Lauren Forchette

Bio: Lauren Forchette is an academic researcher from West Virginia School of Osteopathic Medicine. The author has contributed to research in topics: Internal medicine & Oncology. The author has an hindex of 1, co-authored 1 publications receiving 10 citations.

A Comprehensive Review of COVID-19 Virology, Vaccines, Variants, and Therapeutics.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Throughout the past year, multiple vaccines have already been developed and used, while some others are in the process of being developed. However, the emergence of new mutant strains of SARS-CoV-2 that have demonstrated immune-evading characteristics and an increase in infective capabilities leads to potential ineffectiveness of the vaccines against these variants. The purpose of this review article is to highlight the current understanding of the immunological mechanisms of the virus and vaccines, as well as to investigate some key variants and mutations of the virus driving the current pandemic and their impacts on current management guidelines. We also discussed new technologies being developed for the prevention, treatment, and detection of SARS-CoV-2. In this paper, we thoroughly reviewed and provided crucial information on SARS-CoV-2 virology, vaccines and drugs being used and developed for its prevention and treatment, as well as important variant strains. Our review paper will be beneficial to health care professionals and researchers so they can have a better understanding of the basic sciences, prevention, and clinical treatment of COVID-19 during the pandemic. This paper consists of the most updated information that has been available as of June 21, 2021.

Genetics, Treatment, and New Technologies of Hormone Receptor-Positive Breast Cancer

Abstract: Simple Summary In this review paper, we focused on the discussion of various important aspects of hormone receptor (HR)-positive breast cancer, including HR structure and signaling, genetics (epigenetics and gene mutations), gene expression-based assays, traditional and new drugs for treatment, and new technological uses in diagnosis and treatment. Particularly, we summarized the commonly mutated genes and abnormally methylated genes in HR-positive breast cancer and compared the common gene expression-based assays that are used in breast cancer as prognostic and/or predictive tools in detail. All of these topic discussions have not been fully described and summarized within other research or review articles. Abstract The current molecular classification divides breast cancer into four major subtypes, including luminal A, luminal B, HER2-positive, and basal-like, based on receptor gene expression profiling. Luminal A and luminal B are hormone receptor (HR, estrogen, and/or progesterone receptor)-positive and are the most common subtypes, accounting for around 50–60% and 15–20% of the total breast cancer cases, respectively. The drug treatment for HR-positive breast cancer includes endocrine therapy, HER2-targeted therapy (depending on the HER2 status), and chemotherapy (depending on the risk of recurrence). In this review, in addition to classification, we focused on discussing the important aspects of HR-positive breast cancer, including HR structure and signaling, genetics, including epigenetics and gene mutations, gene expression-based assays, the traditional and new drugs for treatment, and novel or new uses of technology in diagnosis and treatment. Particularly, we have summarized the commonly mutated genes and abnormally methylated genes in HR-positive breast cancer and compared four common gene expression-based assays that are used in breast cancer as prognostic and/or predictive tools in detail, including their clinical use, the factors being evaluated, patient demographics, and the scoring systems. All these topic discussions have not been fully described and summarized within other research or review articles.

Abstract 2489: Study the efficacy of hypomethylating agent in treating regular and brain metastasized HER2-positive breast cancer

Abstract: Breast cancer is the second leading cause of cancer with the highest mortality rate in females in the United States. Late stage breast cancer can metastasize to different locations of the body, and patients with brain metastasis have a poor prognosis and short survival time. HER2-positive breast cancer, composed of ~15-20% of total cases, is aggressive with unfavorable clinical outcomes. Although HER2-targeted therapies are available, they are mostly ineffective against brain metastasis. To study tumor metastasis, we had established the breast cancer brain metastasis preclinical cell and mouse models. Our previous study has shown that the hypomethylating agent azacitidine (AZA) is effective in treating brain metastasis triple-negative breast cancer using in vitro cell and in vivo mouse models. Thus, we hypothesized that AZA will be effective to treat HER2-positive breast cancer. To test our hypothesis, we treated regular (JIMT-1) and brain metastasized (JIMT-1 Br) HER2-positive breast cancer cell lines with various concentrations of AZA, and the IC50 values, cell proliferation, and apoptosis were measured. Our results showed that train metastasized HER2-positive breast cancer JIMT-1 Br cells have similar growth rate compared to their parental regular breast cancer JIMT-1 cells. Regular breast cancer cells are more sensitive to AZA treatment, supported by (1) The IC50 value of AZA in JIMT-1 cells is significantly lower than that in JIMT-1 Br cells; (2) 72 hours of AZA treatment significantly inhibited cell grow in both cell lines, and the inhibition of JIMT-1 growth is greater than that of JIMT-1 Br cells; (3) AZA triggered apoptosis in both cell lines in a dose-dependent manner; (4) Higher concentrations of AZA induced a higher percentage of cell apoptosis in JIMT-1 compared to JIMT-1 Br cells. AZA treatment does not significantly change the expression of metastasis protein markers in either cell line. Epithelial-mesenchymal transition promotes cancer cell invasion and metastasis. Epithelial markers include cytokeratins and E-cadherin, and mesenchymal markers include N-cadherin and vimentin. We measured the expression of those markers in both cell lines after AZA treatment by Western blotting, and found that the expression of pan-cytokeratins and keratin 18 were equivalent between both cell lines upon AZA treatment. However, the expression of keratin 19, E-cadherin, N-cadherin, and vimentin were not detected in either cell line. In conclusion, in this study, we tested the in vitro effects of the hypomethylating agent AZA in both regular and brain metastasized HER2-positive breast cancer cells. We found that AZA inhibits cell growth and promotes apoptosis in both cell types, but the regular breast cancer cells are more sensitive to AZA treatment compared to brain metastasized cells, shown by the differences in IC50 values and extents of cell growth inhibition and apoptosis induction. Citation Format: Tuoen Liu, Christopher Butler, Kelsey Donoughe, Lauren Forchette, William Sebastian, Gabor Szalai, Paul Lockman. Study the efficacy of hypomethylating agent in treating regular and brain metastasized HER2-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2489.

Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy

Abstract: The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.

A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant

Abstract: Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus’s transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.