Expression Levels of Vascular Endothelial Growth Factors A and C in Patients with Peptic Ulcers and Gastric Cancer

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. MATERIALS AND METHODS: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: non-ulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. RESULTS: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. CONCLUSIONS: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

Resistance to HER2-targeted therapy

Production and approval of trastuzumab [Herceptin[registered sign]] for the treatment of metastatic breast cancer [MBC] was a millstone in antibody-based targeted therapy in the cancer treatment. However, despite the early success in the clinical trials, trastuzumab failed to appreciate the initial attraction due to development of resistance to the drug. Majority of patients who benefit from the drug acquire resistance to it and experience tumor recurrence within 1 year. Several molecular and cellular mechanisms underlying the resistance to trastuzumab have been proposed. In this review, first, we provide a brief history leading to production of trastuzumab. Also we consider the cellular and molecular antitumor effects of trastuzumab and then, we discuss the mechanisms underlying trastuzumab resistance in four levels

Toll like receptor-4 896a/g gene variation, a risk factor for migraine headaches

The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 [TLR-4] is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation. This case/control study is aimed to investigate whether TLR- 4 896A/G variation is related to migraine headaches in an Iranian population. A total of 170 migraine patients [130 females, mean age 33.24 +/- 11 years] and 170 age, sex, and ethnicity matched healthy controls [118 females, mean age of 31 +/- 10 years] were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system [ARMS]-PCR. The frequency of G allele was higher in migraine patients than the controls [15% vs. 4.7%; p<0.0001]. Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls [25.3% vs. 8.2%, p=0.00002, OR 3.87, 95% CI; 2.02-7.4]. Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine [OR 3.2, 95% CI 1.23-8.24, p=0.01]. Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.