Studies of transgenic tobacco plants containing Escherichia Coli glutathione reductase.

Thesis (M.Sc.)-University of Natal, 1996.Glutathione reductase (GR) and superoxide dismutase (SOD) enzymes are thought to play an important role in the plant chloroplast antioxidant system. Tobacco plants transformed with E. coli glutathione reductase and superoxide dismutase genes were used to investigate the role of these gene products (enzymes) in the chloroplast antioxidant system. These plants were T1318 (transformants with increased levels of cytoplasmic glutathione reductase activity) and GOR1OT (transformants with increased levels of cytoplasmic' glutathione reductase activity and chloroplastic superoxide dismutase). In addition, 10~M methyl violegen (paraquat), was used to perturb the system experimentally under high light, low light and in darkness. During these experiments GRA (glutathione reductase activity) was assayed and the results expressed as mg-1protein, mg-1 chlorophyll and g-1 tissue, using different types of transgenic plants. T131 B-cytosolic GOR transformants had a higher GRA under high light intensity. Under low light intensity T131B had a small increase in GRA compared to controls (T131 Bs in 1mM CaS04). Also leaf discs in the dark showed similar GRA as did controls. The three treatments had no effect on the GRA of untransformed plants. GOR1OT (cytoplamic GOR and chloroplastic SOD transformants) had a slight increase in GRA under high light intensity and in darkness. At low light intensity GOR10T showed similar results to controls. The results indicate the overall absolute increase in GRA in transgenic plants after methyl violegen treatment. The higher activity than that of nontransgenic controls indicate that bacterial GRA must have also increased following exposure to methyl violegen

Editorial : Cholesterol and cancer drug resistance : molecular, signaling, and therapeutic aspects

No abstract available.The National Research Foundation (NRF) and the the South African Medical Research Council- Self Initiated Research (SAMRC-SIR).https://www.frontiersin.org/journals/geneticsdm2022Medical Oncolog

Aberrant splicing events and epigenetics in viral oncogenomics : current therapeutic strategies

Cancer is a global burden and is the second leading cause of mortality. It is largely a non-communicable disease attributable to the accumulation of damaged DNA and deleterious mutations in vital genes caused by exposure to carcinogens. Besides, viruses with oncogenic potential are also known to cause cancer through infections. Approximately, 12–20% of all cancers have a viral aetiology. Oncovirus infections are potentially modifiable risk factors, and targeting infections can be useful in prevention measures. In 2018, the global cancer cases attributable to infections were estimated to be 2.2 million. The International Agency for Research on Cancer (IARC) has identified seven different cancer-causing viruses namely the Human papillomaviruses (HPV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Epstein–Barr virus (EBV), Human T cell leukaemia virus 1 (HTLV-1), Kaposi’s Sarcoma Herpesvirus (KSHV) and Human immunodeficiency virus 1 (HIV-1). HIV-1 contributes to cancer development through immunosuppression by permitting the co-infection of other oncogenic viruses. With the exception of KSHV, the IARC classified these viruses as group one human carcinogens and further categorised these based on the viral genome as DNA viruses or RNA viruses. HPV, HBV and HCV are major contributors to cancers associated with viral infections, and the number of cases varies based on geographic locations. In 2018, Eastern Asia had the highest number of infection-related cancer, with 37.9 cases per 100,000 person-years, closely followed by Sub-Saharan Africa (SSA) with 33.1 cases per 100,000 person-years. A number of these infection-related cancers can be prevented with effective infection control through available vaccines, awareness and understanding of the risk factors.The Medical Research Council of South Africahttp://www.mdpi.com/journal/cellspm2021Medical Virolog

Splicing machinery genomics events in acute myeloid leukaemia (AML) : in search for therapeutic targets, diagnostic and prognostic biomarkers

Acute myeloid leukemia (AML) is the most common form of acute leukaemia and has the highest mortality rate. Screening for mutations in patients with AML has shown that in many cases genes carrying mutations are involved in the alternate splicing of mRNA. These include members of the Serine Arginine (SR) family of splicing factors, as well as components of the spliceosome. Mutations in associated genes also affect the function of members of the heterogeneous nuclear ribonucleoproteins (hnRNPs). These mutations in splicing factors can lead to changes in the expression of different isoforms whose splicing is controlled by these splicing factors. These different isoforms may have completely different functions, for example, members of the BCl-2 family are alternately spliced to give rise to pro and anti-apoptotic members. Mutations in the splicing factors that control the splicing of these mRNAs can lead to changes in the expression level of these isoforms. In this review we will examine the mechanics of the regulation of the various splice isoforms and how this drives the development of tumors. This information is pertinent for drug discovery, and the splicing factors with the most promise for pharmacological control will be discussed.http://www.ajcr.ushj2021Medical Oncolog

