Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and the diagnosis in early phase is quite difficult. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in PDAC's early diagnosis. In the present study, the animal models were established by embedding 7, 12-dimethylbenzanthracene (DMBA) in pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, ¹H nuclear magnetic resonance(NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. As results, pattern recognition models were successfully established and differential metabolites including glucose, amino acids, carboxylic acids and coenzymes were screened out. Compared with the control, the variation trends of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, indicating to be specific metabolites distinguishing PanIN from PDAC. Our results suggested that the metabonomic strategy of NMR-based techniques combined with multivariate statistical analysis could distinguish the metabolic differences of PanIN, PDAC and normal, demonstrated to be a promising approach in physiopathologic metabolism investigations and early diagnoses of PDAC.

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Identification of anti-cancer chemical compounds using Xenopus embryos

Summary

Cancer tissues have biological characteristics similar to those observed in embryos during development. Many types of cancer cells acquire pro-invasive ability through epithelial-mesenchymal transition (EMT). Similar processes (gastrulation and migration of cranial neural crest cells (CNCCs)) are observed in the early stages of embryonic development in Xenopus during which cells that originate from epithelial sheets through EMT migrate to their final destinations. This study examined Xenopus embryonic tissues to identify anti-cancer compounds that prevent cancer invasion. From the initial test of known anti-cancer drugs, AMD3100 (an inhibitor of CXCR4) and Paclitaxel (a cytoskeletal drug targeting microtubules) effectively prevented migration during gastrulation or CNCCs development. Blind-screening of 100 synthesized chemical compounds was performed, and nine candidates that inhibited migration of these embryonic tissues without embryonic lethality were selected. Of these, C-157 (an analog of podophyllotoxin) and D-572 (which is an indole alkaroid) prevented cancer cell invasion through disruption of interphase microtubules. In addition, these compounds affected progression of mitotic phase and induced apoptosis of SAS oral cancer cells. SAS tumors were reduced in size after intratumoral injection of C-157, and peritoneal dissemination of melanoma cells and intracranial invasion of glioma cells were inhibited by C-157 and D-572. When the other analogues of these chemicals were compared, those with subtle effect on embryos were not tumor suppressive. These results suggest that a novel chemical-screening approach based on Xenopus embryos is an effective method for isolating anti-cancer drugs especially targeting cancer cell invasion and proliferation.

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Awareness of Undergraduate Dental and Medical Students Towards Oral Cancer

Abstract

Oral cancer is a common malignancy in Nepal and many other South East Asian countries, which is predisposed by a variety of potentially malignant oral diseases. Considering the importance of knowledge of health professionals and their role in early diagnosis and reduction of cancer statistics, this study aims to evaluate the awareness of undergraduate dental and medical students towards oral cancer. The study involved undergraduate dental and medical students of BP Koirala Institute of Health Sciences, Nepal. A self-administered questionnaire adapted from Carter to Ogden was distributed. One hundred forty-three dental and 311 medical students responded to the questionnaire. Significantly more dental (80.4 %) than medical students (36.0 %) were found to routinely examine the oral mucosa. Tobacco smoking and chewing were the most commonly recognized risk factors by both medical and dental students. Most of the students found ulcer as the common change associated with oral cancer. Only 30 out of the total students felt very well informed about oral cancer. This study has demonstrated a lack of awareness in some aspects of oral cancer among medical and dental students which highlights the need to frame new teaching methodologies. Similar studies from other health institutions would provide an insight regarding the same and could be a base for formulating a uniform curriculum in the implementation of knowledge regarding oral cancer.

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In Memoriam—Richard F. Bakemeier, MD, MSc

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[Financial stress: A prognostic factor for cancer survival!]

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[Financial stress: A prognostic factor for cancer survival!]

Bull Cancer. 2016 Mar 23;

Authors: Gonçalves A

PMID: 27017058 [PubMed - as supplied by publisher]

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[Prescription of high-cost medicines in French Hospitals: Regulation and procedures of reimbursement].

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[Prescription of high-cost medicines in French Hospitals: Regulation and procedures of reimbursement].

Bull Cancer. 2016 Mar 23;

Authors: Wilkowsky C, Lenain A, Benbekhaled K, Le Gall MJ, Vignot S

Abstract
The high cost of several drugs or medical devices involves specific reimbursement procedures in French hospitals. Specific prescription rules have been developed and a regular survey by regional health authorities is performed. These particular funding procedures allow patients to access to innovative drugs. Some questions have recently been raised in France about the list of cancer drugs that could be concerned by an additional funding by health insurance. In this setting, this article proposes to summarize the current modalities of reimbursement of high-cost medicines in French Hospitals to enlighten the current debate.

PMID: 27017057 [PubMed - as supplied by publisher]

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Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma

Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Alexander Roesch, Annette Paschen, Jenny Landsberg, Iris Helfrich, Jürgen C. Becker, Dirk Schadendorf
Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.



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