scholarly journals Type 2 immunity is maintained during cancer associated adipose tissue wasting

2021 ◽  
Author(s):  
Patrick J Lenehan ◽  
Assunta Cirella ◽  
Amiko M Uchida ◽  
Stephanie J Crowley ◽  
Tatyana Sharova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Metabolic Disorder ◽  
Colorectal Cancers ◽  
Immune Microenvironment ◽  
Gastrointestinal Malignancies ◽  
Regulatory Type

Abstract Cachexia is a systemic metabolic disorder characterized by loss of fat and muscle mass, which disproportionately impacts patients with gastrointestinal malignancies such as pancreatic cancer. While the immunologic shifts contributing to the development of other adipose tissue (AT) pathologies such as obesity have been well described, the immune microenvironment has not been studied in the context of cachexia. Here we assess the immune landscape of visceral AT (VAT) in the setting of pancreatic and colorectal cancers at the transcript, protein, and cellular levels. The cachexia inducing factor IL-6 is strongly elevated in the wasting VAT of cancer bearing mice, but the regulatory type 2 immune landscape which characterizes healthy VAT is maintained. Pathologic skewing toward Th1 and Th17 inflammation is absent. Similarly, the VAT of patients with colorectal cancer is characterized by a Th2 signature with abundant IL-33 and eotaxin-2, albeit also with high levels of IL-6. Our results suggest that wasting AT during the development of cachexia may not undergo drastic changes in immune composition like those seen in obese AT and provide a framework for further analyses of cancer associated cachexia.

scholarly journals Rapid Improvement of the Performance Status and Reduction of the Tumor Size in KRAS-Mutated Colorectal Cancer Patient Receiving Binimetinib, Hydroxychloroquine, and Bevacizumab

2020 ◽  
Vol 13 (2) ◽  
pp. 985-989 ◽  
Author(s):  
Sergey V. Orlov ◽  
Magaripa A. Urtenova ◽  
Maria A. Sviridenko ◽  
Denis V. Nesterov ◽  
Tatiana N. Sokolova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Single Case ◽  
Performance Status ◽  
Colorectal Cancer Patient ◽  
Colorectal Cancers ◽  
Preclinical Studies ◽  
Disease Course ◽  
Rapid Improvement ◽  
Aggressive Disease

Activating RAS mutations occur in more than a half of colorectal cancers (CRCs). RAS-mutated CRCs are notoriously difficult to treat given that they are characterized by the aggressive disease course and the lack of appropriate targeted therapies. Recent preclinical studies demonstrated that RAS-mutated cells escape from therapeutic MEK inhibition by the development of autophagy, and this escape may be prevented by the administration of an antimalarial drug, hydroxychloroquine. The available clinical data are limited to a single case observation involving a patient with KRAS-mutated pancreatic cancer. Here, we report a woman with KRAS G12D-mutated CRC, whose tumor did not respond to conventional therapy. The combination of binimetinib, hydroxychloroquine, and bevacizumab was administered as a last-hope option. The patient experienced rapid improvement of the performance status. The tumor lumps demonstrated 17% reduction in the size within the first 6 weeks of the therapy. This report calls for evaluation of the efficacy of a combination of MEK inhibitors and hydroxychloroquine, possibly with the addition of bevacizumab, in chemotherapy-resistant patients with RAS-mutated cancers.

scholarly journals Universal Screening of Gastrointestinal Malignancies for Mismatch Repair Deficiency at Stanford

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Aser Abrha ◽  
Navika D Shukla ◽  
Rachel Hodan ◽  
Teri Longacre ◽  
Shyam Raghavan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Gastrointestinal Malignancies ◽  
Pathogenic Variants ◽  
Repair Deficiency ◽  
Common Etiology ◽  
Significant Pathway ◽  
Tumor Material

