Patrice Berthezene

Bio: Patrice Berthezene is an academic researcher from French Institute of Health and Medical Research. The author has contributed to research in topics: Calcium oxalate & Pancreatic disease. The author has an hindex of 24, co-authored 41 publications receiving 2236 citations. Previous affiliations of Patrice Berthezene include Necker-Enfants Malades Hospital.

Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma

Abstract: Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the "glycolytic" switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.

Case‐control study on colorectal cancer and diet in marseilles

Abstract: A case-control study of cancer of the colon and rectum was conducted in the Marseilles region of southern France. Cases (399) and a corresponding number of controls, matched for age and sex, were included, the controls being selected from patients undergoing functional re-education for injuries or trauma which reduced their mobility. A dietary history questionnaire was used to determine the usual eating habits during the year preceding diagnosis for cases, or preceding interview for controls. The cases reported lower consumption of vegetables and oil than controls, but no differences were seen in the consumption of meat, bread, eggs or butter. The intake of several nutrients, particularly vitamins B2, B6, C, potassium, iron, magnesium and vegetable fibre, was lower among cases. However, when all these nutrients were analysed jointly and adjusted one for the other, only potassium retained a significant effect. This may be due to the high degree of colinearity between the estimated intake of many nutrients. No association was seen with fat or fibres from cereals.

Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions.

Abstract: Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.

Colorectal polyps and diet: a case-control study in Marseilles.

Abstract: This study investigates the differences in usual past diet between 252 subjects with newly diagnosed adenomatous or villous polyps of the colon and rectum and a group of 238 hospital controls. Cases and controls were interviewed in hospital by 3 nutritionists using a dietary history questionnaire focused on the diet during the preceding year. Nutrient intake was estimated by means of ad hoc food tables adapted from French and British tables. Out of 16 food groups considered in the analyses, the cases reported lower consumption of oil and potatoes and higher consumption of sugar added to food and drink. Among nutrients, we found that cases had a lower consumption of carbohydrates (not taking into account added sugar), potassium, magnesium and vitamin B6. We found a slightly lower intake of fibre and a slightly higher intake of saturated fat among cases, though neither was statistically significant. Intake values for fibre and for carbohydrates were highly intercorrelated and, due to measurement errors, the effect of one may be masked by the other and vice versa. The hypothesis that some components of carbohydrates (starches, fibre and natural sugars but not added sugar) play a protective role in relation to the biology of tumours of the intestinal tract is considered in further multivariate analyses and in the "Discussion".

Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly.

Abstract: Pancreatic exocrine secretion was estimated in 180 normal control patients, free of abdominal and pancreatic disease, aged from 16 to 83 years. Duodenal juice was collected in two 15-min fractions aft

Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence

Abstract: Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods.

Vegetables, Fruit, and Cancer Prevention: A Review

Abstract: In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented. J Am Diet Assoc. 1996; 96:1027-1039.