Medicine and Health Sciences Commons^™

Liquid Biopsy: A Step Closer To Transform Diagnosis, Prognosis And Future Of Cancer Treatments, Saife N. Lone, Sabah Nisar, Tariq Masoodi, Mayank Singh, Arshi Rizwan, Sheema Hashem, Wael El-Rifai, Davide Bedognetti, Surinder K. Batra, Mohammad Haris, Ajaz A. Bhat, Muzafar A. Macha

Journal Articles: Biochemistry & Molecular Biology

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly …

The Current Landscape Of Antibody-Based Therapies In Solid Malignancies, Ashu Shah, Sanchita Rauth, Abhijit Aithal, Sukhwinder Kaur, Koelina Ganguly, Catherine Orzechowski, Grish C. Varshney, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for …

Neutrophils Are Mediators Of Metastatic Prostate Cancer Progression In Bone, Diane L. Costanzo-Garvey, Tyler Keeley, Adam J. Case, Gabrielle F. Watson, Massar Alsamraae, Yangsheng Yu, Kaihong Su, Cortney E. Heim, Tammy Kielian, Colm Morrissey, Jeremy S Frieling, Leah M. Cook

Journal Articles: Pathology and Microbiology

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis …

Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary A. Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.

Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND:

Identification of genes that are synthetic lethal to p53 is an important strategy for anticancer therapy as p53 mutations have been reported to occur in more than half of all human cancer cases. Although genome-wide RNAi screening is an effective approach to finding synthetic lethal genes, it is costly and labor-intensive.

METHODS:

To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines, one next-generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA) project, and one gene expression data from the Cancer …

Inference Of Cancer-Specific Gene Regulatory Networks Using Soft Computing Rules., Xiaosheng Wang, Osamu Gotoh

Journal Articles: Genetics, Cell Biology & Anatomy

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One …