Insulin-like growth factor-1 signaling in renal cell carcinoma.

Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells.

[Effect of Helicobacter pylori eradication on the expression level of SATB1 and c-Myc genes in gastric mucosa of patients with family history of gastric cancer]. / Wplyw eradykacji Helicobacter pylori na poziom ekspresji genów SATB1 i c-Myc w blonie sluzowej zoladka u pacjentów z dyspepsja w zaleznosci od rodzinnego obciazenia wystepowaniem raka zoladka.

UNLABELLED: Helicobacter pylori (H. pylori) is a class 1 gastric carcinogen with the proved influence on gastric cancer development. The products of SATB1 and c-Myc genes play important role in cancer development and their levels are elevated in gastric cancer tissues. The aim of the study was to analyze an effect of H. pylori eradication on the expression of the SATB1 and c-Myc genes in the gastric mucosa of dyspeptic patients with family history of gastric cancer. MATERIAL AND METHODS: Twenty patients enrolled to the studies were divided into two groups: nine patients (group I) without the family history of gastric cancer, and eleven patients with the family history of gastric cancer (group II). Endoscopic biopsies of gastric mucosa were taken from the antrum and corpus of H. pylori-infected subjects before and after bacteria eradication. The corresponding levels of expression were determined by analysis of the respective mRNA levels with the use of the real-time RT-PCR method. The level of each mRNA was normalized to the levels of mRNA of two reference genes, RPL29 and GAPDH. RESULTS: Independently of stomach topography, the antrum versus corpus, in the group I patients the levels of mRNA of SATB1 and c-Myc after eradication were higher in the following cases: SATB1/ GAPDH p = 0.017914 (antrum); SATB1/RPL29 p = 0.046400 (corpus); SATB1/GAPDH p = 0.027709 (corpus). For group II patients no statistically significant increase of the level of the c-Myc and SATB1 genes was observed. CONCLUSIONS: Patients with the family history of gastric cancer and H. pylori infection, with reversible histopathological changes of the gastric mucosa, have significantly higher levels of SATB1 and c-Myc genes expression as compared to the patients without family history of gastric cancer, regardless of the topography of the stomach. After successful eradication, the SATB1 mRNA level in samples of patients with the family history of gastric cancer did not increase, in contrast to the control group of patients. Presumably, the observed effect is associated with hypermethylation of the promoter of that gene. However, the level of c-Myc gene expression was not significantly different before and after removal of the bacteria, for both groups of patients.