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Sample records for advanced gastrointestinal cancer

  1. Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  2. Nutritional status and related factors of patients with advanced gastrointestinal cancer.

    PubMed

    Zhang, Liyan; Lu, Yuhan; Fang, Yu

    2014-04-14

    The scored Patient-Generated Subjective Global Assessment (PG-SGA) is considered to be the most appropriate tool for detecting malnutrition in cancer patients. In particular, malignant tumours derived from the gastrointestinal tract may impair nutrient intake and absorption and cause malnutrition. We carried out a cross-sectional study to assess the nutritional status and related factors of patients with gastrointestinal cancer. Nutritional status was determined using the scored PG-SGA in patients (n 498) with advanced gastrointestinal cancer admitted to the Gastrointestinal Medical Oncology Unit at Beijing Cancer Hospital between 1 August 2012 and 28 February 2013. The possible related factors including age, sex, hospitalisation frequency and pathology were explored. We found that 98% of the patients required nutrition intervention and 54% of the patients required improved nutrition-related symptom management and/or urgent nutritional support (PG-SGA score ≥9). Factors related to malnutrition were age (r 0.103, P<0.01), hospitalisation frequency (r -0.196, P<0.01) and sex (the prevalence of malnutrition was higher in men than in women (9.88 v. 8.54, P<0.01)). Patients with rectal cancer had a lower risk of malnutrition than patients with other types of gastrointestinal cancer (F=35.895, P<0.01). More attention should be paid to the nutritional status of gastrointestinal patients, especially those at a higher risk of malnutrition, such as elderly patients, those hospitalised for the first time, male patients and those with other types of gastrointestinal cancer except rectal cancer. The nutritional status of these patients should be evaluated and they should be given proper nutrition education and nutritional support in a timely manner.

  3. Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-03-28

    Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

  4. Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-01-03

    Adenocarcinoma of Unknown Primary; Adult Cholangiocarcinoma; Gallbladder Carcinoma; Gastric Adenocarcinoma; Malignant Gastrointestinal Neoplasm; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Stage III Ampulla of Vater Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IV Ampulla of Vater Cancer; Stage IV Gallbladder Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer

  5. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update.

    PubMed

    Aprile, Giuseppe; Rihawi, Karim; De Carlo, Elisa; Sonis, Stephen T

    2015-11-07

    Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.

  6. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update

    PubMed Central

    Aprile, Giuseppe; Rihawi, Karim; De Carlo, Elisa; Sonis, Stephen T

    2015-01-01

    Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient’s quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient’s outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient’s compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer. PMID:26557003

  7. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    ClinicalTrials.gov

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  8. Asbestos and Gastrointestinal Cancer

    PubMed Central

    Morgan, Robert W.; Foliart, Donna E.; Wong, Otto

    1985-01-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, we listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, we calculated summary SMRs for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMRs remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. Based on the results after reanalysis, the elevations in summary SMRs for stomach and total gastrointestinal tract cancer are of a magnitude that could result from diagnostic and investigator error. We conclude that more studies are required before stomach and colorectal cancers are documented as asbestos-related diseases. PMID:4036114

  9. Asbestos and gastrointestinal cancer

    SciTech Connect

    Morgan, R.W.; Foliart, D.E.; Wong, O.

    1985-07-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, the authors listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, summary SMRs were calculated for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMR remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. 59 references, 5 tables.

  10. Intensity-modulated radiotherapy reduces gastrointestinal toxicity in locally advanced pancreas cancer

    PubMed Central

    Prasad, Shreya; Cambridge, Lajhem; Huguet, Florence; Chou, Joanne F.; Zhang, Zhigang; Wu, Abraham J.; O'Reilly, Eileen M.; Allen, Peter; Goodman, Karyn A.

    2016-01-01

    Purpose We compared gastrointestinal (GI) and hematologic toxicity in patients with locally advanced pancreas cancer (LAPC) undergoing definitive chemoradiation using intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3D-CRT) planning. Methods and Materials We retrospectively studied 205 patients with LAPC undergoing IMRT (n=134) and 3D-CRT (n=71) between 05/03 and 03/12. Patient, tumor, and treatment characteristics and acute GI/hematology toxicity according to Common Terminology Criteria for Adverse Events v3.0 were recorded. Multivariable logistic regression models were used to test association between acute grade 2+ GI and hematologic toxicity outcomes and predictors. Propensity score analysis for grade 2+ GI toxicity was performed to reduce bias for confounding variables: age, gender, radiation dose, field size, and chemotherapy type. Results Median follow-up time for survivors was 22 months, similar between groups. Median RT dose was significantly higher for IMRT vs. 3D-CRT (5600 cGy vs 5040 cGy, P<.001); concurrent chemotherapy was mainly gemcitabine (56%) or 5-fluorouracil (5-FU, 38%). Grade 2+ GI toxicity occurred in 34% (n=24) of 3D-CRT compared with 16% (n=21) of IMRT patients. Using propensity-score analysis, 3D-CRT had significantly higher grade 2+ GI toxicity (odds ratio, 1.26 [95%CI, 1.08-1.45], P=.001). Grade 2+ hematologic toxicity was similar between IMRT and 3D-CRT groups but was significantly greater in recipients of concurrent gemcitabine over 5-FU (62% vs 29%, P<.0001). Conclusions IMRT is associated with significant lower grade 2+ GI toxicity versus 3D-CRT for patients undergoing definitive chemoradiotherapy for LAPC. Since IMRT is better tolerated at higher doses and may allow further dose escalation, potentially improving local control for this aggressive disease. Further prospective studies of dose-escalated chemoradiation using IMRT are warranted. PMID:26577010

  11. Advances in gastrointestinal bleeding.

    PubMed

    Lanas, Ángel

    2016-09-01

    The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations.

  12. Hereditary gastrointestinal cancer.

    PubMed

    Hata, Keisuke; Yamamoto, Yoko; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kishikawa, Junko; Nagai, Yuzo; Anzai, Hiroyuki; Shinagawa, Takahide; Arakawa, Keiichi; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2016-10-01

    Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.

  13. Hereditary gastrointestinal cancer syndromes.

    PubMed

    Lynch, Henry T; Lynch, Jane F; Shaw, Trudy G

    2011-07-01

    The rapid growth of molecular genetics and its attendant germline mutation discoveries has enabled identification of persons who are at an inordinately high cancer risk and, therefore, ideal candidates for prevention. However, one must fully appreciate the extensive genotypic and phenotypic heterogeneity that exists in hereditary cancer. Once the causative germline mutation has been identified in a patient, high-risk members of the family can be similarly tested and identified and provided highly targeted surveillance and management opportunities. DNA testing can change the individual's presumed risk status and affect decision making by patients and their physicians regarding surveillance and management. Our purpose is to describe familial/hereditary cancers of the gastrointestinal tract, including familial Barrett's esophagus, hereditary diffuse gastric cancer, gastrointestinal stromal tumors, familial adenomatous polyposis and desmoid tumors, Lynch syndrome, small bowel cancer, and familial pancreatic cancer. We use our discussion of Lynch syndrome as a model for diagnostic and clinical translation strategies for all hereditary gastrointestinal tract cancers, which clearly can then be extended to cancer of all anatomic sites. Highly pertinent questions from the patient's perspective include the following: What kind of counseling will be provided to a patient with a Lynch syndrome mutation, and should that counseling be mandatory? Does the proband have the responsibility to inform relatives about the familial mutation, even if the relatives do not want to know whether they carry it? Is the patient is responsible for notifying family members that a parent or sibling has Lynch syndrome? Can notification be forced and, if so, under what circumstances? These questions point out the need for criteria regarding which family members to inform and how to inform them.

  14. Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2017-01-31

    Bile Duct Carcinoma; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Liver Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIA Small Intestinal Cancer; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIB Small Intestinal Cancer; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Liver Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colon Cancer; Stage IVA Esophageal Cancer; Stage IVA Liver Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Esophageal Cancer; Stage IVB Liver Cancer; Stage IVB Rectal Cancer

  15. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014

    PubMed Central

    Tsvetkova, E.; Sud, S.; Aucoin, N.; Biagi, J.; Burkes, R.; Samson, B.; Brule, S.; Cripps, C.; Colwell, B.; Falkson, C.; Dorreen, M.; Goel, R.; Halwani, F.; Maroun, J.; Michaud, N.; Tehfe, M.; Thirlwell, M.; Vickers, M.; Asmis, T.

    2015-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23–25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer. PMID:26300681

  16. Alternative methods of interpreting quality of life data in advanced gastrointestinal cancer patients

    PubMed Central

    Nordin, K; Steel, J; Hoffman, K; Glimelius, B

    2001-01-01

    Understanding of how to analyse and interpret quality of life (QoL) data from clinical trials in patients with advanced cancer is limited. In order to increase the knowledge about the possibilities of drawing conclusions from QoL data of these patients, data from 2 trials were reanalysed. A total of 113 patients with pancreatic, biliary or gastric cancer were included in 2 randomised trials comparing chemotherapy and best supportive care (BSC) with BSC alone. Patient benefit was evaluated by the treating physician (subjective response) and by using selected scales and different summary measures of the EORTC QLQ-C30 questionnaire. An increasing number of drop-outs (mainly due to death) with time did not occur in a random fashion. Therefore, the mean scores in the different subscales of the QLQ-C30 obtained during the follow-up of interviewed patients did not reflect the outcome of the randomised population. The scores of the patient-provided summary measure, ‘Global health status/QoL’, were stable in a rather high proportion of the patients and could not discriminate between the 2 groups. 3 other summary measures revealed greater variability, and they all discriminated between the 2 groups. A high agreement was also seen between the changes in the summary measures and the subjective response. A categorisation of whether an individual patient had benefited or not from the intervention could overcome the problem with the selective attrition. © 2001 Cancer Research Campaign PMID:11720459

  17. Is there a standard of care for the management of advanced pancreatic cancer?. Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 25-27, 2008.

    PubMed

    Saif, Muhammad Wasif

    2008-03-08

    Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the outcome for this disease remains dismal. Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic and targeted agents have been pitted against or combined with gemcitabine in randomized phase III trials and no drug was shown to be superior to single-agent gemcitabine except two gemcitabine-containing combinations: capecitabine plus gemcitabine vs. gemcitabine and erlotinib. In this article, the author debates: "Is there a standard of care for the treatment of advanced pancreatic cancer?". In addition, he summarizes the key studies presented at the "Gastrointestinal Cancers Symposium" held in Orlando, FL, USA on January 25-27, 2008. The studies discussed here include the following: i) a phase I study of a chemotherapy doublet gemcitabine plus capecitabine, combined with a biologic doublet (bevacizumab plus erlotinib) in patients with advanced pancreatic adenocarcinoma (abstract #141); ii) a phase II study of gemcitabine, bevacizumab, and erlotinib in locally advanced and metastatic adenocarcinoma of the pancreas (abstract #151); iii) final results of the multicenter phase II study on gemcitabine, capecitabine, and bevacizumab in patients with advanced pancreatic cancer (abstract #198); iv) interim results from a phase II study of volociximab in combination with gemcitabine in patients with metastatic pancreatic cancer (abstract #142); v) a pilot study of combination chemotherapy with S-1 and irinotecan for advanced pancreatic cancer (abstract #155); vi) a multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer (abstract #212); vii) a phase I/II study of PHY906 plus capecitabine in patients with advanced pancreatic carcinoma (abstract #260); and viii) the final results of a phase II trial of

  18. Updates on surgical management of advanced gastric cancer: new evidence and trends. Insights from the First International Course on Upper Gastrointestinal Surgery--Varese (Italy), December 2, 2011.

    PubMed

    Rausei, Stefano; Dionigi, Gianlorenzo; Sano, Takeshi; Sasako, Mitsuru; Biondi, Alberto; Morgagni, Paolo; Garofalo, Alfredo; Boni, Luigi; Frattini, Francesco; D'Ugo, Domenico; Preston, Shaun; Marrelli, Daniele; Degiuli, Maurizio; Capella, Carlo; Sacco, Rosario; Ruspi, Laura; De Manzoni, Giovanni; Roviello, Franco; Pinotti, Graziella; Rovera, Francesca; Noh, Sung Hoon; Coit, Daniel; Dionigi, Renzo

    2013-11-01

    Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.

  19. Advances in upper gastrointestinal endoscopy

    PubMed Central

    Graham, David G.; Banks, Matthew R.

    2015-01-01

    The rapidly moving technological advances in gastrointestinal endoscopy have enhanced an endoscopist’s ability to diagnose and treat lesions within the gastrointestinal tract. The improvement in image quality created by the advent of high-definition and magnification endoscopy, alongside image enhancement, produces images of superb quality and detail that empower the endoscopist to identify important lesions that have previously been undetectable. Additionally, we are now seeing technologies emerge, such as optical coherence tomography and confocal laser endomicroscopy, that allow the endoscopist to visualize individual cells on a microscopic level and provide a real time, in vivo histological assessment. Within this article we discuss these technologies, as well as some of the results from their early use in clinical studies. PMID:26918137

  20. Cancer stem cells in human gastrointestinal cancer.

    PubMed

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  1. Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

    SciTech Connect

    Nakamura, Akira; Shibuya, Keiko; Matsuo, Yukinori; Nakamura, Mitsuhiro; Shiinoki, Takehiro; Mizowaki, Takashi; Hiraoka, Masahiro

    2012-10-01

    Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel

  2. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers

    PubMed Central

    Kim, Jung Hoon; Kim, Bum Jun; Kim, Hyeong Su; Kim, Jung Han

    2016-01-01

    Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers. PMID:27698896

  3. Updates in Tumor Profiling in Gastrointestinal Cancers.

    PubMed

    Perez, Kimberly; Safran, Howard P

    2015-10-01

    In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.

  4. Molecular Testing for Gastrointestinal Cancer

    PubMed Central

    Lee, Hye Seung; Kim, Woo Ho; Kwak, Yoonjin; Koh, Jiwon; Bae, Jeong Mo; Kim, Kyoung-Mee; Chang, Mee Soo; Han, Hye Seung; Kim, Joon Mee; Kim, Hwal Woong; Chang, Hee Kyung; Choi, Young Hee; Park, Ji Y.; Gu, Mi Jin; Lhee, Min Jin; Kim, Jung Yeon; Kim, Hee Sung; Cho, Mee-Yon

    2017-01-01

    With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians. PMID:28219002

  5. Optimizing early upper gastrointestinal cancer detection at endoscopy.

    PubMed

    Veitch, Andrew M; Uedo, Noriya; Yao, Kenshi; East, James E

    2015-11-01

    Survival rates for upper gastrointestinal cancers are poor and oesophageal cancer incidence is increasing. Upper gastrointestinal cancer is also often missed during examinations; a predicament that has not yet been sufficiently addressed. Improvements in the detection of premalignant lesions, early oesophageal and gastric cancers will enable organ-preserving endoscopic therapy, potentially reducing the number of advanced upper gastrointestinal cancers and resulting in improved prognosis. Japan is a world leader in high-quality diagnostic upper gastrointestinal endoscopy and the clinical routine in this country differs substantially from Western practice. In this Perspectives article, we review lessons learnt from Japanese gastroscopy technique, training and screening for risk stratification. We suggest a key performance indicator for upper gastrointestinal endoscopy with a minimum total procedure time of 8 min, and examine how quality assurance concepts in bowel cancer screening in the UK could be applied to upper gastrointestinal endoscopy and improve clinical practice.

  6. Oxaliplatin Plus Irinotecan in Treating Patients With Metastatic Gastrointestinal Cancer

    ClinicalTrials.gov

    2013-06-24

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  7. Hedgehog signaling and gastrointestinal cancer

    PubMed Central

    Saqui-Salces, Milena; Merchant, Juanita L.

    2017-01-01

    Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De-regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID:20307590

  8. Gastrointestinal Cancer: Nutritional Support

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter reviews the prevalence and causes of malnutrition in cancer, the impact that malnutrition has on clinical outcomes, and the means by which the problem of malnutrition in this setting can best be addressed. The type of cancer is an important determinant of the likelihood of develop...

  9. Paraneoplastic thrombocytosis in gastrointestinal cancer.

    PubMed

    Baranyai, Zsolt; Jósa, Valéria; Tóth, Ambrus; Szilasi, Zsuzsanna; Tihanyi, Balazs; Zaránd, Attila; Harsanyi, Laszlo; Szállási, Zoltán

    2016-06-01

    It has been demonstrated recently in several solid tumors that thrombocytosis at diagnosis may correlate with tumor invasion, metastatic progression and worse outcome. Several details of the pathomechanism of the relationship of thrombocytosis and cancer have been elucidated; however, the complete process is not clearly understood. Several hypotheses have been proposed. Recently, it was suggested that in ovarian cancer elevated IL-6 production by the tumor may induce increased megakaryopoiesis via hepatic thrombopoietin production leading to thrombocytosis. The importance of the prognostic power of elevated platelet count is still debated in gastrointestinal cancer. The aims of this review were to evaluate the prognostic significance of thrombocytosis in gastrointestinal tumors, to see whether clinical practice confirmed the hypotheses and to reveal the causes of the inconsistent findings.

  10. Developments in immunotherapy for gastrointestinal cancer.

    PubMed

    Diaz, J L; Wanta, S M; Fishbein, T M; Kroemer, A

    2015-08-01

    Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy.

  11. Asbestos-Induced Gastrointestinal Cancer: An Update

    PubMed Central

    Kim, Seok Jo; Williams, David; Cheresh, Paul; Kamp, David W

    2016-01-01

    Asbestos-related diseases, such as malignancies and asbestosis, remain a significant occupational and public health concern. Asbestos is still widely used in many developing countries despite being a recognized carcinogen that has been banned over 50 countries. The prevalence and mortality from asbestos-related diseases continue to pose challenges worldwide. Many countries are now experiencing an epidemic of asbestos-related disease that is the legacy of occupational exposure during the 20th century because of the long latency period (up to 40 years) between initial asbestos exposure and exhibition of disease. However, the gastrointestinal (GI) cancers resulting from asbestos exposure are not as clearly defined. In this review, we summarize some of the recent epidemiology of asbestos-related diseases and then focus on the evidence implicating asbestos in causing GI malignancies. We also briefly review the important new pathogenic information that has emerged over the past several years that may account for asbestos-related gastrointestinal cancers. All types of asbestos fibers have been implicated in the mortality and morbidity from GI malignancies but the collective evidence to date is mixed. Although the molecular basis of GI cancers arising from asbestos exposure is unclear, there have been significant advances in our understanding of mesothelioma and asbestosis that may contribute to the pathophysiology underlying asbestos-induced GI cancers. The emerging new evidence into the pathogenesis of asbestos toxicity is providing insights into the molecular basis for developing novel therapeutic strategies for asbestos-related diseases in future management. PMID:27158561

  12. Gastrointestinal and Other Cancers | Division of Cancer Prevention

    Cancer.gov

    [[{"fid":"181","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Gastrointestinal and Other Cancers Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Gastrointestinal and Other Cancers Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Gastrointestinal and Other Cancers Research Group Homepage Logo","title":"Gastrointestinal and Other Cancers Research Group Homepage Logo","height":" | Prevention and early detection of colorectal, esophageal, liver, pancreas and hematolymphoid cancers.

  13. Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers

    ClinicalTrials.gov

    2012-05-24

    Gastrointestinal Neoplasms; Gynecologic Cancers; Gynecologic Cancers Cervical Cancer; Gastric (Stomach) Cancer; Gastro-Esophageal(GE) Junction Cancer; Gastrointenstinal Stromal Tumor (GIST); Colon/Rectal Cancer; Colon/Rectal Cancer Colon Cancer; Colon/Rectal Cancer Rectal Cancer; Colon/Rectal Cancer Anal Cancer; Anal Cancer; Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Pancreatic Cancer

  14. Ubiquitin proteasome system research in gastrointestinal cancer

    PubMed Central

    Zhong, Jia-Ling; Huang, Chang-Zhi

    2016-01-01

    The ubiquitin proteasome system (UPS) is important for the degradation of proteins in eukaryotic cells. It is involved in nearly every cellular process and plays an important role in maintaining body homeostasis. An increasing body of evidence has linked alterations in the UPS to gastrointestinal malignancies, including esophageal, gastric and colorectal cancers. Here, we summarize the current literature detailing the involvement of the UPS in gastrointestinal cancer, highlighting its role in tumor occurrence and development, providing information for therapeutic targets research and anti-gastrointestinal tumor drug design. PMID:26909134

  15. Ubiquitin proteasome system research in gastrointestinal cancer.

    PubMed

    Zhong, Jia-Ling; Huang, Chang-Zhi

    2016-02-15

    The ubiquitin proteasome system (UPS) is important for the degradation of proteins in eukaryotic cells. It is involved in nearly every cellular process and plays an important role in maintaining body homeostasis. An increasing body of evidence has linked alterations in the UPS to gastrointestinal malignancies, including esophageal, gastric and colorectal cancers. Here, we summarize the current literature detailing the involvement of the UPS in gastrointestinal cancer, highlighting its role in tumor occurrence and development, providing information for therapeutic targets research and anti-gastrointestinal tumor drug design.

  16. Upper Gastrointestinal Cancer and Reflux Disease

    PubMed Central

    2013-01-01

    There is a growing evidence that gastroesophageal reflux disease is related to several upper gastrointestinal cancers, mainly the esophageal adenocarcinoma and a certain type of gastric cardia adenocarcinoma. Currently, the incidence of gastroesophageal reflux disease is rapidly increasing in Korea. Therefore, there is a possibility of such increasing cancerous incidents, similar to the western worlds. In this article, the relationship between gastroesophageal reflux disease and several upper gastrointestinal cancers, the components of refluxate which has possible causal relationship with carcinogenesis, and the clinical implications of such relationship in the management of gastroesophageal reflux disease patients are discussed through the review of literature. PMID:23844321

  17. Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer

    PubMed Central

    Huang, Fang; Wang, Bin-Rong; Wu, Ye-Qing; Wang, Fan-Chao; Zhang, Jian; Wang, Yi-Gang

    2016-01-01

    Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell (CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer (liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations. PMID:27672294

  18. [Full attention to several key issues in surgical treatment for the elderly patients with gastrointestinal cancer].

    PubMed

    Zhu, Zhenggang

    2016-05-01

    With the development of population aging in our country, the incidence of gastrointestinal cancer is increasing. The risk of developing gastrointestinal cancer in elderly over 75 years was 5-6 times and the risk of death of gastrointestinal cancer was 7-8 times of the general population. As compared to non-elderly, the incidence of gastric cancer was not decreased obviously but the total incidence of colorectal cancer was increased more quickly. Therefore, screening of gastrointestinal cancer should be performed in the elderly for early discovery, diagnosis and treatment. Because of the insidious onset of the illness in elderly patients, gastrointestinal cancers are mostly diagnosed at advanced or late stage (stage III or IV). Well differentiated cancer is more common, such as papillary or tubular adenocarcinoma. Lauren type, Borrmann II or III are more common in gastric cancer, which are relatively favorable. Compared with non-elderly patients, many elderly patients also suffer from comorbid diseases with higher operation risk and postoperative complication rates. Therefore, we must pay great attention to the perioperative management and the surgical operation for the elderly patients. In this paper, several key issues involved the development trend of incidence and mortality of gastrointestinal cancer, the clinicopathological characteristics, the comorbidity and surgical treatment in the elderly patients with gastrointestinal cancer will be elaborated, aiming at promoting further attention to the clinical therapeutic strategies, management measures and prognostic factors for the elderly patients with gastrointestinal cancer.

  19. State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract

    PubMed Central

    Coda, Sergio; Thillainayagam, Andrew V

    2014-01-01

    Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by

  20. Apigenin and its impact on gastrointestinal cancers.

    PubMed

    Lefort, Émilie C; Blay, Jonathan

    2013-01-01

    Apigenin (4',5,7-trihydroxyflavone, 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many fruits, vegetables, and herbs, the most abundant sources being the leafy herb parsley and dried flowers of chamomile. Present in dietary sources as a glycoside, it is cleaved in the gastrointestinal lumen to be absorbed and distributed as apigenin itself. For this reason, the epithelium of the gastrointestinal tract is exposed to higher concentrations of apigenin than tissues at other locations. This would also be true for epithelial cancers of the gastrointestinal tract. We consider the evidence for actions of apigenin that might hinder the ability of gastrointestinal cancers to progress and spread. Apigenin has been shown to inhibit cell growth, sensitize cancer cells to elimination by apoptosis, and hinder the development of blood vessels to serve the growing tumor. It also has actions that alter the relationship of the cancer cells with their microenvironment. Apigenin is able to reduce cancer cell glucose uptake, inhibit remodeling of the extracellular matrix, inhibit cell adhesion molecules that participate in cancer progression, and oppose chemokine signaling pathways that direct the course of metastasis into other locations. As such, apigenin may provide some additional benefit beyond existing drugs in slowing the emergence of metastatic disease.

  1. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  2. The role of nanotechnology in gastrointestinal cancer.

    PubMed

    Vyas, Dinesh; Castro, Pamela; Saadeh, Yamaan; Vyas, Arpita

    2014-11-01

    The rising interest in the utilization of nanoparticles for diagnosis and treatment in all cancers including gastrointestinal cancer has increased research interest, and funding in the area of medical nanotechnology. Interesting outcomes of research studies on different applications are published every day, and it include approaches such as molecular targeting, photodynamic therapy, and magnetic localization. The discoveries being made by research teams and the hypothesized applications are thus far very promising. There are limitations that must be researched and overcome, but the increasing evidence for the use of nanoparticles in cancer treatment cannot be ignored. In this review, several recent techniques are discussed on the development of more effective and targeted cellular/molecular techniques in the diagnosis and treatment of gastrointestinal cancer.

  3. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016

    PubMed Central

    Bossé, D.; Ng, T.; Ahmad, C.; Alfakeeh, A.; Alruzug, I.; Biagi, J.; Brierley, J.; Chaudhury, P.; Cleary, S.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Ferland, E.; Galiatsatos, P.; Girard, S.; Gray, S.; Halwani, F.; Kopek, N.; Mahmud, A.; Martel, G.; Robillard, L.; Samson, B.; Seal, M.; Siddiqui, J.; Sideris, L.; Snow, S.; Thirwell, M.; Vickers, M.; Goodwin, R.; Goel, R.; Hsu, T.; Tsvetkova, E.; Ward, B.; Asmis, T.

    2016-01-01

    The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5–7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents PMID:28050151

  4. Animal models of gastrointestinal inflammation and cancer.

    PubMed

    Lu, L; Chan, Ruby L Y; Luo, X M; Wu, William K K; Shin, Vivian Y; Cho, C H

    2014-07-11

    Inflammation and cancer are the two major disorders in the gastrointestinal tract. They are causally related in their pathogenesis. It is important to study animal models' causal relationship and, in particular, to discover new therapeutic agents for such diseases. There are several criteria for these models in order to make them useful in better understanding the etiology and treatment of the said diseases in humans. In this regard, animal models should be similar as possible to human diseases and also be easy to produce and reproducible and also economic to allow a continuous replication in different laboratories. In this review, we summarize the various animal models for inflammatory and cancerous disorders in the upper and lower gastrointestinal tract. Experimental approaches are as simple as by giving a single oral dose of alcohol or other noxious agents or by injections of multiple dosages of ulcer inducing agents or by parenteral administration or in drinking water of carcinogens or by modifying the genetic makeups of animals to produce relatively long-term pathological changes in particular organs. With these methods they could induce consistent inflammatory responses or tumorigenesis in the gastrointestinal mucosa. These animal models are widely used in laboratories in understanding the pathogenesis as well as the mechanisms of action for therapeutic agents in the treatment of gastrointestinal inflammation and cancer.

  5. Report from the 13th annual Western canadian gastrointestinal cancer consensus conference; calgary, alberta; september 8-10, 2011.

    PubMed

    Vickers, M M; Pasieka, J; Dixon, E; McEwan, S; McKay, A; Renouf, D; Schellenberg, D; Ruether, D

    2012-12-01

    The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8-10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer.

  6. Autofluorescence endoscopy for detecting gastrointestinal cancer

    NASA Astrophysics Data System (ADS)

    Chen, Xiaodong; Xu, Zhi; Xie, Hongbo; Chen, Dongqing; Yu, Daoyin

    2002-04-01

    A cost-effective autofluorescence detecting system has been developed by our research group to diagnose and localize the early gastrointestinal cancer, which is occult to the traditional means of detection, for example, biopsy. At the early stage, we utilize autofluorescence spectrum detected by OMA (Optical Multichannel Analyzer) to discriminate cancerous tissue. Although this method can effectively distinguish tumors from normal tissues, it is not suitable to be applied in clinic use due to the high cost of the- most-often used OMA-autofluorescence detector. Then we designed a novel Double PMTs (Photomultiply Tube) system, which consists of two parallel-working A/Ds with lower frequency of acquisition, to replace the OMA system, and the results of clinic experiments prove that it can effectively determine gastrointestinal cancers.

  7. Irisin immunohistochemistry in gastrointestinal system cancers.

    PubMed

    Aydin, S; Kuloglu, T; Ozercan, M R; Albayrak, S; Aydin, S; Bakal, U; Yilmaz, M; Kalayci, M; Yardim, M; Sarac, M; Kazez, A; Kocdor, H; Kanat, B; Ozercan, İ H; Gonen, M; Bilgen, M; Balgetir, F

    2016-01-01

    Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.

  8. Recent Advances in Human Protozoan Parasites of Gastrointestinal Tract

    DTIC Science & Technology

    1987-02-01

    frequency of oral-anal sexual contacts. No relation was seen between the presence or chance of gastrointestinal symptoms and infection with E...Lancet May 14: 1103. SPENCER MJ., CHAPIN M.R. & GARCIA L.S. 1962. Dientamoeba fragilis: A gastrointestinal protozoan infection in adults. American...ULIC EIL& p .( RECENT ADVANCES IN HUMAN PROTOZOAN PARASITES OF GASTROINTESTINAL TRACT J.H. Cross REPORT NO. CS -142 AD-A 182 878 ,ji.. ELECTE JULS j

  9. Gastrointestinal metastases from prostate cancer: a review of the literature.

    PubMed

    Maines, Francesca; Caffo, Orazio; Veccia, Antonello; Galligioni, Enzo

    2015-01-01

    The availability of active new drugs for the treatment of advanced castration-resistant prostate cancer has significantly prolonged overall survival, thus changing the natural history of the disease and raising the likelihood of observing metastases in atypical sites. This review of the literature describes the frequency, clinical-pathological features and presenting symptoms of non-liver gastrointestinal metastases (GIm) from prostate cancer. Its purpose is to increase clinical awareness of the increasing incidence of such GIm, contributing to the early detection, accurate diagnosis and, when feasible, appropriate management.

  10. Oral microbiome and oral and gastrointestinal cancer risk.

    PubMed

    Ahn, Jiyoung; Chen, Calvin Y; Hayes, Richard B

    2012-03-01

    A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through chronic inflammation. High-throughput genetic-based assays now make it possible to comprehensively survey the human oral microbiome, the totality of bacteria in the oral cavity. Establishing the association of the oral microbiome with cancer risk may lead to significant advances in understanding of cancer etiology, potentially opening a new research paradigm for cancer prevention.

  11. Translating genomic profiling to gastrointestinal cancer treatment.

    PubMed

    Harada, Kazuto; Mizrak Kaya, Dilsa; Shimodaira, Yusuke; Song, Shumei; Baba, Hideo; Ajani, Jaffer A

    2017-04-01

    Next-generation sequencing enables faster, cheaper and more accurate whole-genome sequencing, allowing genome profiling and discovery of molecular features. As molecular targeted drugs are developed, treatment can be tailored according to molecular subtype. Gastric and colorectal cancers have each been divided into four subtypes according to molecular features. Profiling of the esophageal cancer genome is underway and its classification is anticipated. To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions. However, to overcome therapy resistance and improve prognosis, further individualized therapy is required. Here, we summarize the treatment options for gastrointestinal cancer according to genomic profiling and discuss future directions.

  12. Impact of homeobox genes in gastrointestinal cancer

    PubMed Central

    Joo, Moon Kyung; Park, Jong-Jae; Chun, Hoon Jai

    2016-01-01

    Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal (GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1 (CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett’s esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers. PMID:27729732

  13. Human papillomavirus and gastrointestinal cancer: A review

    PubMed Central

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  14. [Clinical evaluation of ureteral stenting for managing extrinsic ureteral obstruction due to gynecological and gastrointestinal cancer].

    PubMed

    Takehara, Kosuke; Onita, Toru; Mochizuki, Yasushi; Miyata, Yasuyoshi; Igawa, Tsukasa; Sakai, Hideki

    2014-01-01

    We retrospectively reviewed patients who were treated with an indwelling ureteral stent to manage extrinsic ureteral obstruction due to advanced gynecological and gastrointestinal cancers. A total of 34 patients, including 17 with gynecological cancer and 17 with gastrointestinal cancer, underwent a successful initial ureteral stent placement from January 2007 to December 2011. Functional ureteral stent failures, which required percutaneous nephrostomy within 3 months after initial ureteral stenting, occurred in 14 of the 34 patients (41%) during follow-up. The risk factors of functional ureteral stent failure were bilateral ureteral obstruction, elevated serum creatinine level, poor performance status, subsequent therapy for primary cancer after ureteral stent placement, presence of peritonitis carcinomatosa, and gastrointestinal cancer. Patients with gastrointestinal cancer had a higher rate of stent failure than did those with gynecological cancer (p = 0.01). Median survival from the diagnosis of hydronephrosis for patients with gastrointestinal and gynecological cancers was 9 and 23 months, respectively (p = 0. 02). Retrograde ureteral stenting is a useful treatment for malignant ureteral obstruction. However, patients with gastrointestinal cancer had a high stent failure rate and a short survival time from the diagnosis of hydronephrosis. Indications for retrograde ureteral stenting for malignant ureteral obstruction should be carefully considered while taking into account stent failure risk, patient prognosis and quality of life.

  15. Surveillance of patients with hereditary gastrointestinal cancer syndromes.

    PubMed

    Moreira, Leticia; Castells, Antoni

    2016-12-01

    Gastrointestinal cancers are among the most frequent tumors. Although most cases are sporadic, up to 5-6% develops in the context of gastrointestinal hereditary syndromes. These entities have specific characteristics and often a germline mutation identified, thus allowing performing genetic counseling. This review summarizes the most common gastrointestinal hereditary syndromes, focusing on the surveillance recommendations.

  16. Robotics in advanced gastrointestinal surgery: the bariatric experience.

    PubMed

    Kim, Keith; Hagen, Monika E; Buffington, Cynthia

    2013-01-01

    Robotic surgery for laparoscopic procedures such as advanced gastrointestinal surgery and abdominal malignancies is currently on the rise. The first robotic systems have been used since the 1990s with increasing number of clinical cases and broader clinical applications each year. Although high-evidence-level data are scarce, studies suggest that the technical advantages of robotic surgery result in a clinical value for procedures of advanced complexity such as Roux-en-Y gastric bypass and revisional bariatric surgery. Ultimately, the digital interface of the robotic system with the option to integrate augmented reality and real-time imaging will allow advanced applications particularly in the field of gastrointestinal surgery for malignancies.

  17. Cancer Screening Among Patients With Advanced Cancer

    PubMed Central

    Sima, Camelia S.; Panageas, Katherine S.; Schrag, Deborah

    2013-01-01

    Context Cancer screening has been integrated into routine primary care but does not benefit patients with limited life expectancy. Objective To evaluate the extent to which patients with advanced cancer continue to be screened for new cancers. Design, Setting, and Participants Utilization of cancer screening procedures (mammography, Papanicolaou test, prostate-specific antigen [PSA], and lower gastrointestinal [GI] endoscopy) was assessed in 87 736 fee-for-service Medicare enrollees aged 65 years or older diagnosed with advanced lung, colorectal, pancreatic, gastroesophageal, or breast cancer between 1998 and 2005, and reported to one of the Surveillance, Epidemiology, and End Results (SEER) tumor registries. Participants were followed up until death or December 31, 2007, whichever came first. A group of 87 307 Medicare enrollees without cancer were individually matched by age, sex, race, and SEER registry to patients with cancer and observed over the same period to evaluate screening rates in context. Demographic and clinical characteristics associated with screening were also investigated. Main Outcome Measure For each cancer screening test, utilization rates were defined as the percentage of patients who were screened following the diagnosis of an incurable cancer. Results Among women following advanced cancer diagnosis compared with controls, at least 1 screening mammogram was received by 8.9% (95% confidence interval [CI], 8.6%-9.1%) vs 22.0% (95% CI, 21.7%-22.5%); Papanicolaou test screening was received by 5.8% (95% CI, 5.6%-6.1%) vs 12.5% (95% CI, 12.2%-12.8%). Among men following advanced cancer diagnosis compared with controls, PSA test was received by 15.0% (95% CI, 14.7%-15.3%) vs 27.2% (95% CI, 26.8%-27.6%). For all patients following advanced diagnosis compared with controls, lower GI endoscopy was received by 1.7% (95% CI, 1.6%-1.8%) vs 4.7% (95% CI, 4.6%-4.9%). Screening was more frequent among patients with a recent history of screening (16.2% [95

  18. Update in Cancer Chemotherapy: Gastrointestinal Cancer, Cancer of the Stomach and Carcinoid Tumors

    PubMed Central

    Wright, Jane C.

    1986-01-01

    Cancer chemotherapy in the treatment of advanced gastric cancer provides only palliation with perhaps increased survival time in some patients. The primary treatment of gastric carcinomas is surgical, as this is the only hope for cure. It is estimated that 80 to 85 percent of patients with newly diagnosed cases of stomach cancer will be dead of their disease within five years. Radiation therapy alone is seldom employed, except as a palliative measure to control hemorrhage or pain. There are no data to suggest that postoperative radiation increases survival rates. Single-agent chemotherapy is of temporary palliative value in 20 to 30 percent of cases with a duration of response from three to five months. Combination chemotherapy has shown a somewhat higher response rate than single-agent therapy. In advanced gastric cancer, there is no evidence of improved long-term disease-free survival rates with any combination yet reported. The treatment of carcinoid cancer of the intestinal tract is surgical removal, as this offers the only hope of cure. Radiation therapy is of little benefit, except for moderate palliation in cases of extensive liver metasasis. Carcinoid cancers are moderately sensitive to chemotherapy. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers is probably due to lack of data. PMID:3528508

  19. Melatonin as a treatment for gastrointestinal cancer: a review.

    PubMed

    Xin, Zhenlong; Jiang, Shuai; Jiang, Peng; Yan, Xiaolong; Fan, Chongxi; Di, Shouyin; Wu, Guiling; Yang, Yang; Reiter, Russel J; Ji, Gang

    2015-05-01

    Gastrointestinal cancer is a disease that affects the population worldwide with high morbidity and mortality. Melatonin, an endogenously produced molecule, may provide a defense against a variety of cancer types. In particular, the ability of melatonin to inhibit gastrointestinal cancer is substantial. In this review, we first clarify the relationship between the disruption of the melatonin rhythm and gastrointestinal cancer (based on epidemiologic surveys and animal and human studies) and summarize the preventive effect of melatonin on carcinogenesis. Thereafter, the mechanisms through which melatonin exerts its anti-gastrointestinal cancer actions are explained, including inhibition of proliferation, invasion, metastasis, and angiogenesis, and promotion of apoptosis and cancer immunity. Moreover, we discuss the drug synergy effects and the role of melatonin receptors involved in the growth-inhibitory effects on gastrointestinal cancer. Taken together, the information compiled here serves as a comprehensive reference for the anti-gastrointestinal cancer actions of melatonin that have been identified to date and will hopefully aid in the design of further experimental and clinical studies and increase the awareness of melatonin as a therapeutic agent in cancers of the gastrointestinal tract.

  20. Glycomic Approaches for the Discovery of Targets in Gastrointestinal Cancer

    PubMed Central

    Mereiter, Stefan; Balmaña, Meritxell; Gomes, Joana; Magalhães, Ana; Reis, Celso A.

    2016-01-01

    Gastrointestinal (GI) cancer is the most common group of malignancies and many of its types are among the most deadly. Various glycoconjugates have been used in clinical practice as serum biomarker for several GI tumors, however, with limited diagnose application. Despite the good accessibility by endoscopy of many GI organs, the lack of reliable serum biomarkers often leads to late diagnosis of malignancy and consequently low 5-year survival rates. Recent advances in analytical techniques have provided novel glycoproteomic and glycomic data and generated functional information and putative biomarker targets in oncology. Glycosylation alterations have been demonstrated in a series of glycoconjugates (glycoproteins, proteoglycans, and glycosphingolipids) that are involved in cancer cell adhesion, signaling, invasion, and metastasis formation. In this review, we present an overview on the major glycosylation alterations in GI cancer and the current serological biomarkers used in the clinical oncology setting. We further describe recent glycomic studies in GI cancer, namely gastric, colorectal, and pancreatic cancer. Moreover, we discuss the role of glycosylation as a modulator of the function of several key players in cancer cell biology. Finally, we address several state-of-the-art techniques currently applied in this field, such as glycomic and glycoproteomic analyses, the application of glycoengineered cell line models, microarray and proximity ligation assay, and imaging mass spectrometry, and provide an outlook to future perspectives and clinical applications. PMID:27014630

  1. Dual Roles for Immunity in Gastrointestinal Cancers

    PubMed Central

    Ferrone, Cristina; Dranoff, Glenn

    2010-01-01

    Histopathologic examination reveals that most human tumors are associated with diverse immune cell infiltrates, but the roles of host reactions in disease pathogenesis and prognosis remain to be fully clarified. Recent investigations in genetically engineered murine tumor models have uncovered dual functions for immune responses during cancer development and progression. Alterations in tumor cell gene expression profiles and coding sequences may trigger the activation of cytotoxic lymphocytes, which act to restrain tumor growth. In contrast, persistent inflammatory reactions, which may be driven by infection, environmental toxins, or impaired immune regulation, create a microenvironment that fosters tumor cell growth, survival, invasion, and dissemination. The dynamic interplay of these competing responses appears to be a critical event in cancer pathogenesis, with tumor promotion and immune evasion proving dominant in clinically evident disease. Nonetheless, longitudinal studies of patient cohorts have demonstrated that particular histopathologic and genetic signatures of cytotoxic lymphocyte reactions provide important prognostic information. Here, we discuss the dual roles of immunity in cancer development, focusing on gastrointestinal malignancies, given the depth of recent insights into the mechanisms underlying these tumors. PMID:20644090

  2. Immune targeting of cancer stem cells in gastrointestinal oncology

    PubMed Central

    Grossenbacher, Steven K.; Ames, Erik; Murphy, William J.

    2016-01-01

    The cancer stem cell (CSC) hypothesis postulates that a sub-population of quiescent cells exist within tumors which are resistant to conventional cytotoxic/anti-proliferative therapies. It is these CSCs which then seed tumor relapse, even in cases of apparent complete response to systemic therapy. Therefore, therapies, such as immunotherapy, which add a specific anti-CSC strategy to standard cytoreductive treatments may provide a promising new direction for future cancer therapies. CSCs are an attractive target for immune therapies since, unlike chemotherapy or radiotherapy, immune effector cells do not specifically require target cells to be proliferating in order to effectively kill them. Although recent advances have been made in the development of novel systemic and targeted therapies for advanced gastro-intestinal (GI) malignancies, there remains an unmet need for durable new therapies for these refractory malignancies. Novel immunotherapeutic strategies targeting CSCs are in pre-clinical and clinical development across the spectrum of the immune system, including strategies utilizing adaptive immune cell-based effectors, innate immune effectors, as well as vaccine approaches. Lastly, since important CSC functions are affected by the tumor microenvironment, targeting of both cellular (myeloid derived suppressor cells and tumor-associated macrophages) and sub-cellular (cytokines, chemokines, and PD1/PDL1) components of the tumor microenvironment is under investigation in the immune targeting of CSCs. These efforts are adding to the significant optimism about the potential utility of immunotherapy to overcome cancer resistance mechanisms and cure greater numbers of patients with advanced malignancy. PMID:27034806

  3. Report from the 13th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; September 8–10, 2011

    PubMed Central

    Vickers, M.M.; Pasieka, J.; Dixon, E.; McEwan, S.; McKay, A.; Renouf, D.; Schellenberg, D.; Ruether, D.

    2012-01-01

    The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8–10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer. PMID:23300370

  4. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

    PubMed Central

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  5. Cholecystokinin and gastrin receptors targeting in gastrointestinal cancer.

    PubMed

    Rai, Rajani; Chandra, Vishal; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2012-12-01

    Cholecystokinin and Gastrin are amongst the first gastrointestinal hormone discovered. In addition to classical actions (contraction of gallbladder, growth and secretion in the stomach and pancreas), these also act as growth stimulants for gastrointestinal malignancies and cell lines. Growth of these tumours is inhibited by antagonists of the cholecystokinin and gastrin receptors. These receptors provides most promising approach in clinical oncology and several specific radiolabelled ligands have been synthesized for specific tumour targeting and therapy of tumours overexpressing these receptors. Therefore, definition of the molecular structure of the receptor involved in the autocrine/paracrine loop may contribute to novel therapies for gastrointestinal cancer. Hence, this review tries to focus on the role and distribution of these hormones and their receptors in gastrointestinal cancer with a brief talk about the clinical trial using available agonist and antagonist in gastrointestinal cancers.

  6. Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

    PubMed

    Giordani, Erika; Zoratto, Federica; Strudel, Martina; Papa, Anselmo; Rossi, Luigi; Minozzi, Marina; Caruso, Davide; Zaccarelli, Eleonora; Verrico, Monica; Tomao, Silverio

    2016-01-01

    Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

  7. About the Gastrointestinal and Other Cancers Research Group | Division of Cancer Prevention

    Cancer.gov

    The Gastrointestinal and Other Cancers Research Group conducts and supports prevention and early detection research on colorectal, esophageal, liver, pancreatic, and hematolymphoid cancers, as well as new approaches to clinical prevention studies including cancer immunoprevention. |

  8. Trends in Gastrointestinal Cancer Mortality Rate in Hungary.

    PubMed

    Farkas, Klaudia; Szűcs, Mónika; Nyári, Tibor András

    2016-10-01

    The aim of this study was to investigate the annual death trends for gastrointestinal cancer in Hungary between 1963 and 2012. Data on the numbers of cancer deaths were obtained from the published nationwide population register. Numbers of deaths from esophageal, gastric and colorectal cancer were available during the study period. However, the mortality data for hepatic, pancreatic and gallbladder cancer have been published only since 1979. Joinpoint regression was applied to investigate the annual trends in the rates of cancer mortality. The annual mortality rates of gastric and gallbladder cancer decreased throughout the study period. Furthermore, declines in mortality from esophageal and hepatic cancers have been observed since 1998 and 1995, respectively. However, the rates of colorectal and pancreatic cancer mortality have been increasing in the past few years. Nevertheless, the mortality rates of colorectal and pancreatic cancers have increased in males aged 40-59 years during the study period. Moreover, significantly higher risks of gastrointestinal cancer-related deaths have been observed in males as compared with females except for death related to cancer of the gallbladder. The presented data suggest that the Hungarian mortality rates are particularly high. The detection of gastrointestinal cancers at an early stage would significantly improves the outcome of these malignancies.

  9. Advances in colon cancer.

    PubMed

    Levin, Mark

    2003-06-01

    From May 29 to June 5, 2003, the American Society of Clinical Oncology held its 39th Annual Meeting in Chicago, Illinois, U.S.A. The meeting was devoted to the presentation of advances in clinical sciences, diagnosis, prevention and management of malignant disorders, and brings together investigators, clinicians, policy makers and other professionals interested in the science and impact of cancer worldwide. This report will be presented in two parts, the first focusing of colon cancer, and the second on breast cancer will be published in the next issue of Drug News & Perspectives.

  10. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  11. Engagement of Patients With Advanced Cancer

    ClinicalTrials.gov

    2016-11-15

    End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

  12. The therapeutic value of targeting inflammation in gastrointestinal cancers

    PubMed Central

    Sun, Beicheng; Karin, Michael

    2014-01-01

    Inflammation has been implicated in the initiation and progression of gastrointestinal (GI) cancers. Inflammation also plays important roles in subverting immune tolerance, escape from immune surveillance, and conferring resistance to chemotherapeutic agents. Targeting key regulators and mediators of inflammation represents an attractive strategy for GI cancer prevention and treatment. However, the targeting of inflammation in GI cancer is not straight-forward and sometimes inflammation may contribute to tumor regression. We discuss the origins and effects of inflammation in GI cancer and how to target it successfully. PMID:24881011

  13. Role of the microbiome in non-gastrointestinal cancers

    PubMed Central

    Pevsner-Fischer, Meirav; Tuganbaev, Timur; Meijer, Mariska; Zhang, Sheng-Hong; Zeng, Zhi-Rong; Chen, Min-Hu; Elinav, Eran

    2016-01-01

    “The forgotten organ”, the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as “local” and “systemic”, “cancer-stimulating” and “cancer-suppressing” effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment. PMID:27081642

  14. Overview of gastrointestinal cancer prevention in Asia.

    PubMed

    Park, Jong-Min; Lee, Ho-Jae; Yoo, Jun Hwan; Ko, Weon Jin; Cho, Joo Young; Hahm, Ki Baik

    2015-12-01

    "War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic

  15. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  16. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

    PubMed Central

    Verma, Sugreev; Kesh, Kousik; Ganguly, Nilanjan; Jana, Sayantan; Swarnakar, Snehasikta

    2014-01-01

    The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is

  17. A metronomic schedule as salvage chemotherapy for upper gastrointestinal tract cancer.

    PubMed

    Roberto, Michela; Romiti, Adriana; Onesti, Concetta E; D'Antonio, Chiara; Milano, Annalisa; Falcone, Rosa; Barucca, Viola; Palombi, Lucia; Righini, Riccardo; Marchetti, Paolo

    2016-02-01

    In recent years, metronomic chemotherapy, consisting of continuous administration of low doses of cytotoxic agents, has being used as rescue therapy for different tumours. The aim of this study was to retrospectively assess the efficacy and safety of low-dose metronomic, oral capecitabine in pretreated or frail patients with recurrent upper gastrointestinal tract cancer. Patients with pretreated upper gastrointestinal tract cancer or who were not candidates for standard chemotherapy because of toxicity concerns received capecitabine at 1500 mg per day continuously until disease progression or occurrence of toxicity. Forty-seven patients (25 oesophagogastric cancer, 22 pancreatobiliary cancer; 25 men, 22 women; median age 69 years, range 42-90) were included in the study. Forty-five percent of the patients had received at least two previous lines of treatment and the median number of previous treatments was 1 (range 0-5). Twelve (31.6%) patients achieved clinical benefit (one partial response, 11 stable disease), whereas nine (23.7%) patients were progression free for at least 6 months. In an exploratory analysis, there was a significant relationship between performance status and clinical benefit (hazard ratio=8.25; P=0.01). The median overall survival was 5 months. A good performance status was associated with a longer survival (hazard ratio=0.26; P<0.01). No severe toxicity or treatment-related death was reported. Metronomic capecitabine showed good safety and moderate activity in frail or pretreated patients with advanced, upper gastrointestinal tract cancer.

  18. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    ClinicalTrials.gov

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  19. [Hot spots in basic research fields for gastrointestinal cancer].

    PubMed

    Liu, Bingya

    2014-01-01

    Today, the comprehensive surgical treatment for gastrointestinal cancer is almost in the perfect stage. It is difficult to further improve the curative effect by surgery only. To improve the overall curative effect of gastrointestinal tumor, translational medicine research should be promoted in the fields of the early diagnosis, etiology and pathogenesis and comprehensive treatment. Researches of discovering the new tumor markers for early diagnosis of tumor, etiology and pathogenesis involve many aspects, including environmental factors, genetic susceptibility, variation and accumulation of genetics, and epigenetic changes, which should be transferred to new methods of treatment. This review summarizes the gastrointestinal tumor-associated hot topics in the field of basic research and its progress, and provides the clinical clues from their conversion.

  20. Gastrointestinal cancer and brain metastasis: a rare and ominous sign.

    PubMed

    Go, Pauline H; Klaassen, Zachary; Meadows, Michael C; Chamberlain, Ronald S

    2011-08-15

    Metastatic brain tumors represent 20% to 40% of all intracranial neoplasms and are found most frequently in association with lung cancer (50%) and breast cancer (12%). Although brain metastases occur in <4% of all tumors of the gastrointestinal (GI) tract, the incidence of GI brain metastasis is rising in part due to more effective systemic treatments and prolonged survival of patients with GI cancer. Data were collected from 25 studies (11 colorectal, 7 esophageal, 2 gastric, 1 pancreatic, 1 intestinal, 3 all-inclusive GI tract cancer) and 13 case reports (4 pancreatic, 4 gallbladder, and 5 small bowel cancer). Brain metastases are found in 1% of colorectal cancer, 1.2% of esophageal cancer, 0.62% of gastric cancer, and 0.33% of pancreatic cancer cases. Surgical resection with whole brain radiation therapy (WBRT) has been associated with the longest median survival (38.4-262 weeks) compared with surgery alone (16.4-70.8 weeks), stereotactic radiosurgery (20-38 weeks), WBRT alone (7.2-16 weeks), or steroids (4-7 weeks). Survival in patients with brain metastasis from GI cancer was found to be diminished compared with metastases arising from the breast, lung, or kidney. Prolonged survival and improvement in clinical symptoms has been found to be best achieved with surgical resection and WBRT. Although early treatment has been linked to prolonged survival and improved quality of life, brain metastases represent a late manifestation of GI cancers and remain an ominous sign.

  1. Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer

    PubMed Central

    Arner, Peter; Henjes, Frauke; Schwenk, Jochen M.; Darmanis, Spyros; Dahlman, Ingrid; Iresjö, Britt-Marie; Naredi, Peter; Agustsson, Thorhallur; Lundholm, Kent; Nilsson, Peter; Rydén, Mikael

    2015-01-01

    Background Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC. PMID:25898255

  2. NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

    PubMed

    Huang, Tingting; Zhou, Yuhang; Cheng, Alfred S L; Yu, Jun; To, Ka Fai; Kang, Wei

    2016-12-09

    Gastric cancer (GC) ranks the most common cancer types and is one of the leading causes of cancer-related death. Due to delayed diagnosis and high metastatic frequency, 5-year survival rate of GC is rather low. It is a complex disease resulting from the interaction between environmental factors and host genetic alterations that deregulate multiple signaling pathways. The Notch signaling pathway, a highly conserved system in the regulation of the fate in several cell types, plays a pivotal role in cell differentiation, survival and proliferation. Notch is also one of the most commonly activated signaling pathways in tumors and its aberrant activation plays a key role in cancer advancement. Whether Notch cascade exerts oncogenic or tumor suppressive function in different cancer types depends on the cellular context. Mammals have four NOTCH receptors that modulate Notch pathway activity. In this review, we provide a comprehensive summary on the functional role of NOTCH receptors in gastric and other gastrointestinal cancers. Increasing knowledge of NOTCH receptors in gastrointestinal cancers will help us recognize the underlying mechanisms of Notch signaling and develop novel therapeutic strategies for GC.

  3. The gastrointestinal microbiota and colorectal cancer

    PubMed Central

    Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong

    2014-01-01

    The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation. PMID:25540232

  4. The gastrointestinal microbiota and colorectal cancer.

    PubMed

    Keku, Temitope O; Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong

    2015-03-01

    The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.

  5. Epigenetic reduction of DNA repair in progression to gastrointestinal cancer

    PubMed Central

    Bernstein, Carol; Bernstein, Harris

    2015-01-01

    Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal (GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. However, epigenetic alterations that reduce expression of DNA repair genes are frequent in sporadic GI cancers. These epigenetic reductions are also found in field defects that give rise to cancers. Reduced DNA repair likely allows excessive DNA damages to accumulate in somatic cells. Then either inaccurate translesion synthesis past the un-repaired DNA damages or error-prone DNA repair can cause mutations. Erroneous DNA repair can also cause epigenetic alterations (i.e., epimutations, transmitted through multiple replication cycles). Some of these mutations and epimutations may cause progression to cancer. Thus, deficient or absent DNA repair is likely an important underlying cause of cancer. Whole genome sequencing of GI cancers show that between thousands to hundreds of thousands of mutations occur in these cancers. Epimutations that reduce DNA repair gene expression and occur early in progression to GI cancers are a likely source of this high genomic instability. Cancer cells deficient in DNA repair are more vulnerable than normal cells to inactivation by DNA damaging agents. Thus, some of the most clinically effective chemotherapeutic agents in cancer treatment are DNA damaging agents, and their effectiveness often depends on deficient DNA repair in cancer cells. Recently, at least 18 DNA repair proteins, each active in one of six DNA repair pathways, were found to be subject to epigenetic reduction of expression in GI cancers. Different DNA repair pathways repair different types of DNA damage. Evaluation of which DNA repair pathway(s) are deficient in particular types of GI cancer and/or particular patients may prove useful in guiding choice of therapeutic agents in cancer therapy. PMID:25987950

  6. Epigenetic reduction of DNA repair in progression to gastrointestinal cancer.

    PubMed

    Bernstein, Carol; Bernstein, Harris

    2015-05-15

    Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal (GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. However, epigenetic alterations that reduce expression of DNA repair genes are frequent in sporadic GI cancers. These epigenetic reductions are also found in field defects that give rise to cancers. Reduced DNA repair likely allows excessive DNA damages to accumulate in somatic cells. Then either inaccurate translesion synthesis past the un-repaired DNA damages or error-prone DNA repair can cause mutations. Erroneous DNA repair can also cause epigenetic alterations (i.e., epimutations, transmitted through multiple replication cycles). Some of these mutations and epimutations may cause progression to cancer. Thus, deficient or absent DNA repair is likely an important underlying cause of cancer. Whole genome sequencing of GI cancers show that between thousands to hundreds of thousands of mutations occur in these cancers. Epimutations that reduce DNA repair gene expression and occur early in progression to GI cancers are a likely source of this high genomic instability. Cancer cells deficient in DNA repair are more vulnerable than normal cells to inactivation by DNA damaging agents. Thus, some of the most clinically effective chemotherapeutic agents in cancer treatment are DNA damaging agents, and their effectiveness often depends on deficient DNA repair in cancer cells. Recently, at least 18 DNA repair proteins, each active in one of six DNA repair pathways, were found to be subject to epigenetic reduction of expression in GI cancers. Different DNA repair pathways repair different types of DNA damage. Evaluation of which DNA repair pathway(s) are deficient in particular types of GI cancer and/or particular patients may prove useful in guiding choice of therapeutic agents in cancer therapy.

  7. Recent Advances in Endometrial Cancer

    PubMed Central

    Tran, Arthur-Quan; Gehrig, Paola

    2017-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290

  8. Review article: anorexia and cachexia in gastrointestinal cancer.

    PubMed

    Ockenga, J; Valentini, L

    2005-10-01

    In patients with gastrointestinal malignancies, i.e. cancers of the stomach, colon, liver, biliary tract or pancreas, progressive undernutrition can be regularly observed during the course of illness. Undernutrition significantly affects the patients' quality of life, morbidity and survival. Pathogenetically, two different causes are relevant in the development of undernutrition in patients with gastrointestinal cancer. One cause is reduced nutritional intake. This condition is referred to as anorexia and can be worsened by the side effects of cancer therapy. The other cause is the release of endogenous transmitters and/or other products of the tumour leading to the cachexia syndrome, which is characterized by loss of body weight, negative nitrogen balance and fatigue. Cancer anorexia and cancer cachexia may have synergistic negative effects in affecting the patients' status. In this review, current nutritional support strategies with respect to different clinically relevant situations are described. An algorithm of the treatment strategies, including dietetic counselling, oral supplements, enteral and parenteral nutritional support is given. One focus is the approach of nutrition-focused patient care, which shows promising results. In addition, the possibilities of pharmacological intervention are discussed.

  9. AXIN1 and AXIN2 Variants in Gastrointestinal Cancers

    PubMed Central

    Mazzoni, Serina M.; Fearon, Eric R.

    2014-01-01

    Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and AXIN1/2 alterations have been proposed as key defects in some cancers. Here, we review AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development. PMID:25236910

  10. Application of nanotechnology in the treatment and diagnosis of gastrointestinal cancers: review of recent patents.

    PubMed

    Prados, Jose; Melguizo, Consolacion; Perazzoli, Gloria; Cabeza, Laura; Carrasco, Esther; Oliver, Jaime; Jiménez-Luna, Cristina; Leiva, Maria C; Ortiz, Raúl; Álvarez, Pablo J; Aranega, Antonia

    2014-01-01

    Gastrointestinal cancers remain one of the main causes of death in developed countries. The main obstacles to combating these diseases are the limitations of current diagnostic techniques and the low stability, availability, and/or specificity of pharmacological treatment. In recent years, nanotechnology has revolutionized many fields of medicine, including oncology. The association of chemotherapeutic agents with nanoparticles offers improvement in the solubility and stability of antitumor agents, avoidance of drug degradation, and reductions in therapeutic dose and toxicity, increasing drug levels in tumor tissue and decreasing them in healthy tissue. The use of specific molecules that drive nanoparticles to the tumor tissue represents a major advance in therapeutic specificity. In addition, the use of nanotechnology in contrast agents has yielded improvements in the diagnosis and the follow-up of tumors. These nanotechnologies have all been applied in gastrointestinal cancer treatment, first in vitro, and subsequently in vivo, with promising results reported in some clinical trials. A large number of patents have been generated by nanotechnology research over recent years. The objective of this paper is to review patents on the clinical use of nanoparticles for gastrointestinal cancer diagnosis and therapy and to offer an overview of the impact of nanotechnology on the management of this disease.

  11. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    PubMed Central

    Kim, Soo Mi

    2016-01-01

    Studies in humans have shown that 3,3′-diindolylmethane (DIM), which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER) stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers. PMID:27447608

  12. Patient with eight metachronous gastrointestinal cancers thought to be hereditary nonpolyposis colorectal cancer (HNPCC).

    PubMed

    Yamasaki, Yasushi; Matsushima, Masashi; Tanaka, Hisae; Tajiri, Sakurako; Fukuda, Ryuki; Ozawa, Hideki; Takagi, Atsushi; Hirabayashi, Ken-ichi; Sadahiro, Sohtaro

    2010-01-01

    An 81-year-old woman presented with a chief complaint of swelling of both lower legs. She had a history of surgery for cancers of the stomach, rectum and colon. Among her immediate family members, her son had colon and rectal cancers, and her sister had ovarian cancer. After close examination the patient was diagnosed with small intestine cancer and ascending colon cancer. Gene mutation analyses did not reveal any mutations in DNA mismatch repair genes, but MSH-2 protein expression was lost only in the cancer lesions. Here, we report this rare case of eight metachronous gastrointestinal cancers thought to be HNPCC.

  13. Histamine and histamine receptor regulation of gastrointestinal cancers.

    PubMed

    Kennedy, Lindsey; Hodges, Kyle; Meng, Fanyin; Alpini, Gianfranco; Francis, Heather

    2012-10-01

    Histamine is a neurotransmitter released throughout the body that regulates multiple physiological responses. Primarily histamine is acknowledged for its role in inflammatory reactions to foreign pathogens that enter the body. Aside from inflammatory responses, histamine expression and synthesis has been detected in various cancer cell lines and multiple malignancies. Through experimentation histamine has demonstrated its ability to manage proliferation and angiogenesis in these cancerous cells, in either a positive or inhibitory manner. Regulation of angiogenesis and proliferation have been proven to be carried out by the stimulation or inhibition of numerous pathways and secondary response elements, such as VEGFA/C, IP3/Ca(2+), G-proteins, cAMP, and many more. The activation of these different response pathways is linked to the binding of ligands to the histamine receptors H1-H4HR. These receptors exhibit various effects dependent on whether it binds an agonist, antagonist, or its specific ligand, histamine. In cancer cell lines and different tumor cells the binding of these different compounds has shown to be one of the main components in exerting proliferative or antiproliferative changes in the microenvironment. It is also known that the histamine receptors have varying degrees of expression in different forms of cancer, and this expression can impact the tumor in various ways. This clearly indicates the significance of histamine receptors in cancer formation, and one of the aims of this review is to cover this topic concisely and in depth. Histamine is produced from numerous cells such as basophils and mast cells and is synthesized from the enzyme histidine decarboxylase (HDC). In this review we will prominently discuss the function of mast cells and HDC in histamine expression in various gastrointestinal carcinomas. We also briefly discuss current studies to support these claims. In this review we hope to give the reader a clear and comprehensible overview

  14. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer

    PubMed Central

    Santhanam, Srikanth; Alvarado, David M.; Ciorba, Matthew A.

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant side effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapies are a promising new approach to harness the body’s own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway is a particularly promising target for immunotherapy. Indoleamine 2,3 dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and kynurenine pathway metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth and luminal microbiota. This pathway’s role in other gastrointestinal malignancies such as gastric, pancreatic, esophageal and gastrointestinal stromal tumors (GIST) is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal and colitis associated cancer. PMID:26297050

  15. Gastrointestinal and Other Cancers Staff | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  16. Active Gastrointestinal and Other Cancers Grants | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  17. Gastrointestinal and Other Cancers Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  18. Epigenetic therapy in gastrointestinal cancer: the right combination

    PubMed Central

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-01-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  19. Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy.

    PubMed

    Sánchez-Lara, Karla; Ugalde-Morales, Emilio; Motola-Kuba, Daniel; Green, Dan

    2013-03-14

    Cancer patients receiving chemotherapy have a high risk of malnutrition secondary to the disease and treatment, and 40-80 % of cancer patients suffer from different degrees of malnutrition, depending on tumour subtype, location, staging and treatment strategy. Malnutrition in cancer patients affects the patient's overall condition, and it increases the number of complications, the adverse effects of chemotherapy and reduces the quality of life. The aim of the present study was to evaluate weight-loss prevalence depending on the tumour site and the gastrointestinal (GI) symptoms of oncology patients receiving chemotherapy. We included 191 cancer patients receiving chemotherapy. Files of all patients were reviewed to identify symptoms that might potentially influence weight loss. The nutritional status of all patients was also determined. The cancer sites in the patients were as follows: breast (31·9 %); non-colorectal GI (18·3 %); colorectal (10·4 %); lung (5·8 %); haematological (13·1 %); others (20·5 %). Of these patients, 58 % experienced some degree of weight loss, and its prevalence was higher among the non-colorectal GI and lung cancer patients. Common symptoms included nausea (59·6 %), anorexia (46 %) and constipation (31·9 %). A higher proportion of patients with ≥ 5 % weight loss experienced anorexia, nausea and vomiting (OR 9·5, 2·15 and 6·1, respectively). In conclusion, these results indicate that GI symptoms can influence weight loss in cancer patients, and they should be included in early nutritional evaluations.

  20. Chemoprevention of Gastrointestinal Cancer: The Reality and the Dream

    PubMed Central

    Chun, Kyung-Soo; Kim, Eun-Hee; Lee, Sooyeon

    2013-01-01

    Despite substantial progress in screening, early diagnosis, and the development of noninvasive technology, gastrointestinal (GI) cancer remains a major cause of cancer-associated mortality. Chemoprevention is thought to be a realistic approach for reducing the global burden of GI cancer, and efforts have been made to search for chemopreventive agents that suppress acid reflux, GI inflammation and the eradication of Helicobacter pylori. Thus, proton pump inhibitors, statins, monoclonal antibodies targeting tumor necrosis factor-alpha, and nonsteroidal anti-inflammatory agents have been investigated for their potential to prevent GI cancer. Besides the development of these synthetic agents, a wide variety of the natural products present in a plant-based diet, which are commonly called phytoceuticals, have also sparked hope for the chemoprevention of GI cancer. To perform successful searches of chemopreventive agents for GI cancer, it is of the utmost importance to understand the factors contributing to GI carcinogenesis. Emerging evidence has highlighted the role of chronic inflammation in inducing genomic instability and telomere shortening and affecting polyamine metabolism and DNA repair, which may help in the search for new chemopreventive agents for GI cancer. PMID:23560148

  1. The expanding regulatory universe of p53 in gastrointestinal cancer.

    PubMed

    Fesler, Andrew; Zhang, Ning; Ju, Jingfang

    2016-01-01

    Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

  2. Aurora kinase A in gastrointestinal cancers: time to target.

    PubMed

    Katsha, Ahmed; Belkhiri, Abbes; Goff, Laura; El-Rifai, Wael

    2015-05-20

    Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During the last two decades, several studies have shown amplification and overexpression of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated that AURKA not only plays a role in regulating cell cycle and mitosis, but also regulates a number of key oncogenic signaling pathways. Although AURKA inhibitors have moved to phase III clinical trials in lymphomas, there has been slower progress in GI cancers and solid tumors. Ongoing clinical trials testing AURKA inhibitors as a single agent or in combination with conventional chemotherapies are expected to provide important clinical information for targeting AURKA in GI cancers. It is, therefore, imperative to consider investigations of molecular determinants of response and resistance to this class of inhibitors. This will improve evaluation of the efficacy of these drugs and establish biomarker based strategies for enrollment into clinical trials, which hold the future direction for personalized cancer therapy. In this review, we will discuss the available data on AURKA in GI cancers. We will also summarize the major AURKA inhibitors that have been developed and tested in pre-clinical and clinical settings.

  3. Gene-gene interactions in gastrointestinal cancer susceptibility

    PubMed Central

    Kang, Changwon; Kang, Suk-Jo

    2016-01-01

    Cancer arises from complex, multi-layer interactions between diverse genetic and environmental factors. Genetic studies have identified multiple loci associated with tumor susceptibility. However, little is known about how germline polymorphisms interact with one another and with somatic mutations within a tumor to mediate acquisition of cancer traits. Here, we survey recent studies showing gene-gene interactions, also known as epistases, affecting genetic susceptibility in colorectal, gastric and esophageal cancers. We also catalog epistasis types and cancer hallmarks with respect to the interacting genes. A total of 22 gene variation pairs displayed all levels of statistical epistasis, including synergistic, redundant, suppressive and co-suppressive interactions. Five genes primarily involved in base excision repair formed a linear topology in the interaction network, MUTYH-OGG1-XRCC1-PARP1-MMP2, and three genes in mTOR cell-proliferation pathway formed another linear network, PRKAG2-RPS6KB1-PIK3CA. Discrete pairwise epistasis was also found in nucleotide excision repair, detoxification, proliferation, TP53, TGF-β and other pathways. We propose that three modes of biological interaction underlie the molecular mechanisms for statistical epistasis. The direct binding, linear pathway and convergence modes can exhibit any level of statistical epistasis in susceptibility to gastrointestinal cancers, and this is likely true for other complex diseases as well. This review highlights the link between cancer hallmarks and susceptibility genes. PMID:27588484

  4. The use of health functional foods in gastrointestinal cancer patients.

    PubMed

    Kang, Hwa Pyoung; Lee, Hosun; Oh, Tak Geun; Lee, Kyong Joo; Park, Soo Jung; Chung, Moon Jae; Kim, Seung Up; Lee, Hyuk; Park, Jun Chul; Hong, Sung Pil; Park, Jun Yong; Park, Jeong Youp; Bang, Seungmin; Kim, Do Young; Cheon, Jae Hee; Ahn, Sang Hoon; Kim, Tae Il; Park, Seung Woo; Song, Si Young

    2013-01-01

    As an adjunct to cancer treatment, the use of health functional foods (HFFs) seems to be increasing. However, little is known for the use of HFFs among cancer patients in Korea. The aims of this study were to investigate the exposure rate of HFF use among gastrointestinal (GI) cancer patients and to examine the relationship of socio-demographic and disease-related characteristics with the use of HFFs. A total of 126 patients diagnosed with GI cancer participated in the study. A cross-sectional survey was conducted using a questionnaire. Over a half of all the patients surveyed (n = 67; 53.2%) used HFFs. Patients who were younger, had higher income, or longer duration of disease showed a trend to use HFFs more frequently, even though the tendency was not statistically significant. The most commonly used HFF was vitamin complex (n = 20; 16%), followed by red ginseng (n = 15; 12%), and sweet wormwood (Artemisia annua) (n = 11; 8.8%). About 26% of all responders expressed concerns for using HFFs. The primary concern was 'going against physician's recommendations' (36.8%). About 63% of respondents expressed a desire to consult with their physicians and follow their recommendations. More basic scientific data and educational materials regarding HFFs are required for both health-care professionals and cancer patients. A larger sample and size-controlled groups representing each cancer type will continue to be recruited for participation in this survey.

  5. Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor.

    PubMed

    Kovac, Suzana; Xiao, Lin; Shulkes, Arthur; Patel, Oneel; Baldwin, Graham S

    2010-11-05

    The involvement of the gastrointestinal hormone gastrin in the development of gastrointestinal cancer is highly controversial. Here we demonstrate a positive-feedback loop whereby gastrin, acting via the CCK2 receptor, increases its own expression. Such an autocrine loop has not previously been reported for any other gastrointestinal hormone. Gastrin promoter activation was dependent on the MAP kinase pathway and did not involve Sp1 binding sites or epidermal growth factor receptor transactivation. As the treatment of gastrointestinal cancer cells with amidated gastrin led to increased expression of non-amidated gastrins, the positive-feedback loop may contribute to the sustained increase in circulating gastrins observed in colorectal cancer patients.

  6. Cathelicidin a potential therapeutic peptide for gastrointestinal inflammation and cancer.

    PubMed

    Chow, Jimmy Yip Chuen; Li, Zhi Jie; Wu, William Ka Kei; Cho, Chi Hin

    2013-05-14

    Cathelicidins, are host defense peptides synthesized and stored in circulating leukocytes and numerous types of epithelial tissues in particular the gastrointestinal (GI) tract and skin. They have been known for their antimicrobial activities against a variety of microbes. Recently it was discovered that they have other significant biological functions and produce appealing pharmacological actions against inflammation and cancer in the GI tract through defined mechanisms. Experimental evidence shows that these actions could be tissue and disease specific and concentration dependent. This article reviews some of the physiological functions of cathelicidins and also their therapeutic potential in the treatment of inflammation and cancer and also the delivery system for this peptide as targeted therapy for various disorders in the GI tract both in animals and humans.

  7. Compact endoscopic fluorescence detection system for gastrointestinal cancers

    NASA Astrophysics Data System (ADS)

    Nadeau, Valerie; Padgett, Miles J.; Hewett, Jacqueline; Sibbett, Wilson; Hamdan, Khaled; Mohammed, Sami; Tait, Iain; Cushieri, Alfred

    2001-04-01

    We describe a compact endoscopic imaging system for the detection of gastro-intestinal cancers. This system is designed to image ALA-induced PpIX fluorescence and allows the clinician to perform fluorescence endoscopy and white light endoscopy simultaneously. The system comprises a filtered mercury arclamp for illumination and fluorescence excitation, a dual camera system coupled to an endoscope for detection and a desktop PC for processing and display of images. The result is a real-time colour image onto which fluorescence information is superimposed. Preliminary in vivo results indicate an increased fluorescence level within cancers in comparison with normal tissue. In addition, the system allows point spectroscopy to be carried out by the insertion of an optical fibre probe down the biopsy channel of the endoscope.

  8. Gastrointestinal microflora, food components and colon cancer prevention

    PubMed Central

    Davis, Cindy D.; Milner, John A.

    2009-01-01

    Evidence is emerging that the intestinal microbiota is intrinsically linked with overall health, including cancer risk. Moreover, its composition is not fixed, but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols, or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans, and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex relationship deserves greater attention. Thus, a complex interrelationship exists between the intestinal microbiota and colon cancer risk which can be modified by dietary components and eating behaviors. PMID:19716282

  9. Advanced Cancer Detection Center

    DTIC Science & Technology

    2007-10-01

    Cancer Treatment Affecting the Central Nervous System (HLMCC 0707) • Melatonin and sleep hygiene for the treatment of insomnia following cancer...Determinants of Diabetes in the Young. (PI: Jeffrey Krischer, Ph.D.) Moffitt Community Clinical Oncology Program Research Base (PI: Jeffrey Krischer

  10. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: A report of four cases

    PubMed Central

    FUJIHARA, SHINTARO; MORI, HIROHITO; KOBARA, HIDEKI; NISHIYAMA, NORIKO; AYAKI, MAKI; OHATA, RYO; UEDA, NOBUFUMI; SUGIMOTO, MIKIO; KAKEHI, YOSHIYUKI; MASAKI, TSUTOMU

    2015-01-01

    Clinically available targeted agents to treat advanced renal cell carcinoma (RCC) include sunitinib, sorafenib and temsirolimus. Sorafenib and sunitinib have been associated with bleeding in selected trials, but clinical and endoscopic characteristics of gastrointestinal bleeding are not well described. Herein, we report four cases of advanced RCC in which endoscopic hemostasis effectively resolved high-grade, life-threatening gastrointestinal bleeding that occurred during targeted therapy. Although stomatitis and mucositis have occurred during targeted therapies, life-threatening gastrointestinal bleeding is less common. In these four patients, the origins of gastrointestinal bleeding were identified, and complete endoscopic hemostasis was achieved. Endoscopies revealed variable characteristics including angiodysplasia, multiple gastric ulcers and oozing bleeding of the normal mucosa. Although the most effective diagnostic and treatment strategies are disputed, endoscopic examinations are best performed before starting targeted therapies. Additionally, these patients should be monitored even for rare life-threatening events. PMID:26722259

  11. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer.

