Contribution of VEGF polymorphism rs3025020 to short stature and hypertension in elderly Japanese individuals: a cross-sectional study

Background Recently, short stature has been revealed to be positively associated with hypertension, possibly because this indicates lower activity of vascular maintenance, such as angiogenesis. Vascular endothelial growth factor (VEGF) polymorphism (rs3025020) plays an important role in the progression of angiogenesis and may be associated with both hypertension and hypertension-associated short stature. Methods A cross-sectional study of 1377 elderly Japanese individuals aged 60–89 years was conducted. Short stature was defined as the lowest tertile of height (< 160.8 cm for men and < 148.7 cm for women). Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive medication use. Results Independent of known cardiovascular risk factors, short stature was found to be positively associated with hypertension; the fully adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were 1.51 (1.17, 1.96). With the reference group of carriers of the major allele of rs3025020, TT-homozygotes showed significantly lower OR for hypertension and short stature; the fully adjusted ORs (and 95% CIs) were 0.60 (0.41, 0.90) for hypertension and 0.59 (0.38, 0.91) for short stature, respectively. Conclusions Angiogenesis-related genetic factor (rs3025020) is associated with hypertension and short stature, whereas short stature is positively associated with hypertension. Further investigation is necessary in this regard; the capacity for angiogenesis might partly explain the mechanism underlying the inverse association between height and hypertension.

Vascular Endothelial Growth Factor Polymorphism in Bladder Cancer: A Review

Bladder cancer is one of the most common urinary tract cancers. The main risk factors for bladder cancer are tobacco usage, aging, gender, exposure to chemicals and drugs such as cyclophosphamide and chlornaphazine, chronic bladder problems, and genetics. Genetic factors continue to be studied including vascular endothelial growth factor (VEGF) gene polymorphism. Overexpression of VEGF is known to be higher in bladder cancer patient than healthy individual. It is also associated with tumor progression, metastasis, recurrence, and survival since VEGF and its receptor play a key role in angiogenesis. Many studies evaluated the relationship between VEGF polymorphism and the risk of bladder cancer, but the results were inconsistent because of ethnicity and geographical influences. The present study aims to raise knowledge about the role of VEGF polymorphisms on risk of bladder cancer.

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in advanced cancers.

2526 Background: Gemcitabine (gem) with nab-paclitaxel (nab-p) is known to have antitumor activity and a favorable toxicity profile. The addition of bevacizumab (bev) to nab-paclitaxel has also been found to enhance nab-paclitaxel cytotoxicity. Methods: We therefore performed a modified 3+3 dose escalation study with 15 dose levels of fixed dose gem 1000 mg/m2IV (day 1, 8, 15) and escalating doses of nab-p IV (day 1,8, 15) and bev IV (day 1,15) every 28 days. The study design allowed for the possibility of multiple MTDs. Correlative studies on VEGF polymorphism and response were planned. (NCT01113476). Results: 103 patients (45 male) with advanced cancers were enrolled (19 ovarian, 18 pancreatic, and 18 gastroesophageal (GE) cancers among the most common). All patients were ECOG PS 0-2, median age was 60 years (range 17-85), and 51 patients (50%) were gem refractory with a median of 3 prior lines of therapy. 3 DLTs were observed during dose escalation - one with nab-p 50 mg/m2 and bev 10 mg/m2 (grade 3 dysphagia, dehydration), one with nab-p 75 mg/m2 and bev 10 mg/m2 (grade 3 cellulitis) and one with nab-p 150 mg/m2 and bev 5 mg/m2 (grade 3 bacteremia, hypotension). 2 DLTs were observed among the 13 patients in the nab-p 100 mg/m2 and bev 5 mg/m2 expansion cohort (one grade 3 diarrhea, one grade 3 fatigue) and 1 DLT among the 12 patients in the nab-p 75 mg/m2 and bev 10 mg/m2 expansion cohort (grade 3 rectal bleed). Dose escalation up to nab-p 125 mg/m2 and bev 15 mg/m2was well tolerated with no MTD. One patient with gem refractory peritoneal papillary carcinoma achieved a complete response, 13 patients (13%) had partial responses (PR), and 54 patients (52%) had prolonged stable disease (pSD) ≥ 12 weeks. 4 patients achieving PR and 26 patients with pSD were previously gem refractory. 3/6 (50%) small cell cancers achieved PR and all 6 of these patients had tumor shrinkage of at least 25%. 4/19 (21%) ovarian cancers achieved PR, 3/18 (17%) GE cancers achieved PR, and 1/18 (6%) pancreatic cancers achieved PR. Conclusions: The combination of gem 1000 mg/m2, nab-p 125 mg/m2 and bev 15 mg/m2 is safe, well-tolerated, and has activity even at lower doses in advanced malignancies, including gem refractory tumors. Correlative VEGF polymorphism studies are ongoing. Clinical trial information: NCT01113476.