotherapeutical pathological features are important to assess. We examined the surgical specimens of 17 patients after preoperative radiochemotherapy to estimate and grade the histological reactions. A proposal for a grading system for tumor regression (not yet available in the literature) has also been described. All but one of the carcinomas showed different degrees of tumor regression. A total regression was not observed after standardised pathological work up. In only one case a locally curative resection was not possible. We think that preoperative radiochemotherapy is able to reduce tumor mass thus achieving operability in non-curatively operable cases. We recommend standards of pathological work up and regression grading for further studies comparing surgery and radiochemotherapy of rectal carcinoma. Le traitement standard d'un cancer du rectum est chirurgical, toutefois la radiochimiothérapie pré-opératoire est appelée à jouer un r?le croissant, en particulier dans les formes localement avancées de la maladie. Afin d'estimer le pronostic et l'effet de la radiochimiothérapie, il est important d'évaluer les constatations pathologiques secondaires à la radio-chimiothérapie. Nous avons analysé les prélèvements opératoires de dix-sept patients après radio-chimiothérapie pré-opératoire dans le but d'estimer et de graduer les réactions histologiques. Nous décrivons également une proposition d'un système de graduation de la régression tumorale, ce qui n'existe pas encore dans la littérature. A l'exception d'un cancer, toutes les tumeurs présentaient des degrés divers de régression. Une régression totale n'a pas été observée après une technique standard d'analyses pathologiques. Dans un seul de nos cas, une résection curative locale n'a pas été possible. Nous pensons que la radio-chimiothérapie pré-opératoire est capable de réduire le volume tumoral à un point tel qu'il est possible d'opérer des cas qui, initialement, n'auraient pas pu être traités de manière curative. Nous conseillous une technique standard d'analyses pathologiques et de graduation de la régression tumorale qui devrait être utile à l'étude comparative des résultats chirurgicaux et de la radio-chimiothérapie du cancer du rectum. Accepted: 25 November 1996

Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer

Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40mg toremifene or 20mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40mg toremifene and 20mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.breast cancer-cholesterol-triglycerides-tamoxifen-toremifene

Nodal status does not predict micrometastatic burden in the bone marrow of patients with breast cancer

While there are increased HEA positive cells in the bone marrow of women with locally advanced tumours, nodal status does not predict bone marrow positivity in breast cancer. This novel finding offers insights into the differing mechanisms of lymphatic and haematogenous spread in breast cancer.

Early side effects of intrathoracic BCG therapy in patients with stage I squamous cell carcinoma, adenocarcinoma, or large cell lung cancer

Data are presented on 179 stage I lung cancer patients subjected to resection operations and then given adjuvant intrapleural BCG and subsequent isoniazid (INH) therapy and on 167 control patients given intrapleural saline and placebo pills in a two-arm randomized double-blind study. The predominant immediate response to BCG/INH therapy was hyperpyrexia, which was found to be more pronounced in patients with larger induration in pretreatment PPD skin tests. Subsequently, chemical hepatitis (6 cases after BCG/INH versus 1 case after saline/placebo), peripheral neuropathy (3 versus 1), dermatitis/hives (5 versus 2), pleural thickening (4 versus 0), and persistent fever (10 versus 0) were noted. Analysis of laboratory changes measured at 18 weeks following randomization revealed that patients with BCG/INH lost 1.1 kg in weight and 0.30 g/dl in hemoglobin concentration on average, whereas control patients gained 1.2 kg and 0.33 g/dl, respectively. Modest rises in SGOT and alkaline phosphatase were apparent at 6 weeks after instillation of BCG compared with controls, but these differences were no longer statistically signifikant after 18 weeks. These side effects notwhithstanding, the BCG/INH therapy was well tolerated.Members of the Lung Cancer Study Group include R. T. Eagan*, R. E. Lee, W. S. Payne, R. E. Ritts, and L. Weiland from the Mayo Clinic, Rochester; C. F. Mountain*, H. T. Barkley, O. H. Frazier, K. Hermes, E. Hersh, and M. Valdivieso from M.D. Anderson Hospital, Houston; L. D. Hill*, M. D. Hafermann, and E. Morgan from The Mason Clinic, Seattle; P. W. Wright* and K.-E. Hellstrom from the Hutchinson Cancer Center, Seattle; C. Bagley, L. P. Johnson, H. Kellogg, and R. D. Pinkham from the Swedish Medical Center, Seattle; T. D. Ivey from University Hospital, Seattle; S. Hammar from Virginia Mason Hospital, Seattle; W. Nelems from St. Paul's Hospital, Vancouver; R. Feld*, D. Bergsagel, T. C. Brown, J. Curtis, C. Keen, J. F. Pringle, I. Quirt, and L. Yeoh from The Princess Margaret Hospital, Toronto; M. Blackstein and M. Goldberg from Mount Sinai Hospital, Toronto; F. G. Pearson*, D. W. Chamberlain, J. Cooper, W. Evans, and T. Todd from Toronto General Hospital, Toronto; M. Baker and R. Ginsberg from Toronto Western Hospital, Toronto; R. I. Mitchell from Wellesley Hospital, Toronto; E. C. Holmes*, W. F. Coulson, K. P. Ramming, and T. H. Weisenburger from the University of California, Los Angeles; Z. Petrovich from Wadsworth Veterans Hospital, Los Angeles; R. K. Oldham*, J. T. Forbes, F. A. Greco, D. L. Page, R. Prager, R. L. Richardson, and S. L. Stroup from Vanderbilt University, Nashville; J. M. Lukeman* and S. M. Sajjad from the Pathology Reference Center of M.D. Anderson Hospital, Houston; P. Grifone, A. Lebeck, and T. Voss from the Operations Office, Silver Spring, Maryland; M. Gail, W. McGuire, J. Allegra, and L. Rubinstein from the National Cancer Institute, Bethesda, Maryland; and L. Eirich, W. Heineman, and J. Beach from Information Management Services, Bethesda, Maryland. Asterisks designate principal investigators.

“The Cancer Bond”: Exploring the Formation of Cancer Risk Perception in Families with Lynch Syndrome

This study explores the social context of hereditary cancer risk perception in three families, an African-American family, a Mexican-American family, and a Caucasian family, each with Lynch Syndrome documented by a mismatch repair gene mutation. Communication network assessments measured family communication about cancer experiences and genetic testing information among a total of 26 participants. Participant narratives were evaluated to gain insight into how family cancer experiences and genetic testing information have shaped perceptions of cancer risk. Analysis of communication networks indicated that some families discussed cancer experiences to a greater extent than genetic testing information, and vice-versa. Interviews elucidated that sharing both types of health information led participants to conceptualize linkages among a strong family history of cancer, genetic testing information, and cancer prevention strategies. Understanding how different types of family communication influence the formation of perceived hereditary disease risk may enhance efforts to tailor genetic counseling services for families.

Linkage between postabsorptive amino acid release and glutamate uptake in skeletal muscle tissue of healthy young subjects, cancer patients, and the elderly

 Several diseases of varying etiology that are commonly associated with the loss of skeletal muscle mass were found to be associated with a decrease in muscular glutamate and glutathione levels and in glutamate uptake in the postabsorptive state. In view of the Na+ dependency and insulin responsiveness of glutamate transport we studied the postabsorptive glutamate exchange in more detail. Our study demonstrates a linkage between glutamate uptake and the export of other amino acids, suggesting that protein catabolism and the resulting coexport of amino acids plus Na+ substitute for insulin as a driving force for the Na+ gradient in the postabsorptive state. The regression function of the correlation between relative glutamate exchange and cumulative amino acid exchange in cancer patients was lower than that in non-tumor-bearing subjects, suggesting that cancer patients must release more amino acids to achieve the same glutamate uptake. In addition, cancer patients had a lower average cumulative amino acid exchange rate than non-tumor-bearing subjects, suggesting that the abnormally low relative glutamate exchange capacity of cancer patients results mainly from inadequate postabsorptive protein catabolism in the skeletal muscle tissue. Both cancer patients and non-tumor-bearing elderly subjects had higher arterial glutamate levels and alanine release than young subjects, indicative of a substantial glycolytic activity in the skeletal muscle. However, elderly non-tumor-bearing subjects showed, in contrast to cancer patients, in the postabsorptive state a stronger cumulative amino acid release and postabsorptive glutamate uptake than healthy young subjects. These changes are discussed in view of the age-related loss of skeletal muscle mass. Key words Cachexia-Catabolism-Glutamate transport-Amino acid transport-AgingReceived: 22 November 1996 / Accepted: 14 February 1997

Gemcitabine plus dose-escalated epirubicin in advanced breast cancer: results of a phase I study

