Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions.

The present study was undertaken to analyze prognostic and genetic interactions between type 2 diabetes and metastatic colorectal cancer. Patients' survival was depicted through the Kaplan-Meier product limit method. Prognostic factors were examined through the Cox proportional-hazards regression model, and associations between diabetes and clinical-pathologic variables were evaluated by the χ2 test. In total, 203 metastatic colorectal cancer patients were enrolled. Lymph nodes (P = 0.0004) and distant organs (> 2 distant sites, P = 0.0451) were more frequently involved in diabetic patients compared with those without diabetes. Diabetes had an independent statistically significant negative prognostic value for survival. Highly selected patients with cancer and/or diabetes as their only illness(es) were divided into three groups: (a) seven oligo-metastatic patients without diabetes, (b) 10 poly-metastatic patients without diabetes, and (c) 12 poly-metastatic diabetic patients. These groups of patients were genetically characterized through the Illumina NovaSeq 6000 (San Diego, CA, USA) platform and TruSigt™Oncology 500 kit, focusing on genes involved in diabetes and colorectal cancer. Gene variants associated with diabetes and cancer were more frequent in patients in group 3. We found that type 2 diabetes is a negative prognostic factor for survival in colorectal cancer. Diabetes-associated gene variants could concur with malignancy, providing a rational basis for innovative models of tumor progression and therapy.

Prospective Evaluation of Radiotherapy-Induced Immunologic and Genetic Effects in Colorectal Cancer Oligo-Metastatic Patients with Lung-Limited Disease: The PRELUDE-1 Study.

BACKGROUND: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions ("abscopal effect") through stimulation of anti-tumor immune effects ("radiation-induced immunity"). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. AIMS: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses' duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. METHODS: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p0 = 0.0077, with α = 0.05 and 1-ß = 0.60, the final sample size is 25 patients.

Occurrence of variable levels of health-promoting fruit compounds in horn-shaped Italian sweet pepper varieties assessed by a comprehensive approach.

BACKGROUND: Cultivated pepper is a rich source of diverse bioactive compounds with potential properties related to the prevention of major degenerative and proliferative diseases. In the present study, 15 sweet pepper varieties, highly appreciated on the Italian market, were assessed for variation in the content of ascorbic acid, isoprenoids and flavonoids, as well as morpho-agronomic performances and molecular diversity. RESULTS: The collection under study showed a wide variability for all traits considered. Traditional cultivars, although less productive, were characterized by a high content of ß-carotene and ascorbic acid, reaching maximum concentrations of 230.5 mg kg-1 fresh weight (fw) and 2750 mg kg-1 fw, respectively. Strong correlations were demonstrated between neoxanthin and luteolins. Fruit weight was positively correlated with α-tocopherol content and negatively correlated with luteolins content. The genotyping by sequencing platform allowed the identification of 1833 single nucleotide polymorphism, which better defined the relationships among cultivars, based on provenance and improvement rate. CONCLUSIONS: The present study provides an overview of the variability in the expression of fruit nutritional traits in a collection of horn-shaped pepper cultivars, integrating agronomic and molecular data. The impact for breeding and consumers is discussed. © 2017 Society of Chemical Industry.