Marina Tamara Nechifor

Bio: Marina Tamara Nechifor is an academic researcher from University of Bucharest. The author has contributed to research in topics: Keratinocyte & Glutathione reductase. The author has an hindex of 5, co-authored 8 publications receiving 316 citations.

Reactive Oxygen Species, Cancer and Anti-Cancer Therapies

Abstract: Mammalian cells produce reactive oxygen species (ROS) which are carcinogens, key actors of the non-specific immune defense against pathogens and, in a more subtle way, of signal transduction, cellular metabolism and functions. Oxidative stress can induce severe damage to the host which in turn adapted to face oxidative injury. Disruption of redox balance leads to various pathological conditions, such as cancer. In this review we explore the network linking ROS, cancer cells, anti-tumor immunity and therapy. We emphasize recent findings regarding the oxidative tumor microenvironment and the correlation between ROS, proliferation and death of cancer cells. Further-on we highlight that granulocytes, as key inflammatory cells and ROS producers, are nowadays exploited for eradication of cancer cells. Finally, we focus on ROS-inducing anti-neoplastic therapies (radiotherapy and photodynamic therapy) and on controversial issues regarding the interference between chemotherapy, ROS and antioxidants. This review is directed mainly to researchers involved in anti-cancer drug development by pointing out that redox balance is a suitable therapeutic target, either alone or in combination with other pathways of cancer cells killing. We emphasize critical redox- controlled checkpoints that have to be taken into account in drug design for achieving good therapeutic efficiency and convenient side-effects.

Ethanol-induced alterations of the antioxidant defense system in rat kidney.

Abstract: We report here the effects of chronic ethanol consumption on the antioxidant defense sys- tem in rat kidney. Thirty-two male Wistar rats were randomly divided in two identical groups and were treated as follows: control group (water for fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were sacrificed after 10 weeks, and re- spectively 30 weeks of ethanol consumption, and the renal tissue was isolated and analyzed. Results re- vealed that kidney alcohol dehydrogenase activities in- creased significantly after ethanol administration, but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified. The SDS polyacrylamide- gel electrophoretic study of kidney proteins has re- vealed the appearance of two new protein bands after long-term ethanol consumption. The kidney reduced glutathione/oxidized glutathione ratio decreased, indi- cating an oxidative stress response due to ethanol in- gestion. The malondialdehyde contents and xanthine oxidase activities were unchanged. The antioxidant en- zymatic defense system showed a different response during the two periods of ethanol administration. After 10 weeks, catalase, glutathione peroxidase, glu- tathione reductase, and glucose-6-phosphate dehydro- genase were activated, while superoxide dismutase, glutathione transferase, and � -glutamyltranspeptidase levels were stationary. After 30 weeks, superox- ide dismutase and glutathione peroxidase activities were unmodified, but catalase, glutathione trans- ferase, � -glutamyltranspeptidase, glutathione reduc- tase, and glucose-6-phosphate dehydrogenase activi- ties were significantly increased. Remarkable changes have been registered after 30 weeks of ethanol ad- ministration for glutathione reductase and glucose-6- phosphate dehydrogenase activities, including an in-

UVA Irradiation of Dysplastic Keratinocytes: Oxidative Damage versus Antioxidant Defense

Abstract: UVA affects epidermal cell physiology in a complex manner, but the harmful effects have been studied mainly in terms of DNA damage, mutagenesis and carcinogenesis. We investigated UVA effects on membrane integrity and antioxidant defense of dysplastic keratinocytes after one and two hours of irradiation, both immediately after exposure, and 24 h post-irradiation. To determine the UVA oxidative stress on cell membrane, lipid peroxidation was correlated with changes in fatty acid levels. Membrane permeability and integrity were assessed by propidium iodide staining and lactate dehydrogenase release. The effects on keratinocyte antioxidant protection were investigated in terms of catalase activity and expression. Lipid peroxidation increased in an exposure time-dependent manner. UVA exposure decreased the level of polyunsaturated fatty acids, which gradually returned to its initial value. Lactate dehydrogenase release showed a dramatic loss in membrane integrity after 2 h minimum of exposure. The cell ability to restore membrane permeability was noted at 24 h post-irradiation (for one hour exposure). Catalase activity decreased in an exposure time-dependent manner. UVA-irradiated dysplastic keratinocytes developed mechanisms leading to cell protection and survival, following a non-lethal exposure. The surviving cells gained an increased resistance to apoptosis, suggesting that their pre-malignant status harbors an abnormal ability to control their fate.

