El presente artículo, muestra los resultados obtenidos en la investigación científica realizada sobre la industria automotriz de los países emergentes. El objetivo, es determinar los efectos que han ...tenido las exportaciones y las importaciones de la Industria Automotriz sobre la Ventaja Comparativa Revelada (VCR) de los países Brasil, Rusia, India, China, Corea del Sur y México durante el periodo 2000-2018.
Hypertension and cancer are frequently found comorbidity occurring in same individual. This study was intended to evaluate the anticancer effects of commonly used antihypertensive medications and ...chemotherapy on chemoresistant lung cancer cells.
Calcium channel blockers (CCBs), including Verapamil, Diltiazem, and Nifedipine, either alone or combined with docetaxel (DOC) or vincristine (VCR) were used to treat A549 lung adenocarcinoma chemoresistant sublines. Cell viability was determined by MTT assay, and colony formation assay was used to demonstrate the long-term effect of CCBs on proliferation of the sublines. Apoptosis was evaluated by Annexin V assay and autophagy intensity was quantitated from acidic vesicular organelle formation. Pan-caspase inhibitor, shATG5 interference and chloroquine were applied to study the roles of Verapamil on apoptosis and autophagy, with related proteins verified by Western blot analysis.
Results show that 10 μM of Verapamil and Diltiazem, but not Nifedipine, differentially induce autophagy in DOC-resistant or VCR-resistant A549 cells, respectively. When CCBs are combined with DOC or VCR to treat the sublines, 10 μM of Verapamil induces autophagy more significantly than Diltiazem and Nifedipine, respectively, in DOC-resistant (54.91±0.76, 18.03±0.69, 7.05±0.30) or VCR-resistant A549 (32.41±1.04, 21.51±0.63, 7.14±0.24) cells. Inhibition of apoptosis by pan-caspase inhibitor partly reduced cell death indicates association of caspase-dependent cell death but with persistence of autophagy. Inhibition of autophagy by interfering ATG5 expression reduced c-PARP level and apoptotic cells suggest a pro-death role of autophagy. Chloroquine treatment enhanced autophagosome accumulation and cell death but with reduced c-PARP level suggests that mechanism of caspase-independent cell death also contributes to Verapamil/chemotherapy-induced anticancer effects.
Verapamil combined with DOC or VCR induces chemoresistant lung cancer cells to death through autophagy burst and apoptosis more strongly than Diltiazem and Nifedipine. Administering Verapamil or Diltiazem individually with chemotherapy, but not Nifedipine, can be considered in lung cancer patients with hypertension.
Siva-1 is a well-known anti-apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva-1 affects multidrug resistance via the NF-kappaB pathway in gastric cancer is ...currently unknown. The present study aimed to determine the possible involvement of Siva-1 in gastric cancer anticancer drug resistance in vitro. A vincristine (VCR)-resistant KATO III/VCR gastric cancer cell line with stable Siva-1 overexpression was established. The protein expression levels of Siva-1, NF-kappaB, multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) were detected via western blotting. The effect of Siva-1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5-fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. Additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva-1-overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5-fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva-1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva-1 overexpression. Additionally, Siva-1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. Western blot analysis determined that Siva-1 overexpression increased NF-kappaB, MDR1 and MRP1 levels. The current study demonstrated that overexpression of Siva-1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF-kappaB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer. Key words: Siva-1, multidrug resistance, gastric cancer
The clinical significance of GLI1 expression either through canonical Hedgehog signal transduction or through non-canonical mechanisms in rhabdomyosarcoma (RMS) or Ewing sarcoma (EWS) is incompletely ...understood. We tested a role for Hedgehog (HH) signal transduction and GL11 expression in development of vincristine (VCR) resistance in RMS and EWS.
We characterized baseline expression and activity of HH pathway components in 5 RMS (RD, Rh18, Ruch-2, Rh30, and Rh41) and 5 EWS (CHLA9, CHLA10, TC32, CHLA258, and TC71) cell lines. We then established VCR-resistant RMS and EWS cell lines by exposing cells to serially increasing concentrations of VCR and determining the IC
. We defined resistance as a ≥ 30-fold increase in IC
compared with parental cells. We determined changes in gene expression in the VCR-resistant cells compared with parental cells using an 86-gene cancer drug resistance array that included GLI1 and tested the effect of GLI1 inhibition with GANT61 or GLI1 siRNA on VCR resistance.
