Clinicopathological comparison of triple negative breast cancers with non-triple negative breast cancers in a hospital in North India.

INTRODUCTION: Breast cancer is the second most common cancer worldwide (1.3 million cases, 10.9%) and ranks 5 th as cause of death from cancer overall (458,000 cases, 6.1%). Triple-negative breast cancer (TNBC) is a subtype of breast cancer with characteristic biological and pathological features. Among the subgroups of breast cancer, triple negative cancer is particularly feared because it is associated with poor outcome. However, clinical data on TNBC in Asian population are limited. The present study was aimed to find the prevalence of TNBCs and to compare various clinicopathological features of TNBC with non TNBC patients in our population. MATERIALS AND METHODS: Clinical and pathological data of 180 breast cancer patients who visited our department from January 2009 to December 2013 were analyzed. Statistical analysis was done using the Chi-square test and Mann-Whitney U-test. RESULTS: Of 180 cases, 62 (34.4%) had TNBC. Data analysis revealed significant difference in mean age, mean tumor size, tumor grade between TNBC and non-TNBC patients. Axillary lymph node metastasis and lymphovascular involvement were also more in TNBC patients however this was not statistically significant. Extranodal spread was recorded more in non-TNBC patients as compared to TNBC patients, but the results were statistically insignificant. CONCLUSION: Triple negative breast cancer represented 34.4% which is higher than the range normally reported in the literature. TNBC are associated with younger age, large tumor size, high-grade tumors, and a higher rate of axillary lymph node metastasis.

Targeted gene inactivation reveals a functional role of calpain-1 in platelet spreading.

BACKGROUND: Calpains are implicated in a wide range of cellular functions including the maintenance of hemostasis via the regulation of cytoskeletal modifications in platelets. OBJECTIVES: Determine the functional role of calpain isoforms in platelet spreading. METHODS AND RESULTS: Platelets from calpain-1(-/-) mice show enhanced spreading on collagen- and fibrinogen-coated surfaces as revealed by immunofluorescence, differential interference contrast (DIC) and scanning electron microscopy. The treatment of mouse platelets with MDL, a cell permeable inhibitor of calpains 1/2, resulted in increased spreading. The PTP1B-mediated enhanced tyrosine dephosphorylation in calpain-1(-/-) platelets did not fully account for the enhanced spreading as platelets from the double knockout mice lacking calpain-1 and PTP1B showed only a partial rescue of the spreading phenotype. In non-adherent platelets, proteolysis and GTPase activity of RhoA and Rac1 were indistinguishable between the wild-type (WT) and calpain-1(-/-) platelets. In contrast, the ECM-adherent calpain-1(-/-) platelets showed higher Rac1 activity at the beginning of spreading, whereas RhoA was more active at later time points. The ECM-adherent calpain-1(-/-) platelets showed an elevated level of RhoA protein but not Rac1 and Cdc42. Proteolysis of recombinant RhoA, but not Rac1 and Cdc42, indicates that RhoA is a calpain-1 substrate in vitro. CONCLUSIONS: Potentiation of the platelet spreading phenotype in calpain-1(-/-) mice suggests a novel role of calpain-1 in hemostasis, and may explain the normal bleeding time observed in the calpain-1(-/-) mice.

Micro-calpain is essential for postmortem proteolysis of muscle proteins.

The objective of this investigation was to test the hypothesis that -calpain is largely responsible for postmortem proteolysis of muscle proteins. To accomplish this objective, we compared proteolysis of known muscle proteins in muscles of wild type and micro-calpain knockout mice during postmortem storage. Knockout mice (n = 6) were killed along with control mice (n = 6). Hind limbs were removed and stored at 4 degrees C. Muscles were dissected at 0, 1, and 3d postmortem and subsequently analyzed for degradation of nebulin, dystrophin, metavinculin, vinculin, desmin, and troponin T. In a separate experiment, hind limb muscles from knockout (n = 4) and control mice (n = 4) were analyzed at 0, 1, and 3 d postmortem using casein zymography to confirm that mu-calpain activity was knocked out in muscle and to determine whether or not m-calpain is activated in murine postmortem muscle. Cumulatively, the results of the first experiment indicated that postmortem proteolysis was largely inhibited in micro-calpain knockout mice. The results of the second experiment established the absence of micro-calpain in the muscle tissue of knockout mice and confirmed the results of an earlier study that m-calpain is active in postmortem murine muscle. The results of the current study show that even in a species in which m-calpain is activated to some extent postmortem, micro-calpain is largely responsible for postmortem proteolysis. This observation excludes a major role for any of the other members of the calpain family or any other proteolytic system in postmortem proteolysis of muscle proteins. Therefore, understanding the regulation of micro-calpain in postmortem muscle should be the focus of further research on postmortem proteolysis and tenderization of meat.