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Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.
Source: ScienceNOW - Category: Science Authors: Tags: Medicine, Diseases reports Source Type: news

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More than 150 years ago, German pathologist Rudolf Ludwig Karl Virchow (1821-1901) described the finding of the involvement of the left supraclavicular node in gastric cancer.1 It is now known that a number of abdominal and thoracic malignancies have a propensity to metastasize to this anatomic site, which is commonly referred to as Virchow node. Cancers known to spread to Virchow node include malignancies of the lung, pancreas, and esophagus, and adenocarcinoma of the gastric corpus, kidney, ovary, testicle, stomach, corpus uteri, cervix uteri, colon, and rectum.
Source: Urology - Category: Urology & Nephrology Authors: Tags: History Source Type: research
[ASCO- and ESMO-update 2017 - highlights of the 53. meeting of the American Society of Clinical Oncology/ASCO 2017 and European Society for Medical Oncology/ESMO congress 2017]. Z Gastroenterol. 2018 Apr;56(4):384-397 Authors: Ettrich TJ, Ebert M, Lorenzen S, Moehler M, Vogel A, Witkowski L, Seufferlein T, Reinacher-Schick A Abstract At ASCO 2017, and subsequently the ESMO congress 2017, a number of studies were presented which, in part, may change the present standard of therapy in gastrointestinal oncology. The German FLOT4 trial established perioperative Docetaxel, Oxaliplatin and 5-Fluorourac...
Source: Zeitschrift fur Gastroenterologie - Category: Gastroenterology Authors: Tags: Z Gastroenterol Source Type: research
Background: It has been shown that mutations alone are not the sole determinant of response to targeted agents, for example,BRAF mutations predict response to BRAF inhibitors in melanoma but not colon cancer due to differential EGFR signalling in colon cancer. We aimed to study any context-dependent differences in signalling pathways between pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) withKRAS mutations using a targeted phosphoproteomic approach in cell lines exposed to targeted anticancer drugsex vivo.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Although rare, a sigmoid tumor in a patient with known pancreatic adenocarcinoma must raise the suspicion of metastasis.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
AbstractIncreasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I –II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays...
Source: Virchows Archiv - Category: Pathology Source Type: research
BACKGROUND: Mounting evidence, particularly from prospective epidemiologic studies but with additional support from animal models and mechanistic studies, supported conclusions in 2016 by the International Agency for Research on Cancer (IARC) in their review of the preventive effects of weight control on cancer risk. CONTENT: The workgroup concluded that obesity is causally related to cancer at 13 anatomic sites (esophagus: adenocarcinoma; gastric cardia; colon and rectum; liver; gallbladder; pancreas; breast: postmenopausal; uterine endometrial; ovary; kidney: renal cell; meningioma; thyroid; and multiple myeloma). Furth...
Source: Clinical Chemistry - Category: Chemistry Authors: Tags: Endocrinology and Metabolism Reviews Source Type: research
Abstract Multi-omics high throughput analyses lead to the description of multiple molecular subtypes of pancreatic adenocarcinoma with major prognostic impact for most of them. There is no consensual multilevel integrative classification yet like in colon or breast cancers. Genomic classifications have identified a tumor subtype (15% of the patients) with deficient homologous DNA repair-system leading to increase sensitivity to platinum-based therapies and possibly to PARP inhibitors and immunotherapies. Transcriptomic classifications are still debated but all have identified an aggressive subtype with a very poor...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Ascites is the pathological accumulation of fluid within the abdominal cavity. The most common cancers associated with ascites are adenocarcinomas of the ovary, breast, colon, stomach and pancreas. Symptoms include abdominal distension, nausea, vomiting, early satiety, dyspnea, lower extremity edema, weight gain and reduced mobility. There are many potential causes of ascites in cancer patients, including peritoneal carcinomatosis, malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome and ...
Source: Annals of Saudi Medicine - Category: General Medicine Tags: ISSUE 5 Source Type: research
Authors: Liu L, Yao D, Zhang P, Ding W, Zhang X, Zhang C, Gong S, Zhang Y, Wang J, Sun T, Ren Z Abstract Ubiquitin specific peptidase 9, X-linked (USP9X), a significant regulatory protease in protein ubiquitination, has been proven to act as a proto-oncogene in several types of cancers, such as cervix, colon, breast, brain and lung cancers. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to its high invasive and metastatic abilities. Nevertheless, whether USP9X acts as a proto-oncogene or a tumor-suppressor gene in PDAC is controversial and the mechanism of metastas...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Authors: Burdelski C, Jakani-Karimi N, Jacobsen F, Möller-Koop C, Minner S, Simon R, Sauter G, Steurer S, Clauditz TS, Wilczak W Abstract IMP3 is an RNA binding protein required for ribosomal RNA processing, which has been suggested to be a prognostic marker in a large variety of human types of cancer. However, available data on the prevalence of IMP3 expression are largely discrepant. To systematically investigate the epidemiology and clinical relevance of IMP3 expression in human cancers we employed a two-step tissue microarrays (TMAs) approach. First, a normal tissue TMA and a multi-tumor TMA were analyzed ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
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