Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.

BACKGROUND: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed. METHODS: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383). RESULTS: A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro. CONCLUSION: In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

OBJECTIVE: To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. METHODS: Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. RESULTS: Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. CONCLUSION: These regulatory peptides may be involved in the pathophysiology of the testes.

Antibodies to human seminal plasma inhibin adversely affect sperm function parameters.

Polyclonal antibodies to intact inhibin (94 amino acids, R-94, 10.5 kDa) and its sequence specific synthetic fragments (R-9, R-17) were evaluated for their effect on various physical and biochemical parameters of sperm function. Intact inhibit had maximum deleterious effect on quantitative motility and mean forward progression of spermatozoa. Antibodies had no effect on sperm fructolysis and sperm nuclear chromatin decondensation reaction. Sperm plasma membrane was damaged in antibodies treated spermatozoa as evidenced by hypoosmotic swelling test and sperm lipid peroxidation reaction.

Hormonal modulation of biosynthesis of prostatic specific antigen, prostate specific acid phosphatase and prostatic inhibin peptide.

Hormonal modulation of in vitro biosynthesis of three prostatic secretory proteins, prostate specific acid phosphatase (PSAP), prostate specific antigen (PSA) and prostatic inhibin peptide (PIP) by human benign hyperplasia (BPH) tissue was studied. LH and inhibins caused increase in the synthesis of all three proteins whereas FSH enhanced the synthesis of PIP and PSA only but decreased PSAP synthesis. Prolactin and thyroid releasing hormone decreased synthesis of PIP and PSAP. However, PSA synthesis was enhanced by TRH and was decreased by prolactin. Estradiol caused significant increase in PSA and PSAP but no discernible changes in PIP synthesis were noticed. Testosterone caused an increase in PIP, PSA and PSAP. These data indicate that biosynthesis of PIP, PSA and PSAP by BPH tissue is under multihormonal regulation.

Influenza vaccine and anticoagulation control in patients receiving warfarin.

The effects of a trivalent split virion influenza vaccine on anticoagulation control were prospectively evaluated in a sample of well-controlled warfarin recipients. Vaccine-induced changes in prothrombin time ratios were not detected during one month of follow-up after immunisation. The results are supported by the findings of other studies conducted in this country and the USA, which have all refuted the conclusions of early reports that suggested a possible interaction between warfarin and influenza vaccine.