The main obstacle for chemotherapy is tumor drug resistance. Studying the mechanisms of drug resistance and reversing drug resistance is the key to improve the effectiveness of chemotherapy. It has been reported that MKP-1 plays an important role in tumor drug resistance. MKP-1, as a negative regulator of MAPKs, is involved in the MAPKs mediated drug resistance and is regulated by ERK and p38 signaling pathways.However, the relationship between MKP-1 and other drug resistance-related signaling pathways is not clear and requires further investigation.
Drug Resistance, Neoplasm ; physiology ; Dual Specificity Phosphatase 1 ; metabolism ; physiology ; Humans ; Signal Transduction

OBJECTIVETo discuss the novel biomarkers of microRNAs in prostate cancer.

DATA SOURCESThe literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012.

STUDY SELECTIONOriginal articles regarding the novel role of microRNAs in prostate cancer were selected.

RESULTSMicroRNAs play an important role in prostate cancer such as cell differentiation, proliferation, apoptosis, and invasion. Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), drug sensitivity, cancer microenvironment, energy metabolism, androgen independence transformation, and diagnosis prediction.

CONCLUSIONSMicroRNAs are involved in various aspects of prostate cancer biology. The role of microRNA in the initiation and development of prostate cancer deserves further study.

Biomarkers ; analysis ; Drug Resistance, Neoplasm ; Humans ; Male ; MicroRNAs ; analysis ; physiology ; Prostatic Neoplasms ; diagnosis ; drug therapy ; pathology

Acute myeloid leukemia (AML) is a common type of hematopoietic malignancies seriously threatening human life. Resistance to chemotherapy is one of the main reasons for recurrence and refractoriness of acute myeloid leukemia. The mechanisms of chemoresistance are complex. This article reviews the mechanisms of chemoresistance in acute myeloid leukemia,the current research advances and the possible approach for reverse of drug resistance.
Drug Resistance, Neoplasm ; physiology ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; physiopathology

OBJECTIVETo review the central role of leukemia stem cells (LSCs) in drug resistance and metastasis, aiming to provide key insights into leukemogenic pathology and developing novel therapeutic strategies against the relapse of leukemia.

DATA SOURCESThe data used in this review were obtained mainly from the studies reported in PubMed using the key terms "tumor-initiating cells", "leukemia stem cells", "drug resistance" and "metastasis".

STUDY SELECTIONRelevant articles on studies of leukemia stem cells were selected.

RESULTSIncreasing numbers of studies have suggested the importance of cancer stem cells (CSCs) in the initiation and maintenance of cancer, especially in leukemia. This review has summarized the origin, characteristics, isolation and identification of LSCs. It highlights the crucial role of LSCs in drug resistance and metastasis of leukemia by illustrating possible mechanisms and aims to provide novel therapeutic strategies for LSCs-targeted treatment.

CONCLUSIONLSCs play a crucial role in drug resistance and metastasis of leukemia and new promising LSCs-targeted therapies warrant investigation in both experimental models and clinical practice.

Animals ; Drug Resistance, Neoplasm ; physiology ; Humans ; Leukemia ; pathology ; Models, Biological ; Neoplasm Metastasis ; pathology ; physiopathology ; Neoplastic Stem Cells ; metabolism ; pathology ; physiology

Autophagy is a conserved catabolic process characterized by degradation and recycling of cytosolic components or organelles through a lysosome-dependent pathway. It has a complex and close relationship to drug resistance in breast cancer. MicroRNAs (miRNAs) are small noncoding molecules that can influence numerous cellular processes including autophagy, through the posttranscriptional regulation of gene expression. Autophagy is regulated by many proteins and pathways, some of which in turn have been found to be regulated by miRNAs. These miRNAs may affect the drug resistance of breast cancer. Drug resistance is the main cause of distant recurrence, metastasis and death in breast cancer patients. In this review, we summarize the causative relationship between autophagy and drug resistance of breast cancer. The roles of autophagy-related proteins and pathways and their associated miRNAs in drug resistance of breast cancer are also discussed.
Autophagy/physiology* ; Breast Neoplasms/pathology* ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/physiology* ; Signal Transduction/physiology*

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Multidrug resistance-associated proteins (MRPs) play an important role in the process of MDR. As an ATP-binding cassette (ABC) transporter superfamily, MRPs are selective and specific drug efflux pumps. In this paper, physiological characteristics, structural characteristics and resistance profile of MRPs and the associated reversal studies are reviewed.
Antineoplastic Agents ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; metabolism ; physiology ; Neoplasms ; drug therapy ; metabolism

OBJECTIVETo investigate the differential expression of RPL6/Taxreb107 between drug-resistant gastric cancer cell line SGC7901/ADR and gastric cancer cell line SGC7901 as well as its correlation with multiple-drug resistance (MDR) in gastric cancer cells.