Abstract Background In light of recent Food and Drug Administration (FDA) approval of immune checkpoint inhibitors for mismatch repair deficient (dMMR) malignancies, identifying patients with dMMR malignancies has become increasingly important. Although screening for dMMR in colorectal cancer (CRC) is recommended, it is less common for extracolonic gastrointestinal (GI) malignancies. At Stanford Comprehensive Cancer Institute (SCCI), all GI malignancies have been screened for dMMR via immunohistochemistry since January 2016. Methods In this study, we conducted a retrospective review of all patients with GI malignancies screened for dMMR between January 2016 and December 2017. Tumor sequencing was performed on cases negative for germline pathogenic variants where tumor material was available. Results A total of 1425 consecutive GI malignancies were screened for dMMR at SCCI during the study period, and 1374 were included for analysis. dMMR was detected in 7.2% of all GI malignancies. We detected the highest prevalence of dMMR in gastric (15 of 150, 10.0%) followed by colorectal (63 of 694, 9.1%), pancreatic (13 of 244, 5.3%), and gastroesophageal malignancy (6 of 132, 4.5%) patients. Lynch syndrome was the most common etiology for dMMR in colorectal cancer (41.5%), double somatic (confirmed or possible) pathogenic variants the most common etiology in pancreatic cancer (44.4%), and somatic MLH1 hypermethylation the most common etiology in gastric (73.3%) and gastroesophageal cancer (83.3%). Conclusions Given the relatively high incidence of dMMR in GI malignancies, we recommend screening all GI malignancies. Our results suggest that although a rare occurrence, double somatic pathogenic variants may be a biologically significant pathway causing dMMR in pancreatic cancer.

scholarly journals Metformin changes the immune microenvironment of colorectal cancer in patients with type 2 diabetes mellitus

2020 ◽  
Vol 111 (11) ◽  
pp. 4012-4020
Author(s):  
Akira Saito ◽  
Joji Kitayama ◽  
Hisanaga Horie ◽  
Koji Koinuma ◽  
Hideyuki Ohzawa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Immune Microenvironment

scholarly journals Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Nicolas Charette ◽  
Caroline Vandeputte ◽  
Lieveke Ameye ◽  
Camille Van Bogaert ◽  
Jonathan Krygier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Phase Ii ◽  
Prognostic Value ◽  
Advanced Colorectal Cancer ◽  
Phase Ii Trials ◽  
Post Hoc Analysis ◽  
Randomized Phase Ii ◽  
Post Hoc

scholarly journals Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study

2012 ◽  
Vol 167 (4) ◽  
pp. 589-599 ◽  
Author(s):  
Dianna J Magliano ◽  
Wendy A Davis ◽  
Jonathan E Shaw ◽  
David G Bruce ◽  
Timothy M E Davis
Keyword(s):  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Proportional Hazards ◽  
Diabetes Management ◽  
Diabetic Patients ◽  
Diabetes Diagnosis ◽  
Community Based

ObjectiveTo explore the relationship between diabetes and cancer.DesignThe Fremantle Diabetes Study (FDS) was a community-based longitudinal observational study of 1426 subjects, 1294 of which had type 2 diabetes.MethodsThe FDS type 2 cohort and four age-, sex- and postcode-matched controls per case were followed for cancer events from 1993 until mid-2010 and incidence rate ratios (IRRs) were calculated. Competing risks proportional hazards models generated risk factors for incident cancers in the diabetic group.ResultsThere were 309 first cancers over 13 051 patient-years, or 2368 (95% confidence interval (95% CI) 2111–2647)/100 000 patient-years in the diabetes patients vs 1131 over 60 324 patient-years (1875 (1769–1987)/100 000 patient-years) in the controls. For those aged ≥45 years, the risk of all-cause cancer was elevated in type 2 diabetic men (IRRs 1.23, 95% CI 1.04–1.45) and women (1.30, 1.06–1.59). The incidence of colorectal cancer was increased (1.36, 1.01–1.82), especially in diabetic men aged 75–84 years (2.14, 1.22–3.64). Age at diabetes diagnosis (sub-hazard ratio 1.05, 1.02–1.09), calcium channel blocker therapy (2.37, 1.39–4.06), recent exercise (2.11, 1.06–4.20) and serum total cholesterol (0.68, 0.52–0.88) increased colorectal cancer risk. Pancreatic cancer was also more frequent in the diabetic patients (IRR 2.26, 1.20–4.10). Diabetic men and women had similar risks of prostate and breast cancer to those of controls (0.83, 0.59–1.14 and 0.86, 0.52–1.36).ConclusionsType 2 diabetes is associated with a moderately increased cancer risk in well-characterised community-based patients, especially pancreatic cancer and colorectal cancer in older men. Recommended cancer screening should be considered as part of routine diabetes management.

