• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1957-1962
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• 2012

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

• Korean Journal of Bronchoesophagology
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• v.15 no.2
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• pp.49-56
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• 2009

Purpose : To evaluate the treatment outcome for patients with locally advanced, unresectable esophageal cancer treated with relatively high dose radiation therapy(RT). Materials and Methods : From January 2000 to December 2008, 32 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated with radiation therapy(RT) with or without concurrent chemotherapy. Ten patients were excluded from analysis because of distant metastasis and drop off. Patient distributions according to AJCC stages II, III IVa were 7(31.8%), 12(54.6%), 3(13.6%) respectively. The locations of tumor were cervical/upper thorax 3 (13.6%), mid thorax 13(59.1%), and lower thorax/abdominal 6(27.3%), respectively. Eleven patients received RT only, and 11 patients received cisplatin based concurrent chemoradiotherapy(CCRT). Median radiation dose was 65 Gy(range 57.6~72 Gy). Results : The median follow-up was 9.1 months(range 1.9~43.8 months). The response rates for complete response, Partial response, stable disease and Persistent disease were 6(27.3%), 11(50.0%), 4(18.2%) and 1(4.5%), respectively. Two patients(9.1%) suffered from esophageal stenosis and stents were inserted. Two patients(9.1%) had Grade 3 radiation pneumonitis and one of them expired due to acute respiratory distress syndrome(ARDS) at 36 days after completion of radiation therapy. The recurrence rate was 11(50.0%). The patterns of recurrence were persistent disease and local progression in 5(22.7%), local recurrence 3(13.7%) and concomitant local and distant recurrence in 3(13.7%). The overall survival(OS) rate was 32.1% at 2 years and 21.4% at 3 years(median 12.0 months). Disease free survival(DFS) rate was 17.3% at 2 and 3 years. All patients who had no dysphagia at diagnosis showed complete response after treatment and 100% OS at 3 years(p=0.0041). The OS for above 64.8 Gy group and 64.8 Gy or below group at 3 years were 60.6% and 9.1%(p=0.1341). The response to treatment was the only significant factor affecting OS(p=0.004). Conclusion : Relatively high dose radiation therapy in unresectable esophageal cancer tended to have a better outcome without increased complication rate. Further study with more patients is warranted to justify improved result.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.283-289
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• 1998

Purpose : This study was performed to analyze the efficacy of induction chemotherapy fellowed by radiation therapy in locally advanced non-small cell lung cancer Materials and Methods : Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine Patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. Results : Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). Conclusion : In stage III non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.255-262
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• 1997

Purpose : This is retrospective study to compare the results of radiation therapy alone and neoadjuvant chemotherapy and radiation in advanced stage of uterine cervical cancer. Materials and Methods : Seventy-six Patients who were treated with definitive radiation therapy for locally advanced cervical cacinoma between June 1988 and December 1993 at the department of radiation oncology, Keimyung University Dong-san Hospital. Thirty six patients were treated with radiation therapy alone and forty patients were treated with cisplatin based neoadjuvant chemotherapy and radiation therapy. According to FIGO staging system. there were 48 patients in stage IIb, 3 patients in stage IIIa, 23 patients in stage lIIb and two patients in stage IVa with median age of 53 years old. Follow-up periods ranged from 7 to 95 months with median 58 months. Results : Complete response (CR) rate were $86.1\%$ in radiation alone group and $80\%$ in chemoradiation group. There was no statistical difference in CR rate between the two groups. Overall five-year survival rate was $67.3\%$. According to stage, overall five-rear survival rates were $74\%$ in stage IIb, $66.7\%$ in stage IIIa, $49.8\%$ in stage IIb, $50\%$ in stage IVa. According to treatment modality overall five year survival rates were $74.1\%$ in radiation alone and $61.4\%$ in chemoradiation group (P=0.4) Five rear local failure free survival rates were $71.5\%$ in radiation alone group and $60\%$ in chemoradiation group (P=0.17). Five year distant metastasis free survival rates were $80.7\%$ in radiation aione group and $89.9\%$ in chemoradiation group (P=0.42). Bone marrow suppression (more than noted in 3 cases of radiaion alone group and 1 case of chemoradiation group. Grade II retal complication was noted in 5 patients of radiation group and 4 patients In chemoradiation group. Bowel obstruction treated with conservative treatment (1 patient) and bowel perforation treated with surgery (1 patient) were noted in radiation alone group. There was no statistical difference in complication between two groups. Conclusion : There was no statistical difference in survival, failure and complication between neoadjuvant chemotherapy and radiation versus radiation alone in locally advanced uterine cervical carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3429-3436
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• 2013

Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the $IC_{50}$ of 4.0-8 ${\mu}g/mL$. However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug.