METHODSTotal RNA was extracted from SGC7901 and SGC77901/ADR, with internal control RT-PCR, Northern blot, gene cloning and expression, construction of eukaryotic expression vector, gene transfection by electroporation. The accumulation and retention of ADR in transiently transfected cell was detected by flow cytometry.

RESULTSThe internal control RT-PCR and Northern blot showed high RPL6/Taxreb107 expression in SGC7901/ADR cell line. Sense and antisense eukaryonic expression vectors demonstrated by double enzyme digestion were successfully transfected into gastric cancer cell line SGC7901 and SGC7901/ADR respectively by electroporation. The accumulation and retention of ADR detected 48 hours after transfection showed that RPL6 gene had shown effect on drug resistance in gastric cancer cell.

CONCLUSIONThe high expression of RPL6/Taxreb107 in drug resistant gastric cancer cell shows its correlation with multiple-drug resistance in gastric cancer.

DNA-Binding Proteins ; metabolism ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Humans ; Statistics as Topic ; Stomach Neoplasms ; pathology ; Tumor Cells, Cultured

OBJECTIVETo analyze the distribution and significance of occludin mRNA expression in human gastric cancer, as well as its relationship with gastric cancer pathology and multidrug resistance (MDR) in vivo.

METHODSIn situ hybridization (ISH) technique was used to evaluate the expression of occludin mRNA in 42 gastric carcinoma specimens obtained by surgery and 23 relatively normal gastric mucosa obtained by gastric endoscopy. All specimens had been stored in cryostatic section.

RESULTSOccludin mRNA was found positive in the cytoplasm of gastric glandulous epithelia as blue particles with intensive stain in 14 of 42 gastric carcinomas (33.3%), 23 of 42 paracancerous gastric tissues (54.8%), 14 of 23 relatively normal gastric tissues (60.9%), 9 of 16 well differentiated carcinomas (56.3%), 4 of 14 moderately differentiated carcinomas (28.6%), 1 of 10 poorly differentiated carcinomas (10.0%) and none of 2 mucosal carcinomas. There were significant differences in occludin mRNA positive rate between relatively normal gastric tissue and gastric cancer as well as between paracancerous gastric tissue and gastric cancer. The expression of occludin mRNA in moderately and poorly differentiated groups was gradually reduced when compared with well differentiated group, which suggests that there be a significant correlation between tumor differentiation and the expression of occludin mRNA. Furthermore, the positive signals of occludin mRNA distributed extensively in the cytoplasm of SGC7901/VCR cell, being vincristine resistant, derived from parental gastric cell line SGC7901. The positive signals of SGC7901/VCR were stronger than those of SGC7901 cells.

CONCLUSIONOccludin mRNA, being mainly located in epithelial cells and its expression correlated with tumor differentiation, may be involved in the development of multi-drug resistance in gastric cancer.

Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Humans ; In Situ Hybridization ; Membrane Proteins ; genetics ; metabolism ; Occludin ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; Tight Junctions ; metabolism

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.
Antineoplastic Agents ; pharmacology ; Drug Resistance ; Humans ; Neoplasm Staging ; Neoplasms ; drug therapy ; pathology ; Treatment Outcome ; Tumor Microenvironment ; drug effects ; physiology

To study the role of hematopoietic microenvironment abnormality in development of minimal residual disease and its mechanism, the viability of HL-60 cells was investigated by means of bone marrow stromal cell culture system or co-culture system of bone marrow stromal cell with HL-60 cells and idarubicin (IDA), flow cytometry and ELISA. The results showed that viability of HL-60 cells gradually decreased along with the increase of IDA dose and prolongation of culture time. Amount of HL-60 cells co-cultured with leukemia bone marrow stramal cells was significantly increased as compared with that of the control (P < 0.05). Bone marrow stromal cells or stromal cell conditioned medium reduced the effect of IDA on HL-60 cells in culture. In conclusion, leukemia bone marrow stromal cells contribute to increasing resistance of HL-60 cells to chemotherapeutic agents, and play some role in developing minimal residual disease.
Bone Marrow Cells ; physiology ; Cell Survival ; drug effects ; Coculture Techniques ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; HL-60 Cells ; drug effects ; Humans ; Idarubicin ; pharmacology ; Stromal Cells ; physiology