Regulating RNA Binding Motif 5 Gene Expression- A Novel Therapeutic Target for Lung Cancer.

RNA-binding motif protein 5 (RBM5), also known as LUCA-15/H37, is a gene that maps to human chromosome 3p21.3, a critical region that is deleted in a large number of human cancers, of which the majority are lung cancers, and that is predicted to contain one or more tumor suppressor genes (TSGs). RBM5 is a tumor suppressor gene and is most frequently deleted at the earliest stage of lung cancer development. It represents a significant area of recent progress in cancer genomic, cytogenetic, and molecular biological research because of its role in the induction of cell cycle arrest and apoptosis and the regulation of inhibition of in lung cancer metastasis. RBM5 is involved in the suppression of epidermal growth factor receptor (EGFR) expression, thus preventing proliferation, angiogenesis, invasion, and metastasis of lung cancer. In this way it exhibits its tumor suppressive capacity during lung cancer progression. Exploration of RBM5's potential importance in inhibiting tumor metastasis includes downstream players in the RBM5-mediated metastasis suppressor pathway(s). This review highlights the differential expression of the RBM5 tumor suppressor gene which impacts cell proliferation and apoptosis control during lung cancer progression. Regulating RBM5 expression may be a novel therapeutic target for lung cancer.

Copine 3 as a Novel Potential Drug Target for Non-Small-Cell Lung Carcinoma.

Cancer originates from uncontrolled cell division in any part of the body. The universal burden of cancer continues to increase, and its treatment remains ever more challenging. Among several cancers, lung cancer is the second most common, causing 1.6 million deaths worldwide per year. Approximately 85% of lung cancers are non-small-cell lung carcinomas (NSCLCs), which are considerably more difficult to treat than other cancers. Although various imaging, biopsy, and histopathological analyses are widely used, there are no effective or reliable biomarkers for detecting early lung carcinoma, particularly NSCLC. For this reason, the identification of novel biomarkers to serve as therapeutic targets is essential to NSCLC treatment. Copines are a family of membrane-binding proteins that are highly conserved, soluble, ubiquitously expressed, calcium dependent, and found in variety of eukaryotic organisms. Recent research suggests that they may mediate various signaling pathways involved in both tumor progression and metastasis. In the copine gene family, copine 3 is a novel player in regulating NSCLC metastasis. This review highlights copine 3 as a prognostic marker as well as a potential therapeutic target for effective treatment of patients with NSCLC.

Epidermal Growth Factor Receptor Tyrosine Kinase: A Potential Target in Treatment of Non-Small-Cell Lung Carcinoma.

Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations. Another, newer approach is directed against cancer-specific molecules and signaling pathways and thus has more limited nonspecific toxicities. This approach targets the epidermal growth factor receptor (EGFR, HER-1/ErbB1), a receptor tyrosine kinase of the ErbB family, which consists of four closely related receptors: HER-1/ErbB1, HER-2/neu/ErbB2, HER-3/ErbB3, and HER-4/ErbB4. Because EGFR is expressed at high levels on the surface of some cancer cells, it has been recognized as an effective anticancer target. EGFR-targeted therapies include monoclonal antibodies (mAbs) and small-molecule tyrosine kinase inhibitors. Tyrosine kinases are an especially important target because they play an important role in the modulation of growth factor signaling. This review highlights various classes of synthetically derived molecules that have been reported in the last few years as potential EGFR-TK inhibitors (TKIs) and their targeted therapies in NSCLC, along with effective strategies for overcoming EGFR-TKI resistance and efforts to develop a novel potent EGFR-TKI as an efficient target of NSCLC treatment in the foreseeable future.

KAI1/CD82, Metastasis Suppressor Gene as a Therapeutic Target for Non-Small-Cell Lung Carcinoma.

Lung cancer is the most frequent malignancy and the leading cause of cancer-related death worldwide; it is the second most common cancer, comprising 1.69 million deaths worldwide per year. Among these, 85% of lung cancers are non-small-cell lung carcinoma (NSCLC). Metastasis is common in NSCLC patients and are responsible for most deaths. Kang-Ai 1 (KAI1), a tumor metastasis suppressor gene also known as Cluster of Differentiation 82 (CD82), is a member of the membrane tetraspanin protein family, which are capable of inhibiting the metastatic process in NSCLC. KAI1/CD82 suppresses metastasis via multiple mechanisms regulating inhibition of cell motility, adhesion, fusion, and proliferation. KAI1 may attenuate signaling to shut down metastatic colonization through attenuation of epidermal growth factor receptor (EGFR) signaling and inhibition of the Wnt signaling pathways. In this review, we focus on the differential expression of KAI1/CD82, a tumor metastasis suppressor gene that can inhibit cancer invasion and cell metastasis during NSCLC. The differential expression of KAI1/CD82 could prove to be of novel therapeutic significance in treating malignant tumors and in reducing their metastatic potential.

1,2-Diazole prevents cisplatin-induced nephrotoxicity in experimental rats.

BACKGROUND: Cisplatin (a platinum-compound) is a anti-neoplastic drug used in the treatment of various cancers but eventually results in severe adverse effects namely nephrotoxicity or renal disorder through generation of reactive oxygen species (ROS). This biochemical measurements and histopathology analysis investigated a possible protective effect of 1,2-diazole with regards to cisplatin-induced nephrotoxicity in experimental animals. METHODS: Animals were divided into four groups of six mice each. Group A: normal control, vehicle (1% (w/v) gum acacia in phosphate buffer saline (PBS)). Group B: cisplatin group, vehicle + cisplatin (7.5 mg/kg). Group C: 1,2-diazole (10 mg/kg) + cisplatin and Group D: silymarin (50 mg/kg) + cisplatin. Each vehicle/drug treatment was given daily via intraperitoneal (ip) injection for 10 consecutive days starting from day 1. On group B, C and D cisplatin was given in single dose only on day 5 one hour post drug administration. Animals were allowed till 10th day and on day 11 all four groups animals were anesthetized. Blood samples were collected and serum was isolated for biochemical measurements. The rats were then euthanized by cervical dislocation and their kidney was recovered and then prepared for biochemical measurements and histopathology analyses. RESULTS: Pretreatment with 1,2-diazole prevented nephrotoxicity induced by cisplatin through a protective mechanism that involved reduction of increased oxidative stress by significantly increasing the enzymatic and non enzymatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione (GSH) and diminishing the lipid peroxidation (LPO). The pretreatment with 1,2-diazole does not affect superoxide dismutase (SOD), catalase (CAT), serum urea and creatinine level during nephrotoxicity when compared to cisplatin-induced group. Moreover, the 1,2-diazole animals shown significant decrease in urine volume and kidney weight when compared with cisplatin-induced group. Histopathological findings reveals the protective efficacy of 1,2-diazole that restores histopathological changes against nephrotoxicity. CONCLUSION: These analysis will provide a critical evidence that 1,2-diazole could provide a new protective strategy against cisplatin-induced nephrotoxicity.

Kisspeptins (KiSS-1): essential players in suppressing tumor metastasis.

Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP- 10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.