    PubMed

    Tsuei, Jessica; Chau, Thinh; Mills, David; Wan, Yu-Jui Yvonne

    2014-11-01

    Because of increasingly widespread sedentary lifestyles and diets high in fat and sugar, the global diabetes and obesity epidemic continues to grow unabated. A substantial body of evidence has been accumulated which associates diabetes and obesity to dramatically higher risk of cancer development, particularly in the liver and gastrointestinal tract. Additionally, diabetic and obese individuals have been shown to suffer from dysregulation of bile acid (BA) homeostasis and dysbiosis of the intestinal microbiome. Abnormally elevated levels of cytotoxic secondary BAs and a pro-inflammatory shift in gut microbial profile have individually been linked to numerous enterohepatic diseases including cancer. However, recent findings have implicated a detrimental interplay between BA dysregulation and intestinal dysbiosis that promotes carcinogenesis along the gut-liver axis. This review seeks to examine the currently investigated interactions between the regulation of BA metabolism and activity of the intestinal microbiota and how these interactions can drive cancer formation in the context of diabesity. The precarcinogenic effects of BA dysregulation and gut dysbiosis including excessive inflammation, heightened oxidative DNA damage, and increased cell proliferation are discussed. Furthermore, by focusing on the mediatory roles of BA nuclear receptor farnesoid x receptor, ileal transporter apical sodium dependent BA transporter, and G-coupled protein receptor TGR5, this review attempts to connect BA dysregulation, gut dysbiosis, and enterohepatic carcinogenesis at a mechanistic level. A better understanding of the intricate interplay between BA homeostasis and gut microbiome can yield novel avenues to combat the impending rise in diabesity-related cancers.

  12. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer

    PubMed Central

    Tsuei, Jessica; Chau, Thinh; Mills, David; Wan, Yu-Jui Yvonne

    2015-01-01

    Because of increasingly widespread sedentary lifestyles and diets high in fat and sugar, the global diabetes and obesity epidemic continues to grow unabated. A substantial body of evidence has been accumulated which associates diabetes and obesity to dramatically higher risk of cancer development, particularly in the liver and gastrointestinal tract. Additionally, diabetic and obese individuals have been shown to suffer from dysregulation of bile acid (BA) homeostasis and dysbiosis of the intestinal microbiome. Abnormally elevated levels of cytotoxic secondary BAs and a pro-inflammatory shift in gut microbial profile have individually been linked to numerous enterohepatic diseases including cancer. However, recent findings have implicated a detrimental interplay between BA dysregulation and intestinal dysbiosis that promotes carcinogenesis along the gut–liver axis. This review seeks to examine the currently investigated interactions between the regulation of BA metabolism and activity of the intestinal microbiota and how these interactions can drive cancer formation in the context of diabesity. The precarcinogenic effects of BA dysregulation and gut dysbiosis including excessive inflammation, heightened oxidative DNA damage, and increased cell proliferation are discussed. Furthermore, by focusing on the mediatory roles of BA nuclear receptor farnesoid x receptor, ileal transporter apical sodium dependent BA transporter, and G-coupled protein receptor TGR5, this review attempts to connect BA dysregulation, gut dysbiosis, and enterohepatic carcinogenesis at a mechanistic level. A better understanding of the intricate interplay between BA homeostasis and gut microbiome can yield novel avenues to combat the impending rise in diabesity-related cancers. PMID:24951470

  13. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  14. Advanced Prostate Cancer

    MedlinePlus

    ... if it has spread to: • Bones • Lungs • Liver • Brain • Lymph nodes outside the pelvis • Other organs You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed ...

  15. Coping with Advanced Cancer

    MedlinePlus

    ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  16. Gastrointestinal cancers: influence of gut microbiota, probiotics and prebiotics.

    PubMed

    Serban, Daniela Elena

    2014-04-10

    Cancers of the gastrointestinal (GI) tract continue to represent a major health problem, despite progress in therapy. Gut microbiota is a key element related to the genesis of GI cancers, countless papers addressing this burning issue across the world. We provide an updated knowledge of the involvement of gut microbiota in GI tumorigenesis, including its underlying mechanisms. We present also a comprehensive review of the evidence from animal and clinical studies using probiotics and/or prebiotics in the prevention and/or therapy of GI tumours, of GI cancer therapy-related toxicity and of post-operative complications. We summarize the anticarcinogenic mechanisms of these biotherapeutics from in vitro, animal and clinical interventions. More research is required to reveal the interactions of microflora with genetic, epigenetic and immunologic factors, diet and age, before any firm conclusion be drawn. Well-designed, randomized, double blind, placebo-controlled human studies using probiotics and/or prebiotics, with adequate follow-up are necessary in order to formulate directions for prevention and therapy.

  17. Interactions of alcohol and tobacco in gastrointestinal cancer.

    PubMed

    Salaspuro, Mikko; Mikko, Salaspuro

    2012-03-01

    Cancer prevention is based on the identification of specific etiologic factors. Acetaldehyde derived from the alcoholic beverage itself and formed from ethanol endogenously has recently been classified by the International Agency for Research on Cancer/World Health Organization as a group 1 carcinogen to humans. This is based on the uniform epidemiological and biochemical evidence derived from individuals carrying alcohol and aldehyde dehydrogenase gene mutations. After drinking alcohol, these mutations are associated with increased exposure of the upper digestive tract to acetaldehyde and as well with a remarkably increased risk for upper gastrointestinal (GI) tract cancers. Acetaldehyde is the key intermediate in alcoholic fermentation and ethanol oxidation. Therefore, it is widely present in our environment. Furthermore, it is the most abundant carcinogenic compound of tobacco smoke. Most of the known risk factors for upper digestive tract cancer appear to be associated with an enhanced exposure of GI mucosa to locally formed acetaldehyde. In these process microbes, salivary glands and even mucosal cells appear to play an essential role. Consequently, in the presence of ethanol mutagenic acetaldehyde concentrations are found in the saliva, achlorhydric stomach and colon. Equal acetaldehyde concentrations are seen in saliva also during active smoking. ALDH2-deficiency and high active ADH1C result in two- to threefold salivary acetaldehyde concentrations after a dose of alcohol and this prevails for as long as ethanol is present in the blood and saliva. Regarding cancer prevention, the good news is that acetaldehyde exposure can be markedly reduced. This can be achieved by giving high priority for regulatory measures and consumer guidance.

  18. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.

  19. [Therapeutic advances in breast cancer].

    PubMed

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  20. Recent Advances in Management of Laryngeal Cancer

    PubMed Central

    2004-01-01

    Laryngeal cancers account for approximately 1.5% (1~2%) of the total cancers in Korea, and 30% of all head and neck cancers, not including thyroid cancer. Early laryngeal cancer is treated by operation, including transoral laser excision or radiotherapy. Advanced laryngeal cancer has been treated with mutilating operations, such as a total laryngectomy. However, a laryngeal preserving approach, which can improve the quality of life, has recently been tried with advanced laryngeal cancer. PMID:20396561

  1. Risk, diagnosis and treatment to postoperative delirium in elderly patients with gastrointestinal cancers.

    PubMed

    Ma, Li-Na; Zhang, Rui-Li

    2015-01-01

    In recent years, more elderly patients with gastrointestinal cancers have been undergoing surgery. As one of main postoperative complications, postoperative delirium (POD) is harmful and difficult to prevent and treat. Prevention, diagnosis and treatment to POD properly and ptomptly can promote the patient's overall recovery. However, health care providers still have many problems for POD to face in elderly,with gastrointestinal cancers during the clinical care. In this paper, Etiology, damages, prevention, diagnosis and treatment of POD in elderly with gastrointestinal cancer were reviewed, and the prospect of POD was also discussed.

  2. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer.

    PubMed

    Santhanam, Srikanth; Alvarado, David M; Ciorba, Matthew A

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant adverse effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapy is a promising new approach to harness the body's own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway (KP) is a particularly promising target for immunotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and KP metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth, and luminal microbiota. This pathway's role in other gastrointestinal (GI) malignancies such as gastric, pancreatic, esophageal, and GI stromal tumors is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal, and colitis-associated cancer.

  3. Chemokine receptor CXCR4: role in gastrointestinal cancer.

    PubMed

    Lombardi, Lucia; Tavano, Francesca; Morelli, Franco; Latiano, Tiziana Pia; Di Sebastiano, Pierluigi; Maiello, Evaristo

    2013-12-01

    Chemokines (CK)s, small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The CXCL12 [stromal cell-derived factor-1 (SDF-1)] binds primarily to CXC receptor 4 (CXCR4; CD184). The binding of CXCL12 to CXCR4 induces intracellular signaling through several divergent pathways initiating signals related to chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. One of the most intriguing and perhaps important roles that CKs and the CK receptors have is in regulating metastasis. Here, CK receptors may potentially facilitate tumor dissemination at each of the key steps of metastasis, including adherence of tumor cells to endothelium, extravasation from blood vessels, metastatic colonization, angiogenesis, proliferation, and protection from the host response via activation of key survival pathways such as ERK/MAPK, PI-3K/Akt/mTOR, or Jak/STAT, etc. In addition, it is increasingly recognized that CKs play an important role in facilitating communication between cancer cells and non-neoplatic cells in the tumor microenvironment (TME), including endothelial cells and fibroblasts, promoting the infiltration, activation of neutrophils, and tumor-associated macrophages within the TME. In this review, we mainly focus on the roles of chemokines CXCL12 and its cognate receptors CXCR4 as they pertain to cancer progression. In particular, we summarizes our current understanding regarding the contribution of CXCR4 and SDF-1 to gastrointestinal tumor behavior and its role in local progression, dissemination, and immune evasion of tumor cells. Also, describes recent therapeutic approaches that target these receptors or their ligands.

  4. Optical imaging of breast tumors and of gastrointestinal cancer by laser-induced fluorescence.

    PubMed

    Ebert, Bernd; Grosenick, Dirk

    2013-01-01

    Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.

  5. PET/MR Imaging in Cancers of the Gastrointestinal Tract.

    PubMed

    Paspulati, Raj Mohan; Gupta, Amit

    2016-10-01

    PET/computed tomography (PET/CT) is an established hybrid imaging technique for staging and follow-up of gastrointestinal (GI) tract malignancies, especially for colorectal carcinoma. Dedicated hybrid PET/MR imaging scanners are currently available for clinical use. Although they will not replace regular use of PET/CT, they may have utility in selected cases of GI tract malignancies. The superior soft tissue contrast resolution and depiction of anatomy and the functional information obtained from diffusion-weighted imaging (DWI) provided by MR imaging in PET/MR imaging are advantages over CT of PET/CT for T staging and follow-up of rectal carcinoma and for better characterization of liver lesions. Functional information from DWI and use of liver-specific MR imaging contrast agents are an added advantage in follow-up of liver metastases after systemic and locoregional treatment. New radiotracers will improve the utility of PET/MR imaging in staging and follow-up of tumors, which may not be [18F]-2-fluoro-2-deoxy-d-glucose avid, such as hepatocellular carcinoma and neuroendocrine tumors. PET/MR imaging also has application in selected cases of cholangiocarcinoma, gallbladder cancer, and pancreatic carcinoma for initial staging and follow-up assessment.

  6. Parasitological and immunological diagnosis of Strongyloides stercoralis in patients with gastrointestinal cancer.

    PubMed

    Machado, Eleuza R; Teixeira, Eliane M; Gonçalves-Pires, Maria Do Rosario F; Loureiro, Zaira M; Araújo, Rogério A; Costa-Cruz, Julia M

    2008-01-01

    This study examined the frequency of Strongyloides stercoralis infection in patients with gastrointestinal cancer through parasitological and immunological tests. A total of 77 patients were evaluated, 33 with gastrointestinal cancer and 44 controls with other types of cancers. All the patients were undergoing chemotherapy and 14 (18.2%) were receiving concomitant radiotherapy. For a parasitological diagnosis, we applied the Baermann and Lutz methods. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) to detect IgG antibodies using Strongyloides ratti antigens. The frequency of positive S. stercoralis in gastrointestinal cancer diagnosed by parasitological methods was 3 cases (9.1%), by serology it was 8 cases (24.2%). In the control group 1 case (2.3%) of S. stercoralis was diagnosed by parasitological methods and 2 cases (4.5%) by immunological tests (p<0.05). Patients with gastrointestinal cancer had a 6.7-fold greater chance of testing positive for S. stercoralis infection. Our data highlight the importance of parasitological and immunological diagnosis for S. stercoralis in patients with gastrointestinal cancer living in endemic areas of strongyloidiasis, since they have a higher risk of becoming infected with S. stercoralis than patients with other types of cancer.

  7. The role of pleomorphic adenoma gene-like 2 in gastrointestinal cancer development, progression, and prognosis.

    PubMed

    Liu, Bo; Lu, Chong; Song, Yong-Xi; Gao, Peng; Sun, Jing-Xu; Chen, Xiao-Wan; Wang, Mei-Xian; Dong, Yu-Lan; Xu, Hui-Mian; Wang, Zhen-Ning

    2014-01-01

    Numerous previous studies have revealed that pleomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that is active in cancer progression. The aim of this study was to investigate the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer. Immunohistochemical analysis revealed that PLAGL2 was expressed in gastrointestinal tumors and adjacent normal tissues. The expression of PLAGL2 was significantly higher in 225 colorectal cancer tissues than in 66 adjacent non-tumor tissues (P = 0.037). However, expression was not significantly different between 286 gastric tumors and 57 adjacent non-tumor tissues (P = 0.352). Moreover, the PLAGL2 expression level significantly correlated with the depth of tumor invasion in colorectal cancer (P = 0.030). However, the PLAGL2 expression level significantly correlated with tumor size in gastric cancer (P = 0.046). Furthermore, we performed survival analyses and found that neither higher nor lower PLAGL2 expression was a prognostic factor in gastrointestinal cancer. Our findings indicate that PALGL2 serves as a tumor oncoprotein in the development and progression of colorectal cancer. However, the role of this protein in the development, progression and prognosis of gastric cancer is uncertain. Further investigation into the molecular mechanisms of PLAGL2 activity in gastrointestinal cancer is warranted.

  8. Advances in paediatric cancer treatment.

    PubMed

    Saletta, Federica; Seng, Michaela S; Lau, Loretta M S

    2014-04-01

    Four out of five children diagnosed with cancer can be cured with contemporary cancer therapy. This represents a dramatic improvement since 50 years ago when the cure rate of childhood cancer was <25% in the pre-chemotherapy era. Over the past ten years, while improvement in overall survival (OS) has been marginal, progress in pediatric oncology lies with adopting risk-adapted therapeutic approach. This has been made possible through identifying clinical and biologic prognostic factors with rigorous research and stratifying patients using these risk factors, and subsequently modifying therapy according to risk group assignment. This review provides a perspective for eight distinct pediatric malignancies, in which significant advances in treatment were made in the last decade and are leading to changes in standard of care. This includes four hematologic malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)] and four solid tumors [medulloblastoma (MB), low grade glioma (LGG), neuroblastoma (NB) and Ewing sarcoma (ES)]. Together, they comprise 60% of childhood cancer. Improved patient outcome is not limited to better survival, but encompasses reducing both short and long-term treatment-related complications which is as important as cure, given the majority of childhood cancer patients will become long-term survivors. Risk-adapted approach allows treatment intensification in the high-risk cohort while therapy can be de-escalated in the low-risk to minimize toxicity and late sequelae without compromising survival. Advances in medical research technology have also led to a rapid increase in the understanding of the genetics of childhood cancer in the last decade, facilitating identification of molecular targets that can potentially be exploited for therapeutic benefits. As we move into the era of targeted therapeutics, searching for novel agents that target specific genetic lesions becomes a

  9. Thiazolidinediones inhibit REG I{alpha} gene transcription in gastrointestinal cancer cells

    SciTech Connect

    Yamauchi, Akiyo; Takahashi, Iwao; Takasawa, Shin; Nata, Koji; Noguchi, Naoya; Ikeda, Takayuki; Yoshikawa, Takeo; Shervani, Nausheen J.; Suzuki, Iwao; Uruno, Akira; Unno, Michiaki; Okamoto, Hiroshi Sugawara, Akira

    2009-02-13

    REG (Regenerating gene) I{alpha} protein functions as a growth factor for gastrointestinal cancer cells, and its mRNA expression is strongly associated with a poor prognosis in gastrointestinal cancer patients. We here demonstrated that PPAR{gamma}-agonist thiazolidinediones (TZDs) inhibited cell proliferation and REG I{alpha} protein/mRNA expression in gastrointestinal cancer cells. TZDs inhibited the REG I{alpha} gene promoter activity, via its cis-acting element which lacked PPAR response element and could not bind to PPAR{gamma}, in PPAR{gamma}-expressing gastrointestinal cancer cells. The inhibition was reversed by co-treatment with a specific PPAR{gamma}-antagonist GW9662. Although TZDs did not inhibit the REG I{alpha} gene promoter activity in PPAR{gamma}-non-expressing cells, PPAR{gamma} overexpression in the cells recovered their inhibitory effect. Taken together, TZDs inhibit REG I{alpha} gene transcription through a PPAR{gamma}-dependent pathway. The TZD-induced REG I{alpha} mRNA reduction was abolished by cycloheximide, indicating the necessity of novel protein(s) synthesis. TZDs may therefore be a candidate for novel anti-cancer drugs for patients with gastrointestinal cancer expressing both REG I{alpha} and PPAR{gamma}.

  10. Applications and Advancements in the use of High-Resolution Microendoscopy for Detection of Gastrointestinal Neoplasia

    PubMed Central

    Louie, Justin S.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2014-01-01

    The high-resolution microendoscope (HRME) is a novel imaging modality that allows real-time epithelial imaging at subcellular resolution. Used in concert with any standard endoscope, this portable, low cost, ‘optical biopsy’ technology has the ability to provide images of cellular morphology during a procedure. This technology has been the subject of a number of studies investigating its use in screening and surveillance of a range of gastrointestinal neoplasia, including esophageal adenocarcinoma(EAC), esophageal squamous cell cancer(ESCC), colorectal neoplasia(CRC) and anal neoplasia. These studies have shown that HRME is a modality that consistently provides high specificity, negative predictive value, and accuracy across different diseases. In addition, they have illustrated that HRME users can be relatively easily trained in a short period of time and that users have demonstrated solid inter-rater reliability. These features make HRME a potential complement to high definition white light imaging, narrow band imaging and other ‘red flag technologies’ in facilitating real-time clinical diagnosis, endoscopic therapy and margin determination. Further clinical validation is needed to determine whether this translates to reduced procedure times, pathology costs, and follow up procedures. Finally, the HRME has a relatively simple design compared to other similar technologies, making it portable, simple to maintain, and low cost. This may allow the HRME device to function in both advanced care settings as well as in places with less resources and specialized support systems. As a whole, the HRME device has shown good performance along with low-cost and portable construction, and its application in different conditions and settings has been promising. PMID:25108219

  11. Impact of lifestyle factors and nutrients intake on occurrence of gastrointestinal cancer in Tunisian population.

    PubMed

    Baroudi, Olfa; Chaaben, Arij Ben; Mezlini, Amel; Moussa, Amel; Omrane, Ines; Jilson, Irene; Benammar-Elgaaied, Amel; Chabchoub, Soufia

    2014-06-01

    This study aims to show the relationship between lifestyle and risk of colorectal and gastric cancers in Tunisian population. The food frequency survey method was used to obtain information about the dietary intake and way of life. Nutrients intake was calculated according to the food composition database. According to our results, the consumption of vegetables, fruits, fish, as well as coffee seems to be protective against digestive cancer, while the consumption of citrus and olive oil is protective against gastric cancer. Tobacco, alcohol, and tea represent a risk against gastrointestinal cancer. Highly educated people are more conscious of the crucial role of prevention. In addition, nutrients were significantly associated with colorectal and gastric cancer. The findings suggest that lifestyle is associated with a risk of gastrointestinal cancer. Moreover, higher intake of nutrients from foods was observed more in cases with colorectal and gastric cancer than controls.

  12. Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications.

    PubMed

    Yang, Jiqiao; Tan, Qiuwen; Fu, Qingyu; Zhou, Yaojie; Hu, Yuanyuan; Tang, Shenli; Zhou, Yuting; Zhang, Junhui; Qiu, Juanjuan; Lv, Qing

    2017-03-01

    Gastrointestinal microbiome plays as a symbiont which provides protection effect against invading pathogens, aids in the immune system development, nutrient reclamation and absorption as well as molecule breakdown. And it may avert carcinogenesis through these biological activities. By now, studies have been carried out to elaborate the association between gastrointestinal microbiome and breast cancer. It has been implicated that breast cancer was substantially associated with estrogen-dependent and estrogen-independent functions of gastrointestinal microbiome. Evidence from animal experiments also confirmed mammary tumor-related changes in microbial community. The possible mechanisms involve estrogen metabolism, immune regulation, obese status and so forth. Based on the current evidence, cues on future management strategies of breast cancer such as antibiotics and dietary interventions are proposed. In conclusion, large-scale clinical studies and bench-based researches are needed to validate the associations and elaborate the mechanisms, so as to reduce the risk of breast cancer and improve the outcomes of those already diagnosed.

  13. Genetically Engineered Immunotherapy for Advanced Cancer

    Cancer.gov

    In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

  14. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    SciTech Connect

    Uchino, Keita; Hirano, Gen; Hirahashi, Minako; Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi; Tsuneyoshi, Masazumi; Akashi, Koichi

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  15. Common symptoms in advanced cancer.

    PubMed

    Lagman, Ruth L; Davis, Mellar P; LeGrand, Susan B; Walsh, Declan

    2005-04-01

    The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

  16. GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population

    PubMed Central

    Zhou, Liqing; Zhang, Xiaojiao; Chen, Xuechao; Liu, Li; Lu, Chao; Tang, Xiaohu; Shi, Juan; Li, Meng; Zhou, Mo; Zhang, Zhouwei; Xiao, Lingchen; Yang, Ming

    2012-01-01

    Vitamin D has potent anticancer properties, especially against gastrointestinal cancers. Group-specific component (GC), a key member of vitamin D pathway proteins, could bind to and transport vitamin D to target organs. As a polymorphic protein, two common coding single nucleotide polymorphisms (SNP) [Glu416Asp (rs7041) and Thr420Lys (rs4588)] were identified in its gene. These SNPs have been associated to circulating vitamin D levels and several cancer risks in different populations. However, there is no report on their role in gastrointestinal cancer development among Chinese to date. Therefore, we examined the association between these variants and risk of gastrointestinal cancers in a case-control cohort including 964 patients with four gastrointestinal cancers (hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer) and 1187 controls. Odds ratios and 95% confidence intervals were estimated by logistic regression. We found that GC Thr420Lys polymorphism has significant impact on the risk of developing gastrointestinal cancers, especially colorectal cancer. Additionally, subjects who carrying GC Asp416-Lys420 haplotype, which contains the at-risk 420Lys allele, also showed significantly increased risk to develop gastrointestinal cancers. In conclusion, our study demonstrated that common genetic variants and haplo-types in GC may influence individual susceptibility to gastrointestinal cancers in Chinese population. PMID:22328951

  17. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    PubMed

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment.

  18. The perioperative changes in physical function and physique of patients with gastrointestinal cancer.

    PubMed

    Hara, Tsuyoshi; Kubo, Akira

    2015-03-01

    [Purpose] The purpose of this study was to observe the long-term change in physical function and physique from perioperative to discharge of patients with gastrointestinal cancer. [Subjects and Methods] Subjects were 47 perioperative patients with gastrointestinal cancer [25 men and 22 women aged 61.3 ± 11.0 years (mean ± SD)]. Six-minute walk distance was measured for physical function and body mass index and calf circumference were measured for physique. These items were evaluated at three time points: before surgery, after surgery, and after discharge. [Results] Significant declines in physical function and physique were observed temporarily after surgery. Physical function improved equally before surgery in after discharge. On the other hand, postoperative physique was significantly lower than that observed pre-operatively. [Conclusion] These results suggest that the perioperative changes in physical function and physique follow different courses in patients with gastrointestinal cancer.

  19. Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

    PubMed

    Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

    2015-03-01

    Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.

  20. [Chemoradiotherapy for locally advanced cervical cancer].

    PubMed

    Bazaeva, I Ia; Gorbunova, V A; Kravets, O A; Khokhlova, S V; Limareva, S V; Panov, V O; Strel'tsova, O N; Tarachkova, E V

    2014-01-01

    Cervical cancer takes second place in morbidity and third place in mortality from gynecological cancer. Advanced stages among newly diagnosed cases is still large. The "gold standard" of treatment for locally advanced cervical cancer is chemoradiotherapy with cisplatin that results in a lower risk of death. Improvement of radiotherapy methods allowed to bring optimal dose to the primary tumor with the inclusion of regional metastasis areas with less risk of damage to surrounding healthy tissue and organs. The search for alternative combinations of cytostatics, modes of drug administration, adjuvant chemotherapy after chemoradiotherapy showed an increase in survival of patients with locally advanced cervical cancer.

  1. Aminoglutethimide in advanced breast cancer.

    PubMed

    Ceci, G; Passalacqua, R; Bisagni, G; Bella, M; Cocconi, G

    1985-10-31

    From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.

  2. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review.

    PubMed

    East, James E; Vleugels, Jasper L; Roelandt, Philip; Bhandari, Pradeep; Bisschops, Raf; Dekker, Evelien; Hassan, Cesare; Horgan, Gareth; Kiesslich, Ralf; Longcroft-Wheaton, Gaius; Wilson, Ana; Dumonceau, Jean-Marc

    2016-11-01

    Background and aim: This technical review is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy. Methods: This technical review is based on a systematic literature search to evaluate the evidence supporting the use of advanced endoscopic imaging throughout the GI tract. Technologies considered include narrowed-spectrum endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. Main recommendations:1. We suggest advanced endoscopic imaging technologies improve mucosal visualization and enhance fine structural and microvascular detail. Expert endoscopic diagnosis may be improved by advanced imaging, but as yet in community-based practice no technology has been shown consistently to be diagnostically superior to current practice with high definition white light. (Low quality evidence.) 2. We recommend the use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging in the upper and lower GI tracts (strong recommendation, moderate quality evidence). 3. We suggest that training improves performance in the use of advanced endoscopic imaging techniques and that it is a prerequisite for use in clinical practice. A learning curve exists and training alone does not guarantee sustained high performances in clinical practice. (Weak recommendation, low quality evidence.) Conclusion: Advanced endoscopic imaging can improve mucosal visualization and endoscopic diagnosis; however it requires training and the use of validated classification systems.

  3. Octreotide acetate enables the administration of chemoradiotherapy, including the oral anticancer drug S-1, in gastric cancer patients with malignant gastrointestinal obstruction.

    PubMed

    Takahashi, Tsunehiro; Saikawa, Yoshiro; Igarashi, Takahiro; Tsuwano, Shinichi; Kumagai, Koshi; Nakamura, Rieko; Ooyama, Takashi; Wada, Norihito; Takeuchi, Hiroya; Takaishi, Hiromasa; Kitagawa, Yuko

    2010-07-01

    Advanced gastric cancer frequently results in the inability to ingest food or drink orally, a condition called malignant gastrointestinal obstruction (MGO). MGO is clinically defined as a gastrointestinal outlet obstruction caused by a large tumor, or malignant bowel obstruction with peritoneal dissemination. MGO impacts the quality of life by interfering with oral intake and by causing gastrointestinal symptoms, such as nausea, vomiting and abdominal pain. Octreotide acetate (OA) is an analogue of somatostatin which has been increasingly used to relieve gastrointestinal symptoms since it decreases the secretion of digestive juices and increases the absorption of water and electrolytes. In Japan, the oral anticancer drug S-1 was recently adopted as a key chemotherapeutic agent in advanced gastric cancer; however, its oral formulation precludes its utility in the MGO setting. This is a pilot study of chemoradiotherapy plus OA in gastric cancer with MGO. Patients were initially treated with OA to control gastrointestinal symptoms. Following resolution of their symptoms, the patients received chemotherapy with S-1 plus low-dose cisplatin and radiation. Irradiation was targeted at the primary tumor and surrounding lesions, including the lymph nodes. Grade 4 toxicity was observed in only 1 patient, and no treatment-related deaths were noted. After treatment, 3 patients achieved a partial response and 4 achieved stable disease. Of the 9 patients, 8 were able to tolerate solid food orally and were discharged. The outcomes of these cases suggest that OA is a useful adjunctive therapy that enables advanced gastric cancer patients with MGO to receive S-1-containing chemotherapy.

  4. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. PMID:26697225

  5. Multifunctional Nanotherapeutic System for Advanced Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    therapy for drug resistant prostate cancer cells. In addition the findings from this study can be extended to the combinatorial therapy involving...AD_________________ Award Number: W81XWH-11-1-0571 TITLE: “Multifunctional Nanotherapeutic System for Advanced Prostate Cancer ...29September2013 4. TITLE AND SUBTITLE Multifunctional Nanotherapeutic System for Advanced Prostate Cancer 5a. CONTRACT NUMBER W81XWH-11-1-0571 5b

  6. The effect of acupuncture on chemotherapy-associated gastrointestinal symptoms in gastric cancer

    PubMed Central

    Zhou, J.; Fang, L.; Wu, W.Y.; He, F.; Zhang, X.L.; Zhou, X.; Xiong, Z.J.

    2017-01-01

    Background Gastrointestinal (gi) symptoms are the most notable side effects of chemotherapeutic drugs; such symptoms are currently treated with drugs. In the present study, we investigated the effect of acupuncture on gi symptoms induced by chemotherapy in patients with advanced gastric cancer. Methods A cohort of 56 patients was randomly divided into an experimental group and a control group. All patients received combination chemotherapy with oxaliplatin–paclitaxel. Patients in the experimental group received 30 minutes of acupuncture therapy daily for 2 weeks. The frequency and duration of nausea, vomiting, abdominal pain, and diarrhea, the average days and costs of hospitalization, and quality-of-life scores were compared between the groups. Results Nausea was sustained for 32 ± 5 minutes and 11 ± 3 minutes daily in the control and experimental groups respectively (p < 0.05). On average, vomiting occurred 2 ± 1 times daily in the experimental group and 4 ± 1 times daily in the control group (p < 0.05). Abdominal pain persisted for 7 ± 2 minutes and 16 ± 5 minutes daily in the experimental and control groups respectively (p < 0.05). On average, diarrhea occurred 1 ± 1 times daily in the experimental group and 3 ± 1 times daily in the control group (p < 0.05). The average quality-of-life score was higher in the experimental group than in the control group (p < 0.05). No adverse events were observed for the patients receiving acupuncture. Conclusions Acupuncture, a safe technique, could significantly reduce gi symptoms induced by chemotherapy and enhance quality of life in patients with advanced gastric cancer. PMID:28270726

  7. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  8. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    PubMed Central

    Tang, Jia-Cheng; Feng, Yi-Li; Liang, Xiao; Cai, Xiu-Jun

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system. Data Sources: All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were “autophagy” and “5-FU” and (“colorectal cancer” or “hepatocellular carcinoma” or “pancreatic adenocarcinoma” or “esophageal cancer” or “gallbladder carcinoma” or “gastric cancer”). Study Selection: Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy. Results: Most cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials. Conclusion: Autophagy might be a therapeutic target that sensitizes the 5-FU treatment in

  9. Lung cancer metastasis to the gastrointestinal system: An enigmatic occurrence

    PubMed Central

    Badipatla, Kanthi Rekha; Yadavalli, Niharika; Vakde, Trupti; Niazi, Masooma; Patel, Harish K

    2017-01-01

    Adenocarcinoma of the lung infrequently metastasizes to the gastrointestinal tract. We report a rare case of a 65-year-old male with no respiratory symptoms diagnosed with adenocarcinoma of the lung by histopathological examination of metastatic sites which included an ulcer in the gastric body and a mass in the rectum. Metastatic disease also involved the liver as well. Patient was treated with systemic chemotherapy but unfortunately expired five months after the diagnosis was made. PMID:28344748

  10. Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

    PubMed Central

    Zhang, Fei-Fei; Luo, Yu-Hao; Wang, Hui; Zhao, Liang

    2016-01-01

    Long non-coding RNAs (lncRNAs), a newly discovered class of ncRNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lncRNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lncRNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lncRNAs, and evaluate the potential roles of lncRNAs as novel diagnostic biomarkers and therapeutic targets in gastrointestinal cancer. PMID:27818589

  11. Burden of gastrointestinal cancers and problem of the incomplete information; how to make up the data?

    PubMed

    Sharifian, Abdolhamid; Pourhoseingholi, Mohamad Amin; Baghestani, Ahmadreza; Hajizadeh, Nastaran; Gholizadeh, Sepideh

    2016-01-01

    Cancer registration is an important source for measuring the burden of cancer in a population. In practice, however, quite frequently incorrect patients are registered or data items can be inaccurately recorded or not recorded at all. Also the process or quality of these registrations varies among countries. In this paper, we briefly discussed some statistical techniques including; Mortality and Incidence Analysis Model (MIAMOD), Prevalence and Incidence Analysis Model (PIAMOD), Bayesian Inference and Capture-recapture methods, which provide tools to re-correct the incomplete or misclassified cancer statistics with regards to gastrointestinal cancers.

  12. TGF-β Signaling in Gastrointestinal Cancers: Progress in Basic and Clinical Research

    PubMed Central

    Yokobori, Takehiko; Nishiyama, Masahiko

    2017-01-01

    Transforming growth factor (TGF)-β superfamily proteins have many important biological functions, including regulation of tissue differentiation, cell proliferation, and migration in both normal and cancer cells. Many studies have reported that TGF-β signaling is associated with disease progression and therapeutic resistance in several cancers. Similarly, TGF-β-induced protein (TGFBI)—a downstream component of the TGF-β signaling pathway—has been shown to promote and/or inhibit cancer. Here, we review the state of basic and clinical research on the roles of TGF-β and TGFBI in gastrointestinal cancers. PMID:28106769

  13. GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP.

    PubMed

    Riechelmann, Rachel; Coutinho, Anelisa K; Weschenfelder, Rui F; Andrade DE Paulo, Gustavo; Fernandes, Gustavo Dos Santos; Gifoni, Markus; Oliveira, Maria de Lourdes; Gansl, Rene; Gil, Roberto; Luersen, Gustavo; Lucas, Lucio; Reisner, Marcio; Vieira, Fernando Meton; Machado, Marcel Autran; Murad, Andre; Osvaldt, Alessandro; Brandão, Miguel; Carvalho, Elisangela; Souza, Tulio; Pfiffer, Tulio; Prolla, Gabriel

    2016-01-01

    The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

  14. An endoscopic system for the early detection of cancers of the gastrointestinal tract

    NASA Astrophysics Data System (ADS)

    Mckechnie, Tracy; Jahan, Ali; Tait, Iain; Cuschieri, Alfred; Sibbett, Wilson; Padgett, Miles

    1998-06-01

    We report a compact endoscopic imaging system suitable for the early detection of cancers throughout the gastrointestinal tract. The system incorporates a three-color camera to provide a conventional color image, a mercury lamp filtered between 360 and 450 nm to excite the photosensitizer, and an intensified camera to image the resulting fluorescence at 630 nm. Our results on over 30 resected specimens show a high optical contrast between the cancerous and healthy tissue.

  15. Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

    PubMed Central

    Trinchera, Marco; Aronica, Adele; Dall’Olio, Fabio

    2017-01-01

    The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions. PMID:28241499

  16. Rare cause of upper gastrointestinal bleeding owing to hepatic cancer invasion: a case report.

    PubMed

    Wu, Wei-Ding; Wu, Jia; Yang, Hong-Guo; Chen, Yuan; Zhang, Cheng-Wu; Zhao, Da-Jian; Hu, Zhi-Ming

    2014-09-21

    Upper gastrointestinal bleeding refers to bleeding that arises from the gastrointestinal tract proximal to the ligament of Treitz. The primary reason for gastrointestinal bleeding associated with hepatocellular carcinoma is rupture of a varicose vein owing to pericardial hypotension. We report a rare case of gastrointestinal bleeding with hepatocellular carcinoma in a patient who presented with recurrent gastrointestinal bleeding. The initial diagnosis was gastric cancer with metastasis to the multiple lymph nodes of the lesser curvature. The patient underwent exploratory laparotomy, which identified two lesions in the gastric wall. Total gastrectomy and hepatic local excision was then performed. Pathological results indicated that the hepatocellular carcinoma had invaded the stomach directly, which was confirmed immunohistochemically. The patient is alive with a disease-free survival of 1 year since the surgery. Hepatocellular carcinoma with gastric invasion should be considered as a rare cause of upper gastrointestinal bleeding in hepatocellular carcinoma patients, especially with lesions located in the left lateral hepatic lobe. Surgery is the best solution.

  17. Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis on imaging findings.

    PubMed

    Barral, Matthias; Dohan, Anthony; Allez, Matthieu; Boudiaf, Mourad; Camus, Marine; Laurent, Valérie; Hoeffel, Christine; Soyer, Philippe

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers depending on the specific type of IBD, the extent of the disease and its location. Patients with IBD and extensive colonic involvement are at increased risk of colorectal cancer whereas patients with Crohn disease have an increased risk for small-bowel and anal carcinoma. These cancers preferentially develop on sites of longstanding inflammation. In regards to colon cancer, several key pathogenic events are involved, including chromosomal instability, microsatellite instability and hypermethylation. The risk for colon cancer in IBD patients correlates with longer disease duration, presence of sclerosing cholangitis, pancolitis, family history of colorectal cancer, early onset of the disease and severity of bowel inflammation. Identification of increased colorectal cancer risk in individual IBD patients has led to formal surveillance guidelines. Conversely, although an increased risk for other types of cancer has been well identified, no specific formal screening recommendations exist. Consequently, the role of the radiologist is crucial to alert the referring gastroenterologist when a patient with IBD presents with unusual imaging findings at either computed tomography (CT) or magnetic resonance (MR) imaging. This review provides an update on demographics, molecular, clinical and histopathological features of gastrointestinal cancers in IBD patients including colorectal carcinoma, small bowel adenocarcinoma, neuroendocrine tumors and anal carcinoma, along with a special emphasis on the current role of CT and MR imaging.

  18. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  19. Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells

    PubMed Central

    Wang, Shi; Li, Pei; Lu, Sheng-Min; Ling, Zhi-Qiang

    2016-01-01

    Background & Aims: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells. Methods: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts. Results: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells (P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group (P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro. Conclusions: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer. PMID:27194951

  20. Port-site metastasis after laparoscopic surgery for gastrointestinal cancer.

    PubMed

    Emoto, Shigenobu; Ishigami, Hironori; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2017-03-01

    Although the incidence of port-site metastasis after laparoscopic surgery for colorectal cancer has markedly decreased since laparoscopic colectomy was first reported in 1991, it still has not reached zero. In colorectal cancer, the safety of laparoscopic surgery, including the low incidence of port-site metastasis, has been proven in large, randomized trials. In gastric cancer, reports of port-site metastasis are extremely rare, but we should await the results of ongoing trials. This brief review summarizes the current knowledge regarding port-site metastasis after laparoscopic surgery for colorectal and gastric cancer.

