Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India)

The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this case–control study, we investigated whether functional polymorphisms (+405 C > G and +936 C > T) in the VEGF gene are associated with the risk of lung cancer. Genomic DNA was isolated from the blood of 100 lung cancer patients and 150 healthy controls, and total RNA was isolated from 48 tumor tissues and adjacent normal lung tissues. Two DNA polymorphisms (+405 C > G and +936 C > T) in the 3′-untranslated regions (3′-UTR) and 5′-untranslated regions (5′-UTR) of vascular endothelial growth factor A (VEGFA) were studied using PCR–RFLP method, and mRNA expression of VEGFA was studied by quantitative real-time PCR. Polymorphisms in the 5′-UTR (+405 C > G) and 3′-UTR (+936 C > T) did not show significant difference between lung cancer cases and control samples (P = 0.11 and P = 0.09, respectively). VEGF +405 CG and GG are significantly more in age group >50 years old, in all grades, and in early pathological stages (P = 0.04, P = 0.03, and P = 0.006, respectively). Also, increased expression of VEGFA mRNA was noted in tumorous compared to non-tumorous tissue (P < 0.0001). Overexpression of the gene was considered at ΔC _T > 6.0. Within the group of patients with conventional tumor, those with histology other than squamous cell carcinoma (SCC) had a higher level of VEGFA mRNA expression than SCC patients (P = 0.04). Overexpression of VEGFA mRNA was noted in lung cancer and more so in lung cancer with adenocarcinoma and large cell carcinoma histology and in pathological stages III and IV. VEGFA +405 C > G SNP showed an association with age, pathological grade, and stage.     

Atrial septal defect closure in a patient with "irreversible" pulmonary hypertensive arteriopathy

The presence of irreversible pulmonary hypertension in patients with atrial septal defect (ASD) is thought to preclude shunt closure. We report the case of a woman with plexiform pulmonary arteriopathy secondary to an ostium secundum ASD who was able to successfully undergo percutaneous shunt closure following therapy with chronic intravenous prostacyclin (Flolan). One year after closure, the patient was weaned off Flolan over a period of 7 months following the institution of oral Bosentan therapy. Our case illustrates how aggressive vasodilator therapy with prostaglandins may be capable of reducing pulmonary artery pressure and permitting shunt closure in a patient once considered to have "inoperable" pulmonary arteriopathy.     

Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors

Purpose

To define the maximum tolerated dose, clinical toxicities, and pharmacodynamics of bevacizumab, everolimus, and panobinostat (LBH-589) when administered in combination to patients with advanced solid tumor malignancies.

Experiment design

Subjects received 10?mg of panobinostat three times weekly, 5 or 10?mg everolimus daily, and bevacizumab at 10?mg/kg every 2?weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. Protein acetylation was assessed in peripheral blood mononuclear cells (PBMC) both at baseline and on treatment.

Results

Twelve subjects were evaluable for toxicity and nine subjects for response. DLTs in cohort 1 included grade 2 esophagitis and grade 3 oral mucositis; DLTs in cohort -1 were grade 2 ventricular arrhythmia and grade 2 intolerable skin rash. Common adverse events were diarrhea (50?%), headache (33?%), mucositis/stomatitis (25?%), hyperlipidemia (25?%), and thrombocytopenia (25?%). There was 1 partial response; an additional 2 subjects had stable disease as best response. No consistent changes in protein acetylation in PBMC were observed in samples available from eight patients on treatment compared with baseline.

Conclusions

Bevacizumab, everolimus, and panobinostat in combination at the lowest proposed doses did not have an acceptable safety and tolerability profile and did not consistently inhibit HDAC activity; therefore, we do not recommend further evaluation.     

Cooperation between mglu receptors: a depressing mechanism?

Recent findings from the perirhinal cortex have shed new light on the ways in which metabotropic glutamate receptors could be involved in synaptic plasticity, and in particular in long-term depression (LTD) of synaptic transmission. Importantly, these findings have also led to a greater understanding of mechanisms that could regulate mglu-receptor signalling and the ways in which mglu receptors interact with one another.     

Necrotizing fasciitis in an immunocompetent patient with multiple sites of involvement

Necrotizing fasciitis (NF) in an immunocompetent patient with multiple sites of involvement is very rare. We describe a case of E. coli associated necrotizing fasciitis in a middle aged female with three lesions of NF on her lower limbs at the time of presentation. She was managed with broad spectrum intravenous antibiotics, radical surgical debridements with skin grafting, and aggressive supportive care.     

Primary non-Hodgkin's lymphoma of vagina associated with pregnancy

We report a case of non-Hodgkin's lymphoma (NHL) in 23 years old, 36 weeks pregnant female, who presented with a swelling in the vagina. Biopsy of the lesion led to profuse haemorrhage and emergency caesarean-section along with bilateral ligation of internal iliac arteries were required. Recovery was smooth and she was discharged from the hospital on the 5th postoperative day. Histopathology revealed non-Hodgkin's lymphoma, diffuse large B cell type (DLBCL). Further treatment by medical oncologist led to complete resolution of the tumour at three months.