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1.
Drug Res (Stuttg) ; 68(3): 146-152, 2018 03.
Article in English | MEDLINE | ID: mdl-29132176

ABSTRACT

Lung cancer is one of the foremost tumor-associated cause of death in the world. Most of the patients with NSCLC possesses an advanced disease at diagnosis, and are thus probable subject for systemic therapy. This study aims to evaluate the cytotoxicity of vinblastine and docetaxel combined therapy for the treatment of NSCLC, as well as verapamil (VER) enhancement of the combined therapy. We conducted P-glycoprotein (P-gp) gene expression, protein expression with RT-PCR and western blot respectively, apoptotic response of the combined therapy with VER is also determined using DAPI staining (%). Result of DAPI staining confirmed combination therapy promotes cell apoptosis to greater extent as compared to each drug alone. Real-time RT-PCR analysis revealed that mdr-1 expression level increased 6 fold with docetaxel (40 nM) and 2 fold with vinblastine (30 nM) after 24 h (p<0.001). Consequently, combination therapy reduced drug-induced up-regulation of mdr-1 significantly (p<0.05). VER with the drug combination increased P-gp expression (p<0.05). These data provide evidence showing combined therapy is a better approach to improve the efficacy of chemotherapy and decreasing drug resistance.


Subject(s)
Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Taxoids/pharmacology , Verapamil/pharmacology , Vinblastine/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Cell Line, Tumor , Cell Survival/drug effects , Docetaxel , Drug Synergism , Drug Therapy, Combination , Gene Expression/drug effects , Humans
2.
Biomed Pharmacother ; 88: 1046-1053, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28192881

ABSTRACT

Hepatocellular carcinoma is an antecedent of liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. Transforming growth factor-Beta (TGF-b) plays an important role in creating a favorable microenvironment for tumor cell growth via two major mechanisms: an intrinsic activity as an autocrine growth factor and an extrinsic activity by inducing microenvironment changes. Recently stem cell therapy as also been a promising and potential treatment for liver cancer and in addition signaling pathways like GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines has been identified to regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes. Thus stem cell-based therapy, together with signaling pathways can become a practical option in regenerative processes for replacing dead hepatocytes cells. Targeted drug delivery systems (TDDS) via biomaterials are presently been explored for cancer therapeutics especially liver cancer as it allows the enhancement of drug concentration in the liver and decrease the dosage and side effects. This review is intended to give a comprehensive summary of available liver cancer therapy using stem cells, growth factor and biomaterials.


Subject(s)
Biocompatible Materials/therapeutic use , Carcinoma, Hepatocellular/therapy , Intercellular Signaling Peptides and Proteins/therapeutic use , Liver Neoplasms/therapy , Stem Cell Transplantation , Animals , Humans , Stromal Cells/pathology
3.
Biol Trace Elem Res ; 176(2): 328-337, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27600929

ABSTRACT

Selenium is considered as a trace element that plays antioxidant role in the body. So, the aim of this study was to evaluate the effect of selenium on ameliorating of sciatic nerve ischemia-reperfusion injury. Eighty (80) adult male Wistar rats weighing 250-300 g were used. They were divided into 10 groups (n = 8). Then, femoral vessels were obstructed by using 4/0 silk and splitknot techniques. After 3-h ischemia for all the groups, reperfusion was applied for different periods: 3, 7, 14, and 28 days. In half of each experimental group, 0.2 mg/kg selenium was injected intraperitoneally, coinciding with ischemia. After reperfusion, according to the grouping, rats were killed by using high dose of anesthetic drug and then sciatic nerve was removed and fixed. Then, tissue samples were processed and subsequently stained with hematoxylin-eosin, apoptosis, and immunohistochemistry stains. On the third day of reperfusion, the amount of TNF-α as an inflammatory marker of ischemia-reperfusion acute phase increased. On the seventh day of reperfusion, the amount of NF-кB as an apoptotic index and infiltration of mast cells increased in the tissue as a result of development of inflammation. But, on the 14th day of reperfusion, the amount of NF-кB as an apoptotic index decreased to the lowest amount. On the 28th day of reperfusion, the amount of TNF-α as an inflammatory marker decreased to its lowest level. Prescription of selenium concurrent with development of ischemia can reduce the damage caused by sciatic nerve ischemia-reperfusion.


Subject(s)
Ischemia/drug therapy , Peripheral Nerves/drug effects , Reperfusion Injury/drug therapy , Selenium/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Disease Models, Animal , Injections, Intraperitoneal , Ischemia/metabolism , Ischemia/pathology , Male , Peripheral Nerves/metabolism , Peripheral Nerves/pathology , Rats , Rats, Wistar , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Selenium/administration & dosage , Tumor Necrosis Factor-alpha/metabolism
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