• Korean Journal of Head & Neck Oncology
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• v.16 no.2
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• pp.172-176
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• 2000

Objectives: To improve local control and reduce toxicity, 3-D conformal radiotherapy was used as a boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. Materials and Methods: Eight patients with previously untreated nasopharyngeal carcinomas were treated with 3-D conformal radiotherapy following fractionated radiotherapy from September 1998 to April 2000. All patients had biopsy confirmation of disease before radiation therapy. Stages were II in 1, III in 5, and IV in 2. Two patients received cisplatin based chemotherapy in addition to radiation therapy; induction chemotherapy in 1, concurrent chemoradiation in 1. 3-D conformal radiotherapy delivered using 6MV Linac as a boost(range 25.2-28.8Gy, median 25.7Gy) following conventionally fractionated radiotherapy(range 50.4Gy). Average total dose ranged from 75.6-79.2Gy(median 76Gy). Follow-up time was 4-21 months(median 9.6 months). Results: Seven of 8 patients were evaluated radiologically within 3 months after completion of radiation therapy. All 7 patients were seen complete remission. One of 7 patients had distant metastasis after 5 months and local failure after 7 months. The tree interval of local recurrence was ranged from 4 - 21 months(median 10.2 months). One patient without radiological evaluation got complete remission clinically. Treatment related toxicity was grade 1-3 xerostomia, dysphagia, and mucositis. During 3-D conformal radiotherapy, there was no aggravation of any toxicity. Conclusion: Although the number of patients was small and follow-up period was short, 3-D conformal radiotherapy following conventional radiotherapy improved tumor control and dose escalation without increased toxicity. Survival and late toxicity should be evaluated through long term follow-up. In addition, it is necessary to confirm the benefits of 3-D conformal radiotherapy in nasopharyngeal carcinoma with randomized trial.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.120-125
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• 2009

Purpose: We wanted to present the preliminary results of intensity-modulated radiotherapy (IMRT) for the treatment of tonsillar cancer. Materials and Methods: We retrospectively analyzed 12 patients who underwent IMRT for tonsillar cancer at Asan Medical Center between November 2002 and February 2007. Seven patients (58%) received definitive treatment, and five (42%) were treated in the postoperative setting. Among the definitively treated patients, 6 patients received cisplatin-based chemotherapy regimens. Simultaneous modulated accelerated radiation therapy (SMART) was used in nine patients. The prescribed dose was 72 Gy at 2.4 Gy/fraction for the definitively treated cases and 61.6 Gy at 2.2 Gy/fraction for the postoperative cases. The median follow-up period was 34 months. Results: All twelve patients completed treatment without interruption, and eleven showed a complete response. One patient had persistent loco-regional disease after treatment. The three-year estimates of loco-regional control, disease-free survival and overall survival were 91.7%, 91.7%, and 100%. The worst acute mucositis was Grade 1 in four patients, Grade 2 in five patients, Grade 3 in two patients and Grade 4 in one patient. Grade 3 xerostomia was observed in six patients. Conclusion: Intensity-modulated radiotherapy was shown to be a safe and effective treatment modality for tonsillar cancer. Further studies with a larger number of patients and a longer follow-up period are needed to evaluate the ultimate tumor control and late toxicity of IMRT for treating tonsillar cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4153-4158
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• 2014

Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.69 no.6
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• pp.465-468
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• 2010

Spontaneous pneumothorax (SPTx) associated with primary lung cancer is quite rare, but has been reported as the initial presentation or a complication of disease progression. Moreover, chemotherapy-related SPTx in primary lung cancer occurs at a very low frequency, accounting for less than 0.05% of all cases. Here, we report the first case of erlotinib-related SPTx in a patient with advanced lung adenocarcinoma in Korea. After 3 cycles of cisplatin-based chemotherapy as first-line therapy, erlotinib was administered as second-line treatment. Asymptomatic SPTx accompanied by a significant decrease in tumor size was observed in the left lung 7 weeks later. The patient received continuous administration of erlotinib, without additional treatment. This case showed that SPTx can occur in patients with primary lung cancer receiving erlotinib, and asymptomatic chemotherapy-related SPTx in primary lung cancer may not require therapeutic intervention.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.76-83
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• 1995

Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.