Gemcitabine has shown single-agent activity in metastatic breast cancer. Epirubicin is also widely used for the adjuvant and treatment of metastatic breast cancer. The toxicity profiles and modes of action are different which provides a good rationale for studying both drugs in combination. In a phase I study gemcitabine at a fixed dose of 1000 mg/m2 on days 1, 8, 15 of a 28 day cycle was combined with escalated weekly doses of epirubicin starting with an initial dose of 10 mg/m2. Patients had stage IV metastatic disease without previous chemotherapy except as adjuvant treatment. Nineteen patients were included in the study which defined the maximum tolerated dose (MTD) of epirubicin at 20 mg/m2. Myelosuppression was the dose limiting toxicity with leucopenia WHO grade 3 and 4 in 40.0% and 20.0%, neutropenia WHO grade 3 and 4 without neutropenic fever in 20.0% and 40.0% and thrombocytopenia WHO grade 4 in 20.0%. At the epirubicin 15 mg/m2 dose level, leucopenia (11.1% WHO grade 3) and neutropenia (12.5 and 37.5% WHO grade 3 and 4) were reported. Symptomatic toxicity was generally mild: nausea/vomiting in about 20% of patients (WHO grade 3 or 4) on both 15 and 20 mg/m2 epirubicin dose levels. Alopecia WHO grade 3 and 4 was seen in 2 patients at MTD. Four of 19 evaluable patients had a partial response. We conclude that the combination of gemcitabine and epirubicin is well tolerated and has promising activity. A phase II study is underway with gemcitabine 1000 mg/m2 and epirubicin 15 mg/m2 on days 1, 8 and 15 of a 28 day cycle.gemcitabine-epirubicin-phase I study-metastatic breast cancer

Performance of FDG-PET/CT for diagnosis of recurrent uterine cervical cancer

The purpose is to evaluate the accuracy of integrated FDG-PET/CT, compared with PET alone, for diagnosis of suspected recurrence of uterine cervical cancer. Fifty-two women who had undergone treatment for histopathologically proven cervical cancer received PET/CT with suspected recurrence. PET-alone and integrated PET/CT images were evaluated by two different experienced radiologists by consensus for each investigation. A final diagnosis was confirmed by histopathology, radiological imaging, and clinical follow-up for over 1 year. Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/CT were 92.0% (23/25), 92.6% (25/27), and 92.3% (48/52), respectively, while for PET, the corresponding figures were 80.0% (20/25), 77.8% (21/27), and 78.8% (41/52), respectively. PET/CT resolved the false-positive PET results due to hypermetabolic activity of benign/inflammatory lesions and physiological variants, and was able to detect lung metastasis, local recurrence, peritoneal dissemination, para-aortic lymph node metastasis, and pelvic lymph node metastasis missed by PET alone. However, tiny local recurrence and lymph node metastasis could not be detected even by PET/CT. FDG-PET/CT is a useful complementary modality for providing good anatomic and functional localization of sites of recurrence during follow-up of patients with cervical cancer. KeywordsCervical cancer-Recurrence- 18F-FDG-PET/CT

Modulators of arginine metabolism support cancer immunosurveillance

BackgroundTumor-associated accrual of myeloid derived suppressor cells (MDSC) in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G) nitro-L-arginine methyl ester (L-NAME) and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity.

Incidental head and neck 18F-FDG uptake on PET/CT without corresponding morphological lesion: early predictor of cancer development?

PurposeTo retrospectively determine whether increased/asymmetric FDG uptake on PET without a correlating morphological lesion on fully diagnostic CT indicates the development of a head and neck malignancy.

Long-term results for patients with unresectable gastric cancer who received chemotherapy in the Japan Clinical Oncology Group (JCOG) trials

Background. Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer.

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy

The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1–5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2–63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (PPKey wordsLiver metastases from breast cancer-OK-432-Adoptive immunotherapy-Performance status-Interleukin-2

Bangladeshi Dental Students’ Knowledge, Attitudes and Behaviour Regarding Tobacco Control and Oral Cancer

Bangladesh’s oral cancer incidence is high. Dentists can participate in tobacco control. The aim of this study is to explore tobacco use, tobacco control attitudes and oral cancer knowledge among Bangladeshi dental undergraduates. This cross-sectional study used the Global Health Professional Students Survey and the Humphris Oral Cancer Knowledge Scale. One hundred eighty six questionnaires were analysed, a 79% response rate. Tobacco use, oral cancer knowledge, attitudes towards tobacco control and the dentist’s role in tobacco cessation varied significantly between colleges and by gender. Oral cancer knowledge and positive tobacco control attitudes did not influence tobacco use. There is a global problem in preparing dental students for a holistic, integrated approach to oral cancer prevention.

Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer

Aurora-B kinase is a chromosomal passenger protein and is essential for chromosome segregation and cytokinesis. Aurora-B overexpression in various cancer cells induces chromosomal number instability to produce multinuclearity and relates to metastasis. Here, we examined the expression of Aurora-B in oral squamous cell carcinoma (OSCC) to elucidate the relationship between Aurora-B expression and clinico-pathological findings by immunohistochemistry. Aurora-B expression was observed in normal oral squamous epithelia and OSCC cases, but the number of positive cells was significantly higher in OSCC than in normal squamous epithelium (p < 0.01). The labeling index of Aurora-B was significantly correlated with lymph node metastasis (p < 0.01) and histological grades of differentiation (p < 0.01). We also compared Aurora-B expression with Ki-67 expression and a positive correlation was found (p < 0.0001). Moreover, Aurora-B expression is significantly more frequent in multinuclear tumor cells than in total tumor cells. In summary, we found that Aurora-B expression was well correlated with cell proliferation, induction of multinuclear cells, histological differentiation, and metastasis in OSCC. These findings suggest that Aurora-B may be involved in tumor progression and that Aurora-B can be a new diagnostic and therapeutic target for OSCC. KeywordsOral squamous cell carcinoma-Aurora-B-Cell proliferation-Metastasis-Multinuclear cells

Serum carcinoembryonic antigen levels in head and neck cancer

Carcinoembryonic antigen (CEA) levels were estimated in sera of 25 patients with head and neck cancer. The levels were found to be significantly higher in patients as compared to the controls. However, the rise was nearly to the same extent in all the patients studied, irrespective of the site or character of lesion but was directly proportional to the stage of cancer and to the presence of lymphnode metastasis. After radiotherapy serum CEA levels were significantly reduced.

Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature

CA125 is the gold standard tumor marker in ovarian cancer. Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. Thus, it is reasonable to investigate whether CA125 may have utility as a prognostic indicator as well in ovarian cancer. A large number of epidemiological studies have been carried out to this effect. This review summarizes all available epidemiological literature on the association between CA125 levels and survival in ovarian cancer. To place these studies in context, we provide some background information on CA125 and its role in ovarian cancer.

4′- O -Tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study

In a phase II study, 35 patients with advanced breast cancer were treated with 4′-O-tetrahydropyranyldoxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3–15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%–75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21–77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III–IV) and thrombocytopenia (9 patients, WHO grade II–IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II–III. Other treatment-related side effects included alopecia (WHO grade II–III) in 26 patients and stomatitis and diarrhea (WHO grade I–III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700–1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

Local tumor recurrence after curative resection for rectal cancerA ten-hospital review

Local tumor recurrence rates after curative rectal cancer surgery with the end-to-end anastomosis stapler (EEA?) are reportedly high. Therefore, a retrospective review in ten Yale-affiliated hospitals was undertaken to establish the outcome of surgical resection for rectal cancer in this patient population. Of those 373 patients who had had curative resections, 192 (52 percent) were abdominoperineal resections (APR); 105 patients (28 percent) had restorative resections with sutured anastomoses, and the EEA stapler was used in 76 patients (20 percent). There was an equal distribution of tumors in the various Dukes' stages in all three procedures. Local tumor recurrence was: APR 19 percent, SUT 17 percent, and EEA 24 percent, but local tumor recurrence was more frequent after EEA than APR for tumors 7 to 10 cm from the anal verge (32 vs. 13 percent, respectively,P<0.05), and the time to recurrence was least in EEA patients.

Efficacy and safety of trastuzumab plus capecitabine in heavily pretreated patients with HER2-positive metastatic breast cancer

PurposeWe retrospectively evaluated the efficacy and safety of combination therapy of trastuzumab plus capecitabine in heavily pretreated patients with HER2-positive metastatic breast cancer (MBC).

Modified irinotecan plus bolus 5-fluorouracil/L-leucovorin for metastatic colorectal cancer at a single institution in Japan

BackgroundThe modified irinotecan plus bolus 5-fluorouracil/L-leucovorin (IFL) regimen (irinotecan plus bolus 5-fluorouracil/L-leucovorin) used to be one of the standard treatments for metastatic colorectal cancer until approval of oxaliplatin in Japan. We evaluated the efficacy of modified IFL therapy for Japanese patients.

