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The development of newer cisplatin analogs is constantly being investigated owing to its low solubility, poor pharmacokinetics, and dose-related toxicity. In order to address the limitations of current cisplatin therapy, the present study was undertaken. Cisplatin conjugation with an exopolysaccharide extracted from Lactobacillus gasseri (LG-EPS) showed remarkably enhanced and selective anticancer activity by targeting tumor cells overexpressing glucose transporter 1 (GLUT1). The EPS-cisplatin complex exhibited a 600-fold increase in aqueous solubility with a better pharmacokinetic profile (longer half-life) in comparison to cisplatin. Cell viability assay and western blotting demonstrated a strong correlation between the cytotoxicity profile and GLUT1 expressions in different cell lines. The concentration of DNA-bound platinum was also found to be significantly higher in EPS-cisplatin-treated cells. Quercetin, a competitive inhibitor of GLUTs, was shown to prevent this selective uptake of EPS-cisplatin complex. Surprisingly, EPS-cisplatin complex showed an exceptionally safer profile (4 times the maximum tolerated dose of cisplatin) in the acute toxicity study and was also more efficacious against the xenograft mice model. The study suggests that this green glycoconjugation can be an effective and safer strategy to broaden the therapeutic potential of anti-cancer drugs in general and cisplatin in particular. [Display omitted] • Approach for glycoconjugation of cisplatin with probiotic exopolysaccharide (EPS) • EPS glycoconjugation improved the pharmacokinetic and safety profile of cisplatin. • EPS-cisplatin complex exploits Warburg effect to exert selective anti-cancer effect. [ABSTRACT FROM AUTHOR]

This multicentre, retrospective study aimed to establish correlation between estimated tumour volume doubling times (TVDT) from a series of interval breast cancers with their clinicopathological features. The potential impact of delayed diagnosis on prognosis was also explored. Interval cancers, where screening mammograms demonstrated changes that were retrospectively classified as either uncertain or suspicious, were reviewed from five screening units within the UK NHS Breast Screening Programme (NHSBSP). Data collected included the time interval between screening mammogram and cancer diagnosis, the size of the initial mammographic abnormality and of the subsequent cancer, demographics, mammographic density and tumour biology. We estimated volume doubling times and the estimated change in size and node status, which would have followed if these cancers had been detected at the previous screen. 306 interval cancers meeting the inclusion criteria were identified. Average time from screening to diagnosis was 644 days (SD 276 days). 19% were diagnosed in the first twelve months, 42% in the subsequent twelve months and 39% thereafter. Overall average estimated TVDT was 167 days (95% CI 151–186). Significant differences were noted with age (p = 0.01), grade (p < 0.001) and ER status (p < 0.001) with women under 60, grade 3 cancers and ER negative cancers having shorter TVDTs. HER2 positive tumours had shorter doubling times than HER2 negative, but this difference was not statistically significant. It was estimated that diagnosing these cancers at the previous screen would have increased ten-year survival from 82% to 86%. High grade, ER negativity and younger age were associated with shorter durations of TVDT. The role of HER2 status on interval cancer growth rate requires further assessment. It is likely that the delayed diagnosis of interval cancers confers a 4% reduction in ten-year survival. • Unfavourable tumour grade and ER negativity were associated with shorter duration tumour volume doubling time. • Delayed diagnosis of the interval cancers in this series was estimated to reduce ten year survival from 86% to 82%. • Breast cancers in younger women were estimated to display faster growth, i.e., shorter doubling time. [ABSTRACT FROM AUTHOR]

Chalcones/1,3-diphenyl-2-propene-1-one/benzalacetophenone, are the name of structurally related same compound containing two aromatic rings conjunct via bridge system enveloping carbon and keto-ethylenic moiety, considered to be precursors of bioactive flavonoids and isoflavonoids. The molecule owing to presence of dual aromatic rings and keto-ethylenic functionalities act as a versatile and universally accepted lead for search of candidate drug molecule especially anticancer agents. Lower molecular weight, ease of synthetic modification, single step reaction, high yield of pure products are some of the advantages associated with chalcone making it an attractive target for search of better anticancer drug for future. The paper here, thus discuss some of the aspects of chalcone for development of next generation anticancer agents. [ABSTRACT FROM AUTHOR]