Drug-sensitive FGFR3 mutations in lung adenocarcinoma.

Background: Lung cancer is the leading cause of cancer-related deaths across the world. In this study, we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. Materials and methods: Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500 × (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing mutant and wild-type FGFR3 constructs were characterized for anchorage independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models. Results: We present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and shows that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend toward better overall survival, compared with patients lacking actionable alterations or those harboring KRAS mutations. Conclusion: We present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma.

Anticholesterol antibody: the way for reduction of hypercholesterolemia.

Antibodies specific to cholesterol was first reported in 1925. It may develop in the body naturally and it is believed that this antibody has a protective role against harmful forms of cholesterol, such as LDL & VLDL. An immunoglobulin protein, anticholesterol may be found in both circulation as well as digestive tract. Many studies have been done on anticholesterol antibody. Our immune system may produce anticholesterol antibodies in response to elevated levels of cholesterol rich particles, such as LDL & VLDL. It can be induced in animals by conjugating or incorporating the cholesterol antigen into a variety of structures. Immunization markedly decreases the risk of developing atherosclerosis. In comparison to non-tumorous normal subject, the antibody is found to be significantly higher in non-small cell lung cancer (NSCLC). Elevated anti-cholesterol antibodies might be applicable for the serodiagnosis of NSCLC. Some studies showed that LDL immunization induces T-cell dependent antibody formation that protects atherosclerosis. Origo Biosciences scientists had identified a dietary antibody to cholesterol. This protein, when ingested, binds to cholesterol in the human digestive tract and blocks its absorption into the bloodstream. These studies may lead to us to realize the importance of anticholesterol and to find the way for reduction of hypercholesterolemia and thereby reduction of morbidity and mortality.

Studies on serum lipid profile in hypertensive patient.

UNLABELLED: The study was carried out to appraise the serum total cholesterol, triglyceride, HDL-C and LDL-C values in hypertensive patients for providing information to the health-policy planners and also to the clinical practitioners about the importance of routine monitoring of lipid profile in hypertensive patients for prevention of coronary heart disease and other consequences to combat morbidity and mortality and to reinforce the need to consider these parameters in daily clinical practice. It was a cross-sectional study. The study was conducted at Department of Physiology and Biochemistry of Mymensingh Medical College, Medicine Unit of Mymensingh Medical College Hospital and in the community of Sadar, Mymensingh District. The period of the study was January 2005 to December 2005. A total number of seventy subjects were included in this study. Out of them 40 (forty) were hypertensive patients and 30 (thirty) were normotensive & healthy controls. Most of the hypertensive patients (65%) were taking treatment irregularly. Serum total cholesterol, serum triglyceride and serum LDL cholesterol were greater in hypertensive than those of normotensive . The differences of mean of serum total cholesterol, serum LDL cholesterol in between two groups were statistically significant and in case of serum triglyceride it was statistically highly significant. Serum HDL cholesterol was less in hypertensive than those of normotensive. The differences of mean of serum HDL cholesterol in between two groups were statistically highly significant. Among 40 hypertensives the number of "Getting treatment- regular" & "Getting treatment-irregular" was 14 (35%) & 26 (65%) respectively and the values are not statistically significant. Similarly in patients "suffering less than 5 years" and "suffering 5 years & above" the differences are also not statistically significant. CONCLUSION: The observations of this study has revealed that most of the hypertensive patients are taking treatment irregularly and there was significant alteration of serum cholesterol, triglyceride, HDL-C and LDL-C in hypertensive patients. Therefore, for routine monitoring of hypertensive patients to prevent the coronary heart disease (CHD) and other consequences, the reinforcement of the investigations of these parameters may be recommended in daily clinical practice.

Anticandidial activity of some essential oils of a mega biodiversity hotspot in India.

Six essential oils viz. Eucalyptus citriodora, Cymbopogon citratus, Callistemon lanceolatus, Cinnamomum camphora, Citrus limon, Tagetes petula, as well as two standard antibiotics, miconazole and clotrimazole, were tested in vitro for their anticandidial activity. All these essential oils exhibited higher activity than the two synthetic antibiotics. Highest zone of inhibition was recorded in E. citriodora (8.50 mm microl-1) followed by C. lanceolatus (5.63 mm microl-1) establishing their promising anticandidial potential.