scholarly journals INSULIN RESISTANCE IN PATIENTS WITH PANCREATIC AND COLORECTAL CANCER DIAGNOSED AGAINST THE BACKGROUND OF TYPE 2 DIABETES MELLITUS

2021 ◽  
pp. 21-27
Author(s):  
T. S. Vatseba
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Pancreatic Cancer ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Group Ii

Abstract. The aim of the study was to investigate insulin resistance in patients with pancreatic and colorectal cancer diagnosed in people with type 2 diabetes. Materials and methods. 64 patients were examined. They were divided into the following groups: group I – healthy people (control group) (n = 16); group II – patients with type 2 diabetes without cancer (n = 28); group IIIa – patients with type 2 diabetes with pancreatic cancer (n = 10), group IIIb – patients with type 2 diabetes with colorectal cancer (n = 10). The study involved patients from specialized departments of the Ivano-Frankivsk Regional Hospital and the Precarpathian Clinical Oncology Center. Blood insulin levels were determined by enzyme-linked immunosorbent assay, using Insulin ELISA diagnostic kits, EIA-2935. Fasting blood glucose was determined by glucose oxidase method. Compensation for diabetes was assessed by the level of glycated hemoglobin (HbA1c) and determined by ion exchange chromatography. Data analysis was performed using Statistica 12.0 (StatSoft Inc., USA). Differences between the values in the comparison groups were determined by Student’s t-test and were considered significant at P < 0.05. Results. Patients with type 2 diabetes who were diagnosed with pancreatic cancer or colorectal cancer were older, compared with patients with type 2 diabetes without cancer (P < 0.05). Obesity was diagnosed in patients with colorectal cancer of group IIIb, their BMI was higher in comparison with patients of group IIIa who suffered from pancreatic cancer (P < 0.05). BMI in patients of group IIIa was lower than in control group (P < 0.05), in patients of group II (P < 0.05) and in patients of group IIIb with colorectal cancer (P < 0.05). Compared with patients of group II, patients with pancreatic and colorectal cancer had significantly lower insulin levels (P < 0.05), but significantly higher fasting blood glucose levels (P < 0.05). Insulin resistance according to the HOMA-IR index (> 3.0) was detected in both types of cancer. The HOMA-IR index in patients with pancreatic cancer was significantly lower than in patients of group II (P < 0.05). The level of HbA1c in patients with type 2 diabetes without cancer and in patients with cancer diagnosed on the background of diabetes did not differ significantly (P > 0.05). Prior to cancer detection, the same number of patients (50.0%) received metformin-free therapy in both the pancreatic cancer group and the colorectal cancer group. However, the duration of diabetes in patients with pancreatic cancer was 2.90 ± 2.60 years and was significantly shorter than in patients with colorectal cancer 9.70 ± 5.66 (P < 0.05). 80.0% of patients in group IIIa had a history of diabetes less than 5 years, and 80.0% of patients in group IIIb – more than 5 years. Conclusions: 1.In patients with type 2 diabetes mellitus with pancreatic cancer, as well as in patients with colorectal cancer, insulin resistance was detected by the HOMA-IR index, which depended on the combined effect of insulin and hyperglycemia in patients with colorectal cancer and on the fasting blood glucose in patients with pancreatic cancer. 2. The absence of hyperinsulinemia, the short duration of type 2 diabetes in patients with pancreatic cancer may be indirect evidence of cancer induced pancreatogenic diabetes (T3cDM) in the majority of patients of this group. For elderly patients with newly diagnosed diabetes mellitus without obesity, without hyperinsulinemia, screening for pancreatic cancer is recommended.

scholarly journals Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014

2015 ◽  
Vol 22 (4) ◽  
pp. 305
Author(s):  
E. Tsvetkova ◽  
S. Sud ◽  
N. Aucoin ◽  
J. Biagi ◽  
R. Burkes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Metastatic Colorectal Cancer ◽  
Gastrointestinal Cancer ◽  
Neuroendocrine Tumours ◽  
Consensus Conference ◽  
Metastatic Pancreatic Cancer ◽  
Gastrointestinal Malignancies ◽  
Consensus Statements

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23–25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer.

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