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The Dobbs decision overturned the right to abortion in the United States and allowed states to enact total abortion bans. In addition to restricting access to abortion, laws criminalizing pregnancy outcomes deter providers from offering timely, appropriate care for pregnancy complications. To avoid litigation or prosecution, providers are under pressure to strictly guard the privacy of patient health information related to pregnancy. Perinatal care is at risk of repeating the experience of similar enhanced privacy rules for substance use disorders, which have impeded information sharing and care coordination that improves outcomes. [ABSTRACT FROM AUTHOR]

The dietary stilbene resveratrol is a major constituent of a variety of edible plant products, including grapes and peanuts. Resveratrol has been identified as an excellent candidate cancer chemopreventive, based on its safety and efficacy in animal models of carcinogenesis. Resveratrol is a prototype of a plethora of bioactive polyphenols in the food supply that has just begun to be mined for cancer preventive agents. For example, polyphenolic grapeseed fractions were shown recently to potently antagonize chemical carcinogenesis. Taking into consideration that the identification of resveratrol as a cancer preventive agent is largely owed to its high abundance in nature (e.g., it accounts for 5-10% of the grapeskin biomass), it is logical to expect that naturally occurring stilbenes that are superior to resveratrol in their cancer preventive properties await identification. Thus, resveratrol may represent the tip of the iceberg of a broad class of stilbene and related polyphenolic natural products that include safe and highly effective agents for cancer prevention. We hypothesize that resveratrol may be especially suitable as a lead agent for prostate cancer prevention given its ability to: 1) inhibit each stage of multistage carcinogenesis, 2) scavenge incipient populations of androgen-dependent prostate cancer cells through androgen receptor antagonism, and 3) scavenge incipient populations of androgen-independent prostate cancer cells by short-circuiting the epidermal growth factor-receptor (EGFR)-dependent autocrine loops in the cancer cells. KEY WORDS: * resveratrol, prostate cancer prevention * dietary polyphenols * protein kinase C (PKC) * epidermal growth factor receptor (EGFR)

Underrepresentation of individuals with limited English proficiency (LEP) who speak Spanish is ongoing in phase 3 biomedical clinical trials and exacerbates health inequity. This article suggests strategies for increasing representation of Spanish speakers in clinical rials by emphasizing the importance of early engagement with Spanish language communities, inclusive participant recruitment, and collaborative trial design and implementation. Although investigators and institutions administering government-funded research must meet federal requirements for language assistance, journal editors, peer reviewers, institutional review board members, academic health centers, and all beneficiaries of the biomedical and behavioral research enterprise in the United States must motivate linguistic inclusion. [ABSTRACT FROM AUTHOR]

Results of a recent study indicate that protein kinase C-alpha (PKC-alpha) isozymes may be oxidatively inactivated by S-thiolation reactions involving endogenous thiols such as glutathione (GSH). PKC is an isozyme family with 10 mammal members and has an important role in differentiation and growth of cells.

Research was conducted to investigate the effects of resveratrol on protein kinase C (PKC)-catalyzed phosphorylation of the cofactor-independent substrate protamine sulfate which is polybasic protein that activates PKC via a novel mechanism. Results indicate that the efficacy of resveratrol against cellular PKC may reflect antagonism of the phosphorylation of arginine-rich PKC substrates that bear resemblance to protamine sulfate in their interactions with PKC.

Byline: Philip J. Bergman (1), Karen R. Gravitt (1), Nancy E. Ward (1), Pedro Beltran (1), Krishna P. Gupta (2), Catherine A. O'Brian (1) Keywords: protein kinase C (PKC); intrinsic drug resistance; human colon cancer; multidrug resistance (MDR); MDR reversal; N-myristoylated pseudosubstrate peptides Abstract: Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression have been shown to significantly reduce intracellular accumulation of chemotherapeutic drugs, in association with the induction of multidrug resistance (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR cancer cells. These observations constitute solid evidence that PKC plays a significant role in the MDR phenotype of cancer cells. PKC-catalyzed phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as a contributing factor in MDR. At present, the sole drug transport-related event that has been identified as a component of the role of PKC in MDR is PKC-induced expression of the P-glycoprotein-encoding gene mdr1. The objective of this study was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic drugs by cultured human colon cancer cells that lacked P-glycoprotein activity and did not express the drug efflux pump at the level of message (mdr1) or protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly reduced uptake of [[.sup.14]C] Adriamycin and [[.sup.3]H] vincristine in human colon cancer cells devoid of P-glycoprotein activity, and that PKC-inhibitory N-myristoylated PKC-[alpha] pseudosubstrate synthetic peptides potently and selectively induced uptake of the cytotoxic drugs in the phorbol ester-treated and non-treated colon cancer cells. TPA treatment of the cells did not induce expression of either P-glycoprotein or its message mdr1. In contrast with [[.sup.14]C]Adriamycin and [[.sup.3]H] vincristine uptake, [[.sup.3]H] 5-fluorouracil uptake by the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These results indicate that PKC activation can significantly reduce the uptake of multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and that N-myristoylated PKC-[alpha] pseudosubstrate peptides potently and selectively induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by a novel mechanism that does not involve P-glycoprotein and may involve PKC isozyme inhibition. Thus, N-myristoylated PKC-[alpha] pseudosubstrate peptides may offer a basis for the development of agents that reverse intrinsic drug resistance in human colon cancer. Author Affiliation: (1) Department of Cell Biology, U.T.M.D. Anderson Cancer Center, Houston, Texas, USA (2) Environmental Carcinogenesis Laboratory, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow, India Article History: Registration Date: 29/09/2004

The catalytic region of protein kinase C (PKC) is directly inactivated by a sequence of N-myristoylated octapeptide substrate analogs when binding occurs at the protein substrate binding region of PKC(free). The feature which separates N-myristoylated octapeptides from histone substrate and the dead-end inactivator PKC(19-36), is its capacity to bind PKC(free). Exclusive binding of histone and PKC(19-36) to the PKC-ATP complex is observed. Weak competition between protein substrates and inactivating oligonucleotide PKC substrate analogs is one of the restrictions of the analog.

A study was done on the intrinsic ATPase activity of protein kinase C. It was shown that the ATPase activity of PKC is catalyzed at the active site and that PKC contains a potential nucleotide binding site in their catalytic domains. In addition, it was also shown that the regulatory and catalytic properties of the ATpase reactions of the three PHC isozymes are similar despite the critical differences in their consensus sequences.