Mckenna Longacre

Drug Resistance in Cancer: An Overview

Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study.

EMT and tumor metastasis

EMT and MET comprise the processes by which cells transit between epithelial and mesenchymal states, and they play integral roles in both normal development and cancer metastasis. This article reviews these processes and the molecular pathways that contribute to them. First, we compare embryogenesis and development with cancer metastasis. We then discuss the signaling pathways and the differential expression and down-regulation of receptors in both tumor cells and stromal cells, which play a role in EMT and metastasis. We further delve into the clinical implications of EMT and MET in several types of tumors, and lastly, we discuss the role of epigenetic events that regulate EMT/MET processes. We hypothesize that reversible epigenetic events regulate both EMT and MET, and thus, also regulate the development of different types of metastatic cancers.

Cancer Development, Progression, and Therapy: An Epigenetic Overview

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

Public Health in the Vilna Ghetto as a Form of Jewish Resistance

We describe the system of public health that evolved in the Vilna Ghetto as an illustrative example of Jewish innovation and achievement during the Holocaust. Furthermore, we argue that by cultivating a sophisticated system of public health, the ghetto inmates enacted a powerful form of Jewish resistance, directly thwarting the intention of the Nazis to eliminate the inhabitants by starvation, epidemic, and exposure. In doing so, we aim to highlight applicable lessons for the broader public health literature. We hope that this unique story may gain its rightful place in the history of public health as an insightful case study of creative and progressive solutions to universal health problems in one of the most challenging environments imaginable.

The Association Between Atherosclerosis and Low Back Pain: A Systematic Review

To assess the evidence of association between atherosclerosis and low back pain (LBP).

A preliminary comparison of primary care use by refugees before and after acupuncture

Abstract Background: Limited research exits on utilization and cost-effectiveness of acupuncture among underserved communities, and virtually no evidence has been published with respect to refugee populations. In this study, we examined the relationship between acupuncture and the total utilization of primary care services in a cohort of refugee patients with chronic pain. Methods: We retrospectively reviewed the medical records of 16 refugee patients with chronic pain at Boston Medical Center (BMC). The research was IRB-approved. Demographics and total charges associated with primary care over 18 months were collected. Results: Total charges associated with primary care services decreased by 50.2% in our refugee cohort in the 12 months following acupuncture treatment, equivalent to a savings of

Anti-breast Cancer Effects of Histone Deacetylase Inhibitors and Calpain Inhibitor

691 per patient per month. Conclusions: This preliminary review demonstrated a statistically significant decrease in total charges associated with primary care following acupuncture treatment (p=0.0308). This study suggests the need for further investigation of the relation between acupuncture and refugees with chronic pain, as well as the financial implications of this relationship. It is unclear why refugees may seek fewer primary care services after acupuncture treatment. Additional study is needed to further explore whether this relationship is generalizable to other hospital services and to other patient populations.