Suppression of thymidine phosphorylase expression by promoter methylation in human cancer cells lacking enzyme activity

PurposeThymidine phosphorylase (TP, EC 2.4.2.4) activity varies in different human cancer cell lines. Nevertheless, little is known about the regulatory mechanisms of TP expression in such cancers. Promoter methylation of dinucleotide cytosine–guanine (CpG) sites is a known mechanism of reversible gene expression silencing.

Prognostic value of PIK3CA and phosphorylated AKT expression in ovarian cancer

Disrupted phosphatidylinositol 3-kinase (PI3K) activity and its effect on the downstream target AKT plays an important role in malignant diseases. Gain and/or amplification of PIK3CA gene, encoding the catalytic subunit of phosphatidylinositol 3-kinase (p110α) and its increased expression are associated with enhanced PI3K activity in ovarian cancer cell lines. In this study, ovarian carcinomas with documented clinical outcome were assessed for genetic aberrations at the 3q26.3 locus, including PIK3CA, by fluorescence in situ hybridization. PIK3CA amplification was evaluated by quantitative real-time PCR with respect to a control gene situated at 3q13. The expression of p110α, phosphorylated AKT (pAKT) and the proliferation marker Ki-67 were immunohistochemically investigated. PIK3CA amplification and Ki-67 index were strong predictors for an early tumour-associated death. p110α expression correlated with 3q26.3 gain and Ki-67 index but not with the patient outcome. No relationship could be observed between p110α and pAKT or between pAKT and disease outcome. It is interesting to note that cases with a nuclear pAKT immunoreactivity showed a trend of improved overall survival. Our results underline the prognostic significance of PIK3CA in ovarian carcinoma and argue against a simple linear model of PIK3CA gain/amplification followed by PI3K activation and consecutive AKT phosphorylation in ovarian carcinoma. KeywordsPIK3CA-pAKT-Ovarian carcinoma-Prognosis

Biomarkers for assessment of pharmacologic activity for a vascular endothelial growth factor (VEGF) receptor inhibitor, PTK787/ZK 222584 (PTK/ZK): translation of biological activity in a mouse melanoma metastasis model to phase I studies in patients with advanced colorectal cancer with liver metastases

PTK/ZK is a novel, oral angiogenesis inhibitor that specifically targets all 3 vascular endothelial growth factor (VEGF) receptor tyrosine kinases and is currently in phase III clinical trials. In early clinical trials, PTK/ZK demonstrated a dose-dependent reduction in tumor vascular parameters as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and an acute increase in plasma VEGF levels. The reduction in tumor vascularity was significantly correlated with improved clinical outcome in patients with advanced colorectal cancer and liver metastases. To assess the predictive value of a mouse model of tumor metastases, comparisons were performed for the biological activity of PTK/ZK in the mouse model and in patients with liver metastases in the clinical phase I trials. An orthotopic, syngeneic mouse model was used: C57BL/6 mice injected in the ear with murine B16/BL6 melanoma cells which metastases to the cervical lymph-nodes. The primary tumor and spontaneous metastases express VEGF and VEGF receptors and respond to treatment with VEGFR tyrosine kinase inhibitors. PTK/ZK was administered orally, with assesments by DCE-MRI of the metastases and plasma VEGF taken predose and at 3days posttreatment and efficacy determined at 7days posttreatment. Dose-ranging studies in naive mice provided preclinical pharmacokinetic data, while two dose-escalation phase I studies provided clinical pharmacokinetic data. An exposure–response relationship was observed both for mouse metastases (measured as % tumor weight treated/control) and for human liver metastases (measured as % regression). In the B16/BL6 model, the active dose of 50mg/kg PTK/ZK yielded 62.4 (± 16.0) hμM plasma exposure, which is comparable to the plasma area under the concentration time curve (AUC) achieved by the 1000mg dose of PTK/ZK used in clinical trials. At this exposure level in clinical trials, DCE-MRI showed a reduction in the area under the enhancement curve (IAUC) to 47% of baseline. At a similar exposure in the PTK/ZK-treated mice, a reduction in IAUC to 75% of baseline was observed. Furthermore, at doses of 50mg/kg PTK/ZK and above, an increase in plasma VEGF level 10h after drug administration was observed in mice which was consistent with findings from the clinical trials. In conclusion, the preclinical pharmacodynamics of PTK/ZK correlate well with clinical activity in phase I trials over comparable exposures to the drug. Thus, data from this preclinical model proved to be consistent with and thus predictive of the biologic effects of PTK/ZK in phase I/II clinical trials. KeywordsAngiogenesis-VEGF-VEGF receptor inhibitor-Interspecies scaling-Pharmacokinetic

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

AimRecent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion.

Role of decay-accelerating factor in regulating survival of human cervical cancer cells

BackgroundDecay-accelerating factor (DAF) is one of the key molecules involved in cell protection against autologous complement, which restricts the action of complement at critical stages of the cascade reaction. The effect of DAF on the survival of human cervical cancer cell (ME180) has not been demonstrated.

Short-Term Outcome After Laparoscopic or Open Restorative Mesorectal Excision for Rectal Cancer: A Comparative Cohort Study

PurposeThe laparoscopic approach to rectal cancer is still a controversial procedure. A comparative cohort study was conducted to assess short-term results of laparoscopic restorative mesorectal excision.

Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer

To evaluate the influence of inhibitors of prostaglandin synthesis on the incidence of DMH-induced colon cancer, 90 male Sprague-Dawley rats were randomly assigned to: 1) indomethacin 20 mg per liter drinking water, 2) meclofenamate 50 mg per liter drinking water, or 3) normal drinking water (control group). Dimethylhydrazine was given by weekly subcutaneous injections (20 mg/kg body weight) during the first 20 weeks. Thirty-two weeks after the start of treatment and carcinogen exposure, the animals were killed and examined for the number, size, location, and spread of intestinal tumors. Colon cancer incidence was significantly lower in animals receiving indomethacin (56 per cent) compared with the control group (88 per cent) and with the meclofenamate group (90 per cent) (P<0.005). The corresponding figures for tumors in the small intestine were 31, 46, and 35 per cent, respectively. The tumors in indomethacin-treated animals did not differ in number, size, location, or spread from tumors of the other groups, suggesting that indomethacin might influence the carcinogenic process itself, rather than the natural course of the established disease. We conclude that indomethacin significantly reduces the incidence of large-bowel cancer in this animal model and that this observation may have some potential for future chemopreventive studies in human high-risk groups (e.g. ulcerative colitis, familial polyposis). Key wordsColon cancer-DMH-Chemoprevention-Indomethacin-Prostaglandins-Prostaglandin synthesis inhibitors-Experimental colon cancer Presented in part at the XVIIIth Congress of the European Society for Surgical Research, Athens, May 15 to 18, 1983.

PNAs as novel cancer therapeutics

Peptide nucleic acid (PNA) is a hybrid compound with nucleoside bases linked to a peptide-like amide backbone. PNA is capable of sequence-specific base pairing and forms highly stable double and triple helices with natural nucleic acids (DNA, RNA). PNA forms stable hydrogen bonds and is resistant to degradation by nucleases and proteases. Because of these physico-chemical properties, PNA has attracted great attention, since its first description in 1991, as a potential gene-specific drug and a versatile molecular biology tool. More and more laboratories are working with PNA and the number of applications in which PNA proves useful continues to increase. In this chapter, we describe aspects of the biochemistry of peptide nucleic acids and their use as a molecular biology reagent, and then focus on the antisense and anti-gene activity of PNA, with special reference to studies of medical interest, in particular in thePML/RARα and the bcl-2 systems. Key wordsanti-gene-antisense-bcl-2-cancer-oncogene-PNA-therapy-transcription-translation

Early Local Recurrence of Rectal Cancer Showing Extremely Rapid Growth After Curative Surgery: Report of a Case

Key Words: rectal cancer-local recurrence(Received for publication on June 4, 1997; accepted on Jan. 6, 1998)

Inducement of canine gastric cancer by N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG)

Key words: dog, gastric cancer, experiment, ENNGReceived for publication on Apr. 13, 1998; accepted on Aug. 5, 1998

Phytoestrogens have agonistic and combinatorial effects on estrogen-responsive gene expression in MCF-7 human breast cancer cells

Phytoestrogens can exhibit agonistic actions on estrogen-dependent gene expression in breast cancer cells. Since several different phytoestrogens may be found within a single dietary plant source, we sought to investigate whether estrogen-dependent gene expression may be further influenced by the collective treatment of breast cancer cells with multiple phytoestrogens. Accordingly, we transfected MCF-7 breast cancer cells with estrogen-responsive reporters followed by treatment with one of four phytoestrogens (genistein, daidzein, formononetin, and equol) or a combination of these in the absence of estradiol. Our results demonstrated clear-cut agonistic effects of phytoestrogens on estrogen-dependent gene expression. Moreover, combinatorial treatment consistently stimulated reporter activity above that observed for individual phytoestrogens. Inasmuch as the phytoestrogens tested are frequently found together in food sources, these combinatorial responses may more accurately reflect the consequences of in vivo exposure. Key WordsPhytoestrogens-breast cancer-estrogen-gene expression

Erratum to: Comparison of a colonic J-pouch and transverse coloplasty pouch in patients with rectal cancer after an ultralow anterior resection using fecoflowmetric profiles

The online version of the original article can be found at http://dx.doi.org/10.1007/s00384-009-0763-6.

Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

BackgroundWe studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.

Subdermal re-injection: a method to increase surgical detection of the sentinel node in breast cancer without increasing the false-negative rate

PurposeThe aim of this study was to evaluate in breast cancer whether subdermal (SB) re-injection improves surgical detection (SD) of the sentinel node (SN) in patients with negative lymphoscintigraphy on peritumoral (PT) injection, without increasing the false-negative (FN) rate.

Male sexual function after autonomic nerve-preserving operation for rectal cancer

PURPOSE: Sexual dysfunction after surgery of the rectum is a serious complication to male patients. Autonomic nerve-preserving operation for rectal cancer has been performed within the recent ten years to maintain urinary and male sexual functions without spoiling of therapeutic radicality. To clarify male sexual function as the degree of autonomic nerve-preserving operation, the function was outlined through clinical interview. METHOD: In a series of 134 male patients who were undergoing autonomic nerve-preserving operation for rectal cancer, a detailed history of postoperative sexual function was obtained by interviews. RESULTS: In 87.7 and 66.9 percent of patients, erectile and ejaculatory potencies were maintained, respectively, which were higher rates than those after extended and conventional pelvic dissections. According to the preserving extent of autonomic nerve, patients undergoing complete preserving operations showed higher rates of maintained erectile (92.9 percent) and ejaculatory functions (82.5 percent), sexual intercourse (89.9 percent), and orgasm (93.9 percent) compared with those undergoing hemilateral autonomic nerve-preserving (82.3, 47.1, 52.9, 64.7 percent) or partial pelvic plexus-preserving operation (61.1, 0, 26.3, 22.2 percent). CONCLUSION: Pelvic plexus preservation is necessary to maintain erectile potency, and both hypogastric nerve and pelvic plexus preservation are necessary to maintain ejaculate function and orgasm. To maintain satisfactory sexual function, complete autonomic nerve-preserving operation is suitable.Key wordsRectal cancer-Surgery-Sexual function-Autonomic nerve-preserving operationRead at the meeting of the International Society of University Colon and Rectal Surgeons, Crete, Greece, October 25 to 29, 1992.

A novel peptide, selected from phage display library of random peptides, can efficiently target into human breast cancer cell

To develop a targeting vector for breast cancer biotherapy, MDA-MB-231 cell, a human breast cancer cell line, was co-cultured with pC89 (9 aa) phage display library of random peptides. In multiple independent peptide-presenting phage screening trials, subtilisin was used as a protease to inactivate extra-cellular phages. The internalized phages were collected by cell lysising and amplified in E. coli XLI-Blue. Through five rounds of selection, the peptide-presenting phages which could be internalized in MDA-MB-231 cells were isolated. A comparison was made between internalization capacities of peptide-presenting phages isolated from MDA-MB-231 cells and RGD-integrin binding phage by coculturing them with other human tumor cell lines and normal cells. The nucleotide sequences of isolated peptide-presenting phages were then determined by DNA sequencing. To uncover whether phage coat protein or amino acid order was required for the character of the peptide to MDA-MB-231 cells, three peptides were synthesized. They are CASPSGALRSC, ASPSGALRS and CGVIFDHSVPC (the shifted sequence of CASPSGALRSC), and after coculturing them with different cell lines, their targeting capacities to MDA-MB-231 cells were detected. These data suggested that the internalization process was highly selective, and capable of capturing a specific peptide from parent peptide variants. Moreover, the targeting internalization event of peptides was an amino acid sequence dependent manner. The results demonstrated the feasibility of using phage display library of random peptides to develop new targeting system for intracellular delivery of macromolecules, and the peptide we obtained might be modified as a targeting vector for breast cancer gene therapy. Keywordsphage display library of random peptides-specific internalization-breast cancer Supported by the National Natural Science Foundation of China (Grant No. 30460142)

Effect of neoadjuvant chemoradiation on postoperative fecal continence and anal sphincter function in rectal cancer patients

Background and aimsNeoadjuvant chemoradiation (nCRT) followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. This prospective study evaluates the effect of nCRT on postoperative anorectal function and continence.

The Sensory and Coping Intervention for Women Newly Diagnosed with Metastatic Breast Cancer

Preparatory information at the time of metastatic breast cancer diagnosis can be used to enhance patients’ coping ability. Women with metastatic breast cancer evaluated a multimedia educational intervention designed to provide sensory and coping information regarding illness. Twenty women with metastatic breast cancer evaluated the materials. The intervention was evaluated very favorably and women identified the materials as needed information. However, they expressed dislike of content outlining possible concerns suggesting future iterations include only positive content. Findings confirm the acceptability and usability of these materials for further testing and ultimately for integration into cancer care practice.

Portal Vein Interposition Using Homologous Iliac Vein Graft during Extensive Resection for Hilar Bile Duct Cancer

Although autologous vein grafts have been used for portal vein (PV) reconstruction after long-segment portal vein resection during surgery for hilar bile duct cancer, their procurement prolongs operation time and increases morbidity. Less is known regarding the use of homologous vein grafts. The feasibility of homografts for PV reconstruction was preliminarily evaluated in two patients who underwent curative resection for hilar cholangiocarcinoma. Both patients underwent left lobectomy, caudate lobectomy, bile duct resection, and segmental PV resection and interposition vein graft reconstruction. The iliac vein homografts were obtained from deceased organ donors and stored for 1–2days in cold preservation solution without freezing. Neither immunosuppression nor anticoagulation was attempted. One patient has shown good PV patency for 27months. The second patient, who had received adjuvant chemoradiotherapy, showed an asymptomatic waisting at the proximal PV anastomosis site after 4months, which was relieved by percutaneous balloon dilatation, and has been doing well for 12months. In conclusion, our preliminary experience with these two patients suggests that cold-stored iliac vein homografts can be considered as PV substitutes after long PV segment resection during extensive hepatobiliary surgery. KeywordsHilar bile duct cancer-Portal vein-Homograft

Angiotensin II Induces Vascular Endothelial Growth Factor in Pancreatic Cancer Cells Through an Angiotensin II Type 1 Receptor and ERK1/2 Signaling

Vascular endothelial growth factor (VEGF) is a crucial pro-angiogenic component in pancreatic ductal adenocarcinoma (PDA), and its high expression levels have been correlated with poor prognosis and early postoperative recurrence. We have recently shown that high levels of angiotensin II (AngII) type 1 receptor (AT1R) correlate and colocalize with VEGF in invasive PDA and that AngII induces VEGF expression in PDA cell lines. In this study, we explored the signaling mechanisms involved in the AngII-mediated VEGF induction and correlated AT1R and VEGF expression in noninvasive precursor lesions. An AT1R antagonist significantly (p < 0.05) inhibited the AngII-mediated induction of VEGF messenger RNA and protein in all PDA cell lines. AngII-VEGF induction was inhibited by the tyrosine kinase inhibitor genistein, suggesting a mitogen-activated protein kinase signaling mechanism. AngII activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not p38 or c-Jun NH2-terminal MAP kinases. Inhibition of ERK1/2 activation reduced the AngII-induced VEGF synthesis. Immunohistochemical analysis of precursor lesions showed increased expression of AT1R in most ductal cells undergoing metaplasia. Pancreatic intraepithelial neoplasms showed more intense AT1R staining when compared to intraductal papillary mucinous neoplasms, which showed heterogeneous immunoreactivity. VEGF followed the same distribution pattern of AT1R in both lesions. AT1R expression in the premalignant pancreatic lesions suggests its involvement in tumor progression and angiogenesis. Our mechanistic findings provide the first insight into an AngII-initiated signaling pathway that regulates PDA angiogenesis. An AT1R-mediated VEGF induction suggests the possibility of AT1R blockade as a novel therapeutic strategy to control angiogenesis in PDA. KeywordsAngiotensin II-Vascular endothelial growth factor-Pancreatic cancer-Angiogenesis Presented as a poster presentation at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 19–23, 2007 and an oral presentation at the Pancreas Club May 21st, 2007; Washington, DC.