  1. Targeted therapies in advanced differentiated thyroid cancer.

    PubMed

    Carneiro, Raquel M; Carneiro, Benedito A; Agulnik, Mark; Kopp, Peter A; Giles, Francis J

    2015-09-01

    Differentiated thyroid cancer is the most common endocrine malignancy, and its incidence has been rising rapidly over the past 10 years. Although most patients with this disease have an excellent prognosis, a subset develops a more aggressive disease phenotype refractory to conventional therapies. Until recently, there was no effective therapy for these patients. With increasing knowledge of the molecular pathogenesis of thyroid cancer, novel targeted therapies are being developed for this group of patients. Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively. This represents a major innovation in the therapy of patients with advanced thyroid cancer. However, these therapies still have many limitations and further research needs to be pursued with the ultimate goal of providing safe and effective personalized therapy for patients with advanced thyroid cancer.

  2. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    PubMed

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  3. Polyunsaturated Fatty Acids and Their Derivatives: Therapeutic Value for Inflammatory, Functional Gastrointestinal Disorders, and Colorectal Cancer

    PubMed Central

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are bioactive lipids which modulate inflammation and immunity. They gained recognition in nutritional therapy and are recommended dietary supplements. There is a growing body of evidence suggesting the usefulness of PUFAs in active therapy of various gastrointestinal (GI) diseases. In this review we briefly cover the systematics of PUFAs and their metabolites, and elaborate on their possible use in inflammatory bowel disease (IBD), functional gastrointestinal disorders (FGIDs) with focus on irritable bowel syndrome (IBS), and colorectal cancer (CRC). Each section describes the latest findings from in vitro and in vivo studies, with reports of clinical interventions when available. PMID:27990120

  4. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  5. Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract

    PubMed Central

    Pines, Mark

    2014-01-01

    Organ fibrosis and architectural remodeling can severely disrupt tissue function, often with fatal consequences. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli, and the key cellular mediator of fibrosis comprises the myofibroblasts which, when activated, serve as the primary collagen-producing cells. Complex links exist between fibrosis, regeneration and carcinogenesis, and the concept that all organs contain common tissue fibrosis pathways that could be potential therapeutic targets is an attractive one. Because of the major impact of fibrosis on human health there is an unmet need for safe and effective therapies that directly target fibrosis. Halofuginone inhibits tissue fibrosis and regeneration, and thereby affects the development of tumors in various tissues along the gastrointestinal tract. The high efficacy of halofuginone in reducing the fibrosis that affects tumor growth and tissue regeneration is probably due to its dual role in inhibiting the signaling pathway of transforming growth factor β, on the one hand, and inhibiting the development of Th17 cells, on the other hand. At present halofuginone is being evaluated in a clinical trial for other fibrotic indication, and any clinical success in that trial would allow the use of halofuginone, also for all other fibrotic indications, including those of the gastrointestinal tract. PMID:25356039

  6. Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract.

    PubMed

    Pines, Mark

    2014-10-28

    Organ fibrosis and architectural remodeling can severely disrupt tissue function, often with fatal consequences. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli, and the key cellular mediator of fibrosis comprises the myofibroblasts which, when activated, serve as the primary collagen-producing cells. Complex links exist between fibrosis, regeneration and carcinogenesis, and the concept that all organs contain common tissue fibrosis pathways that could be potential therapeutic targets is an attractive one. Because of the major impact of fibrosis on human health there is an unmet need for safe and effective therapies that directly target fibrosis. Halofuginone inhibits tissue fibrosis and regeneration, and thereby affects the development of tumors in various tissues along the gastrointestinal tract. The high efficacy of halofuginone in reducing the fibrosis that affects tumor growth and tissue regeneration is probably due to its dual role in inhibiting the signaling pathway of transforming growth factor β, on the one hand, and inhibiting the development of Th17 cells, on the other hand. At present halofuginone is being evaluated in a clinical trial for other fibrotic indication, and any clinical success in that trial would allow the use of halofuginone, also for all other fibrotic indications, including those of the gastrointestinal tract.

  7. Genetic variation at 8q24, family history of cancer, and upper gastrointestinal cancers in a Chinese population.

    PubMed

    Tarleton, Heather P; Chang, Shen-Chih; Park, Sungshim Lani; Cai, Lin; Ding, Baoguo; He, Na; Hussain, Shehnaz K; Jiang, Qingwu; Mu, Li-Na; Rao, Jianyu; Wang, Hua; You, Nai-Chieh Y; Yu, Shun-Zhang; Zhao, Jin-Kou; Zhang, Zuo-Feng

    2014-03-01

    Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility.

  8. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  9. Excitation-emission matrices and synchronous fluorescence spectroscopy for the diagnosis of gastrointestinal cancers

    NASA Astrophysics Data System (ADS)

    Genova, Ts; Borisova, E.; Penkov, N.; Vladimirov, B.; Zhelyazkova, A.; Avramov, L.

    2016-06-01

    We report the development of an improved fluorescence technique for cancer diagnostics in the gastrointestinal tract. We investigate the fluorescence of ex vivo colorectal (cancerous and healthy) tissue samples using excitation-emission matrix (EEM) and synchronous fluorescence spectroscopy (SFS) steady-state approaches. The obtained results are processed for revealing characteristic fluorescence spectral features with a valuable diagnostic meaning. The main tissue fluorophores, contributing to the observed fluorescence, are tyrosine, tryptophan, NADH, FAD, collagen and elastin. Based on the results of the Mann-Whitney test as useful parameters for differentiation of gastrointestinal cancer from normal mucosa, we suggest using excitation wavelengths in the range 300 - 360 nm for fluorescence spectroscopy and wavelengths intervals of 60 nm and 90 nm for SFS.

  10. Understanding the association between diet and nutrition in upper gastrointestinal cancer.

    PubMed

    Johnson, Ian T

    2015-01-01

    Human vulnerability to cancers of the upper gastrointestinal tract is strongly influenced by environmental factors. The esophagus, in particular, is highly vulnerable to the combined effects of exposure to environmental carcinogens and malnutrition, particularly in certain extreme environments of the developing world. Even in high-income countries, dietary carcinogens and nutrition play a major role in the etiology of oropharyngeal, esophageal and, to a lesser extent, gastric cancers, but the mechanisms are poorly understood. A thorough understanding of the biological mechanisms underlying the vulnerability of these organs to neoplasia would shed further light on the etiology of upper gastrointestinal cancers in all environments. In the meantime, the epidemiological evidence suggests that the risks can be minimized by dietary patterns that adhere closely to current public health recommendations, coupled with maintenance of body mass index within the healthy range.

  11. Alcoholic beverages and carbonated soft drinks: consumption and gastrointestinal cancer risks.

    PubMed

    Cuomo, Rosario; Andreozzi, Paolo; Zito, Francesco Paolo

    2014-01-01

    Alcoholic beverages (ABs) and carbonated soft drinks (CSDs) are widely consumed worldwide. Given the high consumption of these beverages, the scientific community has increased its focus on their health impact. There is epidemiological evidence of a causal association between AB intake and digestive cancer, but the role of alcohol in determining cancer is not fully defined. Experimental studies have so far identified multiple mechanisms involved in carcinogenesis; ethanol itself is not carcinogenic but available data suggest that acetaldehyde (AA) and reactive oxygen species-both products of ethanol metabolism-have a genotoxic effect promoting carcinogenesis. Other carcinogenetic mechanisms include nutritional deficits, changes in DNA methylation, and impaired immune surveillance. As CSDs are often suspected to cause certain gastrointestinal disorders, consequently, some researchers have hypothesized their involvement in gastrointestinal cancers. Of all the ingredients, carbon dioxide is prevalently involved in the alteration of gastrointestinal physiology by a direct mucosal effect and indirect effects mediated by the mechanical pressure determined by gas. The role of sugar or artificial sweeteners is also debated as factors involved in the carcinogenic processes. However, several surveys have failed to show any associations between CSDs and esophageal, gastric, or colon cancers. On the other hand, a slight correlation between risk of pancreatic cancer and CSD consumption has been found.

  12. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology.

    PubMed

    Xue, Yue; Farris, Alton Brad; Quigley, Brian; Krasinskas, Alyssa

    2017-04-01

    The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.

  13. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

    PubMed Central

    Malaguarnera, Mariano; Risino, Corrado; Gargante, Maria Pia; Oreste, Giovanni; Barone, Gloria; Tomasello, Anna Veronica; Costanzo, Mario; Cannizzaro, Matteo Angelo

    2006-01-01

    AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS: Fifty-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: When the cachectic patients with gastro-intestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine (P < 0.005), 0.04 μmol/L in long chain acylcarnitine (P < 0.05), 8.7 μmol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 μmol/L in free carnitine (P < 0.001), 4.60 μmol/L in short chain acylcarnitine (P < 0.001), and 0.60 μmol /L in long-chain acylcarnitine (P < 0.005) and 17.4 μmol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine (P < 0.001), 5.2 μmol /L in short-chain acylcarnitine (P < 0.001), 1.0 μmol/L in long chain acylcarnitine (P < 0.001), and 21.8 μmol/L in total carnitine (P < 0.001). CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients. PMID:16874868

  14. Fish consumption and risk of gastrointestinal cancers: A meta-analysis of cohort studies

    PubMed Central

    Yu, Xiao-Feng; Zou, Jian; Dong, Jie

    2014-01-01

    AIM: To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and the bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to fish intake. When RRs were not available in the published article, they were computed from the exposure distributions. Two investigators extracted the data independently and discrepancies were resolved by discussion with a third investigator. We performed random-effect meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 20-g/d increment of fish consumption. RESULTS: Forty-two studies, comprising 27 independent cohorts, met our inclusion criteria. The studies included 2325040 participants and 24115 incident cases of gastrointestinal cancer, with an average follow-up of 13.6 years. Compared with individuals who did not eat, or seldom ate, fish, the pooled RR of gastrointestinal cancers was 0.93 (95%CI: 0.88-0.98) for regular fish consumers, 0.94 (0.89-0.99) for low to moderate fish consumers, and 0.91 (0.84-0.97) for high fish consumers. Overall, a 20-g increase in fish consumption per day was associated with a 2% reduced risk of gastrointestinal cancers (RR = 0.98; 95%CI: 0.96-1.01). In subgroup analyses, we noted that fish consumption was associated with reduced risk of colorectal (RR = 0.93; 95%CI: 0.87-0.99; P < 0.01), esophageal (RR = 0.91; 95%CI: 0.83-0.99; P < 0.05) and hepatocellular cancers (RR = 0.71; 95%CI: 0.48-0.95; P < 0.01). CONCLUSION: This meta-analysis suggested that fish consumption may reduce total gastrointestinal cancer incidence. Inverse relationships were also detected between fish consumption and specific types of cancers. PMID:25386090

  15. Glycogen synthase kinase-3 beta regulates Snail and β-catenin expression during Fas-induced epithelial-mesenchymal transition in gastrointestinal cancer.

    PubMed

    Zheng, Haoxuan; Li, Wenjing; Wang, Yadong; Liu, Zhizhong; Cai, Yidong; Xie, Tingting; Shi, Meng; Wang, Zhiqing; Jiang, Bo

    2013-08-01

    Fas signalling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but its mechanism of action is still unknown. The effects of Fas-ligand (FasL) treatment and inhibition of Fas signalling on GI cancer cells were tested using invasion assay, immunofluorescence, immunoblot, Reverse Transcription Polymerase Chain Reaction (RT-PCR), quantitative Real-time PCR (qRT-PCR), immunoprecipitation and luciferase reporter assay. Immunohistochemistry was used to analyse the EMT-associated molecules in GI cancer specimens. FasL treatment inhibited E-cadherin transcription by upregulation of Snail in GI cancer cells. The nuclear expression and transcriptional activity of Snail and β-catenin were increased by inhibitory phosphorylation of glycogen synthase kinase-3 beta (GSK-3β) at Ser9 by FasL-induced extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling. Snail associated with β-catenin in the nucleus and, thus, increased β-catenin transcriptional activity. Evaluation of human GI cancer specimens showed that the expression of FasL, phospho-GSK-3β, Snail and β-catenin increase during GI cancer progression. An EMT phenotype was shown to correlate with an advanced cancer stage, and a non-EMT phenotype significantly correlated with a better prognosis. Collectively, these data indicate that GSK-3β regulates Snail and β-catenin expression during Fas-induced EMT in gastrointestinal cancer.

  16. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the stomach: report of three cases.

    PubMed

    Oh, Ji Seon; Lee, Jae-Lyun; Kim, Mi-Jung; Ryu, Min-Hee; Chang, Heung Moon; Kim, Tae Won; Jang, Se Jin; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kang, Yoon-Koo

    2006-01-01

    Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

  17. The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers.

    PubMed

    Vedeld, Hege Marie; Andresen, Kim; Eilertsen, Ina Andrassy; Nesbakken, Arild; Seruca, Raquel; Gladhaug, Ivar P; Thiis-Evensen, Espen; Rognum, Torleiv O; Boberg, Kirsten Muri; Lind, Guro E

    2015-02-15

    We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer. The aim of the present study was to determine whether these four genes, in addition to one gene found to be methylated in colon cancer cell lines (ZNF331), are commonly methylated across gastrointestinal malignancies, as well as explore their role as potential biomarkers. Quantitative methylation specific PCR (qMSP) of colorectal cancer (n=164) and normal colorectal mucosa (n=106) samples showed that all genes were frequently methylated in colorectal cancer (71-92%) with little or no methylation in normal mucosa (0-3%). Methylation of minimum two of these five genes identified 95% of the tumors with a specificity of 98%, and an area under the receiver operating characteristics curve (AUC) of 0.98. For gastric (n=25) and pancreatic (n=20) cancer, the same panel detected 92% and 90% of the tumors, respectively. Seventy-four cancer cell lines were further analyzed by qMSP and real time RT-PCR. In addition to the previously reported DCLK1, a high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18. In conclusion, the high methylation frequency of these genes in colorectal- as well as in gastric-, pancreatic- and bile duct cancer confirmed an epigenetic similarity between gastrointestinal cancer types, and simultaneously demonstrated their potential as biomarkers, particularly for colorectal cancer detection.

  18. Management of Locally Advanced Pancreatic Cancer.

    PubMed

    Martin, Robert C G

    2016-12-01

    The diagnosis for locally advanced pancreatic cancer is based on high-quality cross-sectional imaging, which shows tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and nonthermal ablation modalities. This article presents the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer. Surgical resection offers the best chance of long-term disease control and the only chance for cure for patients with nonmetastatic exocrine pancreatic cancer.

  19. Calcium intake and 28-year gastro-intestinal cancer mortality in Dutch civil servants.

    PubMed

    Slob, I C; Lambregts, J L; Schuit, A J; Kok, F J

    1993-04-22

    The association between calcium intake and gastrointestinal cancer mortality was investigated in a 28-year follow-up study. Data were obtained from a general health examination in 1953-1954 among Dutch civil servants and their spouses, aged 40 to 65 years. Information from 2,591 participants was used for this study. Risk analyses were performed using logistic regression models with the highest quintile of calcium intake as reference. No statistically significant relation between calcium intake and gastrointestinal cancer mortality is observed, although the risk estimate for women with the lowest calcium intake is substantial. Odds ratios (OR) were adjusted for age, energy intake and dietary fiber. After inclusion of other potential confounders to the models (body-mass index and smoking habits), the results hardly differed. Both men and women who died of colorectal cancer had a lower mean calcium intake compared to the rest of the population. For women this was statistically significant. Our results suggest that a low calcium intake may be related to gastrointestinal cancer mortality among women of this study population.

  20. Advances in personalized cancer immunotherapy.

    PubMed

    Kakimi, Kazuhiro; Karasaki, Takahiro; Matsushita, Hirokazu; Sugie, Tomoharu

    2017-01-01

    There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting. Apart from this selective process, anti-tumor immune responses can also be inhibited in multiple different ways which vary from patient to patient. This implies that cancer immunotherapy must be personalized to (1) identify the rate-limiting steps in any given patient, (2) identify and combine strategies to overcome these hurdles, and (3) proceed with the next round of the "Cancer-Immunity Cycle". Cancer cells have genetic alterations which can provide the immune system with targets by which to recognize and eradicate the tumor. Mutated proteins expressed exclusively in cancer cells and recognizable by the immune system are known as neoantigens. The development of next-generation sequencing technology has made it possible to determine the genetic landscape of human cancer and facilitated the utilization of genomic information to identify such candidate neoantigens in individual cancers. Future immunotherapies will need to be personalized in terms of the identification of both patient-specific immunosuppressive mechanisms and target neoantigens.

  1. Discrepancies between attainment and importance of life values and anxiety and depression in gastrointestinal cancer patients and their spouses.

    PubMed

    Nordin, K; Wasteson, E; Hoffman, K; Glimelius, B; Sjödén, P O

    2001-01-01

    Patients' satisfaction with life, viewed in terms of the discrepancy between the perceived attainment and subjective importance of various life values, is a less often studied phenomenon for understanding the psychological adaptation in cancer patients. The main aim of the present study is to investigate the relation between the degree of attainment and importance of life values on the one hand, and anxiety and depression, on the other. A consecutive series of 85 newly diagnosed patients with gastrointestinal (GI) cancers, 52 potentially cured and 33 with an advanced disease, and 26 spouses to the patients with an advanced disease participated. The patients and spouses of non-cured patients filled out questionnaires twice, close to the diagnosis and after 1 (non-cured patients) or 3 months. Overall, large discrepancies between the perceived attainment and importance of life values were associated with high anxiety and depression. For the patients (both cured and non-cured), the discrepancies decreased for several life values over time, as did anxiety and depression. For the spouses of the non-cured patients, there was no decrease either for life value discrepancies or for anxiety/depression. This suggests that patients, in contrast to their spouses, strive to achieve small discrepancies between the perceived attainment and importance of life values, as part of their adjustment to serious diseases, e.g. cancer.

  2. Advances in Breast Cancer Therapy

    DTIC Science & Technology

    2010-06-01

    will be scheduled in Q3 2010 Agustin Garcia, MD University of Southern California / Norris Comprehensive Cancer Center 1441 Eastlake Avenue Los...A 6 6 Agustin Garcia, MD USC / Norris Comprehensive Cancer Center • Q3 Approval by DoD Expected • June -- December Accrual Anticipated at 12

  3. Gastrointestinal hemorrhage due to ileal metastasis from primary lung cancer.

    PubMed

    Liu, Wei; Zhou, Wei; Qi, Wei-Lin; Ma, Ya-Dan; Xu, Yun-Yun

    2015-03-21

    We report a patient with small intestinal metastasis from lung squamous cell carcinoma. A 66-year-old man who underwent radical lung cancer surgery was admitted to our hospital. Before starting his fifth cycle of chemotherapy, he was found to have a positive fecal occult blood test. Abdominal computed tomography scan revealed an ileal tumor with mesenteric lymph node enlargement. He underwent laparoscopic resection of the involved small intestine and mesentery. Histopathological analysis confirmed metastasis from lung cancer. We conducted a review of the literature and 64 documented cases of small intestinal metastasis from lung cancer were found. The pathologic diagnosis, clinical presentation, site of metastasis, and survival time in these cases were reviewed.

  4. Disclosure between patients with gastrointestinal cancer and their spouses.

    PubMed

    Porter, Laura S; Keefe, Francis J; Hurwitz, Herbert; Faber, Michelle

    2005-12-01

    This study examined patterns of disclosure about cancer-related concerns between patients with GI cancer and their spouses, and associations between patient and spouse disclosure and patient adjustment, spouse adjustment, and aspects of relationship functioning. A sample of 47 patients and 45 of their spouses completed a measure of disclosure which included ratings of their level of disclosure and level of holding back from disclosure of cancer-related concerns. Patients completed a measure of quality of life, spouses completed a measure of caregiver strain, and all participants completed measures of psychological distress and relationship functioning (intimacy, empathy, and partner avoidance and criticism). Data analyses revealed that patients and spouses reported moderately high levels of disclosure and low levels of holding back, with patients reporting higher levels of disclosure than spouses. Among patients and spouses, low levels of disclosure and high levels of holding back were associated with poorer relationship functioning. There were also some indications that high levels of holding back, and to a lesser extent low levels of disclosure, were associated with increased psychological distress for both patients and spouses. However, there were no indications that patient or spouse disclosure was harmful for the other person. Considered overall, the results of this study suggest that levels of disclosure between cancer patients and their spouses may be important in understanding how they adjust as a couple to the demands of the patient's illness.

  5. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.

    PubMed

    Syngal, Sapna; Brand, Randall E; Church, James M; Giardiello, Francis M; Hampel, Heather L; Burt, Randall W

    2015-02-01

    This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

  6. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes

    PubMed Central

    Syngal, Sapna; Brand, Randall E.; Church, James M.; Giardiello, Francis M.; Hampel, Heather L.; Burt, Randall W.

    2015-01-01

    This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz–Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer. PMID:25645574

  7. Advances in cryoablation for pancreatic cancer

    PubMed Central

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-01

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID:26811625

  8. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  9. Impact of the difference in surgical site on the physique in gastrointestinal tract cancer patients.

    PubMed

    Hara, Tsuyoshi; Kubo, Akira; Kogure, Eisuke; Ishii, Takaya

    2016-01-01

    [Purpose] The purpose of the present study was to observe physical function, physique (only BMI), and nutrition status (evaluated by serum albumin levels) from before surgery to after discharge among perioperative patients with gastrointestinal tract cancer and to examine the effect of difference in surgical site (i.e., stomach, colon, and rectum) in these patients. [Subjects and Methods] The study subjects were 70 patients who underwent surgical treatment for gastrointestinal tract cancer [36 males and 34 females, aged 59.3 ± 11.4 years (mean ± SD)]. The subjects were classified into three levels according to surgical site (stomach, colon, and rectum). We evaluated patients' physical function, physique, and nutrition status in the three points: before surgery, after surgery, and after discharge. The 6-minute walk distance was measured for physical function. Body mass index was measured for physique. The serum albumin level was measured for nutrition status. [Results] Significant declines in 6-minute walk distance, body mass index, and serum albumin were observed after surgery among the study subjects. In addition, a significant decline in body mass index was observed after discharge compared with before surgery. Regarding body mass index, a significant interaction between surgical site and evaluation times was observed for ANOVA. [Conclusion] These results suggest that BMI after discharge is significantly less than that before surgery and that body mass index changes from before surgery to after surgery are efficacy the difference of surgical site in patients who undergo surgical treatment for gastrointestinal tract cancer.

  10. Relationship between physical activity and function in elderly patients discharged after surgical treatment for gastrointestinal cancer

    PubMed Central

    Hara, Tsuyoshi; Kubo, Akira

    2015-01-01

    [Purpose] The purpose of the present study was to observe changes in physical activity (PA) from before surgery to after discharge among elderly patients with gastrointestinal cancer and to examine the relationships between PA, function, and physique after discharge in these patients. [Subjects and Methods] The study participants were 18 elderly patients who underwent surgical treatment for gastrointestinal cancer [10 males and 8 females, aged 71.4 ± 4.2 years (mean ± SD)]. We evaluated patients’ PA, function, and physique before surgery and after discharge. Calorie consumption as calculated using the International Physical Activity Questionnaire (IPAQ) short version was measured for PA. Isometric knee extension force (IKEF), the timed up and go test (TUGT), and the 6-minute walk distance (6MWD) were measured for function. The body mass index (BMI) was calculated for physique. [Results] Significant declines in PA and BMI were observed after discharge among the study participants. In addition, a significant correlation between PA and IKEF was observed in the discharge phase. [Conclusion] These results suggest that PA after discharge is significantly less than that before surgery and related to the functioning of the lower extremities in the same period in elderly patients who undergo surgical treatment for gastrointestinal cancer. PMID:26504327

  11. Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

    ClinicalTrials.gov

    2016-07-20

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

  12. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  13. New possibilities for cancer therapy with advances in cancer immunology.

    PubMed

    MacLean, G D; Longenecker, B M

    1994-04-01

    There has been progress over the last decade in addressing three questions: Are there cancer-associated antigens that could be targets for immunotherapy? Can the human immune system recognize cancer-associated antigens? Can an anti-cancer immune response affect cancer cells and lead to increased survival? Results from animal model studies have been interpreted by optimists as encouraging, and by pessimists as being irrelevant to human cancer. Earlier studies on "cancer vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal antibodies have enabled identification of relevant cancer-associated antigens or epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the peptide sequences of MUC-1. In parallel with research on immune adjuvants and measures designed to inhibit suppressor activity, these epitopes are being tested for their potential in the immunotherapy of solid tumors. It is clear that some of these cancer-associated epitopes are immunogenic in humans. Mixed responses may relate to cancer heterogeneity and may indicate the importance of multi-epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged disease stability challenges us to re-think the goals of cancer therapy. Recent advances in the knowledge of the effect of cytokines on tumor antigen expression and the regulation of the immune response, coupled with advances in active specific immunotherapy, provide hope that biomodulation may become an important part of the therapy of solid tumors in the next century.

  14. Significance of tumour mass on T-lymphocyte levels in patients with gastrointestinal cancer.

    PubMed

    Shukla, H S; Whitehead, R H; Hughes, L E

    1979-08-01

    The relationship between tumour load and immunity in gastrointestinal cancer has been studied by sequential comparison in patients whose tumour has been removed and those whose tumour was found to be inoperable. Total lymphocyte count, absolute and percentage T- and B-lymphocyte counts, effect of papain on E-rosetting cell levels, and inhibitory effect of cancer sera on E-rosette formation by normal lymphocytes have been studied in 30 patients with stomach or colorectal cancer, and 10 control patients with benign gastrointestinal disease. The examination was done on each patient before and at regular intervals after operation up to 24 weeks. Operable cases, with removal of tumour load, showed a temporary fall in total lymphocyte count and T cell counts, which returned to normal by four weeks postoperatively. Inoperable cases (15 patients) showed a progressive fall in total lymphocyte count and a relatively greater depression of T cell counts, in parallel with increasing tumour mass. E-receptor blocking factor was demonstrated in the sera of cancer patients. This factor was related to tumour mass and presumably was of tumour origin, as it persisted in the inoperable group but disappeared by 12 weeks after tumour removal. The factor explained the excess depresion of T cells over total lymphocytes, but does not explain the continuing depression of total lymphocyte count in the cancer patients.

  15. Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers - Review

    PubMed Central

    Riess, Hanno; Habbel, Piet; Jühling, Anja; Sinn, Marianne; Pelzer, Uwe

    2016-01-01

    Venous thromboembolism event (VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis (CAT), preferably with low molecular weight heparins (LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers. PMID:26989461

  16. Breast cancer. Part 3: advanced cancer and psychological implications.

    PubMed

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  17. Gastrointestinal perforation during regorafenib administration in a case with hepatic metastases of colon cancer.

    PubMed

    Ogata, Kenichi; Takamori, Hiroshi; Umezaki, Naoki; Yagi, Taisuke; Ogawa, Katsuhiro; Ozaki, Nobuyuki; Hayashi, Hiromitsu; Tanaka, Hideyuki; Ikuta, Yoshiaki; Doi, Koichi

    2016-07-20

    Although common side effects of regorafenib include hand-and-foot syndrome and diarrhoea, the incidence of gastrointestinal perforation is reportedly unknown. We describe our experience with the case of a 65-year-old woman treated with regorafenib as a third-line therapy for progressive caecal cancer with multiple hepatic metastases after 4 and 6 courses of systemic mFOLFOX6 + bevacizumab (BV) and FOLFIRI + BV chemotherapy, respectively. The patient used regorafenib for 32 days but visited our hospital with abdominal pain during the second course. She was diagnosed with acute appendicitis and treated conservatively with antibiotics. The abdominal findings did not improve, and a computed tomography evaluation on day 4 of hospitalization revealed free air lateral to the caecal tumour, liver surface, and epigastric region. The patient underwent same-day emergency surgery based on a diagnosis of gastrointestinal perforation with generalized peritonitis. Upon observing digestive fluid leakage into the peri-ileocaecal area and a 5-mm perforation in the appendix, the patient was diagnosed with peritonitis due to gastrointestinal perforation. Ileocaecal resection with D2 debridement was performed, and a colostomy was opened into the ileum and ascending colon. We conclude that our patient developed gastrointestinal perforation during regorafenib therapy and note that clinicians should be aware of this possible complication in patients with a history of prior treatment with BV.

  18. Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers.

    PubMed

    Matthews, Robert; Choi, Minsig

    2016-09-09

    Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it.

  19. MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers

    PubMed Central

    Merhautova, Jana; Demlova, Regina; Slaby, Ondrej

    2016-01-01

    Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy. PMID:27729862

  20. Heat-shock protein 27 (Hsp27) as a target of methylglyoxal in gastrointestinal cancer.

    PubMed

    Oya-Ito, Tomoko; Naito, Yuji; Takagi, Tomohisa; Handa, Osamu; Matsui, Hirofumi; Yamada, Masaki; Shima, Keisuke; Yoshikawa, Toshikazu

    2011-07-01

    The molecular mechanisms underlying the posttranslational modification of proteins in gastrointestinal cancer are still unknown. Here, we investigated the role of methylglyoxal modifications in gastrointestinal tumors. Methylglyoxal is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins. By using a monoclonal antibody to methylglyoxal-modified proteins, we found that murine heat-shock protein 25 and human heat-shock protein 27 were the major adducted proteins in rat gastric carcinoma mucosal cell line and human colon cancer cell line, respectively. Furthermore, we found that heat-shock protein 27 was modified by methylglyoxal in ascending colon and rectum of patients with cancer. However, methylglyoxal-modified heat-shock protein 25/heat-shock protein 27 was not detected in non cancerous cell lines or in normal subject. Matrix-associated laser desorption/ionization mass spectrometry/mass spectrometry analysis of peptide fragments identified Arg-75, Arg-79, Arg-89, Arg-94, Arg-127, Arg-136, Arg-140, Arg-188, and Lys-123 as methylglyoxal modification sites in heat-shock protein 27 and in phosphorylated heat-shock protein 27. The transfer of methylglyoxal-modified heat-shock protein 27 into rat intestinal epithelial cell line RIE was even more effective in preventing apoptotic cell death than that of native control heat-shock protein 27. Furthermore, methylglyoxal modification of heat-shock protein 27 protected the cells against both the hydrogen peroxide- and cytochrome c-mediated caspase activation, and the hydrogen peroxide-induced production of intracellular reactive oxygen species. The levels of lactate converted from methylglyoxal were increased in carcinoma mucosal cell lines. Our results suggest that posttranslational modification of heat-shock protein 27 by methylglyoxal may have important implications for epithelial cell injury in gastrointestinal cancer.

  1. Relationships between gastrointestinal symptoms, uncertainty, and perceived recovery in patients with gastric cancer after gastrectomy.

    PubMed

    Jeon, Byeong Hee; Choi, Mona; Lee, JuHee; Noh, Sung Hoon

    2016-03-01

    This study examines relationships between gastrointestinal symptoms, uncertainty, and perceived recovery in gastric cancer patients after gastrectomy. Data were collected from 146 patients at an outpatient clinic of a university hospital in Seoul, Korea from October to November 2012. The Gastrointestinal Symptoms Rating Scale, the Mishel Uncertainty in Illness Scale, and questions on perceived recovery of physical, psychological, and social functions were analyzed. High gastrointestinal symptom scores were reported in women younger patients (F = 5.55, P = 0.005), and in patients without a family history of gastric cancer. The uncertainty score was higher in patients with low economic (F = 3.84, P = 0.024) and educational status and no family history. Regression analysis revealed uncertainty was the strongest factor associated with recovery. Nurses can assist patients and families to predict and deal with health problems by offering education on progress from diagnosis to postoperative management, promoting all aspects of recovery after gastrectomy.

  2. Emerging role of Hippo pathway in gastric and other gastrointestinal cancers

    PubMed Central

    Kang, Wei; Cheng, Alfred SL; Yu, Jun; To, Ka Fai

    2016-01-01

    More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1 (YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZ-binding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and microRNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis. PMID:26811664

  3. Recent advances in cancer therapeutics.

    PubMed

    Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

    2015-01-01

    In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.

  4. A novel molecular therapy using bioengineered adenovirus for human gastrointestinal cancer.

    PubMed

    Fujiwara, Toshiyoshi

    2011-06-01

    Replication-selective tumor-specific viruses constitute a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Human telomerase is highly active in more than 85オ of primary cancers, regardless of their tissue origins, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter would allow for preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death. Lymphatic invasion is a major route for cancer cell dissemination, and adequate treatment of locoregional lymph nodes is required for curative treatment in patients with gastrointestinal tumors. We demonstrated that intratumoral injection of Telomelysin mediates effective in vivo purging of metastatic tumor cells from regional lymph nodes. Moreover, using noninvasive whole-body imaging, we found that intratumoral injection of Telomelysin followed by regional irradiation induces a substantial antitumor effect, resulting from tumor cell-specific radiosensitization, in an orthotopic human esophageal cancer xenograft model. These results illustrate the potential of oncolytic virotherapy as a promising strategy in the management of human gastrointestinal cancer.

  5. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer.

    PubMed

    Kim, Byung-Gyu; Li, Cuiling; Qiao, Wenhui; Mamura, Mizuko; Kasprzak, Barbara; Kasperczak, Barbara; Anver, Miriam; Wolfraim, Lawrence; Hong, Suntaek; Mushinski, Elizabeth; Potter, Michael; Kim, Seong-Jin; Fu, Xin-Yuan; Deng, Chuxia; Letterio, John J

    2006-06-22

    SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours.

  6. Neurokinin-1 Receptor Antagonists as Antitumor Drugs in Gastrointestinal Cancer: A New Approach

    PubMed Central

    Muñoz, Miguel; Coveñas, Rafael

    2016-01-01

    Gastrointestinal (GI) cancer is the term for a group of cancers affecting the digestive system. After binding to the neurokinin-1 (NK-1) receptor, the undecapeptide substance P (SP) regulates GI cancer cell proliferation and migration for invasion and metastasis, and controls endothelial cell proliferation for angiogenesis. SP also exerts an antiapoptotic effect. Both SP and the NK-1 receptor are located in GI tumor cells, the NK-1 receptor being overexpressed. By contrast, after binding to the NK-1 receptor, NK-1 receptor antagonists elicit the inhibition (epidermal growth factor receptor inhibition) of the proliferation of GI cancer cells in a concentration-dependent manner, induce the death of GI cancer cells by apoptosis, counteract the Warburg effect, inhibit cancer cell migration (counteracting invasion and metastasis), and inhibit angiogenesis (vascular endothelial growth factor inhibition). NK-1 receptor antagonists are safe and well tolerated. Thus, the NK-1 receptor could be considered as a new target in GI cancer and NK-1 receptor antagonists (eg, aprepitant) could be a new promising approach for the treatment of GI cancer. PMID:27488320

  7. The status of lead and cadmium in soils of high prevalenct gastrointestinal cancer region of Isfahan

    PubMed Central

    Mohajer, Reza; Salehi, Mohammad Hassan; Mohammadi, Jahangard; Emami, Mohammad Hassan; Azarm, Taleb

    2013-01-01

    Background: Cadmium and lead compounds are classified as human carcinogens by several regulatory agencies. Twenty five percent of all cancer-related deaths are attributed to gastrointestinal cancers (GI Ca). We investigated the levels of 2 different heavy metals (Cd and Pb) in the soils of the Lenjanat region, Isfahan province, Central Iran where intensive agriculture is surrounded by different industries like steel and cement-making factories and mining and gastrointestinal cancers are very common in this province. Materials and methods: Two hundred topsoil samples (0-20 cm depth) were collected from agricultural and non-agricultural soils of the region and were analyzed for heavy metals. The metal contents were determined by flame atomic absorption spectrometry. Results: The findings of this study showed that frequency of gastrointestinal cancers in the study area have been increased in the recent years. Results of soil samples in this region showed that the mean concentration of Pb and Cd were more than 16 and 1 mg kg−1, respectively. The total Cd concentration in most of the samples exceeded the suggested Swiss thresholds (0.8 mg kg−1) but the mean value of Pb concentration in soil was less than the threshold of 50 mg kg−1 set by Swiss Federal Office of Environmental, Forest and Landscape. Compared to the threshold values for heavy metals (Cd and Pb) in soils, data showed that the studied fields were contaminated especially by Cd. Conclusion: High heavy metals content in the soils seems to play an important etiological role in the carcinogenesis. Excessive accumulation of heavy metals in agricultural soils may not only result in soil contamination, but also lead to elevated heavy metal uptake by crops, and thus affect food quality and safety. Thus, analyzing heavy metals content in crops, water and dust could provide us a better insight to solve the problem. PMID:23930117

  8. The role of TGF-beta and Wnt signaling in gastrointestinal stem cells and cancer.

    PubMed

    Mishra, Lopa; Shetty, Kirti; Tang, Yi; Stuart, August; Byers, Stephen W

    2005-08-29

    The past three decades have seen an unremitting quest to identify and understand gastrointestinal stem cells, their plasticity in differentiating across cell types, as well as their role in normal, regenerative, and cancer cells. A fascinating hallmark of stem cells is their ability to undergo assymetric cell division, which entails replication of the DNA followed by division of the nucleus and partitioning of the cytoplasm to yield two different daughter cells: a stem cell as well as a committed progenitor cell, the latter proliferating into differentiated progeny. We are only just beginning to understand how normally quiescent, tissue-specific stem cells interpret a vast array of signals to develop into the gastrointestinal system. These signaling pathways include the transforming growth factor-beta (TGF-beta) superfamily, Wnt, FGFs, Hedgehog, Hox proteins that originate from surrounding mesodermal/stromal tissue as well as endodermal/epithelial tissue. TGF-beta and wnt proteins are key morphogens that ultimately influence cell division and cell fate, so that gut endodermal stem cells enter the cell cycle, and undergo cell division that ultimately leads to differentiated cells such as functional hepatocytes, gastric parietal cells, or gut epithelial cells. Disruptions and errors in this process usually lead to tissue-specific gastrointestinal cancers such as hepatocellular cancers, gastric adenocarcinomas, and colonic adenocarcinomas. An increasingly complex and coherent view of stem/progenitor cell signaling networks, which coordinate cell growth, proliferation, stress management, and survival, is helping to define the fragile areas where malignancies are likely to develop and shows promise for the development of better cancer therapies.

