Health impact of delayed implementation of cervical cancer screening programs in India: A modeling analysis.

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual-based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age-specific cancer incidence and mortality reductions associated with screening (once-in-a-lifetime among women aged 30-34 years) with one-visit visual inspection with acetic acid (VIA) and one- and two-visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one-visit VIA, two-visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point-of-care one-visit HPV testing in 5 years; and (3) 5-year delayed implementation of screening with current screening tests or point-of-care HPV testing. Immediate implementation of two-visit HPV testing with a switch to one-visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30- to 34-year-old women screened once between 2017 and 2026. Delayed implementation with a one-visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high-burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination

Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers

Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC50 values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin

Investigation of the Antineoplastic Effects of 2-(4-Chlorophenyl)-13α-Estrone Sulfamate against the HPV16-Positive Human Invasive Cervical Carcinoma Cell Line SiHa

Cervical carcinoma is one of the most frequent malignant gynecological cancers in women of reproductive age. Because of the poor tolerability of currently available chemotherapeutic agents, efforts have been focused on developing innovative molecules, including steroids, that exert antineoplastic effects with a better safety profile. In addition to their endocrine properties, certain estrogens exhibit additional biological activities, such as antiangiogenic and anticancer effects. Based on previous studies, the antineoplastic properties of 13α-estrone sulfamate derivatives (13AES1-3) were investigated, and the mechanism of action for the most promising compound 13AES3 was explored. Based on their effects on the viability of different human adherent gynecological cancer cells, the SiHa cervical cell line was used for mechanistic experiments. The most active analog 13AES3 was shown to exert considerable proapoptotic effects, as evidenced by a colorimetric caspase-3 assay and fluorescent double staining. It also elicited antimigratory and anti-invasive effects in a concentration-dependent manner, as evidenced by wound healing and Boyden chamber assays, respectively. Regarding their mechanism of action, 13AES derivatives were shown to inhibit tubulin polymerization, and computer simulations provided a possible explanation for the importance of the presence of the chlorophenyl ring on the estrane skeleton. 13AES3 is considered to be the first 13α-estrone derivative with a significant antineoplastic potency against SiHa cancer cells. Therefore, it might serve as a valuable lead molecule for the design of anticancer agents targeting cervical carcinomas

Microwave-assisted Phospha-Michael addition reactions in the 13α-oestrone series and in vitro antiproliferative properties

exocyclic 16-methylene-17-ketones as a,b-unsaturated ketones were reacted with secondary phosphine oxides as nucleophilic partners. The addition reactions furnished the two tertiary phosphine oxide diastereomers in high yields. The main product was the 16a-isomer. The antiproliferative activities of the newly synthesised organophosphorus compounds against a panel of nine human cancer cell lines were investigated by means of MTT assays. The most potent compound, the diphenylphosphine oxide derivative in the 3-O-methyl-13a-oestrone series (9), exerted selective cell growth-inhibitory activity against UPCI-SCC- 131 and T47D cell lines with low micromolar IC50 values. Moreover, it displayed good tumour selectivity property determined against non-cancerous mouse fibroblast cells