Use of phytohemagglutinin in the treatment of maxillary cancer

Twenty-four patients with maxillary squamous cell carcinoma were treated with 50 g of phytohemagglutinin (PHA), saturated into pieces of gelatin sponge, and applied to the maxillary sinus which was in advance surgically exposed via the peroral route. Treatment was combined with cobalt 60 irradiation at 4,000 rads (200 rads×20 doses over a one month period) and concurrent arterial infusion of 5-fluorouracil (5-FU) with a total dosage of 5,000 mg (250 mg× 20 doses). After 20 treatments with phytohemagglutinin, gross examination showed that tumors were no longer apparent in 83.3% of the cases treated with PHA vs. 52.6% in the control group without PHA. On histological examination, 66.6% in the PHA group showed no signs of tumors vs. 15.8% in the control group. Microscopically, the disappearance of the tumors was frequently observed in tumor of T2 more than that of T3 in extent of primary tumor. No side effects were observed nor was there a significant difference between the control group and the PHA group in the 3-year crude survival rate (control group: 68.4%; PHA group: 62.5%)Behandlung von 24 Patienten mit einem Plattenepithelkarzinom der Kieferhöhle mit 50 g Phytohaemagglutinin (PHA). Das Präparat wurde mittels Gelita in die peroral eröffnete Kieferhöhle eingebracht und die Therapie mit einer Telekobaltbestrahlung von 4000 rad (20×200 rad über einen Monat) sowie arteriellen Infusionen von 5-Fluorouracil (5-FU), 20×250 mg, kombiniert. Nach 20 Behandlungen mit PHA war der Tumor in 83,3% der Fälle verschwunden, während er bei den Patienten ohne PHA-Therapie nur in 62,6% nicht mehr nachzuweisen war. Bei der histologischen Untersuchung fand sich in der PHA-Gruppe in 66,6% kein Tumor mehr, bei der Gruppe ohne PHA dagegen nur in 15,8%. Nebenwirkungen wurden nicht beobachtet. In der 3 Jahre-Überlebensrate bestand zwischen beiden Gruppen kein signifikanter Unterschied.Key wordsPhytohemagglutinin (PHA)-Local treatment of cancer-Maxillary squamous cell carcinomaSchlüsselwörterPhytohaemagglutinin-lokale Krebsbehandlung-Plattenepithelkarzinom der Kieferhöhle

Docosahexaenoic acid induces apoptosis in lung cancer cells by increasing MKP-1 and down-regulating p-ERK1/2 and p-p38 expression

Different agents able to modulate apoptosis have been shown to modify the expression of the MAP-kinase-phosphatase-1 (MKP-1). The expression of this phosphatase has been considered a potential positive prognostic factor in lung cancer, and smoke was shown to reduce the levels of MKP-1 in ferret lung. Our aim was to assess whether the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), known to inhibit the growth of several cancer cells mainly inducing apoptosis, may exert pro-apoptotic effect in lung cancer cells by modifying MKP-1 expression. We observed that DHA increased MKP-1 protein and mRNA expression and induced apoptosis in different lung cancer cell lines (mink Mv1Lu adenocarcinoma cells, human A549 adenocarcinoma and human BEN squamous carcinoma cells). We inhibited the pro-apoptotic effect of DHA by treating the cells with the phosphatase inhibitor Na3VO4 or by silencing the MKP-1 gene with the specific siRNA. This finding demonstrated that the induction of apoptosis by DHA involved a phosphatase activity, specifically that of MKP-1. DHA reduced also the levels of the phosphorylated MAP-kinases, especially ERK1/2 and p38. Such an effect was not observed when the MKP-1 gene was silenced. Altogether, the data provide evidence that the DHA-induced overexpression of MKP-1 and the resulting decrease of MAP-kinase phosphorylation by DHA may underlie the pro-apoptotic effect of this fatty acid in lung cancer cells. Moreover, they support the hypothesis that DHA may exert chemopreventive action in lung cancer. Key wordsApoptosis-Docosahexaenoic acid-Lung cancer cells-MAP kinases-MKP-1

Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine

It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC 531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 g TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.

Cost-Effectiveness of Colorectal Cancer Screening in the Average Risk Population

Colorectal cancer (CRC) is a leading cause of cancer death in North America and in Israel. Risk of CRC increases exponentially with age starting at the age of 50 years. Therefore, people older than 50 years are being considered as an average risk population for CRC. The objective of this study was to obtain an improved assessment of the cost-effectiveness analysis of screening for CRC in the average risk population by using a more accurate technique, namely the Partially Observed Markov Decision Process (POMDP). We conducted a cost-effectiveness analysis within the specific probability rates and costs in Israel.This study revealed that it is highly cost-effective to screen average-risk asymptomatic individuals.

Self-blame, Self-forgiveness, and Spirituality in Breast Cancer Survivors in a Public Sector Setting

Cognitive appraisal affects adjustment to breast cancer. A self-forgiving attitude and spirituality may benefit breast cancer survivors who blame themselves for their cancer. One hundred and eight women with early breast cancers completed questionnaires assessing self-blame, self-forgiveness, spirituality, mood and quality of life (QoL) in an outpatient breast clinic. Women who blamed themselves reported more mood disturbance (p < 0.01) and poorer QoL (p < 0.01). Women who were more self-forgiving and more spiritual reported less mood disturbance and better QoL (p’s < 0.01). Interventions that reduce self-blame and facilitate self-forgiveness and spirituality could promote better adjustment to breast cancer.

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), α-1 globulin, and α-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and α-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

High polymorphism in the trisomic portion of a gastric cancer cell line

BackgroundGenetic instability is a hallmark of malignancy, and microsatellite instability is a widely appreciated mechanism of generating genetic changes. We have recently observed four markers clustered on chromosome 20 that showed the effects of microsatellite instability in the gastric adenocarcinoma cell line SNU-1. Each affected marker had alleles of three different sizes. The aim of this study was to investigate the origin for this high-density polymorphism on a single chromosome.

Cancer risk from inorganics

Inorganic metals and minerals for which there is evidence of carcinogenicity are identified. The risk of cancer from contact with them in the work place, the general environment, and under conditions of clinical (medical) exposure is discussed. The evidence indicates that minerals and metals most often influence cancer development through their action as cocarcinogens.The relationship between the physical form of mineral fibers, smoking and carcinogenic risk is emphasized.

Metastatic bone cancer pain: Etiology and treatment options

Painful metastatic bone disease remains a challenge for physicians. The treatment choices available are wide and varied, with each having its appropriate place in the management of painful bone metastases. Radiotherapy remains the mainstay of treatment with or without surgery. Advances in understanding the intricate pathway responsible for pain generation and the addition of agents such as bisphosphonates to the physician’s armamentarium further assist in the management of painful bone metastases.

Applying Global Frameworks to Assessment in Medical Education: An Example of a Nationally Produced Curriculum for Cancer Education

The past decade has seen an increased effort to standardized medical curricula internationally. Despite these efforts, a lack of standardization remains evident, most likely owing to the lack of specificity with which such frameworks are often (out of necessity) constructed. As such, inconsistencies may arise owing to differences in adopted definitions and approaches to assessment. The authors highlight six key points to aid the individual educator in translating overarching frameworks into specific learning objectives that are measurable, written at a level of generality, complexity and difficulty that is clear, appropriate and explicit in what is required of the student.

Early gastric cancer: Report of 58 cases

Background. This retrospective study was carried out to review our surgical experience and to define the clinicopathologic profile of early gastric cancer in a Western country with one of the highest incidences in the world.

Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients

PurposeThe aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose.

Radiosurgery for brain metastasis from advanced gastric cancer

PurposeWe retrospectively evaluated the survival of patients with brain metastases from advanced gastric cancer (AGC) after radiosurgery (RS).

Serum levels of some acute phase proteins in kidney and urinary tract urothelial cancers

Early diagnosis of kidney and urothelial cancer requires some new sensitive and specific methods. In this study the diagnostic use of serum α1-acid glycoprotein (α1-AG), coeruloplasmin, α1-antitrypsin (α1-AT), α2-macroglobulin (α2-MG) and albumin in patients with kidney, urinary bladder and upper tract urothelial cancer was evaluated. In kidney cancer patients the serum levels of α1-AG, coeruloplasmin and α1-AT were significantly increased over the controls (p<0.001), however, albumin was decreased (p<0.005). Sensitivity was relatively high for α1-AG (85%), albumin (85%) and α1-AT (77%). In patients with urinary tract urothelial cancer α1-AG, α1-AT and coeruloplasmin were also increased but not as much as in kidney cancer. Sensitivity of α1-AT (63%), albumin (75%) and α1-AT (66%) was also lower than in kidney cancer. This study has established the relative importance of α1-AT and albumin determination in patients with kidney as well as with urothelial cancer.