  9. Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Huang, Lanshan; Ren, Fanghui; Tang, Ruixue; Feng, Zhenbo; Chen, Gang

    2016-02-01

    Cyclin E is a critical regulator in cell cycle and promotes the initiation of DNA replication and centrosome duplication in late G1. The overexpression of cyclin E is common in cancers of the digestive system. However, whether cyclin E represents a prognostic biomarker in gastrointestinal cancer remains controversial. We reviewed the published literatures to clarify the association between cyclin E determined by immunohistochemistry (IHC) and survival in gastrointestinal cancer. Literatures were searched in PubMed and Cochrane Library published up to December 1, 2014. A total of 282 articles were initially identified, and 14 articles were included in this study. Meta-analysis was performed for 10 studies with a total of 1300 patients. Combined hazard risk (HR) and corresponding 95% confidence interval (CI) were calculated by random-effect model due to the heterogeneity. The quality of included studies was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies (MINORS). We found that high level of cyclin E was a predicator of poor prognosis among patients with gastrointestinal cancer (HR = 1.67, 95% CI = 1.06-2.63, P = .028). In summary, overexpression of cyclin E is associated with poor prognosis in gastrointestinal cancer and expression of cyclin E determined by IHC might be a prognostic marker for gastrointestinal cancer in clinical practice.

  10. New Treatment in Advanced Thyroid Cancer

    PubMed Central

    Giuffrida, Dario; Prestifilippo, Angela; Scarfia, Alessia; Martino, Daniela; Marchisotta, Stefania

    2012-01-01

    Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment. PMID:23133451

  11. Immunotherapy for lung cancer: advances and prospects

    PubMed Central

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  12. Afatinib in Advanced Refractory Urothelial Cancer

    ClinicalTrials.gov

    2017-03-06

    Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Ureter Cancer

  13. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  14. Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11–12 September 2015

    PubMed Central

    Mulder, K.E.; Ahmed, S.; Davies, J.D.; Doll, C.M.; Dowden, S.; Gill, S.; Gordon, V.; Hebbard, P.; Lim, H.; McFadden, A.; McGhie, J.P.; Park, J.; Wong, R.

    2016-01-01

    The 17th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Edmonton, Alberta, 11–12 September 2015. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastric cancer. PMID:28050139

  15. Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer

    PubMed Central

    Shao, Yang-Guang; Ning, Ke; Li, Feng

    2016-01-01

    P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and “drug-like” properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer. PMID:26811660

  16. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

  17. Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants.

    PubMed

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-12-01

    Parasitic nematodes (roundworms) of livestock have major economic impact globally. In spite of the diseases caused by these nematodes and some advances in the design of new therapeutic agents (anthelmintics) and attempts to develop vaccines against some of them, there has been limited progress in the establishment of practical diagnostic techniques. The specific and sensitive diagnosis of gastrointestinal nematode infections of livestock underpins effective disease control, which is highly relevant now that anthelmintic resistance (AR) is a major problem. Traditional diagnostic techniques have major constraints, in terms of sensitivity and specificity. The purpose of this article is to provide a brief background on gastrointestinal nematodes (Strongylida) of livestock and their control; to summarize conventional methods used for the diagnosis and discuss their constraints; to review key molecular-diagnostic methods and recent progress in the development of advanced amplification-based and sequencing technologies, and their implications for epidemiological investigations and the control of parasitic diseases.

  18. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  19. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  20. Advances in the treatment of testicular cancer

    PubMed Central

    Margel, David; Lubin, Marc Alan; Baniel, Jack

    2015-01-01

    Germ cell tumors (GCT) are relatively uncommon, accounting for only 1% of male malignancies in the United States. It has become an important oncological disease for several reasons. It is the most common malignancy in young men 15-35 years old. GCTs are among a unique numbers of neoplasms where biochemical markers play a critical role. Finally, it is a model of curable cancer. In this review we discuss cancer epidemiology, genetics, and therapeutic principles. Recent advances in the management of stage I GCT and controversies in the management of post chemotherapy residual mass are presented. PMID:26816836

  1. Wernicke encephalopathy after gastrointestinal surgery for cancer: causes of diagnostic failure or delay.

    PubMed

    Rufa, A; Rosini, F; Cerase, A; Giannini, F; Pretegiani, E; Buccoliero, R; Dotti, M T; Federico, A

    2011-04-01

    Wernicke encephalopathy (WE) is a neurological emergency due to thiamine deficiency. We aimed to identify clinical course and causes of diagnostic delay or failure of WE in a group of patients who underwent surgery for gastrointestinal tumors. A retrospective review of clinical, laboratory, neuroimaging, and therapeutic features of 10 patients with WE following abdominal surgery for cancer was carried out. Four patients died; in these subjects, diagnosis was delayed and supplementation of vitamin was absent or likely inadequate. Diagnostic delay or failure was also related to the coexistence of several medical complications at presentation masking typical symptoms of WE. In the surviving patients, outcome was influenced by promptness and type of therapy. Postoperative abdominal bleeding and number of subsequent operations may also had an effect. Postsurgical patients with gastrointestinal tumors may develop a subtle WE. The number of subsequent operations and the severity of postoperative complications may increase the risk of unrecognized WE. The disease should be suspected in postsurgical patients who have unexpected mental status changes, even under prophylactic treatment with vitamins. We suggest that prophylaxis with high doses of thiamine should be undertaken in patients with gastrointestinal tumors before surgery.

  2. Probiotics to prevent gastrointestinal toxicity from cancer therapy: An interpretive review and call to action

    PubMed Central

    Ciorba, Matthew A; Hallemeier, Christopher L; Stenson, William F; Parikh, Parag J

    2016-01-01

    Purpose of Review There is currently an unmet need for agents that can prevent the gastrointestinal toxicity (mucositis, enteritis) associated with chemotherapy and radiation therapy of abdominal and pelvic cancers. Herein we provide an overview of how manipulation of the gut microbiota by probiotic administration affects these gastrointestinal symptoms. We focus this review on published human trials and also provide suggestions on how the field can move forward. Recent Findings Several clinical trials of varying design, patient populations and probiotic product have been reported. Lactobacillus probiotics of adequate dosage demonstrate a potential to reduce gastrointestinal toxicity when administered prophylactically. Common study limitations prevent the widespread adoption of this practice at this point, but are informative for rational design of future trials. Summary No single probiotic strain or product has emerged from human clinical trials for this indication. Further human studies are required to address limitations in the current literature. Preclinical model data should be used to inform the rational design of these new clinical trials to adequately address this important question. PMID:25872116

  3. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.

  4. Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer.

    PubMed

    Prasad, Sahdeo; Tyagi, Amit K

    2015-01-01

    Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described.

  5. Integrated OCT-US catheter for detection of cancer in the gastrointestinal tract

    NASA Astrophysics Data System (ADS)

    Li, Jiawen; Ma, Teng; Cummins, Thomas; Shung, K. Kirk; Van Dam, Jacques; Zhou, Qifa; Chen, Zhongping

    2015-03-01

    Gastrointestinal tract cancer, the most common type of cancer, has a very low survival rate, especially for pancreatic cancer (five year survival rate of 5%) and bile duct cancer (five year survival rate of 12%). Here, we propose to use an integrated OCT-US catheter for cancer detection. OCT is targeted to acquire detailed information, such as dysplasia and neoplasia, for early detection of tumors. US is used for staging cancers according to the size of the primary tumor and whether or not it has invaded lymph nodes and other parts of the body. Considering the lumen size of the GI tract, an OCT system with a long image range (>10mm) and a US imaging system with a center frequency at 40MHz (penetration depth > 5mm) were used. The OCT probe was also designed for long-range imaging. The side-view OCT and US probes were sealed inside one probe cap piece and one torque coil and became an integrated probe. This probe was then inserted into a catheter sheath which fits in the channel of a duodenoscope and is able to be navigated smoothly into the bile duct by the elevator of the duodenoscope. We have imaged 5 healthy and 2 diseased bile ducts. In the OCT images, disorganized layer structures and heterogeneous regions demonstrated the existence of tumors. Micro-calcification can be observed in the corresponding US images.

  6. Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

    PubMed Central

    Prasad, Sahdeo; Tyagi, Amit K.

    2015-01-01

    Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described. PMID:25838819

  7. Management of dysphagia in advanced oropharyngeal cancer.

    PubMed

    Penner, Jamie L; McClement, Susan E; Sawatzky, Jo-Ann V

    2007-05-01

    Individuals with advanced oropharyngeal cancer often experience dysphagia as a result of their illness and its treatment. Research consistently demonstrates that dysphagia and difficulty with oral intake have many implications, including a negative impact on quality of life. Nurses are in a key position to provide support and initiate appropriate interventions for individuals with dysphagia. Using the Human Response to Illness model (Mitchell et al, 1991) as an organising framework, this paper presents a critical review of the empirical literature regarding dysphagia in individuals with advanced oropharyngeal cancer that will: i) provide the reader with a comprehensive understanding of dysphagia; ii) identify current gaps in our knowledge; and iii) establish the foundation for appropriate evidence-based interventions to optimise functioning and quality of life in this patient population.

  8. Usefulness of immunohistochemical studies in diagnosing metachronous gallbladder and small intestinal metastases from lung cancer with gastrointestinal hemorrhage: a case report.

    PubMed

    Tanaka, Masayuki; Kitago, Minoru; Akiyama, Nobuyoshi; Iwamaru, Arifumi; Yamamoto, Tatsuya; Suzuki, Fumio; Hibi, Taizo; Abe, Yuta; Yagi, Hiroshi; Shinoda, Masahiro; Itano, Osamu; Ogata, Kentaro; Kitagawa, Yuko

    2015-02-18

    Isolated metachronous gastrointestinal metastases from advanced-stage lung cancer are rarely diagnosed on the basis of symptoms and resected. In this report, we present a case of resectable metachronous gallbladder and small intestinal metastases of lung cancer. An 86-year-old woman was treated for lung cancer with resection of the right inferior lobe. Five months after the surgery, she was re-admitted because of melena and anemia. Ultrasonography showed a gallbladder tumor with gastrointestinal hemorrhage, and laparoscopic-assisted cholecystectomy was subsequently performed. However, 2 months after this event, the patient presented again with melena and anemia and was diagnosed with a small intestinal tumor. Therefore, laparoscopic-assisted partial resection of the small intestine was performed. Immunohistochemical staining for thyroid transcription factor-1 and cytokeratin 7 confirmed that the two resected tumors were metachronous metastases of the primary lung cancer. The patient died of liver metastases 5 months after the last surgery. Our experience with this case suggests that surgical resection might not be curative but palliative for patients with isolated gallbladder and small intestinal metastases diagnosed on the basis of melena that is resistant to conservative treatment.

  9. Treatment Option Overview (Gastrointestinal Carcinoid Tumors)

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  10. Treatment Options for Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  11. General Information about Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  12. Advances for Studying Clonal Evolution in Cancer

    PubMed Central

    Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

    2013-01-01

    The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

  13. Oral and gastrointestinal symptomatic metastases as initial presentation of lung cancer.

    PubMed

    Jeba, Jenifer; Backianathan, Selvamani; Ishitha, Gunadala; Singh, Ashish

    2016-11-18

    Metastasis to the tongue, duodenum or pancreas from primary lung cancer is uncommon. Primary lung cancer presenting with symptoms related to metastases at these sites, at initial presentation is extremely rare. We report a 45-year-old man with disseminated lung malignancy who presented with dyspepsia, melena, symptoms due to anaemia and swelling in the tongue. Oral examination revealed a hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of metastasis from lung primary. CT revealed lung primary with disseminated metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum and intra-abdominal lymph nodes. The patient was treated with palliative chemotherapy. The unusual presentation and diagnostic details are discussed.

  14. Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer

    PubMed Central

    Li, Jieying; Huang, Jianfei; Huang, Fang; Jin, Qing; Zhu, Huijun; Wang, Xudong; Chen, Meng

    2016-01-01

    Isocitrate dehydrogenase (IDH1) is an NADP-dependent enzyme that catalyzes the decarboxylation of isocitrate to alpha-ketoglutarate. The IDH1-R132H mutation predicts a better clinical outcome for glioma patients, and the expression of IDH1-R132H correlates with a favorable outcome in patients with brain tumors. Here, we investigated IDH1-R132H expression in both gastric (n=526) and colorectal (n=399) tissues by performing immunohistochemistry analyses on tissue microarrays. We also tested whether IDH1-R132H expression correlated with various clinical parameters. In both gastric and colorectal cancer, expression of IDH1-R132H was associated with tumor stage. Patients with low IDH1-R132H expression had a poor overall survival. Our data indicate that IDH1-R132H expression could be used as a predictive marker of prognosis for patients with gastrointestinal cancer. PMID:27655638

  15. Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells.

    PubMed

    Sandoval, Manuel; Okuhama, Nataly N; Clark, Melinda; Angeles, Fausto M; Lao, Juan; Bustamante, Sergio; Miller, Mark J S

    2002-05-01

    Sangre de grado is an ethnomedicinal red tree sap obtained from Croton spp. that is used to treat gastrointestinal ulcers, cancer and to promote wound healing. To evaluate the potential role of sangre de grado (SdG) in cancer we examined its effects on human cancer cells, AGS (stomach), HT29 and T84 (colon). Viability of cells treated with SdG (10-200 microg/ml) decreased (P<0.01) in a dose dependent manner measured over a 24-h period. Cell proliferation at 48 h decreased (P<0.01) in all cells treated with SdG (>100 microg/ml). When cells in suspension were treated with SdG (100 microg/ml) cell adherence was severely compromised (>85%). Cells treated with SdG (100 microg/ml) underwent apoptosis as detected by nucleus condensation and DNA fragmentation determined by ELISA, and flow cytometry. Morphological changes as assessed by acridine orange. These effects were similar to that observed with Taxol (30 microM). A significant alteration of microtubular architecture was equally observed in both stomach and colon cancer cells exposed to SdG (100 microg/ml). The induction of apoptosis and microtubule damage in AGS, HT29 and T84 cells suggest that sangre de grado should be evaluated further as a potential source of anti-cancer agents.

  16. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer

    PubMed Central

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-01-01

    Abstract The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer. From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed. Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474). The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer. PMID:27828865

  17. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer.

    PubMed

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-11-01

    The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer.From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed.Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474).The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer.

  18. Trends in gastrointestinal cancer incidence in Iran, 2001-2010: a joinpoint analysis

    PubMed Central

    Motlagh, Ali; Karimi Jaberi, Maryam

    2016-01-01

    OBJECTIVES The main purpose of this study was to evaluate changes in the time trends of stomach, colorectal, and esophageal cancer during the past decade in Iran. METHODS Cancer incidence data for the years 2001 to 2010 were obtained from the cancer registration of the Ministry of Health. All incidence rates were directly age-standardized to the world standard population. In order to identified significant changes in time trends, we performed a joinpoint analysis. The annual percent change (APC) for each segment of the trends was then calculated. RESULTS The incidence of stomach cancer increased from 4.18 and 2.41 per 100,000 population in men and women, respectively, in 2001 to 17.06 (APC, 16.7%) and 8.85 (APC, 16.2%) per 100,000 population in 2010 for men and women, respectively. The corresponding values for colorectal cancer were 2.12 and 2.00 per 100,000 population for men and women, respectively, in 2001 and 11.28 (APC, 20.0%) and 10.33 (APC, 20.0%) per 100,000 in 2010. For esophageal cancer, the corresponding increase was from 3.25 and 2.10 per 100,000 population in 2001 to 5.57 (APC, 12.0%) and 5.62 (APC, 11.2%) per 100,000 population among men and women, respectively. The incidence increased most rapidly for stomach cancer in men and women aged 80 years and older (APC, 23.7% for men; APC, 18.6% for women), for colorectal cancer in men aged 60 to 69 years (APC, 24.2%) and in women aged 50 to 59 years (APC, 25.1%), and for esophageal cancer in men and women aged 80 years and older (APC, 17.5% for men; APC,15.3% for women) over the period of the study. CONCLUSIONS The incidence of gastrointestinal cancer significantly increased during the past decade. Therefore, monitoring the trends of cancer incidence can assist efforts for cancer prevention and control. PMID:27923268

  19. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Cancer.gov

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  20. Surgery for advanced epithelial ovarian cancer.

    PubMed

    Hacker, Neville F; Rao, Archana

    2016-10-20

    Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively.

  1. Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series.

    PubMed

    Kidambi, Trilokesh D; Pedley, Christina; Blanco, Amie; Bergsland, Emily K; Terdiman, Jonathan P

    2017-03-10

    Lower gastrointestinal (GI) neuroendocrine neoplasms (NENs) of the colon and rectum are uncommon and not traditionally associated with hereditary GI cancer syndromes. However, with widespread implementation of colorectal cancer screening programs, lower GI NENs are being identified with increasing frequency. We report the first case series of six patients with lower GI NENs who were diagnosed with hereditary GI cancer syndromes by germline testing. Two patients presented with poorly differentiated rectal neuroendocrine carcinoma (NECs) with colonic polyposis and were found to have Familial Adenomatous Polyposis and MYH-Associated Polyposis, respectively. Three patients with colorectal NENs (one well differentiated neuroendocrine tumor, NET, and two NECs), all of which displayed abnormal immunohistochemistry for mismatch repair proteins, were diagnosed with Lynch syndrome. One patient with a goblet cell carcinoid was diagnosed with CHEK2 mutations. All patients met genetic testing guidelines and the diagnosis was made utilizing next generation sequencing gene panel tests. Lower GI NETs should therefore be considered a potential hereditary GI cancer syndrome-associated malignancy in patients who otherwise meet criteria for genetic evaluation.

  2. BRAF-activated lncRNA predicts gastrointestinal cancer patient prognosis: a meta-analysis

    PubMed Central

    Wu, Lei; Wu, Miao-Jing; Lu, Shi-Gang; Zhu, Xin-Gen

    2017-01-01

    BRAF activated non-coding RNA (BANCR) is often dysregulated in cancer. We performed a meta-analysis to clarify its functions as a prognostic indicator in malignant tumors. We searched the PubMed, Medline, OVID, Cochrane Library, and Web of Science databases to identify BANCR-related studies. Nine original studies and 898 total patients were included in the meta-analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted from the included studies to determine the relationship between BANCR expression and patient overall survival (OS). Odds ratios (OR) were calculated using RevMan 5.3 software to assess associations between BANCR expression and pathological parameters. High BANCR expression correlated with lymph node metastasis (LNM) (OR = 3.41, 95% CI: 1.82–6.37, P = 0.0001), distant metastasis (DM) (OR = 2.98, 95% CI: 1.76–5.07, P < 0.0001), tumor stage (OR = 3.11, 95% CI: 1.89–5.12, Z = 3.25, P < 0.0001), and poor OS (pooled HR = 1.98, 95% CI: 1.20–3.27, P = 0.008) in gastrointestinal (GI) cancer patients, but not in non-GI cancer patients. Our results support the notion that BANCR as a promising prognostic biomarker in Chinese patients with GI cancer. PMID:28009984

  3. Identification of calgranulin B interacting proteins and network analysis in gastrointestinal cancer cells

    PubMed Central

    Yoo, Byong Chul

    2017-01-01

    Calgranulin B is known to be involved in tumor development, but the underlying molecular mechanism is not clear. To gain insight into possible roles of calgranulin B, we screened for calgranulin B-interacting molecules in the SNU-484 gastric cancer and the SNU-81 colon cancer cells. Calgranulin B-interacting partners were identified by yeast two-hybrid and functional information was obtained by computational analysis. Most of the calgranulin B-interacting partners were involved in metabolic and cellular processes, and found to have molecular function of binding and catalytic activities. Interestingly, 46 molecules in the network of the calgranulin B-interacting proteins are known to be associated with cancer and FKBP2 was found to interact with calgranulin B in both SNU-484 and SNU-81 cells. Polyubiquitin-C encoded by UBC, which exhibited an interaction with calgranulin B, has been associated with various molecules of the extracellular space and plasma membrane identified in our screening, including Na-K-Cl cotransporter 1 and dystonin in SNU-484 cells, and ATPase subunit beta-1 in SNU-81 cells. Our data provide novel insight into the roles of calgranulin B of gastrointestinal cancer cells, and offer new clues suggesting calgranulin B acts as an effector molecule through which the cell can communicate with the tumor microenvironment via polyubiquitin-C. PMID:28152021

  4. Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers

    PubMed Central

    Matthews, Robert; Choi, Minsig

    2016-01-01

    Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it. PMID:27618106

  5. Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy

    PubMed Central

    Liu, Shujun

    2012-01-01

    Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care. PMID:22921595

  6. Radiation therapy for advanced gastric cancer

    SciTech Connect

    Tsukiyama, I.; Akine, Y.; Kajiura, Y.; Ogino, T.; Yamashita, K.; Egawa, S.; Hijikata, J.; Kitagawa, T.

    1988-07-01

    A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

  7. Advances in Radiotherapy Management of Esophageal Cancer

    PubMed Central

    Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

    2016-01-01

    Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

  8. Radiation Therapy for Locally Advanced Esophageal Cancer.

    PubMed

    Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

    2017-04-01

    The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues.

  9. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients.

    PubMed

    Kuiken, Nicoline S S; Rings, Edmond H H M; Tissing, Wim J E

    2015-04-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the intestinal function and thereby the nutritional status and the quality of life, and eventually affects survival. The literature on GI mucositis focuses mainly on adults. This review focuses on data available on GI mucositis in pediatric cancer patients. An evaluation of the clinical presentation and consequences of GI mucositis in children is outlined. The review summarizes key issues for clinicians with respect to risk analysis for developing mucositis and the diagnosis of this condition in children. Information on these issues is obtained from clinical trials in children and adults, and from animal models. Diagnostic tools and assessment of severity of GI mucositis in children is elaborated on. Furthermore, the clinical management of the symptoms and consequences of GI mucositis in children, with specific focus on nutritional support, are discussed.

  10. Association between the -607 C > A polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis.

    PubMed

    Yao, J; Li, Z H; Li, Y X; Zhang, R; Zhang, D G; Xu, Z L; Wang, L S; Wang, J Y

    2015-12-14

    The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta-analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions.

  11. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  12. Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer

    PubMed Central

    Mills, Kathryn; Fuh, Katherine

    2017-01-01

    Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas. PMID:28184293

  13. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients’ conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks. Abbreviations: SEPS = self expanding plastic stent, SREMS = self expanding metal stent, EBRT = Endoscopic brachy radiotherapy, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE

  14. The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

    PubMed Central

    Sikes, Michael; Bruno-Bárcena, José M.

    2011-01-01

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an

  15. Clinicopathologic characteristics and overall survival in patients with bladder cancer involving the gastrointestinal tract.

    PubMed

    D'Souza, Amber M; Phillips, Gary S; Pohar, Kamal S; Zynger, Debra L

    2013-12-01

    Involvement of the gastrointestinal (GI) tract by bladder cancer is rare and documented in only a few case reports with no prognostic information available. The aim of this study was to clinicopathologically characterize patients with pathologically proven bladder cancer in the GI tract. We reviewed pathology reports from cystectomy patients at our institution from 2006 to 2011, identifying those with GI involvement at or after cystectomy. Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazard regression models. Twelve patients had surgical pathology specimens with GI involvement (anus, rectum, colon, and small bowel) at (n = 11) or within 4 months (n = 1) of cystectomy. These patients were noted to be pathologically staged inconsistently. GI involvement was a negative predictor of survival, with a 1.5-year OS of 25 versus 62 % without GI involvement (P < 0.001), similar to our pT4 patients (OS 26 %). In node-negative patients, there was a significantly worse 1.5-year OS with GI involvement compared to those without tumor in the GI tract (P = 0.005). We provide the first case series of patients with bladder cancer in the GI tract. GI involvement is a strong negative predictor of survival and behaves comparable to pT4 patients. However, we recommend that pathologists adhere to the current pT staging guidelines, in which GI involvement is not a criterion, until further research is conducted illustrating if and how it should be incorporated.

  16. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation.

  17. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  18. Gastrointestinal radiation injury: Prevention and treatment

    PubMed Central

    Shadad, Abobakr K; Sullivan, Frank J; Martin, Joseph D; Egan, Laurence J

    2013-01-01

    With the recent advances in detection and treatment of cancer, there is an increasing emphasis on the efficacy and safety aspects of cancer therapy. Radiation therapy is a common treatment for a wide variety of cancers, either alone or in combination with other treatments. Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result. These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment. Radiation injury to the gastrointestinal tract can be minimised by either of two strategies: technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues, and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it. Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques, biological techniques may offer additional further promise. Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure, including biological, chemical and pharmacological agents. In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy, examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level. PMID:23345942

  19. Molecular predictive markers in tumors of the gastrointestinal tract

    PubMed Central

    Papadopoulou, Eirini; Metaxa-Mariatou, Vasiliki; Tsaousis, Georgios; Tsoulos, Nikolaos; Tsirigoti, Angeliki; Efstathiadou, Chrisoula; Apessos, Angela; Agiannitopoulos, Konstantinos; Pepe, Georgia; Bourkoula, Eugenia; Nasioulas, George

    2016-01-01

    Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors’ genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis. PMID:27895815

  20. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

    PubMed

    Jing, Jie-Xian; Wang, Yan; Xu, Xiao-Qin; Sun, Ting; Tian, Bao-Guo; Du, Li-Li; Zhao, Xian-Wen; Han, Cun-Zhi

    2014-01-01

    To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

  1. Palbociclib and Letrozole in Advanced Breast Cancer.

    PubMed

    Finn, Richard S; Martin, Miguel; Rugo, Hope S; Jones, Stephen; Im, Seock-Ah; Gelmon, Karen; Harbeck, Nadia; Lipatov, Oleg N; Walshe, Janice M; Moulder, Stacy; Gauthier, Eric; Lu, Dongrui R; Randolph, Sophia; Diéras, Véronique; Slamon, Dennis J

    2016-11-17

    Background A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. Methods In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. Results The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group. Conclusions Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib

  2. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: The role of inflammation

    PubMed Central

    Lee, Chun Seng; Ryan, Elizabeth J; Doherty, Glen A

    2014-01-01

    Chemotherapy-induced diarrhea (CID) is a common and often severe side effect experienced by colorectal cancer (CRC) patients during their treatment. As chemotherapy regimens evolve to include more efficacious agents, CID is increasingly becoming a major cause of dose limiting toxicity and merits further investigation. Inflammation is a key factor behind gastrointestinal (GI) toxicity of chemotherapy. Different chemotherapeutic agents activate a diverse range of pro-inflammatory pathways culminating in distinct histopathological changes in the small intestine and colonic mucosa. Here we review the current understanding of the mechanisms behind GI toxicity and the mucositis associated with systemic treatment of CRC. Insights into the inflammatory response activated during this process gained from various models of GI toxicity are discussed. The inflammatory processes contributing to the GI toxicity of chemotherapeutic agents are increasingly being recognised as having an important role in the development of anti-tumor immunity, thus conferring added benefit against tumor recurrence and improving patient survival. We review the basic mechanisms involved in the promotion of immunogenic cell death and its relevance in the treatment of colorectal cancer. Finally, the impact of CID on patient outcomes and therapeutic strategies to prevent or minimise the effect of GI toxicity and mucositis are discussed. PMID:24744571

  3. Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

    PubMed Central

    Huang, Liu; Chen, Fengju; Chen, Yangyang; Yang, Xiaomei; Xu, Sanpeng; Ge, Shuwang; Fu, Shengling; Chao, Tengfei; Yu, Qianqian; Liao, Xin; Hu, Guangyuan; Zhang, Peng; Yuan, Xianglin

    2014-01-01

    The predictive value of thymidine phosphorylase gene variants (TP, also called platelet-derived endothelial cell growth factor) and thrombocytosis were controversial and worthy of further study in gastrointestinal cancer (GIC) patients. We screened all of the common missense single nucleotide polymorphisms (MAF ≥ 0.1) in fluoropyrimidines (FU) pathway genes (including TP, TS, ENOSF1 and DPD). Three of them were selected and genotyped using Sequenom MassARRAY in 141 GIC patients. TP expression was assessed by immunohistochemistry. Our aim was to evaluate the prognostic significance of studied genes and platelet counts in GIC patients. Multivariate analyses indicated in rs11479-T allele carriers, platelet counts negatively correlated to overall survival. In addition, T allele of TP: rs11479 was associated with higher TP expression in cancer tissues. We suggest TP: rs11479 variant combined with platelet counts may be useful prognostic makers in GIC patients receiving first-line FU chemotherapy and thrombopoietin factor should be used with caution in the rs11479 T allele bearing patients. PMID:25027354

  4. C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

    ClinicalTrials.gov

    2015-01-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  5. Fatigue in advanced cancer: a prospective study.

    PubMed

    Hauser, Katherine; Walsh, Declan; Rybicki, Lisa A; Davis, Mellar P; Seyidova-Khoshknabi, Dilara

    2008-01-01

    Fatigue is a common advanced cancer symptom. Clinical features are not well known. The authors surveyed consecutive patients admitted to a palliative medicine program to identify clinical correlates of fatigue. Data collected included age, sex, performance status, primary site, prior chemotherapy/radiation therapy, and blood transfusions. Visual analogue scales assessed fatigue, quality of life, and ability to perform daily activities. Weight change was estimated. Laboratory results including lactate dehydrogenase and hemoglobin were recorded. Fatigue severity was associated with brain metastases, poor performance status, poor quality of life, and reduced ability to perform activities. Prior radiation therapy was associated with less severe fatigue. Age, sex, and hemoglobin level were not associated with fatigue. Fatigue was universal on referral. Brain metastases and poor quality of life independently predicted severity. Hemoglobin level did not predict fatigue. Further studies are necessary to define the clinical features and relationships of fatigue.

  6. The Association Between Urinary Cadmium Levels and Dietary Habits with Risk of Gastrointestinal Cancer in Tabriz, Northwest of Iran.

    PubMed

    Ostadrahimi, Alireza; Payahoo, Laleh; Somi, Mohammad Hossein; Khajebishak, Yaser

    2017-01-01

    Cadmium (Cd) is a widespread toxic heavy metal and has long biological half-life. It has potential carcinogenic effects on multiple organ systems of human. However, no studies have evaluated the adverse effects of cadmium on incidence of cancer in gastrointestinal tract. The aim of this study was to investigate the association between urine cadmium (U-Cd) levels and risk of gastrointestinal cancer. This descriptive study was accomplished on 111 GI cancer patients as cases and 111 healthy people as control subjects from January to October in Tabriz, northwest Iran, during 2013. Cadmium in urine samples was measured by graphite furnace atomic absorption spectrophotometer (GFAAS). GI cancer patients had higher urine cadmium levels in comparison to healthy individuals (p < 0.05). The multivariate regression model manifested a significant association between the U-Cd concentrations and the risk of GI cancer (odds ratio (OR) = 1.70, 95 % CI = 1.35-2.20). Cases were 70 % more than controls at risk of cancer incidence. Our data indicates an association between U-Cd levels and GI cancer risk.

  7. Advances in Cancer Immunotherapy in Solid Tumors

    PubMed Central

    Menon, Smitha; Shin, Sarah; Dy, Grace

    2016-01-01

    Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field. PMID:27886124

  8. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    therapy -­‐resistant   prostate   cancer  cells  and  in  combination   therapy  (SOW...treatment resistance in advanced prostate cancer PRINCIPAL INVESTIGATOR: Dr. Karin Scarpinato CONTRACTING ORGANIZATION: Georgia Southern...SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to determine if rescinnamine is effective against prostate cancer and

  9. Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review

    PubMed Central

    Congedo, Teresa; Ricci, Riccardo; Martini, Maurizio; Di Noia, Vincenzo; Di Dio, Carmela; Quirino, Michela; Barone, Carlo; Cassano, Alessandra

    2017-01-01

    Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment. PMID:28280629

  10. Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications.

    PubMed

    Kundu, Somanath; Kumar, Sandeep; Bajaj, Avinash

    2015-07-01

    Increasing incidences of gastrointestinal (GI) cancer are linked to changes in lifestyle with excess of red meat/fat consumption, and elevated secretion of bile acids. Bile acids are strong signaling molecules that control various physiological processes. Failure in bile acid regulation has detrimental effects, often linked with development and promotion of cancer of digestive tract including esophagus, stomach, liver, and intestine. Excessive concentration of bile acids especially lipophillic secondary bile acids are cytotoxic causing apoptosis and reactive oxygen species-mediated damage to the cells. Resistance to this apoptosis and accumulation of mutations leads to progression of cancer. Cytotoxicity of bile acids is contingent on their chemical structure. In this review, we discuss the chemistry of bile acids, bile acid mediated cellular signaling processes, their role in GI cancer progression, and therapeutic potential of synthetic bile acid derivatives for cancer therapy.

  11. An Unusual Case of Gastrointestinal Bleeding from Isolated Gallbladder Varices in a Patient with Pancreatic Cancer Complicated by Portal Biliopathy

    PubMed Central

    Kubachev, Kubach; Abdullaev, Elbrus; Zarkua, Nonna; Abdullaev, Abakar; Fokin, Artur

    2016-01-01

    Portal biliopathy is the complex of abnormalities of extrahepatic and intrahepatic bile ducts, cystic duct, and gallbladder, arising as a result of extrahepatic portal vein obstruction and noncirrhotic portal fibrosis, which can be caused by coagulopathies, tumors, inflammation, postoperative complications, dehydration, and neonatal umbilical vein catheterization. We report a case of a 55-year-old male patient with the history of pancreatic cancer and cholecystoenteric anastomosis presenting with gastrointestinal bleeding from gallbladder varices via the anastomosis. PMID:27800195

  12. Severe prolonged gastroparesis after cytoreductive surgery in an advanced ovarian cancer patient.

    PubMed

    Caprino, P; Fagotti, A; Missere, M; Fanfani, F; Scambia, G

    2006-01-01

    Number and type of complications after ovarian cancer surgery can vary greatly according to both the patient's characteristics, and the extension and type of surgery. Current literature lacks in mentioning specific gastrointestinal side effects, which could be evidenced during the early postoperative course of patients submitted to major gynecological oncologic surgery. A severe gastroparesis prolonged for 2 months after cytoreductive surgery in an advanced ovarian cancer patient was successfully treated with conservative multidrug therapy. Gastroparesis has to be enumerated as a rare but possible event after major gynecological oncologic surgery. A conservative management involving decompressive nasogastric tube, nutritional support, antiemetic drugs, prokinetic drugs is suggested, while surgical therapy is only recommended in a very small subset of unmanageable patients.

  13. Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

    PubMed Central

    Zhang, Xiao-Wei; Li, Jun; Jiang, Yu-Xing; Chen, Yu-Xiang

    2017-01-01

    AIM To perform a meta-analysis to investigate the association between cyclooxygenase-2 (COX-2) -1195G>A gene polymorphism and gastrointestinal cancers. METHODS Publications related to the COX-2 -1195G>A gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from PubMed, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios (ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg’s rank correlation test, and Egger’s linear regression method were applied to analyse whether the included publications had publication bias. RESULTS A total of 24 publications related to the COX-2 -1195G>A gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2 -1195G>A gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer (A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2 -1195G>A gene polymorphism in the Asian population (A vs G: OR = 1.30; AA/AG vs GG: OR = 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis (P < 0.05) and the false positive report probability (P < 0.2) confirmed the reliability of the results. CONCLUSION The results showed that the COX-2 -1195G>A gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.

  14. 3rd Pavia international symposium on advanced kidney cancer.

    PubMed

    Porta, Camillo; Bracarda, Sergio

    2012-02-01

    Kidney cancers' natural history has radically changed in the past few years, due to the development of novel targeted agents. Despite these improvements, several unanswered questions still remain on the table, regarding the best first-line treatment, the ideal sequence of treatments, the management of specific subgroups of patients (e.g., elderly patients or those with comorbidities) and the relevance of prognostic factors, among many others. To foster discussions among clinicians and investigators working in this field, and to exchange different viewpoints concerning the newest advances in kidney cancer pathogenesis and treatment, the 3rd Pavia International Symposium on Advanced Kidney cancer was held in Pavia (Italy) between 30 June and 1 July 2011. The aim of this report is to summarize the most significant advances in the different disciplines applied to advanced kidney cancer, which were presented and discussed during the meeting, and how these advances will be changing the perspective of patients with this disease.

  15. Implications of occult metastatic cells for systemic cancer treatment in patients with breast or gastrointestinal cancer.

    PubMed

    Braun, S; Rosenberg, R; Thorban, S; Harbeck, N

    2001-06-01

    The early and clinically occult spread of viable tumour cells to the organism is becoming acknowledged as a hallmark in cancer progression, since abundant clinical and experimental data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies against epithelial cytokeratins or tumour-associated cell membrane glycoproteins, individual carcinoma cells can be detected in cytological bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of such immunostained cells in bone marrow is prognostically relevant with regard to relapse-free and overall survival, even in malignancies that do not preferentially metastasise to bone. As current treatment strategies have resulted in a substantial improvement of cancer mortality rates, it is noteworthy to consider the intriguing options of immunocytochemical screening of bone marrow aspirates for occult metastatic cells. Besides improved tumour staging, such screening offers opportunities for guiding patient stratification for adjuvant therapy trials, monitoring response to adjuvant therapies (which, at present, can only be assessed retrospectively after an extended period of clinical follow-up), and specifically targeting tumour-biological therapies against disseminated tumour cells. The present review summarises the current data on the clinical significance of occult metastatic cancer cells in bone marrow.

  16. Major clinical research advances in gynecologic cancer in 2015

    PubMed Central

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  17. Major clinical research advances in gynecologic cancer in 2015.

    PubMed

    Suh, Dong Hoon; Kim, Miseon; Kim, Hak Jae; Lee, Kyung Hun; Kim, Jae Weon

    2016-11-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

  18. Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

    PubMed

    Suresh, S; Spatz, J; Mills, J P; Micoulet, A; Dao, M; Lim, C T; Beil, M; Seufferlein, T

    2005-01-01

    We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation

  19. Reprint of: Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

    PubMed

    Suresh, S; Spatz, J; Mills, J P; Micoulet, A; Dao, M; Lim, C T; Beil, M; Seufferlein, T

    2015-09-01

    We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation

  20. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  1. Is early feeding after major gastrointestinal surgery a fashion or an advance? Evidence-based review of literature.