We found evidence for HH pathway activity and GLI1 expression in RMS and EWS cell lines at baseline, and evidence that GLI1 contributes to survival and proliferation of these sarcoma cells. We were able to establish 4 VCR-resistant cell lines (Ruch-2VR, Rh30VR, Rh41VR, and TC71VR). GLI1 was significantly up-regulated in the Rh30VR, Rh41VR, and TC71VR cells. The only other gene in the drug resistance panel that was significantly up-regulated in each of these VCR-resistant cell lines compared with their corresponding parental cells was the GLI1 direct target and multidrug resistance gene, ATP-binding cassette sub-family B member 1 (MDR1). We established major vault protein (MVP), which was up-regulated in both vincristine-resistant alveolar RMS cell lines (Rh30VR and Rh41VR), as another direct target of GLI1 during development of drug resistance. Treatment of the VCR-resistant cell lines with the small molecule inhibitor GANT61 or GLI1 siRNA together with VCR significantly decreased cell viability at doses that did not reduce viability individually.
These experiments demonstrate that GLI1 up-regulation contributes to VCR resistance in RMS and EWS cell lines and suggest that targeting GLI1 may benefit patients with RMS or EWS by reducing multidrug resistance.
Matrine is an active component of Leguminosae plants and is thought to exhibit anti-tumor effects. However, the effects of matrine on drug-resistant cancer have not been fully elucidated. The present ...study aimed to investigate the effects of matrine on vincristine (VCR)-resistant retinoblastoma (RB) cells and to assess the underlying mechanisms governing this effect. The drug-resistant cell line SO-Rb50/VCR was established by incubation with VCR at increasing concentrations. The effects of matrine on SO-Rb50 and SO-RB50/VCR cell growth and proliferation were evaluated using light microscopy and Cell-Counting Kit-8 assay. In addition, the effects of matrine on cell apoptosis, proliferation and cell cycle staging together with its potential underlying mechanisms were investigated. Matrine inhibited the proliferation of SO-Rb50 and SO-RB50/VCR cells in a concentration-dependent manner (0.2-1.1 mg/ml). However, matrine at the half-maximal inhibitory concentration (IC.sub.50) appeared to trigger apoptosis of these cells and had a tendency to arrest the cell cycle at the G0/G1 phase. Matrine treatment also promoted the expression of Bax and reduced the expression of Bcl-2 and cyclin D1 compared with the control. However, matrine was not able to increase the sensitivity of cells to VCR. The results of the present study suggested that matrine has the potential to promote the apoptosis of SO-Rb50/VCR cells and arrest cell cycling, indicating a possible benefit of matrine for the treatment of drug-resistant RB. Key words: matrine, vincristine-resistant retinoblastoma, drug resistance, SO-Rb50
Cancer is a leading burden of disease in Australia and worldwide, with incidence rates varying with age, sex and geographic location. As part of the Ageing, Chronic Disease and Injury study, we aimed ...to map the incidence rates of primary cancer diagnoses across western Victoria and investigate the association of age, accessibility/remoteness index of Australia (ARIA) and area-level socioeconomic status (SES) with cancer incidence.
Data on cancer incidence in the study region were extracted from the Victorian Cancer Registry (VCR) for men and women aged 40+ years during 2010-2013, inclusive. The age-adjusted incidence rates (per 10,000 population/year), as well as specific incidence for breast, prostate, lung, bowel and melanoma cancers, were calculated for the entire region and for the 21 Local Government Areas (LGA) that make up the whole region. The association of aggregated age, ARIA and SES with cancer incidence rates across LGAs was determined using Poisson regression.
Overall, 15,120 cancer cases were identified; 8218 (54%) men and 6902 women. For men, the age-standardised rate of cancer incidence for the whole region was 182.1 per 10,000 population/year (95% CI 177.7-186.5) and for women, 162.2 (95% CI: 157.9-166.5). The incidence of cancer (overall) increased with increasing age for men and women. Geographical variations in cancer incidence were also observed across the LGAs, with differences identified between men and women. Residents of socioeconomically disadvantaged and less accessible areas had higher cancer incidence (p < 0.001).
Cancer incidence rates varied by age, sex, across LGAs and with ARIA. These findings not only provide an evidence base for identifying gaps and assessing the need for services and resource allocation across this region, but also informs policy and assists health service planning and implementation of preventative intervention strategies to reduce the incidence of cancer across western Victoria. This study also provides a model for further research across other geographical locations with policy and clinical practice implications, both nationally and internationally.
