Ki-67 and Its Relation With Complete Pathological Response in Patients With Breast Cancer.

Introduction Ki-67 is a nuclear antigen present in the synthesis phase of the cell cycle. Studies have shown that a high value of Ki-67 results in greater response to chemotherapy with higher incidence of complete pathological response, which ultimately results in improved overall survival. Methods and materials The objective of the study was to determine the frequency of high Ki-67 levels in breast cancer patients and to find the correlation of complete pathological response in breast cancer with Ki-67 levels. It is a descriptive case series with a correlational study design done at Fauji Foundation Hospital Rawalpindi. Eighty patients with locally advanced breast cancer who underwent neoadjuvant chemotherapy followed by surgery were recruited. Their Ki-67 levels were determined on trucut biopsy. Pathological response in the post-op sample was correlated with Ki-67 levels. Results The results showed 27 (33%) patients out of the 80 had high Ki-67 values. Among them 17 (63%) had complete pathological response, seven (26%) showed partial pathological response whereas three (11%) had disease progression. In contrast, out of the 53 patients having low Ki-67 values, only nine (17%) had complete pathological response, 31 (58%) showed partial pathological response and 13 (25%) had progressive disease. A Chi-square test was applied which showed significant correlation between Ki-67 and complete pathological response, with a p value of 0.00018. Conclusion Therefore high Ki-67 values in patients with breast cancer correlated well with attainment of complete pathological response. We can incorporate Ki-67 in the initial clinical assessment of breast cancer patients to help predict effectiveness as well as response to chemotherapy.

Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring.

BACKGROUND: Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring. OBJECTIVE: We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets. METHODS: Cellular and molecular mechanisms underlying these persistent changes were determined in F1 and F2 adult offspring of F0 mothers exposed to two relevant human exposure levels of BPA (10µg/kg/d-LowerB and 10mg/kg/d-UpperB). RESULTS: Both doses of BPA significantly impaired insulin secretion in male but not female F1 and F2 offspring. Surprisingly, LowerB and UpperB induced islet inflammation in male F1 offspring that persisted into the next generation. We also observed dose-specific effects of BPA on islets in males. UpperB exposure impaired mitochondrial function, whereas LowerB exposure significantly reduced ß-cell mass and increased ß-cell death that persisted in the F2 generation. Transcriptome analyses supported these physiologic findings and there were significant dose-specific changes in the expression of genes regulating inflammation and mitochondrial function. Previously we observed increased expression of the critically important ß-cell gene, Igf2 in whole F1 embryos. Surprisingly, increased Igf2 expression persisted in the islets of male F1 and F2 offspring and was associated with altered DNA methylation. CONCLUSION: These findings demonstrate that maternal BPA exposure has dose- and sex-specific effects on pancreatic islets of adult F1 and F2 mice offspring. The transmission of these changes across multiple generations may involve either mitochondrial dysfunction and/or epigenetic modifications. https://doi.org/10.1289/EHP1674.

Evidence for widespread exonic small RNAs in the glaucophyte alga Cyanophora paradoxa.

RNAi (RNA interference) relies on the production of small RNAs (sRNAs) from double-stranded RNA and comprises a major pathway in eukaryotes to restrict the propagation of selfish genetic elements. Amplification of the initial RNAi signal by generation of multiple secondary sRNAs from a targeted mRNA is catalyzed by RNA-dependent RNA polymerases (RdRPs). This phenomenon is known as transitivity and is particularly important in plants to limit the spread of viruses. Here we describe, using a genome-wide approach, the distribution of sRNAs in the glaucophyte alga Cyanophora paradoxa. C. paradoxa is a member of the supergroup Plantae (also known as Archaeplastida) that includes red algae, green algae, and plants. The ancient (>1 billion years ago) split of glaucophytes within Plantae suggests that C. paradoxa may be a useful model to learn about the early evolution of RNAi in the supergroup that ultimately gave rise to plants. Using next-generation sequencing and bioinformatic analyses we find that sRNAs in C. paradoxa are preferentially associated with mRNAs, including a large number of transcripts that encode proteins arising from different functional categories. This pattern of exonic sRNAs appears to be a general trend that affects a large fraction of mRNAs in the cell. In several cases we observe that sRNAs have a bias for a specific strand of the mRNA, including many instances of antisense predominance. The genome of C. paradoxa encodes four sequences that are homologous to RdRPs in Arabidopsis thaliana. We discuss the possibility that exonic sRNAs in the glaucophyte may be secondarily derived from mRNAs by the action of RdRPs. If this hypothesis is confirmed, then transitivity may have had an ancient origin in Plantae.