    PubMed

    Shrikhande, Shailesh V; Shetty, Guruprasad S; Singh, Kailash; Ingle, Sachin

    2009-01-01

    Early enteral nutrition (EN) after major digestive surgery has been receiving increasing attention. Supporting evidence has not been clear. This evidence-based review traces the development of early EN and analyses whether it is indeed an advance. We performed a PubMed search in October 2009 with the key words enteral nutrition, early feeding, and gastrointestinal surgery. Our emphasis was on earliest studies documenting the benefits or adverse effects of EN, comparative studies, documenting the benefits or adverse effects of EN, comparative studies, and randomized controlled trials. Thirty-one results were returned from which 17 were included for evaluation (1979-2009). Fifteen papers concluded that early EN was beneficial. In general, patients put on early EN and immunonutrition postoperatively seemed to have decreased hospital stay, decreased complication rates, decreased treatment and hospital costs, and even decreased morbidity and mortality; however, judicious use has been suggested. One study did not recommend early enteral feeding in well-nourished patients at low risk of nutrition-related complications and another suggested that immunonutrition is not beneficial and should not be used routinely. Early EN has been safely given after major digestive surgery since 1979. It benefits patients undergoing major gastrointestinal (GI) surgeries, with reduction in perioperative infection, better maintainance of nitrogen balance, and shorter hospital stay. Early EN may be superior to total parenteral nutrition (TPN). However, TPN is perhaps better tolerated in the immediate postoperative period. Early enteral immunonutrition should be used only in malnourished and in transfused patients. Early EN after major digestive surgery is an old advance that is now in fashion.

  2. Recent advances in the medical treatment of breast cancer.

    PubMed

    Vorobiof, Daniel A

    2016-01-01

    Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40-50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient's ability to respond to particular chemotherapeutic drugs.

  3. Improving management of patients with advanced cancer

    PubMed Central

    Drudge-Coates, Lawrence

    2010-01-01

    Development of bone metastases in patients with advanced cancer is associated with skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, the requirement for surgery or palliative radiotherapy to bone, and hypercalcemia of malignancy. Skeletal morbidity may reduce patient mobility, limit functional independence, and impair quality of life (QOL). Proactive management of new or worsening bone pain or motor impairment is crucial because of the potential for rapid progression of symptoms. Administration of bisphosphonate therapy as a monthly infusion to patients with bone metastases prevents or delays the onset and reduces the frequency of SREs and provides clinically meaningful improvements in bone pain and QOL. In addition to administration of therapy, the monthly infusion visit allows a dedicated team of healthcare professionals to regularly assess SREs, response to therapy, adverse events (AEs), QOL, and adherence to oral medications and supplements. The continuity of care that occurs during the monthly infusion visit provides oncology nurses with an opportunity to educate patients about effective strategies to manage SREs and AEs. In addition, regular interaction provides oncology nurses with an opportunity to recognize and proactively address subtle changes in the patients’ medical condition. Using a multidisciplinary medical team also eliminates barriers between the various healthcare professionals involved in patient management. Consequently, the monthly infusion visit can result in effective patient management and improved clinical outcomes in patients with malignant bone disease. PMID:21206517

  4. The meaning and validation of social support networks for close family of persons with advanced cancer

    PubMed Central

    2012-01-01

    Background To strengthen the mental well-being of close family of persons newly diagnosed as having cancer, it is necessary to acquire a greater understanding of their experiences of social support networks, so as to better assess what resources are available to them from such networks and what professional measures are required. The main aim of the present study was to explore the meaning of these networks for close family of adult persons in the early stage of treatment for advanced lung or gastrointestinal cancer. An additional aim was to validate the study’s empirical findings by means of the Finfgeld-Connett conceptual model for social support. The intention was to investigate whether these findings were in accordance with previous research in nursing. Methods Seventeen family members with a relative who 8–14 weeks earlier had been diagnosed as having lung or gastrointestinal cancer were interviewed. The data were subjected to qualitative latent content analysis and validated by means of identifying antecedents and critical attributes. Results The meaning or main attribute of the social support network was expressed by the theme Confirmation through togetherness, based on six subthemes covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Three subthemes were identified as the antecedents to social support: Need of support, Desire for a deeper relationship with relatives, Network to turn to. Social support involves reciprocal exchange of verbal and non-verbal information provided mainly by lay persons. Conclusions The study provides knowledge of the antecedents and attributes of social support networks, particularly from the perspective of close family of adult persons with advanced lung or gastrointestinal cancer. There is a need for measurement instruments that could encourage nurses and other health

  5. Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients.

    PubMed

    Iwasa, Satoru; Yamada, Yasuhide; Heike, Yuji; Shoji, Hirokazu; Honma, Yoshitaka; Komatsu, Nobukazu; Matsueda, Satoko; Yamada, Akira; Morita, Michi; Yamaguchi, Rin; Tanaka, Natsuki; Kawahara, Akihiko; Kage, Masayoshi; Shichijo, Shigeki; Sasada, Tetsuro; Itoh, Kyogo

    2016-05-01

    A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose-limiting toxicity (DLT), or safety and immune responses, respectively. Peptide-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty-one patients were vaccinated with KRM-10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment-related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.

  6. Bevacizumab improves survival for patients with advanced cervical cancer

    Cancer.gov

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  7. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Cancer.gov

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  8. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  9. Blocking DNA Repair in Advanced BRCA-Mutated Cancer

    Cancer.gov

    In this trial, patients with relapsed or refractory advanced cancer and confirmed BRCA mutations who have not previously been treated with a PARP inhibitor will be given BMN 673 by mouth once a day in 28-day cycles.

  10. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  11. Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study

    PubMed Central

    Markar, Sheraz R; Mavroveli, Stella; Petrides, Konstantinos V; Scarpa, Marco; Christophe, Veronique; Castoro, Carlo; Mariette, Christophe; Lagergren, Pernilla; Hanna, George B

    2016-01-01

    Introduction Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. Objectives To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. Methods and analysis This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. Ethics and dissemination NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal. PMID:27798009

  12. Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

    PubMed

    Pantaleo, M A; Landuzzi, L; Nicoletti, G; Nanni, C; Boschi, S; Piazzi, G; Santini, D; Di Battista, M; Castellucci, P; Lodi, F; Fanti, S; Lollini, P-L; Biasco, G

    2009-09-01

    The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

  13. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

  14. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  15. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients. PMID:1834291

  16. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

    DTIC Science & Technology

    2013-03-01

    target for therapy of prostate cancer , but approaches aimed at Ras itself, or its critical signaling pathways, which are required in normal tissues...Impact: Current therapies for prostate cancer are inadequate, and aberrant activation of Ras or Ras pathways are common. A novel therapeutic modality...to Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Douglas V. Faller, PhD, MD CONTRACTING ORGANIZATION: Trustees of Boston University

  17. Sipuleucel-T for the treatment of advanced prostate cancer.

    PubMed

    Frohlich, Mark W

    2012-06-01

    Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response to prostate cancer that prolongs the overall survival of men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). The clinical development program and key efficacy, safety, and immune response findings from the phase III studies are presented. The integration of sipuleucel-T into the treatment paradigm of advanced prostate cancer and future directions for research are discussed.

  18. Drug discovery in advanced prostate cancer: translating biology into therapy.

    PubMed

    Yap, Timothy A; Smith, Alan D; Ferraldeschi, Roberta; Al-Lazikani, Bissan; Workman, Paul; de Bono, Johann S

    2016-10-01

    Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs.

  19. Advances in the Management of Biliary Tract Cancers

    PubMed Central

    Ciombor, Kristen Keon; Goff, Laura Williams

    2013-01-01

    Biliary tract cancers (BTC), though uncommon, are highly fatal malignancies, and current treatments fail to cure or control the majority of tumors. Given the complexity of the anatomy and often aggressive nature of the disease, multidisciplinary treatment, including palliation, is often required. However, systemic therapy with cytotoxics and/or targeted agents are routinely the mainstay of treatment for patients with advanced biliary tract cancers, and new targets and agents provide hope for this disease. This article focuses on recent advances in the management of biliary tract cancers, with a special focus on the molecular basis for current therapeutic investigation in this disease. PMID:23416860

  20. A Functional NQO1 609C>T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

    PubMed Central

    Yu, Hongping; Liu, Hongliang; Wang, Li-E; Wei, Qingyi

    2012-01-01

    Background The functional polymorphism (rs1800566) in the NQO1 gene, a 609C>T substitution, leading to proline-to-serine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results. Methodology/Principal Findings We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C>T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95% CI = 1.01 – 1.19, Pheterogeneity = 0.27, I2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, Pheterogeneity = 0.14; I2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies. Conclusions This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyses suggest that further larger studies are needed, especially for non-colorectal GI cancers in Caucasians and GI cancers in Asians. PMID:22272361

  1. Pyroxamide in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-06-04

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  2. Advances of Cancer Therapy by Nanotechnology

    PubMed Central

    Wang, Xu; Wang, Yiqing; Chen, Zhuo Georgia

    2009-01-01

    Recent developments in nanotechnology offer researchers opportunities to significantly transform cancer therapeutics. This technology has enabled the manipulation of the biological and physicochemical properties of nanomaterials to facilitate more efficient drug targeting and delivery. Clinical investigations suggest that therapeutic nanoparticles can enhance efficacy and reduced side effects compared with conventional cancer therapeutic drugs. Encouraged by rapid and promising progress in cancer nanotechnology, researchers continue to develop novel and efficacious nanoparticles for drug delivery. The use of therapeutic nanoparticles as unique drug delivery systems will be a significant addition to current cancer therapeutics. PMID:19688065

  3. Localization of thymidine phosphorylase in advanced gastric and colorectal cancer.

    PubMed

    Kobayashi, Michiya; Okamoto, Ken; Akimori, Toyokazu; Tochika, Naoshige; Yoshimoto, Tadashi; Okabayashi, Takehiro; Sugimoto, Takeki; Araki, Keijiro

    2004-01-01

    Thymidine phosphorylase (TP) is known to be more concentrated in human cancer tissues than in adjacent normal tissue based on findings using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. However, the ultrastructural localization of TP in cancer tissues has not previously been demonstrated. We investigated the localization of TP in gastric cancer and colorectal cancer tissue by ELISA, immunohistochemistry, and immunoelectron microscopy. Between April 1997 and May 2000, we obtained surgically resected specimens from 42, 46, and 36 cases of advanced gastric, colon, and rectal cancer, respectively. ELISA demonstrated that the TP level was higher in cancer tissues than in adjacent normal tissue. Immunohistochemically, cancer cells were positive for the enzyme in some cases. However, in a number of cases immunopositive inflammatory cells were also present in cancerous tissues. At the electron microscope level, TP was diffusely distributed in the cytoplasm of cancer cells and in the mitochondria of the neutrophil in gastric cancer tissue. In rectal cancer tissues, cytoplasmic granules in macrophages in cancer tissues were immunoreactive for the TP. These findings suggest that TP is produced by macrophages and exists in neutrophils and cancer cells.

  4. Advancing Breast Cancer Survivorship among African American Women

    PubMed Central

    Coughlin, Steven S.; Yoo, Wonsuk; Whitehead, Mary S.; Smith, Selina A.

    2015-01-01

    Purpose Advances have occurred in breast cancer survivorship but, for many African American women, challenges and gaps in relevant information remain. Methods This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African American women. Results For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. Conclusions There is a need for a better understanding of breast cancer survivorship among African American women. Additional evaluations of interventions for improving the quality of life and survival of African American breast cancer survivors are desirable. PMID:26303657

  5. The effect of forced expression of mutated K-RAS gene on gastrointestinal cancer cell lines and the IGF-1R targeting therapy.

    PubMed

    Matsunaga, Yasutaka; Adachi, Yasushi; Sasaki, Yasushi; Koide, Hideyuki; Motoya, Masayo; Nosho, Katsuhiko; Takagi, Hideyasu; Yamamoto, Hiroyuki; Sasaki, Shigeru; Arimura, Yoshiaki; Tokino, Takashi; Carbone, David P; Imai, Kohzoh; Shinomura, Yasuhisa

    2017-02-01

    Mutation in K-RAS (K-RAS-MT) plays important roles in both cancer progression and resistance to anti-epidermal growth factor receptor (EGFR) therapy in gastrointestinal tumors. Insulin-like growth factor-1 receptor (IGF-1R) signaling is required for carcinogenicity and progression of many tumors as well. We have previously shown successful therapy for gastrointestinal cancer cell lines bearing a K-RAS mutation using an anti-IGF-1R monoclonal antibody. In this study, we sought to evaluate effects of forced K-RAS-MT expression on gastrointestinal cancer cell lines representing a possible second resistance mechanism for anti-EGFR therapy and IGF-1R-targeted therapy for these transfectants. We made stable transfectants of K-RAS-MT in two gastrointestinal cancer cell lines, colorectal RKO and pancreatic BxPC-3. We assessed the effect of forced expression of K-RAS-MT on proliferation, apoptosis, migration, and invasion in gastrointestinal cancer cells. Then we assessed anti-tumor effects of dominant negative IGF-1R (IGF-1R/dn) and an IGF-1R inhibitor, picropodophyllin, on the K-RAS-MT transfectants. Overexpression of K-RAS-MT in gastrointestinal cancer cell lines led to more aggressive phenotypes, with increased proliferation, decreased apoptosis, and increased motility and invasion. IGF-1R blockade suppressed cell growth, colony formation, migration, and invasion, and up-regulated chemotherapy-induced apoptosis of gastrointestinal cancer cells, even when K-RAS-MT was over-expressed. IGF-1R blockade inhibited the Akt pathway more than the extracellular signal-regulated kinase (ERK) pathway in the K-RAS-MT transfectants. IGF-1R/dn, moreover, inhibited the growth of murine xenografts expressing K-RAS-MT. Thus, K-RAS-MT might be important for progressive phonotype observed in gastrointestinal cancers. IGF-1R decoy is a candidate molecular therapeutic approach for gastrointestinal cancers even if K-RAS is mutated. © 2016 Wiley Periodicals, Inc.

  6. Current advances in T-cell-based cancer immunotherapy.

    PubMed

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  7. Recent advances in lung cancer biology

    SciTech Connect

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  8. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Cancer.gov

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  9. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  10. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  11. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  12. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  13. Targeting notch signaling pathway in cancer: clinical development advances and challenges.

    PubMed

    Takebe, Naoko; Nguyen, Dat; Yang, Sherry X

    2014-02-01

    Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs.

  14. Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009

    PubMed Central

    Song, Huan; Abnet, Christian C.; Andrén-Sandberg, Åke; Chaturvedi, Anil K.; Ye, Weimin

    2016-01-01

    Background Removal of the appendix might induce physiological changes in the gastrointestinal tract, and subsequently play a role in carcinogenesis. Therefore, we conducted a nationwide register-based cohort study in Sweden to investigate whether appendectomy is associated with altered risks of gastrointestinal cancers. Methods A population-based cohort study was conducted using the Swedish national registries, including 480,382 eligible patients followed during the period of 1970–2009 for the occurrence of site-specific gastrointestinal cancer (esophageal/gastric/colon/rectal cancer). Outcome and censoring information was collected by linkage to health and demography registers. We examined the incidence of appendectomy in Sweden using data from 1987–2009. We also calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) to estimate the relative gastrointestinal cancer risk through comparison to the general population. Results We noted an overall decrease in the age-standardized incidence of appendectomy among the entire Swedish population from 189.3 to 105.6 per 100,000 individuals between 1987 and 2009. Grouped by different discharge diagnosis, acute appendicitis, incidental appendectomy, and entirely negative appendectomy continuously decreased over the study period, while the perforation ratio (18%–23%) stayed relatively constant. Compared to the general population, no excess cancer risk was observed for gastrointestinal cancers under study with the exception of a marginally elevated risk for esophageal adenocarcinoma (SIR 1.32, 95% CI 1.09–1.58). Conclusions In Sweden, the incidence of appendectomy and acute appendicitis has decreased during 1987–2009. No excess gastrointestinal cancer risks were observed among these appendectomized patients, with the possible exception of esophageal adenocarcinoma. PMID:26959234

  15. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  16. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  17. Sipuleucel-T: immunotherapy for advanced prostate cancer.

    PubMed

    Olson, Brian M; McNeel, Douglas G

    2011-05-03

    Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a slight survival benefit while being associated with potentially significant side effects. However, the recent approval of sipuleucel-T has given patients with advanced disease an additional treatment option that has demonstrated benefit without the side effects associated with chemotherapy. Sipuleucel-T is an antigen-presenting cell-based active immunotherapy that utilizes a patient's own immune cells, presumably to activate an antigen-specific immune response against tumor cells. This review focuses on the development and implementation of sipuleucel-T as a therapy for prostate cancer. Specifically, we present some of the issues associated with the management of advanced prostate cancer, the research and development that led to the approval of sipuleucel-T, how the approval of sipuleucel-T could change the clinical management of prostate cancer, and current and future areas of investigation that are being pursued with regard to sipuleucel-T and other treatments for advanced prostate cancer.

  18. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  19. Recent advances in personalized lung cancer medicine

    PubMed Central

    Okimoto, Ross A; Bivona, Trever G

    2014-01-01

    The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine. PMID:25506379

  20. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  1. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

    PubMed Central

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-01-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients. PMID:18506179

  2. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-03

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  3. N-nitrosodimethylamine in the Kashmiri diet and possible roles in the high incidence of gastrointestinal cancers.

    PubMed

    Chikan, Naveed A; Shabir, Nadeem; Shaff, Sheikh; Mir, Manzoor R; Patel, Trupti N

    2012-01-01

    The Kashmiri population is culturally distinct with special dietary features owing to the temperate climatic conditions of Kashmir valley. This has habituated the population to preserve food in smoked, pickled and sundried forms which include considerable amounts of N-nitroso compounds (NOCs). These are known to cause cytotoxicity, DNA damage, mutation, unscheduled DNA synthesis and DNA methylation. All of these changes at molecular level are known to contribute to the pathogenesis of cancer. One of the prominent NOCs found in Kashmiri food is N-Nitrosodimethylamine (NDMA). Here we review the occurrence of NDMA in sundried foods, dried fish, kehwa, traditional pickle, Brassica oleracia and tobbaco. We also discuss its possible role in the high prevalence of gastrointestinal cancers in Kashmir.

  4. Evolving treatment paradigms for locally advanced and metastatic prostate cancer.

    PubMed

    Dorff, Tanya B; Quek, Marcus L; Daneshmand, Siamak; Pinski, Jacek

    2006-11-01

    While men with early stage prostate cancer typically enjoy long-term survival after definitive management, for those who present with locally advanced or metastatic disease, survival is compromised. Multimodality therapy can prolong survival in these patients, with state-of-the-art options including intensity-modulated radiation or brachytherapy in conjunction with androgen ablation, adjuvant androgen ablation and/or chemotherapy with radical retropubic prostatectomy. In addition, novel biological therapies are being explored to target the unique molecular changes in prostate cancer cells and their interactions with the microenvironment. With these advances the outlook will undoubtedly improve, even for patients presenting with advanced disease. Careful application of these emerging therapies to a select group of prostate cancer patients most likely to obtain benefit from them is the challenge for urologists, medical oncologists and radiation oncologists for the future.

  5. Nanovector-based therapies in advanced pancreatic cancer

    PubMed Central

    Tsai, Chang-Sung

    2011-01-01

    Systemic therapy for advanced pancreatic cancer has been largely disappointing owing to the unfavorable pharmacokinetic profile and poor penetration of current chemotherapeutic agents ,as well as the fragile patient population with compromised tolerance to toxic chemotherapies. Nanovectors can provide passive drug delivery through abnormal tumor neo-vasculature microanatomy or active targeting via binding to receptors or macromolecules associated with the tumor. In such a manner, nanovector-based therapy may not only modulate the pharmacokinetics and therapeutic index of chemotherapeutic agents but also provide new treatment options in patients with advanced pancreatic cancer. In this article, we present the rationale and currently available clinical results of nanovector-based therapies to highlight the potential use of this class of agent in patients with advanced pancreatic cancer. PMID:22811849

  6. Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells

    PubMed Central

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David Lawson

    2016-01-01

    Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient’s treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research. PMID:27186409

  7. Photodynamic Cancer Therapy—Recent Advances

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2011-09-01

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when "photoradiation therapy" was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  8. Relationship between the Physical and Psychosocial Conditions of Postoperative Gastrointestinal Cancer Patients and their Responses to an Informational Material

    PubMed Central

    Mizuno, Michiyo; Kataoka, Jun; Oishi, Fumiko

    2017-01-01

    Objective: Postoperative patients with gastrointestinal (GI) cancer have multiple adaptation tasks and care needs to improve their quality of life (QOL). Whether their supportive care needs differ according to their physical and psychosocial conditions is unclear. This study investigated patients’ (1) physical and psychosocial conditions (QOL, fatigue, anxiety, cognitive plight, and resilience) and (2) responses to an informational booklet describing cancer patients’ problems and adaptation tasks, and examined the association between the two factors. Methods: A questionnaire survey was conducted to postoperative patients with GI cancer. Results: The mean age of the 69 respondents was 63 years; 59.4% of the respondents were men. Nine patients who did not read the booklet showed high fatigue and cognitive plight and low QOL. The patients (36.2%) who chose “I vaguely understood the content” showed low scores for resilience and cognitive plight while those (8.5%) who chose “I will deal with my tasks as described in the scenarios” showed high scores for both of these variables. Conclusions: The condition of some patients continued to be highly affected by their cancer. In terms of understanding the contents of the booklet, resilience was significant, and cognitive plight did not necessarily have a negative impact. The provision of information by means of a booklet might not be suitable for patients who are highly affected by their cancer. Patients may need additional support to be able to make good use of the information provided in such a booklet. PMID:28217731

  9. Recent advances in the medical treatment of breast cancer

    PubMed Central

    Vorobiof, Daniel A.

    2016-01-01

    Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs. PMID:27990275

  10. Advances in molecular imaging for breast cancer detection and characterization

    PubMed Central

    2012-01-01

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

  11. [Advances in measles virus for cancer therapy].

    PubMed

    Zhou, Duo; Zhao, Zheng-yan

    2015-07-01

    Oncolytic virotherapy is a novel cancer therapy. Vaccine-attenuated strains of measles virus(MV)is an ideal candidate for oncolytic virotherapy which has an excellent safety record. Vaccine-attenuated MV uses CD46 and Nectin-4 molecule as major entry receptors into cells. Vaccine-attenuated MV can selectively infect and kill a wide variety of cancer cells in vitro and in vivo. With the development of molecular cloning, scientists have successfully rescued cDNA of vaccine-attenuated MV and increased its oncolytic efficiency with molecular engineering techniques. Phase I clinical trials of virotherapy for ovarian cancer and multiple myeloma with vaccine-attenuated MV are underway. The preliminary results indicate the promising antitumor potential of vaccine-attenuated MV.

  12. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

    PubMed Central

    Xu, Yu-Ping; Yang, Min

    2016-01-01

    Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC. PMID:26909131

  13. Emerging challenges of advanced squamous cell lung cancer

    PubMed Central

    Zhang, Yi-Chen; Zhou, Qing

    2016-01-01

    Squamous cell lung cancer (SQCLC) is an aggressive type of lung cancer and most are diagnosed at advanced stage. Patients with advanced SQCLC tend to be older, current or former smoker, with central type tumour located near large blood vessels and seldom with druggable genetic alternations. Consequently, progress of targeted therapy and antivascular agents available in lung adenocarcinoma could not be duplicated in this subset of patients. The treatment paradigms have long been dominant by cytotoxic agents and posed many therapeutic challenges. Until recent years, immune checkpoint inhibitors, other monoclonal antibodies and afatinib have been approved for treatment of advanced SQCLC, presenting a novel treatment landscape and initiating the era of precision medicine in this subset of patients. This review will summarise the recent treatment progresses in advanced SQCLC with a focus on checkpoint inhibitors of programmed cell death-1 receptor or its ligand, and discuss the emerging challenges in this new era. PMID:28255454

  14. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association.

  15. New Insight into the Treatment of Advanced Differentiated Thyroid Cancer

    PubMed Central

    Safavi, Arash; Vijayasekaran, Aparna; Guerrero, Marlon A.

    2012-01-01

    The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment of advanced cases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness. PMID:23326755

  16. Role of salvage radiotherapy for regional lymph node recurrence after radical surgery in advanced gastric cancer

    PubMed Central

    Kim, Byoung Hyuck; Kim, Jae-Sung; Kim, Hyung-Ho; Park, Do Joong

    2013-01-01

    Purpose To evaluate the role of salvage radiotherapy (RT) for the treatment of regional lymph node recurrence (RLNR) after radical surgery in advanced gastric cancer. Materials and Methods We retrospectively analyzed medical records of 26 patients who underwent salvage treatment after diagnosis of RLNR between 2006 and 2011. Patients with peritoneal seeding or distant metastasis were excluded. Eighteen patients received RT with or without chemotherapy and the other 8 did chemotherapy only without RT. A three-dimensional conformal RT was performed with median dose of 56 Gy (range, 44 to 60 Gy). Sixteen patients had fluoropyrimidine-based chemotherapy, 5 did taxane-based chemotherapy, and irinotecan was applied in 4. Results With a median follow-up of 20 months (range, 5 to 57 months), median overall survival (OS) and progression-free survival (PFS) after diagnosis of RLNR were 29 months and 12 months in the entire patients, respectively. Radiotherapy (p = 0.007) and disease-free interval (p = 0.033) were statistically significant factors for OS in multivariate analysis. Median OS was 36 months in patients who received RT and 16 months in those who did not. Furthermore, delivery of RT (p < 0.001), complete remission after salvage treatment (p = 0.040) and performance status (p = 0.023) were associated with a significantly better PFS. Gastrointestinal toxicities from RT were mild in most patients. Conclusion Salvage RT combined with systemic chemotherapy may be an effective treatment managing RLNR from advanced gastric cancer. PMID:24137560

  17. Medical Advances and Racial/ethnic Disparities in Cancer Survival

    PubMed Central

    Tehranifar, Parisa; Neugut, Alfred I.; Phelan, Jo C.; Link, Bruce G.; Liao, Yuyan; Desai, Manisha; Terry, Mary Beth

    2013-01-01

    BACKGROUND Although advances in early detection and treatment of cancer improve overall population survival, these advances may not benefit all population groups equally, and may heighten racial/ethnic (R/E) differences in survival. METHODS We identified cancer cases in the Surveillance, Epidemiology, and End Results program, who were ≥ 20 years and diagnosed with one invasive cancer in 1995–1999 (n=580,225). We used 5-year relative survival rates (5Y-RSR) to measure the degree to which mortality from each cancer is amenable to medical interventions (amenability index). We used Kaplan-Meier methods and Cox proportional hazards regression to estimate survival differences between each R/E minority group relative to whites, by the overall amenability index, and three levels of amenability (non-amenable, partly and mostly amenable cancers, corresponding to cancers with 5Y-RSR <40%, 40–69% and ≥ 70%, respectively), adjusting for gender, age, disease stage and county-level poverty concentration. RESULTS As amenability increased, R/E differences in cancer survival increased for African Americans, American Indians/Native Alaskans and Hispanics relative to whites. For example, the hazard rate ratios (95% confidence intervals) for African Americans vs. whites from non-amenable, partly amenable and mostly amenable cancers were 1.05 (1.03, 1.07), 1.38 (1.34,1.41), and 1.41 (1.37, 1.46), respectively. Asians/Pacific Islanders had similar or longer survival relative to whites across amenability levels; however, several subgroups experienced increasingly poorer survival with increasing amenability. CONCLUSIONS Cancer survival disparities for most R/E minority populations widen as cancers become more amenable to medical interventions. Efforts in developing cancer control measures must be coupled with specific strategies for reducing the expected disparities. PMID:19789367

  18. Advances in cancer research: Volume 47

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1986-01-01

    This book contains eight chapters. Some of the titles are: Genetic Epidemiology of Familial Aggregation of Cancer; Terminal Transferase in Normal and Leukemic Cells; Malignant Metamorphosis: Developmental Genes as Culprits for Oncogenesis in Xiphophorus; and Transcription Activation by Viral and Cellular Oncogenes.

  19. Current advances in esophageal cancer proteomics.

    PubMed

    Uemura, Norihisa; Kondo, Tadashi

    2015-06-01

    We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics.

  20. Advances in cancer research. Volume 48

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1987-01-01

    This book contains the following five selections: Oncotrophoblast Gene Expression: Placental Alkaline Phosphatase; Cellular Events during Hepatocarcinogenesis in Rats and the Questions of Premalignancy; Human Papillomaviruses and Genital Cancer; Herpes Simplex Type 2 Virus and Cervical Neoplasia; and Transforming Genes and Target Cells of Murine Spleen Focus-Forming Viruses.

  1. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  2. Evaluation of nutritional status in advanced metastatic cancer.

    PubMed

    Sarhill, N; Mahmoud, F; Walsh, D; Nelson, K A; Komurcu, S; Davis, M; LeGrand, S; Abdullah, O; Rybicki, L

    2003-10-01

    Consecutive cancer referrals to a palliative medicine program were evaluated to assess nutritional status using a standard protocol. The study included 352 patients (180 men, 172 women; median age 61 years, range 22-94 years). The most common diagnosis was lung cancer. All had metastatic disease, 139 with gastrointestinal involvement. The most common gastrointestinal symptoms were weight loss ( n=307), anorexia ( n=285), and early satiety ( n=243). Of those with any weight loss, 71% had lost >or0% of their pre-illness weight. The most common factor identified which might have contributed to weight loss was hypophagia ( n=275/307). Men had lost weight more often and to a greater extent than women. Triceps skinfold (TSF) was measured in 337: 51% had values that suggested severe fat deficiency. Upper mid-arm muscle area (AMA) was measured in 349: 30% had evidence of significant muscle mass reduction. The body mass index (BMI) was normal or increased in most patients. Calculated resting energy expenditure (REE) ( n=324) was high in 41%. C-reactive protein was elevated in 74% of those measured ( n=50). We conclude that: (1).most of this group of cancer patients referred to palliative medicine had severe weight loss; (2).there was a gender difference in the severity and type of weight loss; (3).males lost more weight overall and more muscle than females; (4).males with any degree of weight loss had a higher REE than females; (5).a significant correlation existed between the time from diagnosis to death and the severity of weight loss in the prior month; (6).BMI was normal in most patients, suggesting precancer diagnosis obesity; and (7).both TSF and AMA correlated well with body composition of both fat and protein as determined by bioelectrical impedance.

  3. Recent Advances in Microwave Imaging for Breast Cancer Detection

    PubMed Central

    Kwon, Sollip

    2016-01-01

    Breast cancer is a disease that occurs most often in female cancer patients. Early detection can significantly reduce the mortality rate. Microwave breast imaging, which is noninvasive and harmless to human, offers a promising alternative method to mammography. This paper presents a review of recent advances in microwave imaging for breast cancer detection. We conclude by introducing new research on a microwave imaging system with time-domain measurement that achieves short measurement time and low system cost. In the time-domain measurement system, scan time would take less than 1 sec, and it does not require very expensive equipment such as VNA. PMID:28096808

  4. Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

    PubMed

    Sahami-Fard, Mohammad Hossein; Mousa Mayali, Ali Reza; Tajehmiri, Ahmad

    2016-10-01

    Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0–1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0–1.6, POR=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9–1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8–1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

  5. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  6. Recent advances and future challenges in cancer immunotherapy.

    PubMed

    Okuyama, Namiko; Tamada, Koji; Tamura, Hideto

    Remarkable advances have been made in cancer immunotherapy. Recent treatment strategies, especially chimeric antigen receptor-T (CAR-T) cell therapy and immune checkpoint inhibitors, reportedly achieve higher objective responses and better survival rates than previous immunotherapies for patients with treatment-resistant malignancies, creating a paradigm shift in cancer treatment. Several clinical trials of cancer immunotherapy for patients with various malignancies are ongoing. However, those with certain malignancies, such as low-immunogenic cancers, cannot be successfully treated with T-cell immunotherapy, and subsets of immunotherapy-treated patients relapse, meaning that more effective immunotherapeutic strategies are needed for such patients. Furthermore, the safety, convenience, and cost of cancer immunotherapy need to be improved in the near future. Herein, we discuss recent advances and future challenges in cancer immunotherapy, i.e., the identification of neoantigens for the development of individualized immunotherapies, the development of new CAR-T cell therapies, including so-called armored CAR-T cells that can induce greater clinical effects and thereby achieve longer survival, the development of off-the-shelf treatment regimens using non-self cells or cell lines, and effective cancer immunotherapy combinations.

  7. Recent advances in the field of anti-cancer immunotherapy

    PubMed Central

    Neves, Henrique; Kwok, Hang Fai

    2015-01-01

    Background The main goal of anti-cancer therapy is to specifically inhibit the malignant activity of cancer cells, while leaving healthy cells unaffected. As such, for every proposed therapy, it is important to keep in mind the therapeutic index — the ratio of the toxic dose over the therapeutic dose. The use of immunotherapy has allowed a means to both specifically block protein–protein interaction and deliver cytotoxic events to a tumor-specific antigen. Review scope It is the objective of this review to give an overview on current immunotherapy treatment for cancers using monoclonal antibodies. We demonstrate three exciting targets for immunotherapy, TNF-α Converting Enzyme (TACE), Cathepsin S and Urokinase Plasmogen Activator and go over the advances made with one of the most used monoclonal antibodies in cancer therapy, Rituximab; as well as Herceptin, which is used for breast cancer therapy. Furthermore, we touch on other venues of immunotherapy, such as adaptive cell transfer, the use of nucleic acids and the use of dendritic cells. Finally, we summarize some ongoing studies that spell tentative advancements for anti-cancer immunotherapy. General significance Immunotherapy is at the forefront of anti-cancer therapies, allying both a high degree of specificity to general high effectiveness and fewer side-effects. PMID:26673349

  8. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  9. Prostate cancer: 9. Treatment of advanced disease

    PubMed Central

    Gleave, M E; Bruchovsky, N; Moore, M J; Venner, P

    1999-01-01

    A 70-year-old man is referred to a urologist for recommendations on the management of metastatic prostate cancer. His cancer was diagnosed 5 years ago, and he underwent radical prostatectomy at that time. The tumour was confined to the prostate gland (Gleason score 7), and during surgery the lymph nodes were assessed as being clear of cancer. Before the surgery, the patient's prostate-specific antigen (PSA) level had been 8 ng/mL. After the prostatectomy, PSA was at first undetectable, but recently the PSA level rose to 2 ng/mL and then, at the most recent test, to 16 ng/mL. A bone scan was ordered to investigate back discomfort, which has been persistent but easily controlled with acetaminophen. Unfortunately, the bone scan shows several sites of metastatic disease. The man's medical history includes type 2 diabetes, which has developed during the past 3 years and which is controlled by diet, as well as asymptomatic hypertension, which is managed by means of a thiazide diuretic. The patient asks what treatments are available, what impact they are likely to have on his disease and what risks are associated with the therapies. PMID:9951446

  10. Advances in the understanding of cancer immunotherapy.

    PubMed

    Shore, Neal D

    2015-09-01

    The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies.

  11. Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

    SciTech Connect

    Niazi, Tamim M.; Vuong, Te; Azoulay, Laurant; Marijnen, Corrie; Bujko, Kryzstof; Nasr, Elie; Lambert, Christine; Duclos, Marie; Faria, Sergio; David, Marc; Cummings, Bernard

    2012-11-01

    Purpose: For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients. Methods and Materials: A total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis. Results: The radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P=.39). There was considerable intraclass correlation among the 10 observers. Conclusions: Silver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment.

  12. What Happens after Treatment for Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... for Gastrointestinal Carcinoid Tumors? For some people with gastrointestinal (GI) carcinoid tumor, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. ...

  13. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  14. Advances in pancreatic cancer research: moving towards early detection.

    PubMed

    He, Xiang-Yi; Yuan, Yao-Zong

    2014-08-28

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

  15. Treatment advances in liver-limited metastatic colorectal cancer.

    PubMed

    Alberts, Steven R; Poston, Graeme J

    2011-12-01

    Over the last several decades advances in the management and treatment of patients with liver metastases from colorectal cancer (CRC) has changed a disease with a dismal prognosis to one with a potential for cure in some patients. Advances have been made through coordinated management of patients by surgeons, medical oncologists, radiologists, and other health care professionals coupled with advances in treatment options. Although these advances have clearly impacted patient outcomes, it is clear that the benefit of traditional surgical approaches and the use of cytoxic chemotherapy are reaching a plateau. Continued research to develop new and more active therapies, including targeted or biologic agents, is needed. This review discusses the advances made in management of patients with liver-limited metastatic disease.

  16. Dietary patterns of patients with advanced lung or colorectal cancer.

    PubMed

    Prado, Carla M M; Lieffers, Jessica R; Bergsten, Gabriella; Mourtzakis, Marina; Baracos, Vickie E; Reiman, Tony; Sawyer, Michael B; McCargar, Linda J

    2012-01-01

    The purpose of this study was to identify dietary patterns among patients with advanced cancer. Differences between cancer groups are described, and food groups contributing higher proportions to overall caloric intake are identified. Patients with advanced cancer (n=51) were recruited from a regional cancer centre and completed a three-day dietary record. Food items were categorized according to macronutrient content. After adjustment for body weight, substantial variation in energy intake was observed (range: 13.7 to 55.4 kcal/kg/day). For 49% of patients, protein intake was below recommendations. Overall, patients consumed the largest proportion of their calories from meat (16%), other foods (11%), dessert (9%), fruit (9%), white bread (7%), and milk (7%). Only 5% of patients consumed meal replacement supplements. The results of this descriptive study provide important insights into the dietary habits of patients with advanced cancer. These insights could be translated into the development of effective recommendations for maintaining or improving health and quality of life.

  17. Concurrent apatinib and local radiation therapy for advanced gastric cancer

    PubMed Central

    Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

    2017-01-01

    Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

  18. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  19. Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy.

    PubMed

    Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S; Wunderlich, John R; Dudley, Mark E; Rosenberg, Steven A

    2013-09-01

    Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ~50 × 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3(+)CD8(+) cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

  20. Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study

    PubMed Central

    Ren, JS; Freedman, ND; Kamangar, F; Dawsey, SM; Hollenbeck, AR; Schatzkin, A; Abnet, CC

    2010-01-01

    The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric noncardia cancer, 123 esophageal squamous cell carcinoma (ESCC) and 305 esophageal adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% Confidence Intervals (95%CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of ≥1 cup/day was 0.37 (95%CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95%CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last three years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95%CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. PMID:20395127

  1. Multifunctional Nanotherapeutic System for Advanced Prostate Cancer

    DTIC Science & Technology

    2012-10-01

    delivery of eIF4E siRNA and DTX using dendrimer as a nanocarrier. To this end the objective of this study is to prepare, characterize and test the...multifunctional delivery system by conjugating DTX to dendrimer and complexing eIF4E siRNA to the resulting conjugate. The DTX- dendrimer conjugate...formed complex with siRNA at 20:1 ratio. The dendrimer - siRNA complex was taken up by the prostate cancer cells while the free siRNA was not taken up by

  2. [Management of pregnant women with advanced cervical cancer].

