Angiogenesis has always been the topic of major scientific interest in the field of malignant tumors. Nowadays, targeting angiogenesis has achieved success in various carcinomas by several mechanisms, including the use of anti-angiogenic small molecule receptor tyrosine kinase inhibitors (TKIs). The development of TKIs targeting pro-angiogenic receptors, mainly vascular endothelial growth factor receptor (VEGFR) family, have significantly improved the outcome of certain types of cancers, like renal cell carcinoma, hepatocellular carcinoma, and colorectal carcinoma. However, the general response rate is not very satisfactory. The particular toxicity profile and resistance to anti-angiogenic targeted agents are unavoidable, and no specific marker is available to screen responsive patients to TKIs for precision therapy. To date, about 11 anti-angiogenic TKIs with different binding capacities to angiogenic receptor tyrosine kinase have been approved for the treatment of patients with advanced cancers. This review presents all approved anti-angiogenic small molecule receptor TKIs so far with an emphasis on their indications and clinical efficacy. We also discuss the combination between TKIs and immune checkpoint blockade inhibitors based on the most recent exciting outcome in immunotherapy.
Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration
Coaxial technique is extensively applied to facilitate percutaneous lung lesion biopsy. However, the impact of coaxial technique on diagnostic accuracy remains undecided. We reviewed 485 patients who underwent percutaneous CT-guided needle biopsies of lung lesions in our hospital. All of these biopsies were performed using either a cutting needle alone (n = 268) or a cutting needle combined with a coaxial needle (n = 217). The diagnostic accuracy and complications resulting from the two techniques were then compared. The diagnostic accuracies of the two techniques were comparably high, at 98.2% (with coaxial technique) and 95.9% (without coaxial technique), p = 0.24. Subgroup analysis discovered that for patients with lesions measuring < 1.5 cm and needle path length ≥ 4 cm, the coaxial technique achieved a higher diagnostic accuracy (95.5% vs. 72.7%, p = 0.023). The biopsy was well tolerated in all of the patients. Pneumothorax occurred less often in patients who were biopsied with the coaxial technique (19 versus 43, p = 0.024). Thus, the application of the coaxial technique could improve diagnostic accuracy in patients with small and deep lung lesions, and could reduce the risk of pneumothorax. The combined use of cutting needles with coaxial needles is the preferred technique for performing percutaneous CT-guided lung biopsies.
The relationship between signal transduction and tumors has become one of the foci in cancer research. Signal transducer and activator of the transcription 6 (STAT6) signaling pathway is found to be activated in some cancer cells. But the function of the pathway in cancer cells is unknown. This study was undertaken to investigate the effect of the Stat6 signaling pathway on apoptosis in human colon cancer cells (HT-29 cells) and the possible mechanism of Stat6 by RNA interference techniques. Four eukaryotic expression plasmid vectors of short hairpin RNA (shRNA) specific for the STAT6 gene were designed and generated by molecular biological technology. The plasmid vectors were transfected into HT-29 cells by cation liposomes to block the Stat6 signaling pathway. The expressions of STAT6 mRNA and phosph-Stat6 protein were detected by the reverse transcriptase polymerase chain reaction (RT-PCR) method and flow cytometry respectively to screen the most effective shRNA at 72 hours after transfection. The apoptosis condition of the cells in which the expression of the STAT6 gene had been interfered was analyzed by flow cytometry and confocal microscopy. Both mRNA and protein expression of B cell lymphoma-2 (Bcl-2) and Bax were detected by RT-PCR and western blotting. Two effective eukaryotic expression plasmid vectors of shRNA specific for the STAT6 gene were generated successfully. One can reduce the expression of the STAT6 gene by 82.4% and the other by 56.8% (P<0.01). The apoptotic rate of colon cancer cells in which STAT6 gene expression had been interfered was significantly higher than that in controlled colon cancer cells (P<0.01). In the cells in which the Stat6 signaling pathway was blocked, the levels of mRNA and protein Bcl-2 were significantly decreased, whereas those of Bax were significantly increased (P<0.01). The Stat6 signaling pathway can inhibit apoptosis in human colon cancer cells. The subsequent disorder of Bcl-2/Bax expression may play an important part in that process. The STAT6 gene may serve as a potential target in cancer therapy.
1 April 2016 in Oncology and Translational Medicine
Objective: This study investigated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in predicting clinical outcomes of patients with metastatic colorectal cancer (mCRC) undergoing irinotecanbased first-line chemotherapy. Methods: This study was based on a Chinese prospective multicenter trial (NCT01282658). Baseline complete blood cell counts were performed. Survival was determined using the Kaplan-Meier method. Multivariate analyses based on the Cox regression model were performed to determine the effects of independent biomarkers. Results: A total of 139 patients were evaluated. Values below the median NLR were associated with better progression-free survival (PFS) (9.9 vs 7.7 months, P = 0.043) and overall survival (OS) (21.8 vs 15.1 months, P = 0.013). These effects remained significant in multivariate analysis. Conclusion: NLR is an independent prognostic marker of mCRC treated with first-line irinotecan-based therapy in a Chinese population.