Effects of intraoral prosthetics on swallowing in patients with oral cancer

The swallowing patterns of four patients with oral cancer with intraoral palate reshaping/lowering prostheses were studied with and without their prostheses 3 months postoperatively. The prostheses resulted in improved swallow efficiency, increased duration of tongue contact to the pharyngeal wall, and improved speed of movement of the bolus from the valleculae to the pyriform sinus. These results emphasize the effects of the tongue on the pharyngeal as well as oral stage of the swallow. Key wordsIntraoral prosthesis-Oral cancer

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

ObjectiveTo study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer (NSCLC).

Unique features of breast cancer in Taiwan

Between April 1990 and December 1997, 811 consecutive patients with 830 newly diagnosed breast cancers having their primary treatments in our institution were included in this study. Sixty three percent of breast cancer patients were premenopausal. The early-onset breast cancer (age 40) composed 29.3% of all patients. The five-year survival rate of all patients was 80.4% (95% confidence interval [CI], 76.2–84.6%). The five-year overall survival rate for stage 0 was 95.7% (95% CI, 87.3–100%), stage I, 93.9% (95% CI, 88.9–98.9%), stage II, 88.5% (95% CI, 82.0–95.1%), stage III, 65.0% (95% CI, 54.0–75.9%), and stage IV, 18.5% (95% CI, 3.4–33.7%). Multivariate analysis of primary operable breast cancer revealed that axillary lymph node involvement, high nuclear grade and early-onset breast cancer (age 40) were poor prognostic factors. The early-onset breast cancer had a more aggressive clinical behavior than that of the older age group, their five-year disease-free survival rates for stage I, stage II and stage III diseases being only 64.7%, 66.5%, and 43.3%, respectively. In these patients the only meaningful prognostic factor was extensive axillary lymph node metastasis (10). In summary, breast cancer patients in Taiwan tend to be younger than their counterpart in western countries. The early-onset breast cancer had poorer prognostic features for all stages comparing to the older age group. Standard pathologic factors are not good predictors of their outcome. For these patients new biologic markers need to be sought to distinguish between high and low risk and the treatment strategy for them should be guided by the aggressive characteristics of the disease.breast cancer-database-prognosis-Taiwan-young age

In vitro evaluation of the effects of gefitinib on the modulation of cytotoxic activity of selected anticancer agents in a panel of human ovarian cancer cell lines

PurposeThis study was conducted to determine the in vitro optimal combination of selected anticancer agents with gefitinib and evaluate its effect on the expression of correlative biological targets in the cell-signaling pathway. In addition, the effect of gefitinib on the expression of ATP-binding cassette (ABC) transport proteins was evaluated.

Expression of cell adhesion molecules in an established and characterized new human renal cell cancer line, CCF-RC7

In order to investigate the importance of cell adhesion molecules (CAMs) in renal cell carcinoma (RCC), a cell line, designated as CCF-RC7, was established from a human RCC of the clear cell type. CCF-RC7 was passaged over 50 times in vitro for 31/2 years. The cell line has an epithelial morphology and a doubling time of 30 h, forming colonies in soft agar with an average efficiency of 10.4% and producing clear cell tumors in athymic nude mice. CCF-RC7 cells have an aneuploid-hypotetraploid karyotype with a modal chromosome number of 82 and rearrangements in chromosomes 9, 12 and 14. Immunohistochemical and flow immunocytometric analyses revealed high expression of ICAM-1 (CD54), and Hermes antigen (CD44), which was significantly upregulated by cytokine and PMA treatment. VLA-4 was expressed on approximately 20% of tumor cells and could not be altered by cytokine or PMA stimulation. High expression of sialyl Lewis X was also demonstrated by immunohistological examination. This newly characterized cell line will serve as a useful model for the study of CAMs during hematogenous metastasis and host defense mechanisms in human RCC.Key wordsKidney neoplasms-Tumor cells-Cultures-Cell adhesion molecules

Preoperative transcatheter arterial chemo-embolization for locally advanced breast cancer —Application of new thrombotic materials—

The anticancer drugs, Adriamycin and Mitomycin were individually immobilized on absorbable gelatin materials, together with a blood clotting factor, Factor XIII and thrombin, using a special technique. The materials were applied as thrombotic agents in preoperative therapeutic transcatheter arterial embolization for patients with locally advanced breast cancer. This approach to preoperative management proved to be superior to intra-arterial infusion therapy currently applied in various clinics. Key wordsblood clotting factor XIII-transcatheter arterial chemoembolization (TACE)-(locally advanced) breast cancer

A Pilot Study of Lay Health Worker Outreach and Colorectal Cancer Screening Among Chinese Americans

The research team recruited eight Chinese American (seven females, one male) lay health workers (LHWs). They received 12h of training about colorectal cancer (CRC), its screening, and basic health education techniques. Each LHW were asked to recruit ten participants and conduct two educational sessions. Of the 81 participants recruited, 73 had not received colorectal cancer screening. Their mean age was 63.0years, and 72.6% were women. Knowledge of colorectal cancer, its causes, and its screening increased significantly. Receipt of first colorectal cancer screening test increased from 0.0% at baseline to 55.7% for fecal occult blood tests, 7.1% for sigmoidoscopy, and 7.1% for colonoscopy. LHW outreach is feasible and may be effective in promoting CRC screening among Chinese Americans.

Multi-institutional study of risk factors of liver metastasis from colorectal cancer: correlation with CD10 expression

BackgroundThe risk factors for liver metastasis from colorectal cancer are still unclear. We therefore evaluated the relationships between various clinicopathological factors, including CD10 expression, liver metastasis, and survival, in patients with colorectal cancer.

Parental Attitudes, Beliefs, and Perceptions about Genetic Testing for FAP and Colorectal Cancer Surveillance in Minors

Familial adenomatous polyposis (FAP) is the second most common hereditary colorectal cancer syndrome and confers a nearly 100% lifetime risk of developing colorectal cancer. Understanding factors that facilitate and inhibit genetic testing and cancer surveillance in children who are members of families affected by FAP will better equip clinicians to clarify misunderstandings and facilitate appropriate care. The aims of this study were to examine parental attitudes and beliefs regarding endoscopic surveillance and genetic testing in minors at risk for developing FAP. This cross-sectional study includes analyses of qualitative and quantitative interview data collected from parents of children with or at risk for FAP. This report includes data from 28 parents with a total of 51 biological children between 10–17years of age. The parents had a clinical and/or genetic diagnosis of FAP. Most commonly reported facilitators included provider recommendation (surveillance) and personalized medical management (genetic testing). Most commonly reported barriers included lack of provider recommendation (surveillance) and cost (genetic testing).

Effect of neoadjuvant chemoradiation on postoperative fecal continence and anal sphincter function in rectal cancer patients

Background and aimsNeoadjuvant chemoradiation (nCRT) followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. This prospective study evaluates the effect of nCRT on postoperative anorectal function and continence.

Androgen deprivation therapy and risk for diabetes and cardiovascular disease in prostate cancer survivors

Gonadotropin-releasing hormone (GnRH) agonists are the mainstay of treatment for recurrent and metastatic prostate cancer. GnRH agonists are also an important part of therapy for many men with localized or locally advanced prostate cancer. Although GnRH agonists improve survival in certain settings, they involve adverse effects including vasomotor flushing, obesity, and osteoporosis. This article describes the evidence that GnRH agonists increase risk for diabetes and cardiovascular disease and reviews the potential mechanisms for treatment-related morbidity.

Suprarenal Clostridium septicum Aortitis with Rupture and Simultaneous Colon Cancer

We report a case of combined colon cancer and Clostridium septicum aortitis involving the suprarenal abdominal aorta with rupture. An 82-year-old male presented with fever, abdominal pain, and back pain associated with constipation. He was successfully treated by in situ aortic graft placement with polytetrafluroethylene and concomitant colon resection. Only 20 other cases of C. septicum mycotic aneurysm, aortitis, or aortic dissection have been reported. Concomitant surgical treatment for Clostridium aortitis or mycotic abdominal aortic aneurysm and colon cancer can be accomplished successfully in selected cases when the diagnosis of both conditions is made preoperatively.