    PubMed

    Vincens, C; Dupaigne, D; de Tayrac, R; Mares, P

    2008-04-01

    The purpose of this study is to update the management of pregnant women with advanced cervical cancer, thanks to a literature review indexed in Medline((R)) (from 1980 till 2006 using those keywords: advanced cervix cancer, neoadjuvant chemotherapy and pregnancy), ScienceDirect (from 1990 till 2006) and the French Encyclopédie Médico-Chirurgicale. It occurs that pregnancy is a privileged period to diagnose cervical cancer, particularly in early stages. We ought to beware of symptoms such as vaginal bleeding, which could be underestimated during pregnancy. Colposcopically selected biopsies are reference techniques to confirm the diagnostic. The assessment of extension includes an abdominal and pelvic MRI and echography and a radiography of the chest for locally advanced stages. The decision to interrupt pregnancy should be based on a collegial evaluation and depends on state and histology of disease, patient's desire for pregnancy, as well as gestational age and disease evolution. Cesarean is preferred to natural delivery even though survival rates are the same. The cesarean section prevents from short-term complications and recurrence on the episiotomy, but the hysterotomy type is controversial throughout literature. The prognosis of cervical cancer does not seem to be influenced by pregnancy. Management is the same, even though we have to adapt the treatment from the pregnancy state. No study could show the benefit and the safety of neoadjuvant chemotherapy during pregnancy, due to few cases, but it could be a solution with patients suffering from an advanced cancer and not willing to stop pregnancy. To conclude, the detection by cervical smears should be systematic during pregnancy. When cancer is diagnosed, cesarean section is the favourite way to deliver. Pregnancy does not modify disease's prognosis and the therapeutic choice depends on the stage of the disease.

  3. Pharmacotherapy options for advanced thyroid cancer: a systematic review.

    PubMed

    Lerch, Christian; Richter, Bernd

    2012-01-01

    Poor prognosis of anaplastic thyroid cancer and advanced disease in differentiated and medullary thyroid cancer, together with absence of effective therapeutic measures, has induced recent intensified basic and clinical research in this area. The aim of this article is to assess the effects of new drug treatment for advanced thyroid cancer. We searched MEDLINE and EMBASE until the end of September 2011 for relevant data. Further sources were reference lists of original publications and review articles. We included prospective studies that investigated drug interventions for advanced thyroid cancer published in any language. We did not include trials solely communicated as abstracts. For inclusion, studies had to report overall survival, progression-free survival or similar, or response outcomes. Data were extracted by one author and checked by the other. All tables are part of this publication. Because only non-comparative studies were included, we had to focus on descriptive analysis. Twenty-four studies with 715 patients were included; 18 studies investigated kinase inhibitors, the remainder various drugs. All studies reported response (only one complete response was observed; proportions of partial response were up to 49%). Median progression-free survival was about 12 months, ranging from 3.7 to 27.9 months. Adverse events (at least grade 3) of kinase inhibitors included hypertension, hand foot syndrome and diarrhoea (10%, 16% and 9%, respectively). Due to bias-prone data, any interpretation of newer pharmacotherapy options for advanced thyroid cancer is limited because only non-comparative studies could be included. Therefore, we strongly argue the need for adequate randomized controlled trials that should provide a better basis for therapeutic decision making in thyroid cancer.

  4. Advances and Implications in Nanotechnology for Lung Cancer Management.

    PubMed

    Sarkar, Sana; Osama, Khwaja; Jamal, Qazi Mohammad Sajid; Kamal, Mohammad Amjad; Sayeed, Usman; Khan, M Kalim A; Siddiqui, Mohd Haris; Akhtar, Salman

    2016-11-14

    Lung cancer is one of the most important chronic diseases in the field of respiratory medicine. Conventional treatment strategies for lung cancer include chemotherapy, surgery and radiation therapy. These current therapies lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence.Nanotechnological intervention has greatly revolutionized the therapy of lung cancer by surmounting the current limitations in conventional therapies. Nanoparticles (NPs) achieve preferential accumulation in the tumor cells by employing two mechanisms: passive and active targeting. Several nanoscale drug delivery systems for lung cancer treatment are currently in clinical trials and few of them are already commercially available. Recently, the interest to develop pulmonary delivery system of nano-based drug formulations suitable for lung cancer has been also increased which have resulted in more effective and advanced treatment of Lung cancer. However, although nanotechnology based drug carriers for lung cancer treatment have established outstanding therapeutic potential at both preclinical and clinical Phases, but there are still many limitations to be solved. This review details the till date drug nanocarriers researches performed for lung cancer therapy.

  5. Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

    PubMed

    van Hooft, Jeanin E; van Halsema, Emo E; Vanbiervliet, Geoffroy; Beets-Tan, Regina G H; DeWitt, John M; Donnellan, Fergal; Dumonceau, Jean-Marc; Glynne-Jones, Robert G T; Hassan, Cesare; Jiménez-Perez, Javier; Meisner, Søren; Muthusamy, V Raman; Parker, Michael C; Regimbeau, Jean-Marc; Sabbagh, Charles; Sagar, Jayesh; Tanis, Pieter J; Vandervoort, Jo; Webster, George J; Manes, Gianpiero; Barthet, Marc A; Repici, Alessandro

    2014-11-01

    This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). This Guideline was also reviewed and endorsed by the Governing Board of the American Society for Gastrointestinal Endoscopy (ASGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered as an alternative to emergency surgery in those who have an increased risk of postoperative mortality, I. e. American Society of Anesthesiologists (ASA) Physical Status ≥ III and/or age > 70 years (weak recommendation, low quality evidence). 4 SEMS placement is recommended as the preferred treatment for palliation of malignant colonic obstruction (strong recommendation, high quality evidence), except in patients treated or considered for treatment with antiangiogenic drugs (e. g. bevacizumab) (strong recommendation, low quality evidence).

  6. Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence; Chang, Stephanie; Kuo, Timothy; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Greco, Ralph; Yang, George P.; Koong, Albert C.

    2008-11-01

    Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

  7. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2016 Keynote Lecture Polyvalent Vaccines Targeting Oncogenic Driver Pathways A special keynote lecture became part of the NCI Summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 21, 2016 at 1:30pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Mary L. (Nora) Disis, MD. |

  8. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2015 Keynote Lecture HPV Vaccination: Preventing More with Less A special keynote lecture became part of the NCI summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 23, 2015 at 3:00pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Douglas Lowy, NCI Acting Director. |

  9. Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic

    PubMed Central

    Dev, Rony; Hui, David; Chisholm, Gary; Delgado-Guay, Marvin; Dalal, Shalini; Del Fabbro, Egidio; Bruera, Eduardo

    2015-01-01

    Background Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients. Aims The aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE. Methods A retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups. Results Thirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively. Conclusion Hypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss

  10. Advances in the treatment of advanced oestrogen-receptor-positive breast cancer.

    PubMed

    Turner, Nicholas C; Neven, Patrick; Loibl, Sibylle; Andre, Fabrice

    2016-12-06

    Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.

  11. Improving Goals of Care Discussion in Advanced Cancer Patients

    ClinicalTrials.gov

    2016-12-20

    Primary Stage IV Hepatobiliary; Esophageal; Colorectal Cancer; Glioblastoma; Cancer of Stomach; Cancer of Pancreas; Melanoma; Head or Neck Cancer; Stage III; Stage IV; Lung Cancers; Pancreatic Cancers

  12. Advances in Lipidomics for Cancer Biomarkers Discovery

    PubMed Central

    Perrotti, Francesca; Rosa, Consuelo; Cicalini, Ilaria; Sacchetta, Paolo; Del Boccio, Piero; Genovesi, Domenico; Pieragostino, Damiana

    2016-01-01

    Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy. PMID:27916803

  13. Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

    PubMed

    Wang, Kui; Kievit, Forrest M; Zhang, Miqin

    2016-12-01

    Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment.

  14. [A case of metachronous gastrointestinal perforation of a patient with metastatic rectal cancer during treatment with bevacizumab-based chemotherapy].

    PubMed

    Sadatomo, Ai; Koinuma, Koji; Miki, Atsushi; Horie, Hisanaga; Yasuda, Yoshikazu

    2013-07-01

    A 64-year-old man received mFOLFOX6+bevacizumab chemotherapy for metastatic lung cancer after rectal cancer resection( Stage IV). After 28 courses, he had an abdominal pain with fever, and computed tomography showed pelvic abscess with stercolith of appendix. He was diagnosed as acute appendicitis with intra-abdominal abscess, and emergency appendectomy with drainage was performed. Two days after the operation, he was suspected to have a sutural leakage as was suggested from the properties of his drainage, therefore re-operation was performed. A small hole of the ileum, about 2mm in diameter, was observed. The margin of the hole showed neither inflammatory nor neoplastic change, and a suturing closure of the hole was performed. The post-operative course was uneventful. Histopathological findings of the resected appendix suggested that the perforation was caused by necrosis of metastatic cancer cells penetrating the appendiceal wall. This is a case of a bevacizumab-related metachronous perforation that occurred in different gastrointestinal origins within a very short term.

  15. Could clinical pathways improve the quality of care in patients with gastrointestinal cancer? A meta-analysis.

    PubMed

    Song, Xu-Ping; Tian, Jin-Hui; Cui, Qi; Zhang, Ting-Ting; Yang, Ke-Hu; Ding, Guo-Wu

    2014-01-01

    This meta-analysis was performed to assess the implementation effects of clinical pathways in patients with gastrointestinal cancer. A comprehensive search was conducted in the Cochrane Library, PubMed, EMBASE, Web of Science and Chinese Biomedical Literature Database (from inception to May 2014). Selection of studies, assessing risk of bias and extracting data were performed by two reviewers independently. Outcomes were analyzed by fixed-effects and random-effects model meta-analysis and reported as mean difference (MD), standardized mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI). The Jadad methodological approach was used to assess the quality of included studies and the meta-analysis was conducted with RevMan 5.1 software. Nine citations (eight trials) involving 642 patients were included. The aggregate results showed that a shorter average length of stay [MD = -4.0; 95% CI (-5.1, -2.8); P < 0.00001] was observed with the clinical pathways as compared with the usual care. A reduction in inpatient expenditure [SMD = -1.5; 95% CI (-2.3, -0.7); P = 0.0001] was also associated with clinical pathways, along with higher patient satisfaction [OR = 4.9; 95% CI (2.2, 10.6); P < 0.0001]. Clinical pathways could improve the quality of care in patients with gastrointestinal cancer, as evidenced by a significant reduction in average length of stay, a decrease in inpatient expenditure and an improvement in patient satisfaction. Therefore, indicators and mechanisms within clinical pathways should be a focus in the future.

  16. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

  17. Comparison of the prevalence of malnutrition diagnosis in head and neck, gastrointestinal and lung cancer patients by three classification methods

    PubMed Central

    Platek, Mary E.; Popp KPf, Johann V.; Possinger, Candi S.; DeNysschen, Carol A.; Horvath, Peter; Brown, Jean K.

    2011-01-01

    Background Malnutrition is prevalent among patients within certain cancer types. There is lack of universal standard of care for nutrition screening, lack of agreement on an operational definition and on validity of malnutrition indicators. Objective In a secondary data analysis, we investigated prevalence of malnutrition diagnosis by three classification methods using data from medical records of a National Cancer Institute (NCI)-designated comprehensive cancer center. Interventions/Methods Records of 227 patients hospitalized during 1998 with head and neck, gastrointestinal or lung cancer were reviewed for malnutrition based on three methods: 1) physician diagnosed malnutrition related ICD-9 codes; 2) in-hospital nutritional assessment summary conducted by Registered Dietitians; and 3) body mass index (BMI). For patients with multiple admissions, only data from the first hospitalization was included. Results Prevalence of malnutrition diagnosis ranged from 8.8% based on BMI to approximately 26% of all cases based on dietitian assessment. Kappa coefficients between any methods indicated a weak (kappa=0.23, BMI and Dietitians and kappa=0.28, Dietitians and Physicians) to fair strength of agreement (kappa=0.38, BMI and Physicians). Conclusions Available methods to identify patients with malnutrition in an NCI designated comprehensive cancer center resulted in varied prevalence of malnutrition diagnosis. Universal standard of care for nutrition screening that utilizes validated tools is needed. Implications for Practice The Joint Commission on the Accreditation of Healthcare Organizations requires nutritional screening of patients within 24 hours of admission. For this purpose, implementation of a validated tool that can be used by various healthcare practitioners, including nurses, needs to be considered. PMID:21242767

  18. Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Yoon, Ji-Young; Koo, Yu-Jin; Kim, Mi-Jung; Kim, Tae-Jin; Lim, Kyung-Taek

    2014-01-01

    Objective To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. Methods Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. Results Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. Conclusion IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study. PMID:25469337

  19. Ontario-wide Cancer TArgeted Nucleic Acid Evaluation

    ClinicalTrials.gov

    2016-09-14

    Breast Cancer; Lung Cancer; Colorectal Cancer; Melanoma; Gynecological Cancer; Genitourinary Cancer; Pancreatobiliary Cancer; Gastrointestinal Cancer; Head and Neck Cancer; Rare Cancer; Unknown Primary Cancer

  20. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  1. Next-generation sequencing: advances and applications in cancer diagnosis

    PubMed Central

    Serratì, Simona; De Summa, Simona; Pilato, Brunella; Petriella, Daniela; Lacalamita, Rosanna; Tommasi, Stefania; Pinto, Rosamaria

    2016-01-01

    Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis. DNA sequencing includes whole-genome, whole-exome, and targeted sequencing, which focuses on a selection of genes of interest for a specific disease. RNA sequencing facilitates the detection of alternative gene-spliced transcripts, posttranscriptional modifications, gene fusion, mutations/single-nucleotide polymorphisms, small and long noncoding RNAs, and changes in gene expression. Most applications are in the cancer research field, but lately NGS technology has been revolutionizing cancer molecular diagnostics, due to the many advantages it offers compared to traditional methods. There is greater knowledge on solid cancer diagnostics, and recent interest has been shown also in the field of hematologic cancer. In this review, we report the latest data on NGS diagnostic/predictive clinical applications in solid and hematologic cancers. Moreover, since the amount of NGS data produced is very large and their interpretation is very complex, we briefly discuss two bioinformatic aspects, variant-calling accuracy and copy-number variation detection, which are gaining a lot of importance in cancer-diagnostic assessment. PMID:27980425

  2. Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

    ClinicalTrials.gov

    2016-12-20

    Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

  3. What Happens After Treatment for Gastrointestinal Stromal Tumor?

    MedlinePlus

    ... Tumor Is No Longer Working Gastrointestinal Stromal Tumor (GIST) After Treatment What Happens After Treatment for Gastrointestinal ... For some people with a gastrointestinal stromal tumor (GIST), treatment may remove or destroy the cancer. Completing ...

  4. Recent advances in immunotherapy for hepatocellular cancer.

    PubMed

    Butterfield, Lisa H

    2007-02-10

    There is a continuing need for innovative, alternative therapies for hepatocellular carcinoma (HCC). Immunotherapy of cancer is attractive because of the exquisite specificity of the immune response. Activation of an HCC-specific response can be accomplished by strategies targeting tumour-associated antigens (for example: alpha fetoprotein (AFP)) or viral antigens in those patients infected with hepatitis B or C. Uncharacterised and mutated antigens can also be targeted with whole tumour cell or tumour lysate-based immunisation strategies. Viral vectors coding for genes which make the patient's tumour immunogenic can allow the immune system to naturally evolve specificity against immunogenic target antigens. Strategies which have been tested in human clinical trials include adoptive transfer of lymphocytes, cytokine injections, autologous tumour-pulsed dendritic cells (DC) as well as AFP-derived peptides in adjuvant and pulsed onto autologous DC. These trials, testing novel immune-based interventions in HCC subjects, have resulted in immunological responses and some have impacted recurrence and survival of HCC subjects.

  5. Chemotherapy Resistance Mechanisms in Advanced Skin Cancer

    PubMed Central

    Kalal, Bhuvanesh Sukhlal; Upadhya, Dinesh; Pai, Vinitha Ramanath

    2017-01-01

    Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma. PMID:28382191

  6. Pre-tumour clones, periodic selection and clonal interference in the origin and progression of gastrointestinal cancer: potential for biomarker development.

    PubMed

    Baker, Ann-Marie; Graham, Trevor A; Wright, Nicholas A

    2013-03-01

    Classically, the risk of cancer progression in premalignant conditions of the gastrointestinal tract is assessed by examining the degree of histological dysplasia. However, there are many putative pro-cancer genetic changes that have occurred in histologically normal tissue well before the onset of dysplasia. Here we summarize the evidence for such pre-tumour clones and the existing technology that can be used to locate these clones and characterize them at the genetic level. We also discuss the mechanisms by which pre-tumour clones may spread through large areas of normal tissue, and highlight emerging theories on how multiple clones compete and interact within the gastrointestinal mucosa. It is important to gain an understanding of these processes, as it is envisaged that certain pre-tumour changes may be powerful predictive markers, with the potential to identify patients at high risk of developing cancer at a much earlier stage.

  7. Characterizing variability in in vivo Raman spectra of different anatomical locations in the upper gastrointestinal tract toward cancer detection

    NASA Astrophysics Data System (ADS)

    Bergholt, Mads Sylvest; Zheng, Wei; Lin, Kan; Ho, Khek Yu; Teh, Ming; Yeoh, Khay Guan; So, Jimmy Bok Yan; Huang, Zhiwei

    2011-03-01

    Raman spectroscopy is an optical vibrational technology capable of probing biomolecular changes of tissue associated with cancer transformation. This study aimed to characterize in vivo Raman spectroscopic properties of tissues belonging to different anatomical regions in the upper gastrointestinal (GI) tract and explore the implications for early detection of neoplastic lesions during clinical gastroscopy. A novel fiber-optic Raman endoscopy technique was utilized for real-time in vivo tissue Raman measurements of normal esophageal (distal, middle, and proximal), gastric (antrum, body, and cardia) as well as cancerous esophagous and gastric tissues from 107 patients who underwent endoscopic examinations. The non-negativity-constrained least squares minimization coupled with a reference database of Raman active biochemicals (i.e., actin, histones, collagen, DNA, and triolein) was employed for semiquantitative biomolecular modeling of tissue constituents in the upper GI. A total of 1189 in vivo Raman spectra were acquired from different locations in the upper GI. The Raman spectra among the distal, middle, and proximal sites of the esophagus showed no significant interanatomical variability. The interanatomical variability of Raman spectra among normal gastric tissue (antrum, body, and cardia) was subtle compared to cancerous tissue transformation, whereas biomolecular modeling revealed significant differences between the two organs, particularly in the gastroesophageal junction associated with proteins, DNA, and lipids. Cancerous tissues can be identified across interanatomical regions with accuracies of 89.3% [sensitivity of 92.6% (162/175) specificity of 88.6% (665/751)], and of 94.7% [sensitivity of 90.9% (30/33) specificity of 93.9% (216/230)] in the gastric and esophagus, respectively, using partial least squares-discriminant analysis together with the leave-one tissue site-out, cross validation. This work demonstrates that Raman endoscopy technique has

  8. Australasian Gastrointestinal Trials Group (AGITG) Contouring Atlas and Planning Guidelines for Intensity-Modulated Radiotherapy in Anal Cancer

    SciTech Connect

    Ng, Michael; Leong, Trevor; Chander, Sarat; Chu, Julie; Kneebone, Andrew; Carroll, Susan; Wiltshire, Kirsty; Ngan, Samuel; Kachnic, Lisa

    2012-08-01

    Purpose: To develop a high-resolution target volume atlas with intensity-modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of anal cancer. Methods and Materials: A draft contouring atlas and planning guidelines for anal cancer IMRT were prepared at the Australasian Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert panel of radiation oncologists contoured an anal cancer case to generate discussion on recommendations regarding target definition for gross disease, elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV) and planning target volume (PTV) margins, dose fractionation, and other IMRT-specific issues were also addressed. A steering committee produced the final consensus guidelines. Results: Detailed contouring and planning guidelines and a high-resolution atlas are provided. Gross tumor and elective target volumes are described and pictorially depicted. All elective regions should be routinely contoured for all disease stages, with the possible exception of the inguinal and high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the elective pelvic nodal groups are recommended, while respecting anatomical boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and 45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided for OAR delineation. Conclusion: These consensus planning guidelines and high-resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG) elective nodal ano-rectal atlas and provide additional anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of IMRT for anal cancer.

  9. Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer

    PubMed Central

    Davidson, Susan E; Gillespie, Catherine; Allum, William H; Swarbrick, Edwin

    2011-01-01

    Backgound The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed. Methods A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments. Results Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent

  10. Reducing Toxicity of Radiation Treatment of Advanced Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    malignant tissues. A major effort focused on the effects these drugs on myeloid (bone marrow-derived) cells. This is based on our finding that...the last progress report we further presented data supporting the notion that the radioprotecive effect of RTA 408 is a ‘class’ effect of drugs that...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Toxicity is a major impediment to effective radiation therapy of locally advanced prostate cancer

  11. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    PubMed Central

    Kwak, Yoo-Kang; Lee, Jong Hoon; Lee, Myung-Ah; Chun, Hoo-Geun; Kim, Dong-Goo; You, Young Kyoung; Hong, Tae-Ho

    2014-01-01

    Purpose Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Materials and Methods Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. Results With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Conclusion Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival. PMID:25061572

  12. Navigating the evolving therapeutic landscape in advanced prostate cancer.

    PubMed

    Crawford, E David; Petrylak, Daniel; Sartor, Oliver

    2017-03-07

    Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year. The overall 5-year survival rate for prostate cancer is very high. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop castration-resistant prostate cancer (CRPC) within 5 years, with median survival for those with metastatic CRPC ranging from approximately 15 to 36 months in recent studies. With the advent of several new drugs in the past 5 years to treat CRPC, the challenge facing clinicians is how to best sequence or combine therapies or both to optimize outcomes. A better understanding of the disease process and the role of the androgen receptor as a target for both therapy and resistance have led to the consideration of biomarkers as an approach to aid in selecting the appropriate agent for a given patient as patients respond to or tolerate different drugs differently. Research to identify new prognostic biomarkers, which are associated with outcome measures, as well as predictive biomarkers, which predict response or resistance to therapy is ongoing. The treatment of advanced prostate cancer and the research related to biomarkers are discussed.

  13. Glucose Addiction in Cancer Therapy: Advances and Drawbacks.

    PubMed

    Granja, Sara; Pinheiro, Céline; Reis, Rui Manuel; Martinho, Olga; Baltazar, Fátima

    2015-01-01

    While normal differentiated cells primarily use mitochondrial respiration to generate the required energy for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions. This phenomenon is known as the "Warburg effect" or aerobic glycolysis and the metabolic reprogramming of cancer cells towards this altered energy metabolism is currently recognized as one of the "hallmarks of cancer". Aerobic glycolysis underlies the rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. The search for suitable targets, however, is limited by the high plasticity of the metabolic network that can induce compensatory routes. Deregulated glucose metabolism is a prominent feature associated with resistance to classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of different therapeutic strategies targeting the glucose "addiction" of tumor cells, highlighting their potential as effective weapons against cancer. We further discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, where the combination with glycolysis inhibitors could prove extraordinarily useful.

  14. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  15. Advancing cancer control research in an emerging news media environment.

    PubMed

    Smith, Katherine C; Niederdeppe, Jeff; Blake, Kelly D; Cappella, Joseph N

    2013-12-01

    Cancer is both highly feared and highly newsworthy, and there is a robust body of research documenting the content and effects of cancer news coverage on health behaviors and policy. Recent years have witnessed ongoing, transformative shifts in American journalism alongside rapid advances in communication technology and the public information environment. These changes create a pressing need to consider a new set of research questions, sampling strategies, measurement techniques, and theories of media effects to ensure continued relevance and adaptation of communication research to address critical cancer control concerns. This paper begins by briefly reviewing what we know about the role of cancer news in shaping cancer-related beliefs, attitudes, behaviors, and policies. We then outline challenges and opportunities, both theoretical and methodological, posed by the rapidly changing news media environment and the nature of audience engagement. We organize our discussion around three major shifts associated with the emerging news media environment as it relates to health communication: 1) speed and dynamism of news diffusion, 2) increased narrowcasting of media content for specialized audiences, and 3) broadened participation in shaping media content. In so doing, we articulate a set of questions for future theory and research, in an effort to catalyze innovative communication scholarship to improve cancer prevention and control.

  16. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  17. Advancing Cancer Control Through Research and Cancer Registry Collaborations in the Caribbean

    PubMed Central

    Banydeen, Rishika; Rose, Angela M.C.; Martin, Damali; Aiken, William; Alexis, Cheryl; Andall-Brereton, Glennis; Ashing, Kimlin; Avery, J. Gordon; Avery, Penny; Deloumeaux, Jacqueline; Ekomaye, Natasha; Gabriel, Owen; Hassell, Trevor; Hughes, Lowell; Hutton, Maisha; Jyoti, Shravana Kumar; Layne, Penelope; Luce, Danièle; Patrick, Alan; Prussia, Patsy; Smith-Ravin, Juliette; Veronique-Baudin, Jacqueline; Blackman, Elizabeth; Roach, Veronica; Ragin, Camille

    2016-01-01

    Background Few national registries exist in the Caribbean, resulting in limited cancer statistics being available for the region. Therefore, estimates are frequently based on the extrapolation of mortality data submitted to the World Health Organization. Thus, regional cancer surveillance and research need promoting, and their synergy must be strengthened. However, differences between countries outweigh similarities, hampering registration and availability of data. Methods The African-Caribbean Cancer Consortium (AC3) is a broad-based resource for education, training, and research on all aspects of cancer in populations of African descent. The AC3 focuses on capacity building in cancer registration in the Caribbean through special topics, training sessions, and biannual meetings. We review the results from selected AC3 workshops, including an inventory of established cancer registries in the Caribbean region, current cancer surveillance statistics, and a review of data quality. We then describe the potential for cancer research surveillance activities and the role of policymakers. Results Twelve of 30 Caribbean nations have cancer registries. Four of these nations provide high-quality incidence data, thus covering 14.4% of the population; therefore, regional estimates are challenging. Existing research and registry collaborations must pave the way and are facilitated by organizations like the AC3. Conclusions Improved coverage for cancer registrations could help advance health policy through targeted research. Capacity building, resource optimization, collaboration, and communication between cancer surveillance and research teams are key to obtaining robust and complete data in the Caribbean. PMID:26678981

  18. Nutritional status of patients with gastrointestinal cancer receiving care in a public hospital; 2010-2011.

    PubMed

    Dias do Prado, Corina; Alvares Duarte Bonini Campos, Juliana

    2013-01-01

    Objetivo: Identificar el estado nutricional de los pacientes con cáncer gastrointestinal y verificar su asociación con características demográficas y clínicas. Métodos: Se realizó un estudio transversal, con un diseño de muestreo no probabilístico. Los participantes fueron 143 pacientes adultos con cáncer gastrointestinal, que reciben atención en el Hospital Amaral Carvalho (Jaú-SP, Brasil) entre noviembre de 2010 y octubre de 2011. Se realizó una encuesta para recoger información con el fin de caracterización demográfica y clínica. Para identificar el estado nutricional se aplico la Valoración Subjetiva Global - Generada por el Paciente Score (VSGGP score). La razón de prevalencia (RP) fue estimada. El nivel de significancia adoptado fue de 5%. Resultados: La edad media de los pacientes fue de 57,45 (DE = 9,62) AÑOs, con los estadíos III y IV de la enfermedad es la más frecuente (39,2% y 35,0%). Había 44,8% de prevalencia de la malnutrición. La persona desnutrida tenía problemas más frecuentes para comer. La estadística descriptiva y la prueba de Chi-cuadrado (< 0,001), presentaron menor deseo de comer (p < 0,001), más náuseas (p = 0,001), vómitos (p = 0,006), estreñimiento (p < 0,001) y dolor (p < 0,001) que los pacientes eutróficos y se declararon enfermos por el olor de los alimentos (p = 0,012), dificultad para tragar (p = 0,002) y la saciedad precoz (p = 0,020) com más frecuencia. En cuanto a la proporción de prevalencia, se observó una probabilidad mayor de individuos desnutridos expuestos a una porción más grande de los síntomas relacionados en la puntuación VSG-GP score. Conclusión: La alta prevalencia de desnutrición se observó en pacientes con cáncer gastrointestinal, con asociación significativa con los síntomas clínicos directamente relacionados con el proceso de alimentación.

  19. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  20. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    PubMed Central

    Zhou, Yufeng

    2014-01-01

    Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU) is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS) score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered. PMID:25053938

  1. Drugging Chromatin in Cancer: Recent Advances and Novel Approaches

    PubMed Central

    Cai, Sheng F.; Chen, Chun-Wei; Armstrong, Scott A.

    2015-01-01

    Chromatin regulatory mechanisms play a major role in the control of gene expression programs during normal development and are disrupted in specific disease states, particularly in cancer. Important mediators of chromatin regulatory processes can broadly be classified into writers, erasers, and readers of covalent chromatin modifications that modulate eukaryotic gene transcription and maintain the integrity of the genome. The reversibility and disease-specific nature of these chromatin states make these regulators attractive therapeutic targets. As such, there is an ever-increasing number of candidate therapies aimed at targeting cancer-associated chromatin states that are in various stages of preclinical and clinical development. In this review, we discuss recent advances that have been made in the rational therapeutic targeting of chromatin regulatory mechanisms and highlight certain cancers where there is a specific rationale to assess these therapeutic approaches. PMID:26590715

  2. Evidence-based approaches to other symptoms in advanced cancer.

    PubMed

    Dy, Sydney Morss; Apostol, Colleen C

    2010-01-01

    Dyspnea, nausea and vomiting, anorexia, fatigue, and sleep disturbances are common and distressing in advanced cancer. We updated previous systematic reviews of how these symptoms can be alleviated with targeted literature searches. The approach to these symptoms requires comprehensive symptom assessment; treating underlying causes when benefits exceed risks; prioritizing treatment, as patients usually have many symptoms; and addressing psychosocial and spiritual distress. For dyspnea, evidence supports systemic opioids and nonpharmacological treatments such as a fan. The strongest evidence supports metoclopramide for cancer-related nausea and octreotide for bowel obstruction. For anorexia, enteral or parenteral nutrition is indicated with obstruction and expected prognosis of at least 6 weeks. Evidence supports several drugs for appetite affecting quality of life. For fatigue, evidence supports psychosocial interventions and methylphenidate. For insomnia, evidence supports cognitive-behavioral therapy in cancer; no sleep agents have superior effectiveness.

  3. Radiotherapy combined with surgery as treatment for advanced cervical cancer.

    PubMed

    Perches, R D; Lobaton, A T; Garcia, M C

    1983-12-01

    Experience obtained in a group of 44 patients with advanced cervical cancer is reported here. In this study, patients with residual cancer underwent laparotomy eight weeks after one or two different radiotherapy protocols. Sixty-eight percent of patients underwent radical surgery, 85% of patients pelvic exenterations, and 15% radical hysterectomies. In 27% of patients, no evidence of residual cancer was found in surgical specimens. Radical surgery was well tolerated, and one-third of patients were free of disease for one year or more. Control of disease was obtained in 50% of pelvic exenterations and in 60% of radical hysterectomies, regardless of prognosis, clinical stage or radiotherapy scheme. Although results show an improvement of up to 22% when comparing this to other more conventional treatments, we have concluded that we must obtain a wider experience in order to support our findings.

  4. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  5. Evaluation of rational extent lymphadenectomy for local advanced gastric cancer

    PubMed Central

    Liang, Han; Deng, Jingyu

    2016-01-01

    Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes (PAN) in JCOG9501, the clinical benefit of D2+ para-aortic nodal dissection (PAND) for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.11 nodes has been controversial, and however, the final results from the randomized trial of JCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as M1 stage in the current version of the Japanese classification. We propose that D2+No.14v and +No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients. PMID:27647967

  6. Ixabepilone in Treating Patients With Advanced Urinary Tract Cancer

    ClinicalTrials.gov

    2013-01-23

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  7. The Inflammatory-Nutritional Index; assessing nutritional status and prognosis in gastrointestinal and lung cancer patients.

    PubMed

    Pastore, Carla Alberici; Orlandi, Silvana Paiva; Gonzalez, Maria Cristina

    2014-03-01

    Objetivo: Evaluar la capacidad pronostica del Índice Inflamatorio-Nutricional (INI) en pacientes con cáncer del tracto gastrointestinal y pulmón. Métodos: Estudio longitudinal, con pacientes de un servicio de quimioterapia en Brasil, entre Julio de 2008 y Mayo de 2010. INI (Albúmina/CRP) y el estadio nutricional (Valoración Global Subjetiva-SGA) fueran evaluados. INI de riesgo fue definido como menor que 0.35. El tiempo medio de acompañamiento fue 1.6 año. Analices estadísticas fueran realizadas con el programa Stata 11.1™. Resultados: Fueron evaluados 74 pacientes, con edad media de 63.4 años, la mayoría hombres (58%) e con cáncer gastrointestinal (71%). Desnutrición fue identificada en 87% de los pacientes (22% con desnutrición grave). El INI medio fue 2.67 y 54% de los individuos presentaban INI de riesgo. Durante el acompañamiento hubieran 49 óbitos (66%). El tiempo mediano de sobrevida de los pacientes con INI de riesgo fue significantemente más corto que de los pacientes con INI normal (p = 0.002). El grupo con INI de riesgo llevó 0.78 año para decaer 50%, en cuanto el grupo con INI normal llevó 2.78 año (p = 0.001). INI de riesgo y desnutrición grave fueron factores independientes de peor sobrevida. Conclusión: El INI demostró capacidad pronostica en esta amuestra y puede ser una herramienta útil, basada testes rutineros y disponibles, para evaluar pacientes con cáncer.

  8. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  9. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of gastrointestinal cancers with peritoneal metastases: Progress toward a new standard of care.

    PubMed

    Sugarbaker, Paul H

    2016-07-01

    Peritoneal metastases from gastrointestinal cancer was, in the past, accepted as an inevitable component of the natural history of these diseases. It is a major cause of intestinal obstruction, fistula formation, and bowel perforation as the recurrent malignancy progresses to a terminal condition. Peritoneal metastases may be caused by full thickness penetration of the bowel wall by the primary cancer or by spilled cancer cells released into the peritoneal space by surgical trauma. Two new surgical technologies that have evolved to manage peritoneal metastases are cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This combined treatment strategy uses peritonectomy procedures and visceral resections to reduce the disease in the abdomen and pelvis to a macroscopic volume. Then, HIPEC is used to preserve the complete cytoreduction by controlling the minimal residual disease. Since the extent of peritoneal metastases, as measured by the peritoneal cancer index (PCI), is crucial to a favorable outcome, prognostic indicators are used to select patients for treatment. The combined treatment may be used to prevent peritoneal metastases in gastrointestinal cancer patients having a resection of the primary malignancy. This is especially important in gastric cancer patients with serosal invasion. The combined treatment may be used synchronously with the primary cancer resection if peritoneal metastases are already apparent. The treatment is most frequently used with metachronous peritoneal metastases diagnosed in follow-up. Cure of peritoneal metastases is an option in selected patients and its knowledgeable use is progressing towards a new standard of care.

  10. Practical use of advanced mouse models for lung cancer.

    PubMed

    Safari, Roghaiyeh; Meuwissen, Ralph

    2015-01-01

    To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre

  11. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  12. Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

    PubMed Central

    Moehler, Markus; Sprinzl, Martin F; Abdelfattah, Murad; Schimanski, Carl C; Adami, Bernd; Godderz, Werner; Majer, Klaus; Flieger, Dimitri; Teufel, Andreas; Siebler, Juergen; Hoehler, Thomas; Galle, Peter R; Kanzler, Stephan

    2009-01-01

    AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan ± bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase II trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS: In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients (47% vs 24%), and more patients had colon as the primary tumor site (58.8% vs 48.2%) with fewer patients having sigmoid colon as primary tumor site (5.9% vs 20.7%). Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev: 82% vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates were 70.6% and 75.9%, respectively. No complete responses were observed. The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev, respectively. The median overall survival for CAPIRI was 15 mo (458 d) and for CAPIRI-Bev 24 mo (733 d). These differences were not statistically different. In the CAPIRI-Bev, group, two patients underwent a full secondary tumor resection after treatment, whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION: Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal. PMID:19152449

  13. Fatal systemic candidiasis of gastrointestinal origin: an experimental model in mice compromised by anti-cancer treatment.

    PubMed

    Sandovsky-Losica, H; Barr-Nea, L; Segal, E

    1992-01-01

    An experimental model of fatal systemic candidiasis originating from the gastrointestinal (GI) tract of compromised mice is presented. ICR female mice were compromised by a single anti-cancer treatment: irradiation (4 or 6 Greys i.e. 400-600 rads), methotrexate (MTX) (3 mg per mouse, intraperitoneally) or 5-fluorouracil (5FU) (200 mg kg-1, intravenously). Three days later, compromised and non-treated control mice were exposed to Candida albicans administered orally. Morbidity and mortality due to candidiasis were monitored for 30 days post-candidal inoculation. Increased and longer GI colonization was noted among the MTX and 5FU treated mice, or 6 Greys irradiated mice (up to 92.3% for over 30 days in anti-cancer treated mice). The stomach was found to be the major part of the GI tract involved in fungal colonization. A significant number (53.8-83.3%) of the anti-cancer treated mice developed systemic candidiasis originating from the GI tract, which was fatal in 30-80% of the infected animals. In systemically infected animals, candidal antigen was demonstrated in the serum, and fungal abscesses containing C. albicans were observed in the liver, kidneys and spleen. C. albicans was isolated from the infected organs. The severity of the infection, as reflected by the number of fungi in visceral organs, and by mortality during the 30 days post-candidal inoculation, indicated differences in the course and nature of the infection among the three treatment groups (i.e. MTX, 5FU, 6 Greys).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Early enteral nutrition in combination with parenteral nutrition in elderly patients after surgery due to gastrointestinal cancer

    PubMed Central

    Huang, Dongping; Sun, Zhufeng; Huang, Jianwei; Shen, Zhaozai

    2015-01-01

    Objective: To evaluate the therapeutic effects of nutritional support via different routes in elderly patients after surgery for gastrointestinal (GI) cancer. Methods: 105 patients with GI cancer were randomly divided into early enteral nutrition (EEN) group (n = 35), total parenteral nutrition (TPN) group (n = 35) and EN+PN group (n = 35). Results: The nutrition status and immunity were significantly compromised in all patients, while the liver function was improved at 3 days after surgery as compared to those before surgery. At 7 days after surgery, they returned to preoperative level. The nutrition status was comparable among 3 groups at 3 and 7 days after surgery (P > 0.05). ALT, AST, ALP and GGT in TNP group were significantly higher than those in EEN group and EN+PN group (P < 0.05), whereas there was no significant difference in the liver function between EEN group and EN+PN group (P > 0.05). The CD3+ cells, CD4+ cells and CD4/CD8 in EEN group and EN+PN group were significantly higher than those in TPN group (P < 0.05), but significant difference was not observed between EEN group and EN+PN group (P > 0.05). The NK cells in EN+PN group were significantly higher than in TPN group (P < 0.01). The incidence of diarrhea in EEN group was significantly higher than in TPN group and EN+PN group (P < 0.05). Conclusion: EN+PN is superior to EEN alone and TPN alone in the old patients with GI cancer in reducing the postoperative complications, improving the immunity and decreasing the hospital stay. PMID:26550350

  15. Clinical trials update: Medical management of advanced breast cancer.

    PubMed

    Major, Maureen A

    2003-12-01

    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.

