Agent For Management Of Cancer Research Articles

Screening Campaign and Docking Investigations in Identifying New Hit Compounds as Inhibitors of Human Carbonic Anhydrases Expressed In Tumour Cells.

The tumor-expressed human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII have been extensively studied to develop anticancer agents targeting solid tumors in combined therapy. These CA isoforms are considered key factors in controlling tumor microenvironment (TME) of cancer lines that develop high metastatic activity. Herein, we report the discovery of potent hCA IX/hCA XII inhibitors that were disclosed through a screening campaign on an in-house collection of arylsulfonamides preliminary tested toward other hCAs. Among them, the N-(4-sulfamoylphenyl)naphthalene-2-carboxamide (12) and N-(4-sulfamoylphenyl)-3,4-dihydroisoquinoline-2(1H)-carbothioamide (15) proved to be the most intriguing hCA IX/hCA XII inhibitors displaying favourable selectivity ratios over widespread hCA I and hCA II isoforms. To explore their binding mode, we conducted docking studies that described the poses of the best inhibitors in the catalytic site of hCA IX and hCA XII, thus suggesting the privileged pattern of interactions. These structural findings might further improve the knowledge for a successful identification of new sulfonamides as adjuvant agents in cancer management.

Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer.

Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential −0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.

Gold Nanoparticles - Synthesis and Applications in Cancer Management

Gold nanoparticles (AuNPs) are one of the most widely studied nanomaterials in the last decade, and are emerging as promising agents in cancer management. Gold nanostructures in varying size and shape, such as rods, triangles, hexagons, octagons, cubes, nanowires, nanospheres, etc. could be synthesized using various well-established physical and chemical techniques. Synthesis of AuNPs, using green chemistry approaches that utilize various materials of biological origin, such as proteins, polysaccharides, microorganisms, plant and cell extracts, have received increasing attention. AuNPs have numerous physical assets that make them appealing for applications in cancer management, including imaging, drug delivery, photothermal therapy and many more. Considering the widespread impact of AuNPs in cancer, an increasingly large number of patents have been awarded for the synthesis and medical applications of AuNPs. Owing to the importance of AuNPs in cancer management, the present review focuses on their modes of synthesis and widespread applications in cancer management, with special reference to recent patents.

Apigenin Sensitizes Huh-7 Human Hepatocellular Carcinoma Cells to TRAIL-induced Apoptosis

TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.

Policy Implications of Oral Agents

With the increasing use of oral antineoplastic agents in cancer management, patients and family members need to understand of how to obtain, safely handle, and store the medication, how and when the medications should be taken, and when to report toxic side effects to accomplish efficacious treatment. Research-based articles and conference presentations. Cancer centers to modify policies, protocols, or practices to assure safe and proper administration of oral antineoplastic agents. Clinicians need to monitor and facilitate administration of oral antineoplastic agents, and ultimately improve clinical outcomes.

The Challenges of Oral Agents as Antineoplastic Treatments

Given the increasing use of oral antineoplastic agents in cancer management, patient adherence is critical to successful treatment outcomes. This article reviews the scope of the problem and issues of adherence to oral antineoplastic agents. Research-based and other articles, newsletters, and conference presentations. Suboptimal adherence to oral antineoplastic agents is a significant clinical problem that may result in disease or treatment complications, adjustment in treatment regimen, disease progression, and premature death. Healthcare providers need to monitor and facilitate adherence by identifying barriers and implementing strategies to assure adherence, and therefore, improve clinical outcomes.

Changing Healthcare Practice for Older Adults with Late‐Stage Non‐Small Cell Lung Cancer: Practical Considerations of Targeted Therapy in Primary Care and Oncology

Healthcare practice for cancer care is rapidly evolving because of advances in technology, scientific discovery, drug development, and aging demographics in America. Among the substantive changes in science and drug development is targeted therapy. Targeted agents are changing the scope of practice in treating lung cancer-the leading cause of cancer death in older adults. Given the growing use of these agents in cancer management, shared awareness of practical management considerations between specialists and primary care providers is important. This article reviews targeted therapy in late-stage non-small cell lung cancer (NSCLC) and shared care concerns in continuity of care of older Americans with this disease. Important practice points for providers caring for older patients with late-stage lung cancer treated with targeted therapy are presented through an educational guide addressing potential management concerns.

Risks and Benefits of Erythropoiesis-Stimulating Agents in Cancer Management

Anemia is frequently diagnosed in patients with cancer and its treatment is an important clinical problem. The deficiency in red blood cells (RBCs) can be a debilitating problem, and anemia correlates with poor performance status, deteriorates quality of life, and may negatively influence the prognosis of cancer patients. The development of recombinant human erythropoietins (rhEPO) provides a therapeutic option in patients with mild to moderate anemia. However, clinical experience demonstrates that more than half of anemic cancer patients are not treated. There is clear evidence that rhEPO reliably increases haemoglobin (Hb) levels in patients suffering from cancer-related or treatment-associated anemia. The dosing and management of these patients should strictly follow evidence-based guidelines of the clinical societies, as well as the manufacturer's recommendations. Furthermore, treatment of patients beyond the correction of anemia must be regarded as potentially harmful and should only be conducted in an experimental clinical setting. In this review, recently published recommendations and standards for the use of rhEPO will be discussed.

In Vivo Antitumor Activity of ZYD88, a Chinese Herbal Medicine, in Animal Models with S180 Sarcoma and Ehrlich Tumor

Cancer is a leading cause of death in the world. The continuous development of effective and nontoxic therapeutic agents is a major task in the battle of cancer. We report the in vivo effects of a Chinese herbal medicine, ZYD88, on the inhibition of tumor growth in an S(180) xenograft animal model and the improvement of animal survival in the Ehrlich tumor model. Oral administration of ZYD88 in mice with the xenograft S(180) sarcoma significantly inhibited tumor growth in a dose-dependent manner. Moreover, ZYD88 given to the animals with Ehrlich ascitic tumors by gavage significantly prolonged the life span compared with that of animals treated with saline. In both animal models, the effects of ZYD88 were comparable to those of a standard chemotherapeutic agent, cyclophosphamide, although it had few side effects. These results clearly demonstrated the in vivo anticancer activity of ZYD88 in two different animal models and suggest that ZYD88 is a potential agent for the clinical management of cancer and warrants further preclinical and clinical investigations.