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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Publication date: Available online 9 November 2018Source: Cancer GeneticsAuthor(s): Eveline E. Vietsch, Garrett T. Graham, Justine N. McCutcheon, Aamir Javaid, Giuseppe Giaccone, John L. Marshall, Anton WellsteinCancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level withou...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
Publication date: Available online 9 November 2018Source: Cancer GeneticsAuthor(s): Eveline E. Vietsch, Garrett T. Graham, Justine N. McCutcheon, Aamir Javaid, Giuseppe Giaccone, John L. Marshall, Anton WellsteinCancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level withou...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
CONCLUSION: In Burkina Faso rural area, primary digestive cancers occur in young patients with no predominance of sex. Colorectal cancer remains the most common. PMID: 30392708 [PubMed - as supplied by publisher]
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Oncogenic Kras are genetic dependencies for the majority of pancreatic and colorectal adenocarcinomas; however, much remains to be understood regarding its tropism to these carcinomas. Recently developed organoid technology presents a more representative model culture system for pancreatic and colon epithelial tissues as well as better fostering the culture of nonimmortalized cells than two-dimensional culture. These advantages enable cancer researchers to directly compare tumor and normal tissue models to better study tumor initiation as well as therapeutic efficacy. Although in vivo models better model the complexity of ...
Source: Cold Spring Harbor perspectives in medicine - Category: Research Authors: Tags: Ras and Cancer in the 21st Century TECHNIQUE Source Type: research
Conclusion: Radiolabeled FAPIs allow fast imaging with very high contrast in tumors having a high stromal content and may therefore serve as pantumor agents. Coupling of these molecules to DOTA or other chelators allows labeling not only with 68Ga but also with therapeutic isotopes such as 177Lu or 90Y.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Translational Source Type: research
ConclusionsThe synchronous sigmoid colon cancer and pancreatic cystic incidentaloma is a rare presentation, which, to the best of our knowledge, has not been reported in the literature. We report the surgical management of this case and present a review of the literature. Genetic studies may be conducted to find out whether there is common genetic mutation resulting in these two malignancies, and may be helpful in screening programs.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
Mutations or other alterations in theRET gene have been implicated in a variety of malignancies – most commonly thyroid, but also chronic myelomonocytic leukemia, acute myeloid leukemia, and lung, breast, pancreatic, and colon cancers. Here we present a case of a gentlemen initially diagnosed with and treated for non-small cell lung adenocarcinoma. Genomic profiling of his tumor specimen rev ealed aRET point mutation with a known association with medullary thyroid cancer (MTC). Further pathological and molecular diagnostic evaluation confirmed a diagnosis of MTC, leading to a change in treatment from standard chemoth...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
AbstractA promising approach capitalizing on the specific and highly sensitive characteristics of the body ’s own immune system is demonstrated in the context of revealing pancreatic ductal adenocarcinoma cancer (PDAC). IgA from a local biofluid called gastrointestinal lavage fluid (GLF) is used to investigate glycan reactivity to show the potential of this approach. IgA antibody responses, just as wit h IgG, result in amplification of a small signal which aids in detecting changes from a healthy state. IgA from GLF was screened against glycan arrays containing 609 glycan structures to investigate differential bindin...
Source: Glycoconjugate Journal - Category: Biochemistry Source Type: research
Objectives The link between inflammation and carcinogenesis is irrefutable. Trying to pinpoint key factors at play, cancer research has found interest in Toll-like receptors (TLRs), through which pathological molecular patterns trigger immune cell response. TLRs appear to show prognostic value in adenocarcinomas of the mouth, colon and ovaries. We set out to investigate whether the expression of Toll-like receptors 1, 3, 5, 7 and 9 could be used for prognostic evaluation in pancreatic ductal adenocarcinoma (PDAC) patients.
Source: Pancreatology - Category: Gastroenterology Authors: Tags: 5. Pancreatic Cancer II Source Type: research
The objectives of this first-in-human study were to evaluate the safety, biodistribution and dosimetry of this αvβ6-directed imaging probe. Methods: [18F]αvβ6-BP was prepared per current good manufacturing practice (cGMP) under the guidelines of USP Chapter using N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) and the product was formulated in saline/ethanol (
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: First-in-Human & amp; New Human Applications Source Type: research
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