  16. Control of Advanced Cancer: The Road to Chronicity

    PubMed Central

    Lage, Agustin; Crombet, Tania

    2011-01-01

    Despite the recent trend toward a slight decrease in age-adjusted cancer mortality in some countries, crude mortality rates will continue to increase, driven by the demographic shift towards an aged population. Small molecules (small molecules and biologics) are not only a new therapeutic acquisition, but the tools of a more fundamental transition: the transformation of cancer from a rapidly fatal disease into a chronic condition. Antibodies and cancer vaccines can be used for a long time, even beyond progressive disease, and in aged patients, usually unfit for more aggressive conventional treatments. However, this transition to chronicity will require novel developmental guidelines adequate to this kind of drugs, for which optimal dose is not usually the maximal tolerated dose, pharmacokinetics does not define treatment schedule, and tumor shrinkage is not a good correlate of survival. The ongoing cancer immunotherapy program (including several monoclonal antibodies and therapeutic vaccines) at the Centre of Molecular Immunology can illustrate the issues to be addressed, both biological and social, along the path to transform advanced cancer into a chronic non-communicable disease compatible with years of quality life. PMID:21556173

  17. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  18. MALNUTRITION IN PATIENTS WITH GASTROINTESTINAL CANCER: EFFECTIVENESS OF DIFFERENT DIAGNOSTIC METHODS.

    PubMed

    Dias do Prado, Corina; Alvares Duarte Bonini Campos, Juliana

    2015-07-01

    Objetivo: estimar la efectividad de los diferentes métodos para la identificación y/o presencia de desnutrición en las personas con riesgo de cáncer gastrointestinal. Métodos: los participantes fueron 143 pacientes con cáncer gastrointestinal, atendidos en la sala del Hospital Clínico de Oncología Amaral Carvalho (Jau-SP). No se excluyeron los pacientes ingresados en la unidad de cuidados intensivos, con enfermedad terminal o con miembros amputados que recibieron transfusiones de sangre en el último mes, con hemorragias clínicamente relevantes, que recibieron albúmina intravenosa y aquellos con infección no controlada. El estado nutricional de los participantes se clasificó de acuerdo a la relación Peso Real y Peso Habitual (PR/PH), Índice de Masa Corporal (IMC), Índice de Riesgo Nutricional (IRN) y porcentaje de ajuste (% score). Como método estándar de oro se utilizó la Evaluación Global Subjetiva. Fue evaluada la eficacia de los métodos para detectar el riesgo de desnutrición o la presencia de desnutrición. La curva ROC fue construido y su área (AUROC) se estimó. Las áreas se compararon mendiante z estadística. Para cada método resuelto el mejor punto de corte. Resultados: de los pacientes, el 74,1% había avanzado en el estado de la enfermedad y el 83,2% fueron sometidos a métodos quimioterápicos. Todos los métodos de tratamiento mostraron una adecuada capacidad discriminatoria para detectar el riesgo de desnutrición y la presencia de la misma. El IMC fue significativamente mejor para la detección de la desnutrición que para el riesgo de desnutrición. El riesgo PR/PH fue significativamente mejor para detectar el riesgo de desnutrición que otros métodos. Los puntos de corte fueron inferiores a los puntos de corte recomendados para población normativa con los métodos PR/PH, NRI y porcentaje de ajuste (% score). Para el punto de corte del IMC fue mayor que el recomendado para la población normativa. Conclusión: los m

  19. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  20. Cancer Pain Control for Advanced Cancer Patients by Using Autonomic Nerve Pharmacopuncture

    PubMed Central

    Kang, Hwi-joong; Yoon, Jung-won; Park, Ji-hye; Cho, Chong-kwan; Yoo, Hwa-seung

    2014-01-01

    Objectives: The purpose of this study is to report a case series of advanced cancer patients whose cancer pain was relieved by using autonomic nerve pharmacopuncture (ANP) treatment. ANP is a subcutaneous injection therapy of mountain ginseng pharmacopuncture (MGP) along the acupoints on the spine (Hua-Tuo-Jia-Ji-Xue; 0.5 cun lateral to the lower border of the spinous processes of vertebrae) to enhance the immune system and to balance autonomic nerve function. Methods: Patients with three different types of cancer (gastric cancer, lung cancer, colon cancer with distant metastases) with cancer pain were treated with ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5 sites (total 12 ─ 20 mL injection) of each patient’s dorsum by using the principle of symptom differentiation. During ANP treatment, the visual analogue scale (VAS) for pain was used to assess their levels of cancer pain; also, the dosage and the frequency of analgesic use were measured. Results: The cancer pain levels of all three patients improved with treatment using ANP. The VAS scores of the three patients decreased as the treatment progressed. The dosage and the frequency of analgesics also gradually decreased during the treatment period. Significantly, no related adverse events were found. Conclusion: ANP has shown benefit in controlling cancer pain for the three different types of cancer investigated in this study and in reducing the dosage and the frequency of analgesics. ANP is expected to be beneficial for reducing cancer pain and, thus, to be a promising new treatment for cancer pain. PMID:25780711

  1. Role of stenting in gastrointestinal benign and malignant diseases

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Arena, Monica; Miraglia, Stefania; Consolo, Pierluigi; Iabichino, Giuseppe; Virgilio, Clara; Luigiano, Carmelo

    2015-01-01

    Advances in stents design have led to a substantial increase in the use of stents for a variety of digestive diseases. Initially developed as a non-surgical treatment for palliation of esophageal cancer, the stents now have an emerging role in the management of malignant and benign conditions as well as in all segments of the gastrointestinal tract. In this review, relevant literature search and expert opinions have been used to evaluate the key-role of stenting in gastrointestinal benign and malignant diseases. PMID:25992186

  2. Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2015-09-30

    Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  3. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers

    PubMed Central

    Shapira, Shiran; Pleban, Shlomo; Kazanov, Diana; Tirosh, Peter; Arber, Nadir

    2016-01-01

    Background Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities. Aim To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents. Methods Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva) and biological agent (Cetuximab). It was also combined with humanized anti-CD24 mAbs (was developed by us). Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model. Results Terpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10–90% in 0.005–0.1%). Terpinen-4-ol and various anti-cancer agents (0.2μM oxaliplatin and 0.5μM fluorouracil) demonstrated a synergistic inhibitory effect (83% and 91%, respectively) on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 μM) resulted in impressive efficacy of 80–90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150μg/ml)-induced growth inhibition (90%). Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2%) treatment alone and with cetuximab (10mg/kg) (40% and 63%, respectively) as compare to the control group. Conclusion Terpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in

  4. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances.

    PubMed

    Simpson, Guy R; Relph, Kate; Harrington, Kevin; Melcher, Alan; Pandha, Hardev

    2016-01-01

    Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena.

  5. Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes

    PubMed Central

    Forastiere, Arlene A.; Weber, Randal S.; Trotti, Andy

    2015-01-01

    Purpose To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy. Methods The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed. Results There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients. Conclusion The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment. PMID:26351339

  6. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  7. Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer

    PubMed Central

    Bailleux, Caroline; Falk, Alexander Tuan; Chand-Fouche, Marie-Eve; Gautier, Mathieu; Barranger, Emmanuel

    2016-01-01

    Purpose There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB) boost for locally advanced cervical cancer. Material and methods From 01.2011 to 12.2014, 33 patients (pts) presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid) and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results Median age was 56.4 years (27-79). Clinical stages were: T2b = 23 pts (69.7%), T3a = 1 pt (3%), T3b = 6 pts (18.2%), and T4a = 3 pts (9.1%). Median HDRB prescribed dose was 21 Gy (21-27). Median CTVCT (16 pts) and HR-CTVMRI (17 pts) were 52.6 cc (28.5-74.3), 31.9 cc (17.1-58), respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5), 84.8 Gy (80.6-91.4), respectively. Median EQD2αβ3 (CT/MRI) for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9), 64.4 Gy (51.9-77.4), and 60.4 Gy (50.9-81.1), respectively. Median follow-up was 14 months (ranged 6-51). Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pts, G3 infection = 2 pts), and 27% (G1 diarrhea = 9 pts), respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion); no bleeding was

  8. Advanced Cancer Genomics Institute: Genetic Signatures and Therapeutic Targets in Cancer Progression

    DTIC Science & Technology

    2015-04-01

    Covaris E210: DNA shearer used to produce next-gen libraries v) Caliper Sciclone: liquid handling robotic station vi) Autoloader-2: robotic platform...the NGS capabilities funded through the NFGC/TATRC mechanism have been published: 1. Hennon MW, Yendamuri S. Advances in lung cancer surgery . J

  9. Do We Know What Causes Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... We Know What Causes Gastrointestinal Carcinoid Tumors? Can Gastrointestinal Carcinoid Tumors Be Prevented? Back To Top Imagine a world free from cancer. Help make it a reality. DONATE Cancer Information ...

  10. Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Musio, Daniela; Izzo, Luciano; Pugliese, Federico; Izzo, Paolo; Bolognese, Antonio

    2013-01-01

    Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered. PMID:24392453

  11. Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings

    PubMed Central

    Hodges, Kyle; Kennedy, Lindsey; Meng, Fanyin; Alpini, Gianfranco; Francis, Heather

    2012-01-01

    Paul Ehrlich, a German scientist, discovered what is known as the mast cell in the late 1800’s, which has proven to be an important player in the immune system of vertebrates. Mast cells are ubiquitous throughout the tissues of the human body and play numerous roles, both beneficial and destructive. We know they are important in our army of immunity warrior cells, which defend us against viruses, bacteria and parasitic invaders. They are also very well known for the havoc they wreak, causing uncomfortable symptoms due to their release of histamine and other mediators which cause the all too familiar itching, sneezing, urticaria and rhinorrhea of allergic responses. Mast cell activities are diverse and include painful inflammatory reactions in autoimmune conditions such as rheumatoid arthritis. In the gastrointestinal system, mast cells are implicated in diverse actions such as increased gastric acid secretion, polyp formation and uncomfortable conditions such as Irritable Bowel Syndrome. The role of immunology and mast cells in these areas is intriguing but less well understood than their role in allergic responses. Because mast cells have been implicated in both physiologic as well as pathogenic processes, they have been the subjects of avid study. Review of the current literature on mast cell biology reveals that there are many studies of their presence within the tumor microenvironment and evidence, which supports mast cell influence on tumor angiogenesis, tumor invasion, and immune suppression. The studies reviewed in this article concentrate largely on mast cells in human GI malignancies. This review also provides background information regarding mast cells, such as their origination, their location within the body, how they are activated and how they function as mediators. PMID:22943044

  12. Pharmacokinetics of rac-leucovorin vs [S]-leucovorin in patients with advanced gastrointestinal cancer.

    PubMed Central

    Mader, R M; Steger, G G; Rizovski, B; Sieder, A E; Locker, G; Gnant, M F; Jakesz, R; Rainer, H

    1994-01-01

    1. The pharmacokinetics of [R]-leucovorin ([R]-LV), [S]-leucovorin ([S]-LV) and the circulating metabolite [S]-5-methyltetrahydrofolate ([S]-5-MTHF) were studied after administration of racemic LV and [S]-LV in 21 subjects. 2. After intravenous infusion of 600 mg m-2 rac-LV (group 1, n = 7) or 300 mg m-2 [S]-LV (group 3, n = 7), the decay of [S]-LV in plasma was biexponential with a distribution half-life of 0.8 to 1 h and an elimination half-life of 11 to 23 h. When rac-LV was administered as a 2 h i.v. infusion (400 mg m-2) following a loading dose of 200 mg m-2 (group 2, n = 7), the plasma concentrations of [R]-LV and [S]-5-MTHF decayed monoexponentially with mean (+/- s.d.) half-lives of 10 +/- 3 h and 7 +/- 2 h, respectively. 3. The AUC of [S]-5-MTHF was significantly higher after infusion of 300 mg m-2 [S]-LV than after infusion of 600 mg m-2 rac-LV (83 +/- 22 micrograms ml-1 h vs 53 +/- 22 micrograms ml-1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8198932

  13. Pharmacokinetics of rac-leucovorin vs [S]-leucovorin in patients with advanced gastrointestinal cancer.

    PubMed

    Mader, R M; Steger, G G; Rizovski, B; Sieder, A E; Locker, G; Gnant, M F; Jakesz, R; Rainer, H

    1994-03-01

    1. The pharmacokinetics of [R]-leucovorin ([R]-LV), [S]-leucovorin ([S]-LV) and the circulating metabolite [S]-5-methyltetrahydrofolate ([S]-5-MTHF) were studied after administration of racemic LV and [S]-LV in 21 subjects. 2. After intravenous infusion of 600 mg m-2 rac-LV (group 1, n = 7) or 300 mg m-2 [S]-LV (group 3, n = 7), the decay of [S]-LV in plasma was biexponential with a distribution half-life of 0.8 to 1 h and an elimination half-life of 11 to 23 h. When rac-LV was administered as a 2 h i.v. infusion (400 mg m-2) following a loading dose of 200 mg m-2 (group 2, n = 7), the plasma concentrations of [R]-LV and [S]-5-MTHF decayed monoexponentially with mean (+/- s.d.) half-lives of 10 +/- 3 h and 7 +/- 2 h, respectively. 3. The AUC of [S]-5-MTHF was significantly higher after infusion of 300 mg m-2 [S]-LV than after infusion of 600 mg m-2 rac-LV (83 +/- 22 micrograms ml-1 h vs 53 +/- 22 micrograms ml-1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Gastrointestinal radiation injury: Symptoms, risk factors and mechanisms

    PubMed Central

    Shadad, Abobakr K; Sullivan, Frank J; Martin, Joseph D; Egan, Laurence J

    2013-01-01

    Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer. Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality. Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy, which significantly reduces their quality of life as well as adding an extra burden to the cost of health care. The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology. Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury, relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity. The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms, to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury. PMID:23345941

  15. Locally advanced prostate cancer: current controversies and optimisation opportunities.

    PubMed

    Sridharan, S; Dal Pra, A; Catton, C; Bristow, R G; Warde, P

    2013-08-01

    Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

  16. [Satisfaction with immunotherapy in patients with advanced cancer].

    PubMed

    Moriyama, Yoshiaki; Fujisawa, Fumika; Kotani, Junko; Ohnishi, Masayuki; Watanabe, Toru

    2015-04-01

    Patient satisfaction with cancer immunotherapy, which is not covered by health insurance in Japan, was evaluated among 65 patients with advanced cancer who had received immunotherapy in our hospital for 2 years. Satisfaction measures were based on patients' expectations for medical care, cost, and staff services, and involved a questionnaire consisting of 25 items. Results of the questionnaire analysis showed that most patients, who expected much of antigen-specific vaccination such as dendritic cells (DC) pulsed tumor-associated antigens, were dissatisfied with the high cost of private immunotherapy(i. e., not covered by medical insurance), and were unable to perceive the effectiveness of the treatment because there was no quantitative analysis of killer T cells induced by immunotherapy. Therefore, it is critically important for us to confirm the safety and efficiency of cancer immunotherapy, before introducing medical insurance for cancer patients in Japan. In addition, the quantitative measurement of killer T cells induced by DC peptide vaccines should be considered, to meet patients' expectations.

  17. Locally advanced rectal cancer: the importance of a multidisciplinary approach.

    PubMed

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-12-14

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

  18. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Mahadevan, Anand; Jain, Sanjay; Goldstein, Michael; Miksad, Rebecca; Pleskow, Douglas; Sawhney, Mandeep; Brennan, Darren M.D.; Callery, Mark; Vollmer, Charles

    2010-11-01

    Purpose: Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. Patients and Methods: A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with {>=}12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. Results: With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. Conclusion: Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

  19. Preclinical activity of MBM-5 in gastrointestinal cancer by inhibiting NEK2 kinase activity

    PubMed Central

    Zhu, Mengli; Zhu, Tong; Jiang, Tongtong; Frett, Brendan; Hu, Wenhao; Li, Hong-yu; Ma, Mingliang; Zhang, Xiongwen

    2016-01-01

    NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner. This inhibition impeded mitotic progression by inducing chromosome segregation defects and cytokinesis failure; therefore leading to accumulation of cells with ≥4N DNA content, which finally underwent apoptosis. More importantly, MBM-5 treatment effectively suppressed the tumor growth of human gastric and colorectal cancer cells xenografts. Taken together, we demonstrated that MBM-5 effectively inhibited the kinase activity of NEK2 and showed a potential application in anti-cancer treatment regimens. PMID:27764815

  20. Detection of gastrointestinal cancer by elastic scattering and absorption spectroscopies with the Los Alamos Optical Biopsy System

    SciTech Connect

    Mourant, J.R.; Boyer, J.; Johnson, T.M.; Lacey, J.; Bigio, I.J.; Bohorfoush, A.; Mellow, M.

    1995-03-01

    The Los Alamos National Laboratory has continued the development of the Optical Biopsy System (OBS) for noninvasive, real-time in situ diagnosis of tissue pathologies. In proceedings of earlier SPIE conferences we reported on clinical measurements in the bladder, and we report here on recent results of clinical tests in the gastrointestinal tract. With the OBS, tissue pathologies are detected/diagnosed using spectral measurements of the elastic optical transport properties (scattering and absorption) of the tissue over a wide range of wavelengths. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, exhibit significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes m an optical signature that is derived from the wavelength-dependence of elastic scattering. Additionally, the optical geometry of the OBS beneficially enhances its sensitivity for measuring absorption bands. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope or catheter, or to direct surface examination, as well as interstitial needle insertion. Data acquistion/display time is <1 second.

  1. Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists.

    PubMed

    Kirsch, Richard; Messenger, David E; Riddell, Robert H; Pollett, Aaron; Cook, Megan; Al-Haddad, Sahar; Streutker, Catherine J; Divaris, Dimitrios X; Pandit, Rajani; Newell, Ken J; Liu, Jimin; Price, Russell G; Smith, Sharyn; Parfitt, Jeremy R; Driman, David K

    2013-02-01

    Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection. Forty hematoxylin and eosin (H&E)-stained slides were circulated to 6 GI and 6 non-GI pathologists who independently assessed the VI status as positive, negative, or equivocal. Six weeks later, 40 corresponding Movat-stained slides were recirculated together with the original H&E slides and reassessed for VI status. Detection of VI was >2-fold higher with a Movat stain compared with an H&E stain alone (46.4% vs. 19.6%, P=0.001). GI pathologists detected VI more frequently than non-GI pathologists on both H&E (30.0% vs. 9.2%, P=0.029) and Movat (58.3% vs. 34.6%, P=0.018) stains. There was higher interobserver agreement in the case of a Movat stain, particularly for extramural VI (H&E: κ=0.23 vs. Movat: κ=0.41). A poststudy survey indicated that GI pathologists and non-GI pathologists applied similar diagnostic criteria but that GI pathologists more frequently applied "orphan arteriole" and "protruding tongue" signs as diagnostic clues to VI. This study confirms that VI is underdetected on H&E and highlights the role of elastin staining in improving VI detection and interobserver agreement. Strategies to improve VI detection are warranted.

  2. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

    2012-07-15

    Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

  3. An integrated psychological strategy for advanced colorectal cancer patients

    PubMed Central

    Pugliese, Patrizia; Perrone, Maria; Nisi, Enrica; Garufi, Carlo; Giannarelli, Diana; Bottomley, Andrew; Terzoli, Edmondo

    2006-01-01

    Background There is evidence regarding the usefulness of psychosocial intervention to improve health related quality of life (HRQOL) in adult cancer patients. The aim of this report is to describe an integrated approach and to evaluate its feasibility in routine clinical practice in 98 advanced colorectal cancer (ACC) patients during chronomodulated chemotherapy. Methods A prospective non-randomised design was developed and applied in a cancer out-patient setting. The intervention consisted of an integrated approach, whereby the psycho-oncologist had an active role in the health care team with the physician and routinely included psychological understanding in the medical treatment program. The psychological evaluation assessed: a) adaptation, awareness, psychopathological disorders through a psychodynamic interview; b) anxiety and depression using the HAD scale; c) subjective perception of care quality through a structured interview and d) HRQOL evaluation assessment with the EORTC QLQ C30. Outcomes data were collected before and after 18 weeks of chemotherapy. Results After 18 weeks of chemotherapy a significant improvement of adaptation and awareness was observed. The HADs results showed a significant decrease in anxiety when compared to pre-treatment. The structured interview showed a significant increase of patients who positively experienced the impact of medical treatment on HRQOL, anxiety, depression, interpersonal relationships, free-time and who positively experienced the care quality. Indeed, a majority of patients positively experienced the team relationship modality during the whole treatment. All scales on the EORTC questionnaire remained unchanged during the entire treatment. Conclusion Our results suggest that it is feasible to carry out an integrated approach during chemotherapy. These results seem to support the integrated approach as a tool in aiding advanced colorectal cancer patients' ability to cope with their diagnosis and treatment although

  4. [Locally advanced prostate cancer: definition, prognosis and treatment].

    PubMed

    Plantade, Anne; Massard, Christophe; de Crevoisier, Renaud; Fizazi, Karim

    2007-07-01

    According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still

  5. [Audit: medical record documentation among advanced cancer patients].

    PubMed

    Perceau, Elise; Chirac, Anne; Rhondali, Wadih; Ruer, Murielle; Chabloz, Claire; Filbet, Marilène

    2014-02-01

    Medical record documentation of cancer inpatients is a core component of continuity of care. The main goal of the study was an assessment of medical record documentation in a palliative care unit (PCU) using a targeted clinical audit based on deceased inpatients' charts. Stage 1 (2010): a clinical audit of medical record documentation assessed by a list of items (diagnosis, prognosis, treatment, power of attorney directive, advance directives). Stage 2 (2011): corrective measures. Stage 3 (2012): re-assessment with the same items' list after six month. Forty cases were investigated during stage 1 and 3. After the corrective measures, inpatient's medical record documentation was significantly improved, including for diagnosis (P = 0.01), diseases extension and treatment (P < 0.001). Our results highlighted the persistence of a weak rate of medical record documentation for advanced directives (P = 0.145).

  6. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy

    PubMed Central

    Yang, Hu

    2015-01-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. PMID:26706410

  7. Cancer-related Fatigue in Patients with Advanced Cancer Treated with Autonomic Nerve Pharmacopuncture.

    PubMed

    Park, Ji-hye; Jeon, Hyung-jun; Kang, Hwi-joong; Jeong, In-Sook; Cho, Chong-kwan; Yoo, Hwa-seung

    2015-06-01

    The purpose of this study was to observe the effects of autonomic nerve pharmacopuncture (ANP) treatment on cancer-related fatigue (CRF) in patients with advanced cancer. This observational case study was conducted at the East West Cancer Center of Daejeon University's Dunsan Korean Medical Hospital. Two patients were observed. One patient was diagnosed with left thymic cancer metastatic to the left pleura. The other patient had terminal-stage cervical cancer with iliac bone and lumbar 5 metastases. We injected mountain ginseng pharmacopuncture (MGP) into acupoints alongside the spine (Hua-Tuo-Jia-Ji-Xue, EX B2). We examined the patients for CRF using the Korean version of the Revised Piper Fatigue Scale (RPFS-K), which is a self-assessment tool. The scores on the RPFS-K for both patients tended to decrease during the treatment. Laboratory findings, including hematological changes, were also checked. Liver and renal function tests showed that the treatment was safe. Although further large-population studies are necessary, this case study suggests that ANP has a favorable effect on CRF in patients with advanced cancer.

  8. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  9. Biophotonic endoscopy: a review of clinical research techniques for optical imaging and sensing of early gastrointestinal cancer

    PubMed Central

    Coda, Sergio; Siersema, Peter D.; Stamp, Gordon W. H.; Thillainayagam, Andrew V.

    2015-01-01

    Detection, characterization, and staging constitute the fundamental elements in the endoscopic diagnosis of gastrointestinal diseases, but histology still remains the diagnostic gold standard. New developments in endoscopic techniques may challenge histopathology in the near future. An ideal endoscopic technique should combine a wide-field, “red flag” screening technique with an optical contrast or microscopy method for characterization and staging, all simultaneously available during the procedure. In theory, biophotonic advances have the potential to unite these elements to allow in vivo “optical biopsy.” These techniques may ultimately offer the potential to increase the rates of detection of high risk lesions and the ability to target biopsies and resections, and so reduce the need for biopsy, costs, and uncertainty for patients. However, their utility and sensitivity in clinical practice must be evaluated against those of conventional histopathology. This review describes some of the most recent applications of biophotonics in endoscopic optical imaging and metrology, along with their fundamental principles and the clinical experience that has been acquired in their deployment as tools for the endoscopist. Particular emphasis has been placed on translational label-free optical techniques, such as fluorescence spectroscopy, fluorescence lifetime imaging microscopy (FLIM), two-photon and multi-photon microscopy, second harmonic generation (SHG) and third harmonic generation (THG) imaging, optical coherence tomography (OCT), diffuse reflectance, Raman spectroscopy, and molecular imaging. PMID:26528489

  10. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  11. Endoscopic Ultrasound-Guided Drainage of Intra-Abdominal Abscess after Gastric Perforation in a Patient Receiving Ramucirumab and Paclitaxel for Advanced Gastric Cancer.

    PubMed

    Mandai, Koichiro; Shirakawa, Atsushi; Uno, Koji; Yasuda, Kenjiro

    2017-01-01

    Gastrointestinal perforation is a serious adverse event that occurs in approximately 1% of patients receiving ramucirumab and paclitaxel. A 67-year-old man with unresectable advanced gastric cancer was admitted to our hospital and treated with ramucirumab and paclitaxel. Gastric perforation occurred during the second cycle of chemotherapy. Although the patient's condition improved without surgery, an abscess developed in the intra-abdominal fluid collection resulting from the perforation. We performed endoscopic ultrasound-guided abscess drainage. The patient improved and was discharged in satisfactory condition. Endoscopic ultrasound-guided drainage is a treatment option for patients with intra-abdominal abscess following gastric perforation due to ramucirumab.

  12. Endoscopic Ultrasound-Guided Drainage of Intra-Abdominal Abscess after Gastric Perforation in a Patient Receiving Ramucirumab and Paclitaxel for Advanced Gastric Cancer

    PubMed Central

    Mandai, Koichiro; Shirakawa, Atsushi; Uno, Koji; Yasuda, Kenjiro

    2017-01-01

    Gastrointestinal perforation is a serious adverse event that occurs in approximately 1% of patients receiving ramucirumab and paclitaxel. A 67-year-old man with unresectable advanced gastric cancer was admitted to our hospital and treated with ramucirumab and paclitaxel. Gastric perforation occurred during the second cycle of chemotherapy. Although the patient's condition improved without surgery, an abscess developed in the intra-abdominal fluid collection resulting from the perforation. We performed endoscopic ultrasound-guided abscess drainage. The patient improved and was discharged in satisfactory condition. Endoscopic ultrasound-guided drainage is a treatment option for patients with intra-abdominal abscess following gastric perforation due to ramucirumab. PMID:28203161

  13. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    PubMed Central

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  14. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

    DTIC Science & Technology

    2014-04-01

    Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer PRINCIPAL INVESTIGATOR: Thomas S. Griffith, Ph.D. CONTRACTING ORGANIZATION...CONTRACT NUMBER Immunotherapy for Advanced Breast Cancer 5b. GRANT NUMBER W81XWH-11-1-0271 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Thomas...increased risk of developing cancers , including breast cancer . The reasons for this are likely complex and multi- factorial, but a state of generalized

  15. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

    2007-01-01

    A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries

  16. Locally advanced rectal cancer: time for precision therapeutics.

    PubMed

    Weiser, Martin R; Zhang, Zhen; Schrag, Deborah

    2015-01-01

    The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

  17. [Vital prognosis in advanced cancer patients: a systematic literature review].

    PubMed

    Tavares, Teresa; Gonçalves, Edna

    2013-01-01

    Prognostication is a critical medical task for the adequacy of treatment and management of priorities and expectations of patients and families. In 2005, the European Association of Palliative Care (EAPC) published recommendations on the formulation of vital prognosis in advanced cancer patients. The aim of this study is to analyze the literature subsequent to this review and to update the presented recommendations. Using the same strategy of the EAPC group, we performed a systematic literature search in the electronic databases PubMed and Scopus, which included original studies in adults with advanced cancer, without tumor-directed treatment, with a median survival of less than 90 days. The articles were analyzed and classified according to the level of evidence by two independent reviewers. The 41 articles analyzed allowed to keep grade A recommendations for clinical estimation of survival and Palliative Prognostic score and now also for Palliative Prognostic Index, performance status, dyspnea, lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C-reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as predictors reached grade B. To formulate the vital prognosis and to communicate it properly to the patient and family are core competencies of physicians, particularly of those who deal with end of life patients. The clinical impression combined with scientific evidence allows us to estimate more accurately the survival, allowing prioritizing and managing more appropriately the existing resources.

  18. Therapeutic implication of HER2 in advanced biliary tract cancer

    PubMed Central

    Cha, Yongjun; Ha, Hyerim; Park, Ji Eun; Bang, Ju-Hee; Jin, Mei Hua; Lee, Kyung-Hun; Kim, Tae-Yong; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue

    2016-01-01

    Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. PMID:27517322

  19. Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

    SciTech Connect

    Valdagni, Riccardo; Rancati, Tiziana Fiorino, Claudio; Fellin, Gianni; Magli, Alessandro; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Greco, Carlo; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Vavassori, Vittorio

    2008-07-15

    Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the

  20. Genetic variation in C20orf54, PLCE1 and MUC1 and the risk of upper gastrointestinal cancers in Caucasian populations.

    PubMed

    Palmer, Andrew J; Lochhead, Paul; Hold, Georgina L; Rabkin, Charles S; Chow, Wong-Ho; Lissowska, Jolanta; Vaughan, Thomas L; Berry, Susan; Gammon, Marilie; Risch, Harvey; El-Omar, Emad M

    2012-11-01

    Recently, two large genome-wide association studies, conducted in Chinese populations, have reported associations between upper gastrointestinal cancer and the rs2274223, rs13042395 and rs4072037 polymorphisms in PLCE1, C20orf54 and MUC1, respectively. We aimed to determine whether similar associations existed for Caucasian populations. We genotyped two population-based, case-control studies of upper gastrointestinal cancer; the first study included 290 gastric cancer (GC) cases and 376 controls and the second study included 306 GC cases, 107 oesophageal adenocarcinoma cancer cases, 52 oesphageal squamous cell cancer cases and 211 controls. Odds ratios (OR) and 95% confidence intervals (CIs) were computed from logistic models and adjusted for confounding variables. The rs4072037 polymorphism in MUC1 was associated with a reduced risk of GC of intestinal histological type (OR 0.4; 95% CI 0.2-0.9) and a reduced risk of oesophageal squamous cell cancer (OR 0.5; 95% CI 0.2-1.0), but not oesphageal adenocarcinoma. Similarly, rs2274223 in PLCE1 was associated with a reduced risk of oesophageal squamous cell cancer (OR 0.5; 95% CI 0.3-1.0), but not oesphageal adenocarcinoma. We observed no association between rs13042395 in Corf54 and the risk of gastric or oesphageal cancer in either of the two studies. Our findings for rs4072037 and the risk of GC are in agreement with one previous report for a Caucasian population. To the best of our knowledge, this is the first study to report an association between rs2274223 and rs4072037 and the risk of oesophageal squamous cell carcinoma in a Caucasian population.

  1. Operative management of locally advanced, differentiated thyroid cancer

    PubMed Central

    Wang, Laura Y.; Nixon, Iain J.; Patel, Snehal G.; Palmer, Frank L.; Tuttle, R. Michael; Shaha, Ashok; Shah, Jatin P.; Ganly, Ian

    2016-01-01

    Background The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome. Methods We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis. Results The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11–91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival

  2. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.

    PubMed

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-05-27

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases.

  3. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

    PubMed Central

    2013-01-01

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases. PMID:23711194

  4. [A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer].

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Nakano, Mae; Ichikawa, Hiroshi; Hanyu, Takaaki; Nakano, Masato; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kosugi, Shinichi; Minagawa, Masahiro; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

  5. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  6. Urgent cancer referral guidelines: a retrospective cohort study of referrals for upper gastrointestinal adenocarcinoma.

    PubMed

    Panter, Simon J; Bramble, Mike G; O'Flanagan, Hilda; Hungin, A Pali S

    2004-08-01

    Dyspepsia in primary care is common and guidelines indicate that patients with alarm symptoms, as defined by the urgent cancer referral guidelines, should be investigated by gastroscopy. The specificity and sensitivity of alarm symptoms is poor and only a small percentage of patients will turn out to have malignant disease. This primary care study shows that employing current guidelines will identify only 72% of patients at their initial visit to a general practitioner, but this figure could be increased to 86% if the guidelines included patients with weight loss or anaemia in the absence of dyspepsia. Past performance indicates that the majority of patients with the commonest symptom complex were not referred quickly and less than half were seen within 4 weeks.

  7. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  8. Endoscopic Placement of Metal Stents in Treating Patients With Cancer- Related Duodenal Obstruction

    ClinicalTrials.gov

    2012-05-31

    Colorectal Cancer; Constipation, Impaction, and Bowel Obstruction; Extrahepatic Bile Duct Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Pancreatic Cancer; Quality of Life; Small Intestine Cancer

  9. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    PubMed

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  10. [Contemporary methods of treatment in local advanced prostate cancer].

    PubMed

    Brzozowska, Anna; Mazurkiewicz, Maria; Starosławska, Elzbieta; Stasiewicz, Dominika; Mocarska, Agnieszka; Burdan, Franciszek

    2012-10-01

    The prostate cancer is one of the most often cancers amongst males. Its frequency is increasing with age. Thanks to widespread of screening denomination of specific prostate specific antigen (PSA), ultrasonography including the one in transrectal (TRUS), computed tomography, magnetic resonance and especially the awareness of society, the number of patients with low local advance of illness is increasing. The basic method of treatment in such cases is still the surgical removal of prostate with seminal bladder or radiotherapy. To this purpose tele-(IMRT, VMAT) or brachytherapy (J125, Ir192, Pa103) is used. In patients with higher risk of progression the radiotherapy may be associated with hormonotherapy (total androgen blockage-LH-RH analog and androgen). Despite numerous clinical researches conducted there is still no selection of optimal sequence of particular methods. Moreover, no explicit effectiveness was determined. The general rule of treatment in patients suffering from prostate cancer still remains individual selection of therapeutic treatment depending on the age of a patient, general condition and especially patient's general preferences. In case of elderly patients and patients with low risk of progression, recommendation of direct observation including systematical PSA denomination, clinical transrectal examination, TRUS, MR of smaller pelvis or scintigraphy of the whole skeleton may be considered.

  11. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  12. Outcomes of temporal bone resection for locally advanced parotid cancer.

    PubMed

    Mehra, Saral; Morris, Luc G; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H

    2011-11-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death.

  13. Outcomes of Temporal Bone Resection for Locally Advanced Parotid Cancer

    PubMed Central

    Mehra, Saral; Morris, Luc G.; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H.

    2011-01-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death. PMID:22547966

  14. Assessing needs of family members of inpatients with advanced cancer.

    PubMed

    Bužgová, R; Špatenková, N; Fukasová-Hajnová, E; Feltl, D

    2016-07-01

    To provide high-quality and effective cancer care, problems and unmet needs of family members during their relatives' hospitalisation have to be identified as well. The aims were to determine how needs of family members of patients with terminal cancer are met and to analyse factors that influence them. The needs were assessed with the Family Inventory of Needs. Each item (n = 20) represents one need of family members, for which the importance and satisfaction are rated. The study comprised 270 family members of hospitalised advanced cancer patients staying in the University Hospital Ostrava who were receiving palliative care. The family members preferred sufficient basic information and patient comfort. The unmet needs were support of hope (73%) and provision of information (65%). The unmet needs were more frequently identified by women, individuals with lower education, younger persons, unemployed, patients' children and family members of patients with generally unfavourable health status (P < 0.05). There was a correlation between lower quality of life and higher numbers of unmet needs. Targeted interventions aimed at meeting important needs of the family members may improve their quality of life.

  15. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    SciTech Connect

    Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May; Littell, Ramey; Cunha, J. Adam M.; Sethi, Rajni A.; Chan, John K.; Hsu, I-Chow

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  16. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    NASA Astrophysics Data System (ADS)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  17. Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients.

    PubMed

    Mateen, Farrah; Jatoi, Aminah

    2006-10-01

    Anorexia, or loss of appetite, is a troubling symptom for many patients with advanced cancer. The early observation that breast cancer patients, who were prescribed megestrol acetate as a cancer treatment, went on to increase their appetite and gain weight has given rise to a large number of clinical trials that have tested this progestational drug as a palliative agent for the cancer anorexia/weight loss syndrome. This review focuses on these trials, summarizing their findings and providing a practical approach for prescribing megestrol acetate to advanced cancer patients who suffer from the cancer anorexia/weight loss syndrome.

  18. The holistic management of consequences of cancer treatment by a gastrointestinal and nutrition team: a financially viable approach to an enormous problem?

    PubMed

    Muls, Ann C; Lalji, Amyn; Marshall, Christopher; Butler, Lewis; Shaw, Clare; Vyoral, Susan; Mohammed, Kabir; Andreyev, H Jervoise N

    2016-06-01

    There is no national NHS tariff to fund services for patients experiencing long-term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation-induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at £1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff.

  19. Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

    PubMed Central

    Kobayashi, Mitsuyoshi; Mori, Hirohito; Ebara, Kazuo

    2014-01-01

    We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2) and paclitaxel (60 mg/m2). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer. PMID:25298899

  20. [A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine, Cisplatin, and Trastuzumab].

    PubMed

    Oneda, Yasuo; Tamura, Shigeyuki; Murakami, Kouhei; Takeno, Atsushi; Kuwahara, Ryuichi; Akiyama, Yasuki; Sakamoto, Takuya; Inatome, Junichi; Naito, Atushi; Katsura, Yoshiteru; Ohmura, Yoshiaki; Kagawa, Yoshinori; Egawa, Chiyomi; Takeda, Yutaka; Kato, Takeshi

    2016-11-01

    A 70-year-old-man, whose chief complaint was epigastric pain, was referred to our hospital and diagnosed with advanced gastric cancer with multiple liver metastases.