The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology

Abstract: Reactive oxygen species (ROS) and the closely related reactive nitrogen species (RNS) are often generated in applications of atmospheric pressure plasmas intended for biomedical purposes. These species are also central players in what is sometimes referred to as ‘redox’ or oxidation‐reduction biology. Oxidation‐reduction biochemistry is fundamental to all of aerobic biology. ROS and RNS are perhaps best known as disease-associated agents, implicated in diabetes, cancer, heart and lung disease, autoimmune disease and a host of other maladies including ageing and various infectious diseases. These species are also known to play active roles in the immune systems of both animals and plants and are key signalling molecules, among many other important roles. Indeed, the latest research has shown that ROS/RNS play a much more complex and nuanced role in health and ageing than previously thought. Some of the most potentially profound therapeutic roles played by ROS and RNS in various medical interventions have emerged only in the last several years. Recent research suggests that ROS/RNS are significant and perhaps even central actors in the actions of antimicrobial and anti-parasite drugs, cancer therapies, wound healing therapies and therapies involving the cardiovascular system. Understanding the ways ROS/RNS act in established therapies may help guide future efforts in exploiting novel plasma medical therapies. The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but these species are just as important in plants. It appears that there are opportunities for useful applications of plasmas in this area as well. (Some figures may appear in colour only in the online journal)

Industrial applications of crustacean by-products (chitin, chitosan, and chitooligosaccharides): A review

Abstract: Background Food processing produces large quantities of by-products. Disposal of waste can lead to environmental and human health problems, yet often they can be turned into high value, useful products. For example, crustacean shell wastes from shrimp, crab, lobster, and krill contain large amounts of chitin, a polysaccharide that may be extracted after deproteinisation and demineralization of the exoskeletons. Scope and approach This review summarizes the current state of knowledge of these crustacean shellfish wastes and the various ways to use chitin. This biopolymer and its derivatives, such as chitosan, have many biological activities (e.g., anti-cancer, antioxidant, and immune-enhancing) and can be used in various applications (e.g., medical, cosmetic, food, and textile). Key findings and conclusions Due to the huge waste produced each year by the shellfish processing industry and the absence of waste management which represent an environmental hazard, the extraction of chitin from crustaceans’ shells may be a solution to minimize the waste and to produce valuable compound which possess biological properties with application in many fields. As a food waste, it is important to also be aware of the non-food uses of these wastes.

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS -generating agents

Abstract: PurposeTherapeutic selectivity is one of the most important considerations in cancer chemotherapy. The design of therapeutic strategies to preferentially kill malignant cells while minimizing harmful effects to normal cells depends on our understanding of the biological differences between cancer and normal cells. We have previously demonstrated that certain agents generating reactive oxygen species (ROS) such as 2-methoxyestradiol (2-ME) preferentially kill human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The purpose of the current study was to investigate the biochemical basis for such selective anticancer activity.MethodsFlow cytometric analyses were utilized to measure intracellular O2− levels and apoptosis. MTT assays were used as indicators of cellular viability. Western blot analysis was used to measure the expression of antioxidant enzymes in cancer and normal cells.ResultsMalignant cells in general are more active than normal cells in the production of O2−, are under intrinsic oxidative stress, and thus are more vulnerable to damage by ROS-generating agents. The intrinsic oxidative stress in cancer cells was associated with the upregulation of SOD and catalase protein expression, likely as a mechanism to tolerate increased ROS stress. The increase in SOD and catalase expression was observed both in primary human leukemia cells and in primary ovarian cancer cells. Both malignant cell types were more sensitive to 2-ME than their normal counterparts, as demonstrated by the significant accumulation of O2− and subsequent apoptosis. The administration of ROS scavengers in combination with 2-ME prevented the accumulation of O2− and abrogated apoptosis induction.ConclusionsO2− is an important mediator of 2-ME-induced apoptosis. The increased oxidative stress in cancer cells forces these cells to rely more on antioxidant enzymes such as SOD for O2− elimination, thus making the malignant cells more vulnerable to SOD inhibition than normal cells.

Pectin and Pectinases: Production, Characterization and Industrial Application of Microbial Pectinolytic Enzymes

Abstract: Departamento de Bioquimica e Microbiologia Instituto de Biociencias Universidade Estadual Paulista, UNESP, Avenida 24A, 1515, CEP 13506-900 Rio Claro, SP