Role and merits of green based nanocarriers in cancer treatment

The use of nanocarriers for biomedical applications has been gaining interests from researchers worldwide for the delivery of therapeutics in a controlled manner. These “smart” vehicles enhance the dissolution and the bioavailability of drugs and enable their delivery to the target site. Taking the potential toxicity into consideration, the incorporation of natural “green” materials, derived from plants or microbial sources, in the nanocarriers fabrication, improve their safety and biocompatibility. These green components can be used as a mechanical platform or as targeting ligand for the payload or can play a role in the synthesis of nanoparticles. Several studies reported the use of green based nanocarriers for the treatment of diseases such as cancer. This review article provides a critical analysis of the different types of green nanocarriers and their synthesis mechanisms, characterization, and their role in improving drug delivery of anticancer drugs to achieve precision cancer treatment. Current evidence suggests that green-based nanocarriers can constitute an effective treatment against cancer.The National Research Foundation of South Africa and the South African Medical Research Council (SAMRC).https://www.mdpi.com/journal/cancersam2022Internal Medicin

Efavirenz induces DNA damage response pathway in lung cancer

The cell-cycle related genes are potential gene targets in understanding the effects of efavirenz (EFV) in lung cancer. The present study aimed at investigating the expression changes of cell-cycle related genes in response to EFV drug treatment in human non-small cell lung carcinoma (A549) and normal lung fibroblast (MRC-5) cells. The loss in nuclear integrity in response to EFV was detected by 4′, 6-diamidino2-phenylindole (DAPI) staining. Gene expression profiling was performed using human cell cycle PathwayFinder RT2 Profiler™ PCR Array. The expression changes of 84 genes key to the cell cycle pathway in humans following EFV treatment was examined. The R2 PCR Array analysis revealed a change in expression of selected gene targets (including MAD2L2, CASP3, AURKB). This change in gene expression was at least a two-fold between test (EFV treated) and the control. RT-qPCR confirmed the PCR array data. In addition to this, the ATM signaling pathway was shown to be upregulated following EFV treatment in MRC-5 cells. In particular, ATM’s upstream activation resulted in p53 upregulation in normal lung fibroblasts. Interestingly, the p53 signaling pathway was activated irrespective of the repressed ATM pathway in A549 cells as revealed by the Ingenuity Pathway Analysis (IPA). These EFV effects are similar to those of ionizing radiation and this suggests that EFV has anti-tumour properties.South African Medical Research Council (SAMRC)http://www.impactjournals.com/oncotargethj2021Internal Medicin

Current Immunotherapeutic Treatments in Colon Cancer

The immune system is able to act against cancer cells and consequently these cells have developed a range of responses to evade or suppress the immune systems anticancer responses. The concept of cancer immunotherapy is based on techniques developed to restore or boost the ability of the immune system to recognize and target tumor cells. It is known that colon cancer does initiate an immune response and that this type of cancer initiates pathways and responses to evade or suppress the immune system. This chapter will discuss some of the dominant therapies being developed to treat colon cancer based on the concept of cancer immunotherapy. Cancer vaccines are based on the concept of providing the immune system with antigen targets derived from tumor-specific molecules, while monoclonal antibodies involve the development of antibodies specifically targeting proteins expressed on the surface of tumor cells. Antibody-based immunotherapy has further applications in the use of bispecific antibodies (BsAb), which are synthetic antibodies designed to be able to recognize two different antigens or epitopes and in this way can increase the immunoresponse and limit immune evasion observed in mono-targeted therapy. Immune checkpoint inhibitors target proteins that are responsible for keeping immune responses in check. Tumor cells overexpress these proteins in order to evade the immune response. Blocking these proteins will lead to an increased immune response against these cells. Cytokine-based immunotherapies involve the use of the immune systems’ own molecular messengers that are responsible for a robust immune response, to boost the antitumor response of the immune system. Oncolytic viral therapy is based on the use of viruses that selectively infect and replicate in cancer and associated endothelial cells and subsequently kills these cells. Adoptive immunotherapy involves the use of immune cells from the patient to be cultured and altered in the laboratory and then reintroduced to boost the immune response. This is normally performed with T cells. Immunotherapy may be the next logical step in the development of an effective therapy for colon cancer and other cancers. The combination of these therapies with traditional chemotherapy or radiotherapy has shown promise in cancer treatment

