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The aim of current study was to evaluate the genetic variation in all the genes encoding pro- and anti-inflammatory cytokines in association with breast cancer development in patients from Malwa region of Punjab. The importance of the levels of interleukin (IL)-17, tumor necrosis factor, interferon γ, IL-10, IL-6, IL-4, and IL-2 with respect to clinicopathological data, prognosis, and disease-free survival was also determined in these patients. Two hundred and fifty female breast cancer patients and 250 age-matched controls were screened for variations in cytokine-encoding genes using global screening array microchip. The level of cytokines was estimated in 150 patients and 60 age-matched controls using BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 cytokine kit by BD Accuri flow cytometer. The difference in cytokine levels was evaluated by Mann-Whitney test. No significant variation in the genes encoding various cytokines was found between patients and controls. Out of the seven cytokines evaluated, the levels of IL-6 and IL-17a were found to be significantly high in patients in comparison with controls ( p = 0.001 and 0.02, respectively). The elevated levels of these cytokines are also associated significantly with poor outcome. We did not find any specific variation in the genes encoding various cytokines between patients and controls. However, there was a significant difference in the serum levels of IL-6 and IL-17a between patients and controls, and the elevated levels of these two cytokines associated significantly with poor outcome in breast cancer patients and, therefore, can be used as prognostic markers.

HER2 positive breast cancer is characterized by the low survival rate in the metastatic patients. Development of resistance and disease-relapse are the major problems associated with the currently available therapies for HER2 positive breast cancer. There are two major targeted therapies for HER2 positive breast cancer viz. monoclonal antibodies and tyrosine-kinase inhibitors, and both of these therapies have their advantages and limitations. To address the limitations associated with the existing therapies, use of antibodies and TKIs as combination therapy proved to be more effective. Various chemical modifications can be performed on tyrosine-kinase inhibitors to develop novel ligands with increased selectivity for HER2 kinase. A number of tyrosine-kinase inhibitors are in various phases of clinical trials for the treatment of HER2 positive breast cancer. In the current review article, recent developments on various HER2 tyrosine-kinase inhibitors have been reported. Various structurally different scaffolds bind to the HER2 receptor and exhibit potent anti-cancer activities. The structural and pharmacophoric requirements of the scaffolds are discussed in detail so as to discover effective drug candidates for the treatment of HER2 positive breast cancer.

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In the current review article, we have summarized the genomic alterations that are responsible for overexpression of HER2 and therefore, increased risk of breast cancer. In addition, the gene variants affecting response towards trastuzumab-therapy have also been discussed.

Background: Perimenopause refers to the period around menopause (40-55 years). This includes the period before menopause and the first year after menopause. Perimenopausal age is an important stage in a women’s life. Many women are diagnosed with hypothyroidism at midlife. Hypothyroidism - both overt and subclinical are associated with increased risk of CVS diseases. Subclinical hypothyroidism is more important as this stage is usually ignored from treatment point of view and if early intervention is done in SCH worsening of metabolic derangement may be avoided. Objectives: The present study was aimed to know the prevalence of subclinical hypothyroidism and associated dyslipidemia in perimenopausal females. Material and Methods: In our retrospective study we took 100 perimenopausal females (40-55years) who were investigated for thyroid and lipid profile. Atherogenic indices like TC/HDL-c, LDL-c/HDL-c, TG/HDL-c ratios were calculated from the individual lipid profile parameters. The reference guidelines for lipid profile was according to NCEP ATP III. Result: Subclinical hypothyroidism was found to be present in 18% of perimenopausal females The mean TSH levels were found to be higher in SCH as compared to euthyroid females with a mean value of 7.56±3.54(μIU/ ml). Dyslipidemia was seen in patients with SCH. TSH levels were found to be positively correlated with total cholesterol. Conclusion: We conclude that subclinical hypothyroidism is present in 18% females of perimenopausal age group. Increased TSH levels are associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio and non cholesterol HDL. In perimenopausal women the condition is usually underdiagnosed and ignored but subclinical hypothyroidism in these females should be screened and treated timely to decrease the risk of accelerated atherosclerosis and premature coronary artery disease in them.

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Introduction: Diabetic nephropathy is one of the most common and serious complications of long standing type 2 diabetes mellitus. Microalbuminuria is a strong predictor of diabetic nephropathy. Homocysteine level plays an important role in pathogenesis of diabetic microvascular complications, particularly diabetic nephropathy. Vitamin B 12 , Folic acid and Vitamin B 6 facilitate homocysteine metabolism. Methods: This case-control study was carried out at a tertiary care centre. Total 150 subjects were enrolled, which included 60 cases of type 2 diabetes with microalbuminuria, 60 cases of type 2 diabetes without microalbuminuria and 30 healthy controls. Besides routine investigations, fasting blood glucose, glycated haemoglobin, and homocysteine levels in serum were measured. All subjects were screened for microalbuminuria. Statistical analysis was done. Results: Homocysteine levels, fasting blood glucose and glycated haemoglobin were significantly higher in patients of type 2 diabetes with microalbuminuria as compared to those without microalbuminuria (p = 0.00, p = 0.01, p = 0.01). Strong positive correlation was observed between the homocysteine levels and degree of microalbuminuria(r = +0.758, p = 0.00), and also between the fasting blood glucose levels and degree of microalbuminuria (r = +0.259, p = 0.02). Conclusions: It would be useful to perform an early screening for raised homocysteine levels and for low vitamin levels in the patients of uncontrolled diabetics. This would help to evaluate the need of folic acid, Vitamin B 12 and Vitamin B 6 supplements since these supplements can be beneficial for delaying the progress of diabetic nephropathy in these patients.