• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• BMB Reports
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• v.43 no.12
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• pp.781-788
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• 2010

An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

• Journal of Life Science
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• v.26 no.9
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• pp.1088-1096
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• 2016

Despite that moderate hyperthermia can exert various antitumor activities such as direct cytotoxic effects on tumor cells, effects on tumor vasculatures and immunological effects, hyperthermia has been usually combined with radiotherapy or chemotherapy due to its limited efficacy in cancer treatment, showing some positive clinical benefits with generally well-tolerated side effects. Since heat shock responses itself can interfere with the anti-tumor effects of hyperthermia, not all of these studies might have demonstrated positive clinical outcomes in cancer patients. Therefore, the negative anti-tumor effect of hyperthermia should be reduced to enhance the effectiveness of hyperthermia. Although the responses to heat stress of tumor tissues containing vessels, immune cells, connective tissues as well as cancer cells, are very complicated, it is needed to study in the near future if some clinically available drugs, which can modulate heat stress responses, can improve the efficacy of hyperthermia in patients with cancer. In this review, the effect of clinical hyperthermia centered on non-invasive external hyperthermia using radiofrequency at moderate temperature will be discussed, since it is the state-of-the-art technology in the current clinical practice of hyperthermia, and a moderate operational temperature is used to increase the therapeutic effectiveness of conventional therapy without additional toxicity to normal tissues.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.44-52
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• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.672-683
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• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.