Richard H. Matthews

Bio: Richard H. Matthews is an academic researcher from Beth Israel Deaconess Medical Center. The author has contributed to research in topics: Chinese hamster ovary cell & Oxidative stress. The author has an hindex of 12, co-authored 15 publications receiving 691 citations. Previous affiliations of Richard H. Matthews include Emory University & Missouri University of Science and Technology.

Multiple Management Modalities in Esophageal Cancer: Epidemiology, Presentation and Progression, Work-up, and Surgical Approaches

Abstract: Annually, approximately 13,200 people in the U.S. are diagnosed with esophageal cancer and 12,500 die of this malignancy. Of new cases, 9,900 occur in men and 3,300 occur in women. In part I of this two-part series, we explore the epidemiology, presentation and progression, work-up, and surgical approaches for esophageal cancer. In the 1960s, squamous cell cancers made up greater than 90% of all esophageal tumors. The incidence of esophageal adenocarcinomas has risen considerably over the past two decades, such that they are now more prevalent than squamous cell cancer in the western hemisphere. Despite advances in therapeutic modalities for this disease, half the patients are incurable at presentation, and overall survival after diagnosis is grim. Evolving knowledge regarding the etiology of esophageal carcinoma may lead to better preventive methods and treatment options for early stage superficial cancers of the esophagus. The use of endoscopic ultrasound and the developing role of positron emission tomography have led to better diagnostic accuracy in this disease. For years, the standard of care for esophageal cancer has been surgery; there are several variants of the surgical approach. We will discuss combined modality approaches in part II of this series.

Multiple management modalities in esophageal cancer: combined modality management approaches.

Abstract: The overall success rate nationally in treating esophageal carcinomas remains poor, with over 90% of patients succumbing to the disease. In part I of this two-part series, we explored epidemiology, presentation and progression, work-up, and surgical approaches. In part II, we explore the promising suggestions of integrating chemotherapy and radiation therapy into the multimodal management of esophageal cancers. Alternative approaches to resection alone have been sought because of the overall poor survival rates of esophageal cancer patients, with failures occurring both local-regionally and distantly. Concomitant chemotherapy and radiation therapy (XRT) have been shown, by randomized trial, to be more effective than XRT alone in treating unresectable esophageal cancers and also have shown promise as a neoadjuvant treatment when combined with surgery in the multimodal treatment of this disease. Various studies have also addressed issues such as preoperative chemotherapy, radiation dose escalation, chemotherapy/XRT as a definitive treatment versus use as a surgical adjuvant, and alternative chemotherapy regimens. There are suggestions of some progress, but this remains a difficult problem area in which management is continuing to evolve.

Regulation of gene expression by reactive oxygen

Abstract: Reactive oxygen intermediates are produced in all aerobic organisms during respiration and exist in the cell in a balance with biochemical antioxidants. Excess reactive oxygen resulting from exposure to environmental oxidants, toxicants, and heavy metals perturbs cellular redox balance and disrupts normal biological functions. The resulting imbalance may be detrimental to the organism and contribute to the pathogenesis of disease and aging. To counteract the oxidant effects and to restore a state of redox balance, cells must reset critical homeostatic parameters. Changes associated with oxidative damage and with restoration of cellular homeostasis often lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant defense enzymes, and structural proteins. In this review, we examine the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.

Chelation in Metal Intoxication

Abstract: Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

Can antioxidant be beneficial in the treatment of lead poisoning

Abstract: Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species, reducing the antioxidant defense system of cells via depleting glutathione, inhibiting sulfhydryl-dependent enzymes, interfering with some essential metals needed for antioxidant enzyme activities, and/or increasing susceptibility of cells to oxidative attack by altering the membrane integrity and fatty acid composition. Consequently, it is plausible that impaired oxidant/antioxidant balance can be partially responsible for the toxic effects of lead. Where enhanced oxidative stress contributes to lead-induced toxicity, restoration of a cell's antioxidant capacity appears to provide a partial remedy. Several studies are underway to determine the effect of antioxidant supplementation following lead exposure. Data suggest that antioxidants may play an important role in abating some hazards of lead. To explain the importance of using antioxidants in treating lead poisoning the following topics are addressed: (i) Oxidative damage caused by lead poisoning; (ii) conventional treatment of lead poisoning and its side effects; and (iii) possible protective effects of antioxidants in lead toxicity.