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Despite advances in surgery, radiotherapy and chemotherapy, the overall 5‑year survival rate of patients with OSCC has not ...significantly improved. In addition, the prognosis of patients with advanced‑stage OSCC remains poor. Therefore, it is necessary to develop novel therapeutic modalities. Vincristine (VCR), a naturally occurring vinca alkaloid, is a classical microtubule‑destabilizing agent and is widely used in the treatment of a number of cancers. Despite the proven antitumor benefits of VCR treatment, one of the major reasons for the failure of treatment is drug resistance. Changes in the tumor microenvironment are responsible for cross‑talk between cells, which may facilitate drug resistance in cancers; secreted proteins may promote communication between cancer cells to induce the development of resistance. To identify the secreted proteins involved in VCR resistance, conditioned media was obtained, and an antibody array was conducted to screen a comprehensive secretion profile between VCR‑resistant (SAS‑VCR) and parental (SAS) OSCC cell lines. The results showed that amphiregulin (AREG) was highly expressed and secreted in SAS‑VCR cells. Pretreatment with exogenous recombinant AREG markedly increased drug resistance against VCR in OSCC cells, as assessed by an MTT assay. Colony formation, MTT and western blot assays were performed to investigate the effects of AREG knockdown on VCR sensitivity. The results indicated that AREG expression can regulate VCR resistance in OSCC cells; overexpression of AREG increased VCR resistance in parental cells, whereas AREG knockdown decreased the VCR resistance of resistant cells. In addition, it was also demonstrated that the glycogen synthase kinase‑3β pathway may be involved in AREG‑induced VCR resistance. These findings may provide rationale to combine VCR with blockade of AREG‑related pathways for the effective treatment of OSCC.
Multidrug resistance in cancer cells is a primary factor affecting therapeutic efficacy. Heat shock 27 kD protein 1 (HSP27) is associated with cell apoptosis and resistance to chemotherapy. However, ...the mechanisms underlying HSP27-associated pathways in colon cancer cells remain unclear. Therefore, the present study used short hairpin (sh) RNA to inhibit HSP27 expression in colon cancer cells in order to investigate the effects
and
. Flow cytometry was used to investigate cell apoptosis and a xenograft model was employed to examine the tumorigenesis. Protein expression was measured by Western blotting. The results revealed that suppression of HSP27 expression significantly increased cell apoptosis, inhibited tumor growth and enhanced sensitivity to the anti-cancer agents 5-fluorouracil (5-FU) and vincristine (VCR). shHSP27 significantly decreased the expression of notch receptor 1 and the phosphorylation level of Akt and mTOR, and enhanced the effect of 5-FU and VCR. In conclusion, HSP27 suppression enhanced the sensitivity of colon cancer cells to 5-FU and VCR, and increased colon cancer cell apoptosis with and without chemotherapy. Therefore, the development of novel therapeutic agents that inhibit the expression of HSP27 may offer a new treatment option for colon cancer.
Phyllodes tumors of the breast (PTB) are uncommon stromal-epithelial neoplasms, with the main recommended treatment being surgical removal. However, even with adequate resection, the risk of ...recurrence in the malignant form remains as high as 40%, and there is no recognized consensus on the most effective drugs for PTB. In the present study, an ex vivo model of malignant phyllodes and derived primary cell cultures were used to evaluate the effectiveness of a panel of different drugs, including the Bcl-2/Bcl-xL inhibitor ABT-263, salinomycin (SAL), doxorubicin (DOX), paclitaxel (TAX), vincristine (VCR), colchicine (COL) and cisplatin (CIS). ABT-263, SAL and DOX were highly effective towards phyllodes spindle cells when assessed in the ex vivo model, contributing to ~98% tumor cell death. Furthermore, ABT-263 was highly selective for tumor cells in this system, and exhibited little toxic effect on adjacent normal epithelial cells. Furthermore, consistent with findings in the ex vivo model, ABT-263 was significantly less toxic towards MCF 10A non-tumorigenic breast epithelial cells compared with SAL and DOX. A conditional reprogramming strategy was subsequently used, involving Rho kinase inhibition, to successfully generate primary phyllodes tumor cells that could be cultured for several passages. The primary cells were sensitive to DOX with an IC.sub.50 of 0.40+ or -0.07 microM in a standard viability assay and the preliminary results were obtained indicating sensitivity to ABT-263 and SAL. The present study demonstrated the feasibility of using explants and primary cells for drug discovery, selectively targeting PTB cells. Key words: malignant phyllodes tumor, breast, pathology, chemotherapy, ex vivo
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