These results suggest that hCG, through its binding to the LH/CG receptor, may augment proliferation and inhibit apoptosis in choriocarcinoma JAr cells, and that the introduction of an antisense gene may be a potential approach to the inhibition of choriocarcinoma cell growth.
The present study was conducted to determine whether T(3) receptor exists in early placental extravillous trophoblasts (EVTs) and evaluate the influence of T(3) on Fas/Fas ligand expression, caspase-3, and poly (ADP-ribose) polymerase (PARP) cleavage and apoptosis in cultured early placental EVTs. EVTs with invasive phenotype, isolated from normal placental explants from early pregnancy through preincubation on human fibronectin-coated dishes and exhibited cytokeratin 7 and human placental lactogen immunopositive staining, were cultured in the absence or presence of T(3) (10(-7) to 10(-9) m). The presence of T(3) receptor in cultured EVTs was examined by immunocytochemistry, RT-PCR, and Southern blot analysis. Fas sensitivity was determined by treating the cells with an agonistic Fas antibody. Apoptosis was assessed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, flow cytometry, and Hoechst nuclear staining. Fas and Fas ligand expression and caspase-3 and PARP cleavage were evaluated by immunocytochemistry. Early placental EVTs expressed a 212-bp c-erb Abeta1 transcript and the T(3) receptor protein and exhibited significant levels of apoptosis in culture. Treatment with T(3) reduced the expression of Fas and Fas ligand as well as cleavage of caspase-3 and PARP and suppressed apoptosis in cultured EVTs. Although addition of agonistic Fas antibody increased apoptosis in these cells, this response was markedly attenuated by the presence of T(3). These results demonstrate that T(3) receptor is present in early placental EVTs and that T(3) suppresses apoptosis by down-regulating the expression of Fas and Fas ligand. These findings are consistent with the hypothesis that T(3) promotes EVT invasion to the decidua by suppressing apoptosis in early pregnancy.
Background: In Japan, pharmacoeconomic requirements for list-price adjustment were institutionalized in April 2019 following provisional implementation of a new Health Technology Assessment (HTA) program 2016-2019. Since April 2019, submission of cost-effectiveness evidence to the Central Social Insurance Medical Council (Chuikyo) as part of the Japanese Ministry of Health, Labour, and Welfare has been mandatory for selected pharmaceuticals and medical devices. Methods: Based on a review of publications and commentaries since April 2019, together with views from a group of experts on key issues to be addressed, this report provides an update on recent HTA developments and key challenges still to be addressed. Results and Discussion: Japan's new HTA program is a first step toward development of a universal healthcare system that can be sustainable for many years into the future. Currently, Japan's HTA program requires provision of incremental cost-effectiveness ratios (ICERs) as evidence, with quality-adjusted life years as the preferred outcome measure. Prices can be adjusted both upward and downward according to the degree of the ICER estimate. Japan is the first country to have adopted an algorithmic method for "ICER-based" pricing; however, HTA measures that extend beyond a single ICER estimate are needed to take full advantage of HTA in the future. In particular, generation of evidence of value should support changes to the healthcare system so that incentives for innovation are not diminished while industry and government are not overburdened by the generation or assessment of evidence. There is a need to ensure scientifically sound HTA expertise across all sectors in Japan, and therefore enhancement of HTA literacy and capability among healthcare professionals, academia, government, and industry should be a priority.
In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.
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