Treatment Response Monitoring Using a Tumor-Informed Circulating Tumor DNA Test in an Advanced Triple-Negative Breast Cancer Patient: A Case Report.

Triple-negative breast cancer (TNBC) is highly aggressive disease that is often refractory to surgery and multiple lines of therapy. Although the repertoire of FDA-approved treatments has expanded, there is an unmet need for biomarkers that can aid in appropriate selection and timing of therapy. We present a case of highly aggressive treatment-resistant TNBC that employed a comprehensive genomic profiling (CGP)-based assay to identify therapeutic targets, followed by longitudinal circulating tumor DNA (ctDNA) testing.

BESPOKE IO protocol: a multicentre, prospective observational study evaluating the utility of ctDNA in guiding immunotherapy in patients with advanced solid tumours.

Introduction: Immunotherapy (IO) has transformed the treatment paradigm for a wide variety of solid tumours. However, assessment of response can be challenging with conventional radiological imaging (eg, iRECIST), which do not precisely capture the unique response patterns of tumours treated with IO. Emerging data suggest that circulating tumour DNA (ctDNA) can aid in response assessment in patients with solid tumours receiving IO.

Chemical synthesis, pharmacological evaluation and in silico analysis of new 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives as potential anti-mitotic agents.

We have synthesized new, biologically active mono- and di-substituted 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives bearing electron withdrawing groups and electron donating groups. These derivative structures were characterized by their spectral and analytical data. The newly synthesized hexahydropyrazole analogues were evaluated for their in vitro anticancer activity against breast and lung cancer cell lines using a cytotoxicity bioassay.

Synthesis and aromatase inhibitory activity of some new 16E-arylidenosteroids.

A new series of 16E-arylidene androstene derivatives has been synthesized and evaluated for aromatase inhibitory activity. The impact of various aryl substituents at 16 position of the steroid skeleton on aromatase inhibitory activity has been observed. The 16E-arylidenosteroids 6, 10 and 11 exhibited significant inhibition of the aromatase enzyme.

Synthesis, antimicrobial activity and QSAR studies of new 2,3-disubstituted-3,3a,4,5,6,7-hexahydro-2H-indazoles.

Antimicrobial activity of synthesized 2,3-disubstituted-3,3a,4,5,6,7-hexahydro-2H-indazole derivatives indicated that 3-(4-chlorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (6) and 3-(4-fluorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (20) were the most active compounds. Further, the results of QSAR studies indicated the importance of topological parameters (2)chi and (2)chi(v) in defining the antimicrobial activity of hexahydroindazoles.

3,4-Disubstituted-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones: synthesis, antimicrobial evaluation and QSAR investigations using Hansch analysis.

The 3,4-disubstituted-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives were synthesized and characterized by physicochemical and spectral means, and the results of antimicrobial study of these compounds against Staphylococcus aureus, Escherichia coli, and Candida albicans by tube dilution method indicated that 4-(4-chlorophenyl)-3-(4-nitrophenylsulfonyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione 6 and 4-(4-fluorophenyl)-3-(4-nitrophenylsulfonyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione 12 were the most potential ones. Further, the QSAR studies by Hansch analysis applied to find out the correlation between physicochemical characteristics of synthesized compounds with antimicrobial activity demonstrated the contribution of electronic parameter, total energy (Te) and the topological parameter (valence second order molecular connectivity index (2 chi v). Excellent statistically significant models were developed by Hansch approach (r2 = 0.

Synthesis and cytotoxic studies of hydroximino derivatives of some 16E-arylidenosteroids.

Oxime and dioxime derivatives of various 16E-arylidenosteroids in the androstene series have been prepared and evaluated at the National Cancer Institute (NCI), Bethesda (USA) for their antineoplastic activity against various tumor cell lines in order to determine the structural requirements for cytotoxic activity. Aldol condensation of dehydroepiandrosterone (DHA) and DHA acetate with various aldehydes followed by treatment with hydroxylamine hydrochloride resulted in the formation of 16E-arylidenosteroid-oxime system. Oximes 15, 16 and compound 20 with a higher degree of oxidation in ring A have been found active in a 60 cell line antitumor prescreen by virtue of their cytotoxic effect against one or more tumor cell line and were further referred for in vivo hollow fiber bioassay.