Drug and Alcohol Rehabilitation: In Vitro and in Vivo Growth Inhibition of Drug-Resistant Ovarian Carcinoma Cells Using a Combination of Cisplatin and a TRAIL-Encoding Retrovirus.

In vitro and in vivo growth inhibition of drug-resistant ovarian carcinoma cells using a combination of cisplatin and a TRAIL-encoding retrovirus.

Filed under: Drug and Alcohol Rehabilitation

Oncol Lett. 2012 Dec; 4(6): 1254-1258
Li F, Guo Y, Han L, Duan Y, Fang F, Niu S, Ba Q, Zhu H, Kong F, Lin C, Wen X

Retroviruses encoding the TNF-related apoptosis-inducing ligand (TRAIL) gene were generated by transient transfection of the retrovirus packing cell line BOSC 23 using TRAIL-encoding plasmid. The retrovirus was able to transduce drug-resistant A2780/DDP ovarian carcinoma cells in vitro and induce TRAIL expression in the cells, as detected by western blot assay. Furthermore, the TRAIL protein led to the growth inhibition of the cells via a caspase-activated apoptotic mechanism. It was confirmed that exposure of such cells to cisplatin in combination with the TRAIL-encoding retrovirus resulted in higher anticancer activity in vitro and in the xenograft A2780/DDP tumor in a nude mouse model. This study suggests that chemotherapy in combination with TRAIL gene therapy may be an efficient approach to treat drug-resistant ovarian cancer.
HubMed – drug

Effects of the proapoptotic regulator Bcl-2/adenovirus EIB 19-kDa-interacting protein 3 on the chemosensitivity of human colon cancer cell lines.

Filed under: Drug and Alcohol Rehabilitation

Oncol Lett. 2012 Dec; 4(6): 1195-1202
Wang Z, Huang C, Zeng J, Deng Q, Zeng H, Liu Z, Peng X, Bi F, Tang Q, Li Z

In the clinical setting, drug resistance remains a significant obstacle for successful chemotherapy. Bcl-2/adenovirus EIB 19-kDa-interacting protein 3 (BNIP3) is a proapoptotic member of the Bcl-2 family. To address its potential as a therapeutic target for chemosensitisation, this study investigated the effect of BNIP3 expression on chemosensitivity and reversal of oxaliplatin (L-OHP) resistance in human colon cancer cell lines. A plasmid expressing the BNIP3 gene was transfected into human parental colon cancer cell lines (SW620 and colo320) and L-OHP-resistant colon cancer cell lines (SW620/L-OHP and colo320/L-OHP) using Lipofectamine™ 2000, and the transfection efficiency was determined using fluorescence optics. Western blot analysis identified that SW620/L-OHP and colo320/L-OHP cells expressed lower levels of BNIP3 protein compared with the SW620 and colo320 cells. Transfection with the recombinant BNIP3 plasmid revealed an increase in BNIP3 expression in tumour cells. Following transfection with pDsRed-BNIP3, the chemosensitivity of parental and L-OHP-resistant cell lines to L-OHP was increased (P<0.01), as detected by the Cell Counting Kit-8 (CCK8) assay. Hoechst 33342 staining and flow cytometry revealed that the effects on L-OHP-induced apoptosis were enhanced by the overexpression of BNIP3. Chemosensitisation in human colon cancer cells was observed following treatment with the recombinant BNIP3 plasmid in vitro. The results of this study suggest that BNIP3 is a potential therapeutic target for reversing the resistance of L-OHP-resistant colon cancer cells to L-OHP. HubMed – drug

Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test.

Filed under: Drug and Alcohol Rehabilitation

Oncol Lett. 2012 Oct; 4(4): 621-624
Ochiai T, Nishimura K, Watanabe T, Kitajima M, Nakatani A, Inou T, Washio M, Sakuyama N, Sato T, Kishine K, Ochi T, Okubo S, Futagawa S, Mashiko S, Nagaoka I

The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly-targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second-line chemotherapy must be abandoned in certain cases. Where possible, the most effective regimen should be selected as the first line of treatment. The aim of this study was to determine whether first-line chemotherapy may be individualized using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Specimens of primary tumors were obtained from 43 CRC patients who had received no preoperative chemotherapy. Informed consent to measure drug sensitivity was obtained from all patients. The CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally cultured tumor cells in a small collagen gel droplet. The CD-DST was performed and the growth inhibition rate (IR) was obtained under incubation conditions (5-FU with l-OHP at 6.0 and 3.0 ?g/ml, or 5-FU with SN-38 at 6.0 and 0.2 ?g/ml, respectively, for 24 h). The cumulative distributions of the growth IRs under each condition were evaluated based on the evidence that the clinical response rates to FOLFOX and FOLFIRI were almost the same. Individualization of first-line treatment was possible in all patients, with FOLFOX and FOLFIRI showing higher efficacy in 26 and 15 patients, respectively, and equal efficacy in 2 cases. This method has the potential to facilitate the establishment of individualized first-line chemotherapy for CRC and improve the prognosis in such patients.
HubMed – drug

Mirabegron: a review of recent data and its prospects in the management of overactive bladder.

Filed under: Drug and Alcohol Rehabilitation

Ther Adv Urol. 2012 Dec; 4(6): 315-24
Sacco E, Bientinesi R

Mirabegron is a novel, once-daily, orally active, first-in-class, potent ?(3)-adrenoceptor agonist recently approved by Food and Drug Administration for overactive bladder therapy. Phase II studies and four large-scale phase III multinational randomized, controlled trials have supported the efficacy and tolerability of mirabegron in the clinical trial setting of patients with overactive bladder for up to 12 weeks of therapy and in the long term (12 months). The reported incidence and severity of treatment-emergent and serious adverse effects were similar to antimuscarinics, but with a more than threefold lower incidence of dry mouth compared with tolterodine. However, the effects on the cardiovascular system, pharmacokinetic interactions with other drugs, and increased incidence of new malignant events will require careful evaluation in the near future.
HubMed – drug

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