A new sphincter-preserving operation for low rectal cancer: ultralow anterior resection and colorectal/coloanal anastomosis by supporting bundling-up method

PurposeThe introductions of total mesorectal excision and double-stapling technique into colorectal surgery have promoted the clinical application of sphincter preservation. However, for the tumors localized on the middle or lower level of rectum, sphincter-preservation approaches might be problematic in some patients. We introduce in this report a new sphincter-preserving technique for low rectal cancer.

Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature

CA125 is the gold standard tumor marker in ovarian cancer. Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. Thus, it is reasonable to investigate whether CA125 may have utility as a prognostic indicator as well in ovarian cancer. A large number of epidemiological studies have been carried out to this effect. This review summarizes all available epidemiological literature on the association between CA125 levels and survival in ovarian cancer. To place these studies in context, we provide some background information on CA125 and its role in ovarian cancer.

Serum carcinoembryonic antigen levels in head and neck cancer

Carcinoembryonic antigen (CEA) levels were estimated in sera of 25 patients with head and neck cancer. The levels were found to be significantly higher in patients as compared to the controls. However, the rise was nearly to the same extent in all the patients studied, irrespective of the site or character of lesion but was directly proportional to the stage of cancer and to the presence of lymphnode metastasis. After radiotherapy serum CEA levels were significantly reduced.

An incident case-referent study on plasma enterolactone and breast cancer risk

Objective: Using a nested case-referent design, we evaluated the relationship between plasma levels of the lignan enterolactone and the risk of developing breast cancer. Methods: 248 cases and 492 referents were selected from three population-based cohorts in northern Sweden. Blood samples were donated at enrolment. All blood samples were stored at −80 °C. Cases and referents were matched for age, date of blood sample and sampling centre. Breast cancer cases were identified through the regional and national cancer registries. Results: Plasma enterolactone was lower among smokers in all cohorts and in subjects with BMI < 23 and BMI > 28 in one of the cohorts. Low plasma concentrations of enterolactone, below the 12.5th percentile (mean plasma enterolactone 2.9 nmol/l), were associated with an increased risk of breast cancer. Also, high values of plasma enterolactone, above the 87.5th percentile (mean plasma enterolactone 58.2 nmol/l) were significantly associated with an increased breast cancer risk among women from two cohorts with only incident cases and a higher number of pre-menopausal women. High plasma enterolactone concentrations among older women from a mammary screening project with mostly prevalent cases were associated with a non-significant slightly reduced breast cancer risk. Conclusion: Very low plasma concentrations of enterolactone were associated with an increased breast cancer risk in all three cohorts. In two of the cohorts, with only incident cases, very high plasma concentrations were also associated with an increased breast cancer risk. In the third cohort with mainly screen-detected cases from a mammary screening program, high plasma enterolactone concentrations were associated with a weak decreased breast cancer risk. Key words plasma – enterolactone – phyto-oestrogens – breast cancerReceived: 4 January 2002, Accepted: 2 July 2002

Cancer patients‘ lymphocytes contain CD3+CD4+cells that proliferate in response to autologous tumor cells in the presence of exogenous low-dose interleukin-2 and autologous accessory cells

To see whether cancer patients possess CD3+ CD4+ lymphocytes able to proliferate in response to autologous tumor cells (Auto-Tu), this lymphocyte subset was isolated either by positive or negative selection, both methods resulting in highly enriched CD4+ populations.Unseparated and isolated CD3+ CD4+ lymphocytes were then assayed for proliferating activity in the presence or absence of various amounts of Auto-Tu, with or without recombinant interleukin-2 (IL-2) (1.5–15 U/ml) and DR+ adherent cells or E– lymphocytes as autologous accessory cells (Auto-AC). Isolated CD3+ CD4+ lymphocytes were stimulated by Auto-Tu alone in only 1 out of 12 cases. CD3+ CD4+ cells failed to proliferate significantly in response to low doses of IL-2 alone but the addition of Auto-Tu caused stimulation in 8 out of 12 cases (67%). The further addition of Auto-AC to Auto-Tu + IL-2 resulted in enhanced response of isolated CD3+ CD4+ lymphocytes in 6 out of 8 cases tested. When reactivities to Auto-Tu in the presence of IL-2 and IL-2 + Auto-AC were considered together, positive responses of CD3+ CD4+ lymphocytes were seen in 11 out of 12 cases (92%). On the other hand, unseparated lymphocytes were stimulated by Auto-Tu alone in none out of 12 cases. Unseparated lymphocytes, however, responded to IL-2 in 11 out of 12 cases; such a response was increased by the addition of Auto-Tu in only 2 cases. Moreover, the IL-2 proliferation of unseparated lymphocytes was suppressed in 4 and in 3 out of 12 cases tested when Auto-Tu or Auto-Tu + Auto-AC were added respectively. These data indicate that lymphocytes of cancer patients contain CD3+ CD4+ cells that are usually unable to proliferate in response to Auto-Tu only. This proliferation, however, occurs when low doses of exogenous IL-2 are present and can be further amplified by the addition of Auto-AC. No response of CD4+ cells is observed in the presence of DR+ Auto-AC + IL-2 except in 2 out of 7 cases tested (28%), suggesting an Auto-Tu-restricted reactivity of CD3+ CD4+ lymphocytes in the majority of cases.

Biological features and chemosensittvity of human colorectal cancer xenografted in nude mice

The chemosensitivity of human colorectal cancer was studied in relation to the biological features of the tumor using a human tumor/nude mouse in-vivo system. The biological features included the histological type, growth rate, mucus secretion and productivity of CEA of the tumor. The overall sensitivity to four anticancer agents examined (5-FU, MMC, CPA and CDDP) was relatively insignificant. The heterogeneity of chemosensitivity among primary, metastatic and recurrent lesions of the same patient was demonstrated. A tumor line obtained from poorly differentiated adenocarcinoma showed better responses to 3 of 4 agents. Tumor doubling time evaluated as an indicator of tumor growth rate showed a significant correlation with sensitivity to MMC. The time also showed a tendency to correlate with sensitivity to CDDP. The tumor with shorter tumor doubling time presented had more remarkable sensitivity to such agents. Similar correlation was observed in the mucus secretion shown by Aldan-blue (AB) staining and sensitivity to MMC and CDDP. Tumors with less significant AB staining showed more remarkable sensitivity to these agents. The productivity of CEA revealed a tendency to correlate with sensitivity to MMC and CPA. These results indicated that histological type, growth rate, mucus secretion by AB staining and productivity of CEA of the tumor might be parameters of chemosensitive differences of human colorectal cancer. Key wordsBiological feature-Chemosensitivity-Colorectal cancer-Nude mouse

Atrial fibrillation and survival in colorectal cancer

BackgroundSurvival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer.

Sequential vinorelbine–capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial

PurposeTo evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients.

Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients

The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.

Expression of BI-1 protein and its significance in breast cancer

ObjectiveTo investigate the correlations of expression of Bax inhibitor-1 (BI-1) gene and the receptors of estrogen and progestogen in breast cancer and its significance.

Cancer of the endometrium: current aspects of diagnostics and treatment

BackgroundEndometrial cancer represents a tumor entity with a great variation in its incidence throughout the world (range 1 to 25). This suggests enormous possibilities of cancer prevention due to the fact that the incidence is very much endocrine-related, chiefly with obesity, and thus most frequent in the developed world. As far as treatment is concerned, it is generally accepted that surgery represents the first choice of treatment. However, several recommendations seem reasonable especially with lymphadenectomy, even though they are not based on evidence. All high-risk cases are generally recommended for radiotherapy.

The importance of KRAS status in managing metastatic colorectal cancer

In the past decade, the standard of care for advanced colorectal cancer has been in a state of flux with the introduction of new agents in the treatment of stage IV disease; however, the 5-year survival rate for advanced disease remains low. Investigators are trying to identify biomarkers that may be predictive and/or prognostic for these agents and thereby improve patient outcomes. This article discusses recent discoveries that have identified the importance of KRAS mutational status in predicting responses to epidermal growth factor receptor-targeting antibodies (cetuximab and panitumumab) in the management of metastatic colon cancer.

A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck

Background: Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was initiated to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of HU in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck.Methods: Patients were required to have histologically-documented and radiographically-staged locally advanced SCC of the hypopharynx (AJC stages II, III or IV), oropharynx (AJC stage IV), or oral cavity (AJC stage IV) not amenable to reasonable surgical resection. Eligible patients had adequate bone marrow, hepatic, and renal function and had to give informed consent. Concomitant, hyperfractionated, accelerated radiation therapy (CHRT) consisted of 1.2 Gy BID (6 hour minimum interfraction interval) on weekdays and 1.2 Gy delivered daily on the weekends to a total tumor dose of 74.4 Gy. Continuous infusion hydroxyurea (CHU) was administered at 0.25–0.375 mg/m2/min as a continuous intravenous infusion daily for 5 days with weekends days off for the duration of the radiation therapy. The dose of HU was increased by 0.125 mg/m2/min between dose levels until DLT was reached in 2/6 patients. If the primary had a complete clinical response and biopsies were negative, planned neck dissections were performed.