Exploiting the molecular basis of oesophageal cancer for targeted therapies and biomarkers for drug response : guiding clinical decision-making

Worldwide, oesophageal cancer is the sixth leading cause of deaths related to cancer and represents a major health concern. Sub-Saharan Africa is one of the regions of the world with the highest incidence and mortality rates for oesophageal cancer and most of the cases of oesophageal cancer in this region are oesophageal squamous cell carcinoma (OSCC). The development and progression of OSCC is characterized by genomic changes which can be utilized as diagnostic or prognostic markers. These include changes in the expression of various genes involved in signaling pathways that regulate pathways that regulate processes that are related to the hallmarks of cancer, changes in the tumor mutational burden, changes in alternate splicing and changes in the expression of non-coding RNAs such as miRNA. These genomic changes give rise to characteristic profiles of altered proteins, transcriptomes, spliceosomes and genomes which can be used in clinical applications to monitor specific disease related parameters. Some of these profiles are characteristic of more aggressive forms of cancer or are indicative of treatment resistance or tumors that will be difficult to treat or require more specialized specific treatments. In Sub-Saharan region of Africa there is a high incidence of viral infections such as HPV and HIV, which are both risk factors for OSCC. The genomic changes that occur due to these infections can serve as diagnostic markers for OSCC related to viral infection. Clinically this is an important distinction as it influences treatment as well as disease progression and treatment monitoring practices. This underlines the importance of the characterization of the molecular landscape of OSCC in order to provide the best treatment, care, diagnosis and screening options for the management of OSCC.The South African Medical Research Council (SAMRC), The National Research Foundation (NRF) and Discovery Health.https://www.mdpi.com/journal/biomedicinesam2023Medical OncologySurger

Role and merits of green based nanocarriers in cancer treatment

The use of nanocarriers for biomedical applications has been gaining interests from researchers worldwide for the delivery of therapeutics in a controlled manner. These “smart” vehicles enhance the dissolution and the bioavailability of drugs and enable their delivery to the target site. Taking the potential toxicity into consideration, the incorporation of natural “green” materials, derived from plants or microbial sources, in the nanocarriers fabrication, improve their safety and biocompatibility. These green components can be used as a mechanical platform or as targeting ligand for the payload or can play a role in the synthesis of nanoparticles. Several studies reported the use of green based nanocarriers for the treatment of diseases such as cancer. This review article provides a critical analysis of the different types of green nanocarriers and their synthesis mechanisms, characterization, and their role in improving drug delivery of anticancer drugs to achieve precision cancer treatment. Current evidence suggests that green-based nanocarriers can constitute an effective treatment against cancer

Mitotic syndicates Aurora Kinase B (AURKB) and mitotic arrest deficient 2 like 2 (MAD2L2) in cohorts of DNA damage response (DDR) and tumorigenesis

Aurora Kinase B (AURKB) and Mitotic Arrest Deficient 2 Like 2 (MAD2L2) are emerging anticancer therapeutic targets. AURKB and MAD2L2 are the least well studied members of their protein families, compared to AURKA and MAD2L1. Both AURKB and MAD2L2 play a critical role in mitosis, cell cycle checkpoint, DNA damage response (DDR) and normal physiological processes. However, the oncogenic roles of AURKB and MAD2L2 in tumorigenesis and genomic instability have also been reported. DDR acts as an arbitrator for cell fate by either repairing the damage or directing the cell to self-destruction. While there is strong evidence of interphase DDR, evidence of mitotic DDR is just emerging and remains largely unelucidated. To date, inhibitors of the DDR components show effective anti-cancer roles. Contrarily, long-term resistance towards drugs that target only one DDR target is becoming a challenge. Targeting interactions between protein-protein or protein-DNA holds prominent therapeutic potential. Both AURKB and MAD2L2 play critical roles in the success of mitosis and their emerging roles in mitotic DDR cannot be ignored. Small molecule inhibitors for AURKB are in clinical trials. A few lead compounds towards MAD2L2 inhibition have been discovered. Targeting mitotic DDR components and their interaction is emerging as a potent next generation anti-cancer therapeutic target. This can be done by developing small molecule inhibitors for AURKB and MAD2L2, thereby targeting DDR components as anti-cancer therapeutic targets and/or targeting mitotic DDR. This review focuses on AURKB and MAD2L2 prospective synergy to deregulate the p53 DDR pathway and promote favourable conditions for uncontrolled cell proliferation.http://www.elsevier.com/locate/reviewsmrhttp://www.elsevier.com/locate/mutrespm2022Internal Medicin