scholarly journals OBSERVATIONS ON THE MECHANISM OF ACTION OF ESTROGENS AT THE CELLULAR LEVEL

1962 ◽  
Vol 2 (3) ◽  
pp. 367-372 ◽  
Author(s):  
CLAUDE A. VILLEE
Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3467
Author(s):  
Albert Jang ◽  
Oliver Sartor ◽  
Pedro C. Barata ◽  
Channing J. Paller

Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes. Poly (ADP-ribose) polymerase (PARP) inhibitors take advantage of HRR deficiency to kill tumor cells based on the concept of synthetic lethality. Several PARP inhibitors (PARPis) have been successful in various malignancies with HRR gene mutations including BRCA1/2, especially in breast cancer and ovarian cancer. More recently, olaparib and rucaparib were approved for mCRPC refractory to novel hormonal therapies, and other PARPis will likely follow. This article highlights the mechanism of action of PARPis at the cellular level, the preclinical data regarding a proposed mechanism of action and the effectiveness of PARPis in cancer cell lines and animal models. The article expands on the clinical development of PARPis in mCRPC, discusses potential biomarkers that may predict successful tumor control, and summarizes present and future clinical research on PARPis in the metastatic disease landscape.


1972 ◽  
Vol 59 (4) ◽  
pp. 299-304 ◽  
Author(s):  
Gail Sansone-Bazzano ◽  
Ronald M. Reisner ◽  
Gaetano Bazzano

Author(s):  
Surabhi Gautam ◽  
Rima Dada

Complex chronic lifestyle disorders are the leading causes of death and disability worldwide. Stress and anxiety associated with today's hectic life schedule and polluted environment have contributed a lot in triggering and causing many chronic diseases and decreased quality of life, even with pharmacologic treatment. Most of the chronic complex diseases, such as chronic obstructive pulmonary disease, depression, autoimmune diseases, cancer, cardiovascular diseases, obesity, and diabetes mellitus share underlying mechanisms like high levels of stress, anxiety, depression, oxidative stress, shorter telomeres, persistent activation of hypothalamo-pituitary adrenal axis, inflammation and dysregulated immune system, and thus need to be managed by an integrated approach that targets both mind and body. The individuals with these conditions have been reported to benefit from yoga, but the underlying mechanism of action of yoga remains unclear. The aim of this chapter is to summarize the mechanism of action underlying the cumulative effect of yoga on multiple pathways at a cellular level.


1981 ◽  
Vol 240 (4) ◽  
pp. E391-E393
Author(s):  
D. L. Vesely

The objective of the present investigation was to determine whether angiotensin II at physiological levels has part of its mechanism of action through stimulation of the activity of guanylate cyclase (EC 4.6.1.2), the enzyme that catalyzes the conversion of guanosine triphosphate to cyclic GMP. Angiotensin II enhanced guanylate cyclase activity three-to fivefold in rat aorta, heart, and kidney at a concentration of 1 nM. Dose-response curves revealed that near maximal stimulation of guanylate cyclase with angiotensin II was observed at a concentration as low as 10 pM. The guanylate cyclase cofactor manganese was necessary for the maximal enhancement of guanylate cyclase by angiotensin II. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of angiotensin II at the cellular level.


1991 ◽  
Vol 35 (1) ◽  
pp. 92-92
Author(s):  
SO Skouby ◽  
O Andersen ◽  
KR Pedersen ◽  
L Molsted-Petersen ◽  
C Kuhl

2016 ◽  
Vol 96 (1) ◽  
pp. 127-149 ◽  
Author(s):  
Karl Swann ◽  
F. Anthony Lai

The most fundamental unresolved issue of fertilization is to define how the sperm activates the egg to begin embryo development. Egg activation at fertilization in all species thus far examined is caused by some form of transient increase in the cytoplasmic free Ca2+ concentration. What has not been clear, however, is precisely how the sperm triggers the large changes in Ca2+ observed within the egg cytoplasm. Here, we review the studies indicating that the fertilizing sperm stimulates a cytosolic Ca2+ increase in the egg specifically by delivering a soluble factor that diffuses into the cytosolic space of the egg upon gamete membrane fusion. Evidence is primarily considered in species of eggs where the sperm has been shown to elicit a cytosolic Ca2+ increase by initiating Ca2+ release from intracellular Ca2+ stores. We suggest that our best understanding of these signaling events is in mammals, where the sperm triggers a prolonged series of intracellular Ca2+ oscillations. The strongest empirical studies to date suggest that mammalian sperm-triggered Ca2+ oscillations are caused by the introduction of a sperm-specific protein, called phospholipase C-zeta (PLCζ) that generates inositol trisphosphate within the egg. We will discuss the role and mechanism of action of PLCζ in detail at a molecular and cellular level. We will also consider some of the evidence that a soluble sperm protein might be involved in egg activation in nonmammalian species.


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