AI Article Synopsis

  • Obesity increases the risk of pancreatic cancer, and calorie restriction (CR) can prevent this by lowering IGF-1 levels and reducing cancerous lesion formation.
  • In a study, a 30% CR diet for 14 weeks in transgenic mice showed decreased pancreatic lesions and lower levels of cancer markers compared to a control diet.
  • Additionally, reducing IGF-1 through CR or genetic modification led to smaller pancreatic tumors, indicating that targeting IGF-1 could be an effective strategy for preventing pancreatic cancer.

Article Abstract

Risk of pancreatic cancer, the fourth deadliest cancer in the United States, is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of IGF-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 levels and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing COX-2 [bovine keratin-5 promoter (BK5.COX-2)]. These findings in CR mice correlated with reductions in Ki-67-positive cells, vascular luminal size, VEGF expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101 cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1-deficient (LID) mice. The approximate 65% reduction of serum IGF-1 levels in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131443PMC
http://dx.doi.org/10.1158/1940-6207.CAPR-11-0027DOI Listing

Publication Analysis

Top Keywords

pancreatic cancer
12
calorie restriction
8
levels igf-1
8
serum igf-1
8
igf-1 levels
8
control diet
8
jc101 cells
8
lid mice
8
pancreatic
7
igf-1
7

Similar Publications

Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation.

View Article and Find Full Text PDF

Denosumab, an anti-RANKL antibody, induces bone metabolism to a low-turnover bone status by arresting osteoclast activity. Frequent adverse events include infusion reactions, fever and hypocalcaemia but not hypophosphataemia. We report a case of severe hypophosphataemia associated with secondary hyperparathyroidism following denosumab administration in a young boy with recurrent osteosarcoma who was successfully treated with evocalcet.

View Article and Find Full Text PDF

A girl in early adolescence presented with complaints of abdominal pain lasting for 4 months, along with a palpable lump in the epigastric region. A CT scan revealed a large solid-cystic mass lesion measuring 9.5×10.

View Article and Find Full Text PDF

Background/aims: Pathological evaluation is crucial for diagnosing biliary lesions and determining appropriate treatment strategies. However, tissue sampling via the transpapillary route can be difficult. In this study, we aimed to assess the efficacy and safety of a novel tapered-tip sheath system for tissue sampling from biliary strictures.

View Article and Find Full Text PDF

Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021: GI Cancer Mortality and Risk Factors.

Am J Med

January 2025

Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA; BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA. Electronic address:

Objective: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors: smoking, alcohol, and metabolic disturbances.

Methods: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!