Identification of altered genes associated with non-small cell lung cancer promotion and progression

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New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer

Resistance to chemotherapeautic drugs is one of the main obstacles to effective cancer treatment. Multidrug resistance (MDR) is defined as resistance to structurally and/or functionally unrelated drugs, and has been extensively investigated for the last three decades. There are two types of MDR: intrinsic and acquired. Tumor microenvironment selection pressure leads to the development of intrinsic MDR, while acquired resistance is a consequence of the administered chemotherapy. A central issue in chemotherapy failure is the existence of heterogeneous populations of cancer cells within one patient and patient-to-patient variability within each type of cancer. Numerous genes and pathways contribute to the development of MDR in cancer. Point mutations, gene amplification or other genetic or epigenetic changes all affect biological functions and may lead to the occurrence of MDR phenotype. Similar to the characteristics of cancerogenesis, the main features of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells, drugs need to reach their intracellular target molecules. The overexpression of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to decreased uptake of the drug and intracellular drug accumulation, minimising drug-target interactions. New agents being or inspired by natural products that sucessfully target these mechanisms are the main subject of this review. Two key approaches in combating MDR in cancer are discussed (i) finding agents that preserve citotoxicity toward MDR cancer cells; (ii) developing compounds that restore the cytotoxic activity of classic anticancer drugs.Ministry of Education, Science and Technological Development of the Republic of Serbia {[}III41031]; COST Actions {[}CM1106, CM1407

Identification of altered genes associated with non-small cell lung cancer promotion and progression

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Effect of sulfinosine [(R,S)-2-amino-9-beta-D-ribofuranosylpurine-6-sulfinamide] on lung carcinoma cell lines and its role in overcoming multidrug resistance

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Loss of heterozygosity of PTEN in patients with non-small cell lung cancer treated and not treated with neoadjuvant chemotherapy

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Loss of heterozygosity of PTEN in patients with non-small cell lung cancer treated and not treated with neoadjuvant chemotherapy

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NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells

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Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma

Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80\% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAG LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy. (C) 2014 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia {[}III41031

Genomic instability in non-small cell lung cancer assessed by arbitrarily primed polymerase chain reaction

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Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to chemosensitize anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we investigated and correlated the expression of phosphatase and tensin homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and p53 genes in samples of patients with ATC. Furthermore, we evaluated the potential of inhibition of these pathways on chemosensitization of ATC using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results revealed a negative correlation between the activity of RAS-MAPK-ERK and PI3K-AKT-mTOR pathways in samples of patients. To be specific, the PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or high pERK expression. In vitro results suggest that the inhibition of either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity of thyroid cancer cells to classic chemotherapeutics. This may form a basis for the development of novel genetic-based therapeutic approach for this cancer type.Ministry of Education, Science and Technological Development, Republic of Serbia {[}III41031