• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4717-4721
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• 2013

Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosedn for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and ${\chi}^2$-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

• Journal of Ginseng Research
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• 제40권3호
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• pp.304-308
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• 2016

Background: Joboksansam, Korean bird wild ginseng, is an artificially cultivated wild ginseng germinated from bird feces. Although numerous pharmacologic activities of wild ginsengs have been reported, the beneficial effect of joboksansam in cancer has not been elucidated. In this study, we investigated the in vivo and in vitro anticancer activities of joboksansam powder. Methods: To evaluate the in vivo anticancer activity of joboksansam, we established a xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity induced by joboksansam powder was also investigated in vitro using (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of this powder on the activation of cell survival signaling involving Akt and Src was examined with immunoblot analysis. Results: Joboksansam powder displayed strong inhibitory activity against the increased tumor size, increased weight of total body and cancer tissues, and mortality of tumor-bearing mice. Joboksansam powder also suppressed the activation of survival regulatory enzymes Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of tumor tissues. Interestingly, the viability of RMA cells in vitro was directly decreased by joboksansam treatment. Conclusion: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.355-362
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• 2014

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

• Radiation Oncology Journal
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• 제13권4호
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• pp.303-309
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• 1995

목적 : 근치적 방사선치료를 받은 비소세포 폐암 환자의 생존율과 생존율에 영향을 미치는 예후인자를 알아보고, 방사선조사량을 6500 cGy로 증가시키는 것이 국소관해율과 생존율에 영향을 미치는지 여부를 알아보기 위하여 본 연구를 계획하였다. 방법 : 조직학적으로 증명된 비소세포 폐암으로 진단 받고, 원격전이는 없으나 수술 불가능한 환자를 대상으로 근치적 방사선치료를 시행하였다. A군은 하루에 180 cGy에서 200 cGy 씩 조사하여 6000 cGy 이하를 조사하였고, B군은 같은 방법으로 6500 cGy까지 조사하였다. 결과 : 98명 전체 환자의 1년, 2년, 3년 생존율은 각각 54.0%, 26.6%, 16.4%였으며 정중앙 생존기간은 13개월이었다. 예후인자중 통계학적으로 의미있는 것은 병기와 N-병기였으며 방사선조사량은 의미가 없었다. 국소관해율과 생존율에 있어서도 A군과 B군 사이에 차이는 없었다. 결론 : 비소세포 폐암의 치료 성적을 올리기 위해서 단순히 방사선조사량을 6500 cGy까지 올리는 것은 의미가 없다 하겠고, 더 많은 방사선량을 조사할 수 있도록 다분할 방사선치료를 시행하거나 혹은 동시 화학-방사선요법등 다른 치료방법을 고려해야 할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10171-10174
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• 2015

Background: The purpose of this study was to determine the prognostic significance of the maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients undergoing surgical treatment for non-small cell lung cancer. Materials and Methods: Seventy-eight consecutive patients (58 with adenocarcinomas, 20 with squamous cell carcinomas) treated with potentially curative surgery were retrospectively reviewed. Results: The SUVmax was significantly higher in the patients with recurrent than with non-recurrent adenocarcinoma (p<0.01). However, among the patients with squamous cell carcinoma, there were no differences with or without recurrence (p=0.69). Multivariate analysis indicated that the SUVmax of adenocarcinoma lesions was a significant predictor of disease-free survival (p=0.04). In addition, an SUVmax of 6.19, the cut-off point based on ROC curve analysis of the patients with pathological IB or more advanced stage adenocarcinomas, was found to be a significant predictor of disease-free survival (p<0.01). Conclusions: SUVmax is a useful predictor of disease-free survival in patients with resected adenocarcinoma, but not squamous cell carcinoma. Patients with adenocarcinoma exhibiting an SUVmax above 6.19 are candidates for more intensive adjuvant therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7497-7500
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• 2013

Background: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. Materials and Methods: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. Results: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, $9.5{\pm}4.3cm$, was larger than non palpable masses, $5.3{\pm}2.7cm$ (p<0.001). Conclusions: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

• Journal of Chest Surgery
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• 제45권1호
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• pp.40-44
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• 2012

Background: The experience of a single-institution regarding surgery for small cell lung cancer (SCLC) was reviewed to evaluate the surgical outcomes and prognoses. Materials and Methods: From July 1990 to December 2009, thirty-four patients (28 male) underwent major pulmonary resection and lymph node dissection for SCLC. Lobectomy was performed in 24 patients, pneumonectomy in eight, bilobectomy in one, and segmentectomy in one. Surgical complications, mortality, the disease-free survival (DFS) rate, and the overall survival rate were analyzed retrospectively. Results: The median follow-up period was 26 months (range, 4 to 241 months), and there was one surgical mortality (2.9%). Six patients (17.6%) experienced recurrence, all of which were systemic. Eight patients died during follow-up; four died of disease progression and the other four died of pneumonia or of another non-cancerous cause. The three-year DFS rate was $79.2{\pm}2.6%$ and the overall survival rate was $66.4{\pm}10.5%$. Recurrence or death was significantly prevalent in the patients with lymph node metastasis (p=0.001) as well as in those who did not undergo adjuvant chemotherapy (p=0.008). The three-year survival rate was significantly greater in the patients with pathologic stage I/II cancer than in those with stage III cancer (84% vs. 13%, p=0.001). Conclusion: Major pulmonary resection for small cell lung cancer is feasible in selected patients. Patients with pathologic stage I or II disease showed an excellent survival rate after surgery and adjuvant treatment. Prospective randomized studies will be needed to define the role of surgery in early-stage small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5375-5378
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• 2013

Background: This study was undertaken to evaluate the surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. Data for 58 patients who underwent modified radical hysterectomy or radical hysterectomy with pelvic lymphadenectomy between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinico-pathological risk factors (nodal metastasis, parametrial involvement), adjuvant treatment, 5-year disease-free survival and 5-year overall survival. All pathologic slides were reviewed by a gynecologic pathologist. Follow-up methods included at least cervical cytology and colposcopy with directed biopsy if indicated. Univariate analysis was performed to identify factors associated with median survival. At the median follow up time of 73 months, the 5-year disease-free survival and the 5-year overall survival were 97.4% and 97.4%, respectively. Two (3.4%) patients had pelvic lymph node metastases. In a univariate analysis, there was no statistically significant association between survival and prognostic factors such as age, histological cell type, lymph-vascular space invasion, vaginal margin status and lymph node status. Surgical and survival outcomes of women with stage IA2 cervical cancer are excellent. No parametrial involvement was detected in our study. Patients with stage IA2 cervical cancer may be treated with simple or less radical hysterectomy with pelvic lymphadenectomy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9673-9678
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• 2014

Background: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Materials and Methods: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. Results: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Conclusions: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.