Ligature of lingual artery or arteries preliminary to removal of portion or entire of the tongue for cancer

[Read in the Section of Surgery, April 10, 1891.]

Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients

PurposeThe aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose.

Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine

It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC 531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 g TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.

Animal models of exocrine pancreatic cancer

Clinically and biologically relevant animal models are manda-tory to further evaluate both the pathophysiology and novel strategies for diagnosis and treatment of exocrine pancreatic cancer. This review briefly summarizes the features of human pancreatic cancer in order to define requirements for animal models of the disease. The described model systems in rodents include pancreatic cancer induced by chemicals, pancreatic cancer in transgenic, and immunodeficient animals. Keywords Pancreatic cancer-Exocrine-Animal modelAccepted: 20 April 2000

Analysis of hTERT mRNA expression in biliary tract and pancreatic cancer

Background/PurposeTelomerase, an enzyme that prevents the loss of telomere regions consisting of TTAGGG repeats, which maintain the stability of cells, is considered to be involved in cell immortality and cancer growth. Recent genetic analysis has shown that the mRNA for the catalytic subunit of human telomerase reverse transcriptase (hTERT) is expressed in many cancer tissues.

Content of 8-Hydroxy-2-Deoxyguanosine in Steroid Receptor-Positive and Receptor-Negative Breast Cancer Cells

The content of DNA damage marker 8-hydroxy-2-deoxyguanosine in 16 receptor-negative and 18 receptor-positive human breast neoplasms was measured by immunohistochemical methods. Positive staining was revealed in 81.3±9.8 and 50.0±11.7% samples of groups 1 and 2, respectively. The effect of arylhydrocarbon receptor agonist β-naphthoflavone on the content of 8-hydroxy-2-deoxyguanosine and number of estrogen and progesterone receptors was evaluated in MCF-7 breast cancer cells. The degree of genotoxic damage significantly increased 1 h after combined treatment with estradiol and β-naphthoflavone (in contrast to individual treatment) and remained practically unchanged in the follow-up period. According to the estrogen effect-switching phenomenon, genotoxic damage can contribute to the development of R− breast cancer. Key Wordsbreast cancer-MCF-7 cell line-estrogen and progesterone receptors-8-hydroxy-2-deoxyguanosine __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 7, pp. 100–103, July, 2005

Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells

The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45α−γ and down-regulation of c-Myc. In treated cells, GADD45α−γ and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial ‘intrinsic’ pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-κB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs. Keywords.Marine agents-apoptosis-BAD-c-myc-GADD45-non small cell lung cancer Received 7 June 2006; received after revision 13 July 2006; accepted 9 August 2006

Endoscopic Ultrasound with Conventional Probe and Miniprobe in Preoperative Staging of Esophageal Cancer

BackgroundUsing an endoscopic ultrasound (EUS) miniprobe, even highly stenotic esophageal cancers precluding the passage of a conventional probe can be examined without prior dilatation.

Radiosurgery for brain metastasis from advanced gastric cancer

PurposeWe retrospectively evaluated the survival of patients with brain metastases from advanced gastric cancer (AGC) after radiosurgery (RS).

Positive interactions between human interferon and cepharanthin against human cancer cells in vitro and in vivo

A human tumor microcytotoxicity-viable cell-staining assay was used to test the antiproliferative effect of recombinant human interferon-beta or -gamma alone and in combination with bisbenzylisoquinoline alkaloid cepharanthin against four human tumor cell lines in vitro and in nude mice. Results obtained in the in vitro study indicate that combinations of interferon-beta/-gamma with cepharanthin show synergistic and, occasionally, additive antiproliferative effects in a dose-dependent manner on tumor viable cell-staining assay. Interferon-gamma combined with cepharanthin suppressed the growth of all four human tumor cell lines (RPMI 4788, PC 10, HeLa, ZR-75-1), and this enhanced antiproliferative effect was not dependent on the interferon species involved, including interferon-beta and -gamma. In an experimental model of pulmonary metastasis, in which human colon tumor cells were inoculated i.?v. into nude mice, interferon-gamma alone exerted significant inhibitory activity against pulmonary metastasis in a dose-dependent manner, and cepharanthin alone also significantly inhibited metastasis. Furthermore, a combination of interferon-gamma with cepharanthin resulted in a considerable suppression of pulmonary metastasis. These studies indicate that due to their therapeutic potential, combinations of recombinant human interferon-beta or -gamma with cepharanthin might be a promising therapy for pulmonary metastasis of human cancers.

The Helicase-Like Transcription Factor and its implication in cancer progression

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of chromatin-remodeling factors. Several SWI/SNF genes are disrupted in cancer, suggesting their possible role as tumor suppressors. Similarly, the HLTF gene was found to be inactivated by hypermethylation in a significant number of colon, gastric and uterine tumors, indicating that HLTF silencing may confer a growth advantage and that HLTF could be considered as a tumor suppressor gene. However, 20-fold HLTF overexpression was detected in various transformed cell lines, suggesting that HLTF could be associated with neoplastic transformation and act more like an oncogene. Moreover, HLTF activation was recently linked to the initial steps of carcinogenesis in an experimental model of estrogen-induced kidney tumors. Those apparently contradictory observations suggest that HLTF might play various roles in cancer. In this review, we will try to reconcile all these data in order to specify the role of HLTF in cancer progression. Keywords.Cancer-HLTF-oncogene-PAI-1-promoter methylation-SMARCA3-SWI/SNF-tumor suppressor Received 24 August 2007; received after revision 17 October 2007; accepted 23 October 2007

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

AimRecent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion.

Preoperative transcatheter arterial chemo-embolization for locally advanced breast cancer —Application of new thrombotic materials—

The anticancer drugs, Adriamycin and Mitomycin were individually immobilized on absorbable gelatin materials, together with a blood clotting factor, Factor XIII and thrombin, using a special technique. The materials were applied as thrombotic agents in preoperative therapeutic transcatheter arterial embolization for patients with locally advanced breast cancer. This approach to preoperative management proved to be superior to intra-arterial infusion therapy currently applied in various clinics. Key wordsblood clotting factor XIII-transcatheter arterial chemoembolization (TACE)-(locally advanced) breast cancer

Effects of intraoral prosthetics on swallowing in patients with oral cancer

The swallowing patterns of four patients with oral cancer with intraoral palate reshaping/lowering prostheses were studied with and without their prostheses 3 months postoperatively. The prostheses resulted in improved swallow efficiency, increased duration of tongue contact to the pharyngeal wall, and improved speed of movement of the bolus from the valleculae to the pyriform sinus. These results emphasize the effects of the tongue on the pharyngeal as well as oral stage of the swallow. Key wordsIntraoral prosthesis-Oral cancer

Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo

Purpose: The goal of this study is to investigate the inhibitory effects and mechanism of elemene on the growth of laryngeal cancer cells in vitro and in vivo. Methods: Laryngeal cancer cells (HEp-2 cells) were grown in elemene, cisplatin, or a combination of the drugs. The cytotoxic, or apoptotic, effects of elemene on the cells were evaluated by a 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide assay, flow cytometry, and a caspase-3 activity assay. A Western blot was used to semi-quantify the protein expression of eukaryotic initiation factors (eIF4E and eIF4G), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF); RT-PCR analysis semi-quantified the mRNA transcript expression of bFGF and VEGF. The HEp-2 cells were transplanted subcutaneously to BALB/c nude mice to produce solid tumors. Elemene and cisplatin were administered to the mice either as individual drugs or in combination. The tumors were excised and immunostained to determine the effect each drug had on tumor size, eIF levels, angiogenic factors, and microvessel density (MVD). Results: Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC50 of 346.5μM (24h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity, and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo, the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD. Conclusions: Elemene inhibits the growth of HEp-2 cells in vitro and in vivo. These data provide useful information for further clinical study on the treatment of LSCC by elemene. KeywordsElemene-Laryngeal squamous cell carcinoma-Apoptosis-EIF-Angiogenesis Grant support: Shanghai Municipal Health Service Grant 014119047

Multi-institutional study of risk factors of liver metastasis from colorectal cancer: correlation with CD10 expression

BackgroundThe risk factors for liver metastasis from colorectal cancer are still unclear. We therefore evaluated the relationships between various clinicopathological factors, including CD10 expression, liver metastasis, and survival, in patients with colorectal cancer.

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

ObjectiveTo study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer (NSCLC).