Clinical outcome of adjuvant endocrine treatment according to Her-2/neu status in breast cancer.

BACKGROUND & OBJECTIVES: An association between over-expression of proto-oncogene Her-2/neu and resistance to tamoxifen in estrogen receptor (ER) positive, primary and metastatic breast cancer has been suggested. HR+/Her-2/neu+ patients have a poor response to endocrine therapy, making this group a matter of debate. The present study was carried out to examine whether Her-2/neu expression in breast cancer patients predicted tamoxifen effectiveness. METHODS: An enzyme-linked immunosorbent assay (ELISA) specific for the extracellular domain of the Her-2/neu oncoprotein product was used to detect serum Her-2/neu levels in 207 patients with histological confirmed breast cancer. Tissue Her-2 /neu expression was studied in 100 breast cancer patients by immunohistochemistry (IHC) and compared with serum Her-2/neu levels by ELISA. RESULTS: Among 207 histologically confirmed breast cancer patients, 53 were serum Her-2/neu positive. Patients who were treated with surgery, chemotherapy, and radiotherapy showed significantly (P<0.05) reduced serum Her-2/neu levels, showing good response to treatment. Patients who were treated with tamoxifen in addition to the above regimen did not show any significant reduction in serum Her-2/neu levels showing resistance to treatment. INTERPRETATION & CONCLUSIONS: The present findings study support the hypothesis that Her-2/neu overexpression contributes to tamoxifen resistance. Trastuzumab or other growth factor inhibitors should be used in combination with tamoxifen, since monotherapy is not likely to be optimal in HR+/Her-2/neu+ tumours.

Simultaneous estimation of four proton pump inhibitors--lansoprazole, omeprazole, pantoprazole and rabeprazole: development of a novel generic HPLC-UV method and its application to clinical pharmacokinetic study.

A highly selective, sensitive and accurate HPLC method has been developed and validated for the estimation of four proton-pump inhibitors (PPI), lansoprazole (LPZ), omeprazole (OPZ), pantoprazole (PPZ) and rabeprazole (RPZ), with 500 microL human plasma using zonisamide as an internal standard (IS). The sample preparation involved simple liquid-liquid extraction of LPZ, OPZ, PPZ and RPZ and IS from human plasma with ethyl acetate. The baseline separation of all the peaks was achieved with 0.1% triethylamine (pH 6.0):acetonitrile (72:28, v/v) at a flow rate of 1 mL/min on a Zorbax C(8) column. The total chromatographic run time was 11.0 min and the simultaneous elution of IS, OPZ, RPZ, PPZ and LPZ occurred at approximately 2.42, 4.45, 5.02 and 9.37 min, respectively. The method was proved to be accurate and precise at linearity range of 20.61-1999.79 ng/mL with a correlation coefficient (r) of >or=0.999. The limit of quantitation for each of the PPI studied was 20.61 ng/mL. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers.

Evaluation of immunohistochemistry and enzyme linked immunosorbent assay for HER-2/neu expression in breast carcinoma.

HER-2 is overexpressed in approximately 20-30% of invasive Breast Cancer. ECD of the HER-2 protein is frequently cleaved and released into the circulation, where it can be detected by ELISA in up to 45% of patients with metastatic breast cancer. The objective of our study was to compare the current methods for the detection of HER-2 protein. Tissue HER-2 levels were studied in 100 breast cancer patients by IHC and compared with serum HER-2 levels by ELISA. IHC frequency was 29%. Serum HER-2 ECD was positive in 42% of patients. A statistically significant correlation was observed. HER-2 detected by IHC correlates significantly with serum HER-2 levels detected by ELISA. Thus, ELISA is a reliable and economical tool to assess the HER-2 status in tumors, when breast tissue sample is not available.

Clinical utility of serum human epidermal receptor-2/neu detection in breast cancer patients.

BACKGROUND & OBJECTIVE: In breast cancer, the HER-2/neu gene is amplified in 20-30 per cent of cases. The mechanism by which the amplification/overexpression occurs is not known. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and thus might help in management of the disease. The present study was therefore to estimate the serum HER-2/neu levels in breast cancer patients and associate with other prognostic factors. METHODS: Serum HER-2/neu levels were studied in 207 patients with cancer breast, 15 benign breast diseases (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node and hormone receptor status were compared with serum HER-2/neu levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively related with hormone receptor positivity. INTERPRETATION & CONCLUSION: HER-2/neu serum test could be done more frequently in women with breast cancer irrespective of the hormone receptor status, to suggest modifications in systemic adjuvant therapy, including possibly the use of Herceptin.

Correlation study of Carcino Embryonic Antigen & Cancer Antigen 15.3 in pretreated female breast cancer patients.

Carcino Embryonic Antigen (CEA) and Cancer Antigen 15.3 (CA15.3) are the most common tumor markers in breast cancer patients. Measurement of circulating tumor markers is a non-invasive quantitative method. Serum levels of CEA and CA 15.3 were studied in female breast cancer patients prior to treatment. To evaluate the utility of these markers, 207 Breast carcinoma patients belonging to all the stages were considered. Healthy age matched 75 female individuals formed the control group. The serum levels of CEA and CA 15.3 were analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Results were taken and compared with stages, tumor size, node and grade. The serum CA 15.3 levels were significant in all the study parameters whereas serum CEA levels showed no significant changes with any of the parameters. Measurement of serum CA 15.3 levels showed significant correlation (24.8%) with advanced stages and larger tumor sizes, whereas serum CEA levels did not show any significant correlation in breast cancer patients prior to treatment.

Synthesis of Pyrimidine Incorporated Piperazine Derivatives and their Antimicrobial Activity.

Thiophene substituted chalcones (1a-e) were cyclised with thiourea in presence of potassium hydroxide to get 4-substituted-6-(thiophen-2-yl)pyrimidine-2-thiols (2a-e) which were then stirred with methyl iodide to obtain 4-substituted-2-(methylsulfanyl)-6-(thiophen-2-yl)pyrimidines (3a-e). Compounds (3a-e) were refluxed with different N-methylpiperazine and N-phenylpiperazine to afford 4-substituted-2-(4-methylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (4a-e) and 4-substituted-2-(4-phenylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (5a-e). The structures of all the newly synthesised compounds 4b, 4d, 5a and 5b showed good antibacterial activity at 40µg/mlconcentration. Compounds 4a, 4d, 4e, 5c and 5e showed significant antifungal activity at 40 µg/ml concentration compared with standard drugs.