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Not AvailableCluster analysis using Mahalnobis D2 was performed using 97 groundnut diverse genotypes for 14 yield contributing and water use efficiency related traits. The genotypes were grouped into twelve clusters based on D2 statistic. Cluster II was the largest with 54 genotypes followed by cluster I with 33 genotypes and remaining ten clusters had one genotype each. The inter cluster D2 values revealed maximum divergence between cluster VI and cluster III (1736), followed by cluster XII and cluster III (1622); cluster VI and cluster X11 (1389); cluster IX and cluster XI (1171) and cluster XI and cluster II (1041). It was observed that plant height was the largest contributor (65%) towards genetic divergence followed by days to maturity (10%) and secondary branches per plant (10%), SPAD Chlorophyll Meter Reading (SCMR; 4.3%) kernel length and hundred pod weight (1.2%) and Specific Leaf Area (SLA; 0.06%) contributed the least for divergence. Estimates of GCV and PCV were high for plant height, primary and secondary branches and pod yield per plant indicating higher genetic variation present in the genotypes studied. High heritability coupled with high genetic advance as per cent of mean was observed for days to fifty per cent flowering, secondary branches per plant, hundred pod and kernel weight, kernel length and, SCMR. SLA exhibited moderate estimates of heritability and genetic advance as per cent of meanNot Availabl

CYP2D6 phenotype indicative for optimized antiestrogen efficacy associates with outcome in early breast cancer patients

BACKGROUND: Endoxifen serum concentrations seem to correlate with outcome in breast cancer (BC) patients. Concurrently, cytochrome P450 2D6 (CYP2D6) enzyme activity and dextromethorphan (DM) metabolism are deemed a surrogate marker for the formation of endoxifen. Here, we conducted a matched cohort study to determine the impact of an extensive CYP2D6 phenotype on relapse in patients with early-stage estrogen receptor (ER)-positive BC and adjuvant tamoxifen intake. METHODS: CYP2D6 extensive metabolism was determined upon appropriate dextromethorphan/dextrorphan (DM/DX) urinary excretion ratios (≤0.30). Fifty-nine BC patients were identified as extensive phenotype metabolizers, while for 148 matched controls, CYP2D6 was not determined. Patients and controls did not differ with respect to age, stage, hormone receptor status, HER2, grade, menopausal status, chemotherapy and antihormonal therapy. Survival analysis was performed according to clinical follow-up. RESULTS: Disease-free survival (DFS) of patients identified as extensive CYP2D6 metabolizers did not differ significantly from controls (p = 0.10). However, when patients with ER expression of ≤20 % were excluded from the analysis, DFS was associated with a more favorable outcome (p = 0.06). CONCLUSIONS: This study suggests a positive association between extensive CYP2D6 metabolism and outcome in early-stage ER-positive BC patients using tamoxifen and in particular, when a sufficient number ERs are represented on the primary tumor

The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs

Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy (Cyclophosphamide, CP and Doxorubicin, DOX)-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: 1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; 2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; 3) self-dimerization or binding to IGFBP-3 may not be involved in HN’s effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects