Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.
Objective: The current study aimedto screen for possible factors which affect prognosis of chondrosarcoma. Methods: Thirty seven cases were selected and analyzed statistically. The patients received surgical treatment at our hospital between December 2005 and March 2008. All of them had complete follow-up data. The survival rates were calculated by univariate analysis using the Kaplan-Meier method and tested by Log-rank. ${\chi}^2$ or Fisher exact tests were carried out for the numeration data. The significant indexes after univariate analysis were then analyzed by multivariate analysis using COX regression model. Based on the literature, factors of gender, age, disease course, tumor location, Enneking grades, surgical approaches, distant metastasis and local recurrence were examined. Results: Univariate analysis showed that there were significant differences in Enneking grades, surgical approaches and distant metastasis related to the patients' 3-year survival rate after surgery (P<0.001). No significant difference was not found in gender, age, disease course, tumor location or local recurrence (P>0.05). Multivariate analysis showed that Enneking grade (P=0.007) and surgical approaches (P=0.010) were independent factors affecting the prognosis of chondrosarcoma, but distant metastasis was not (P=0.942). Conclusion: Enneking grades, surgical approaches and distant metastasis are risk factors for prognosis of chondrosarcoma, among which the former two are independent factors.
Iqbal, Hassan;Bhatti, Abu Bakar Hafeez;Hussain, Raza;Jamshed, Arif
Asian Pacific Journal of Cancer Prevention
/
v.15
no.5
/
pp.2195-2199
/
2014
Background: Despite being rare in incidence, malignant tumors of major salivary glands show diverse histological variation. There are limited data on major salivary gland tumor management and outcome from Pakistan. The objective of this study was to share our experience with management of malignant tumors of major salivary glands. Materials and Methods: Patients who received treatment at Shaukat Khanum Cancer Hospital and Research Center from July 2002 to June 2011 with an underlying diagnosis of a major salivary gland malignancy were included. Patient characteristics and treatment modalities were assessed. Local, regional and distant failures were determined. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier curves and the Log rank test was used to determine statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazard regression. Results: The parotid gland was the primary site of origin in 104 (80%) patients. Mucoepidermoid carcinoma (43%) and adenoid cystic carcinoma (24%) were the most common histological types. Surgery followed by adjuvant radiation remained the mainstay treatment modality with 81 (62%) patients. Nineteen (15%) patients were treated with surgery alone and 30 (23%) patients with locally advanced surgically inoperable tumors received radiation only. Forty one (32%) patients failed the treatment (local 12, regional 11, locoregional 5, distant 13). The expected 5 year DFS and OS were 65% and 74% respectively. On multivariate analysis, grade was the only independent predictor of DFS and nodal involvement was the only independent predictor of overall survival. Conclusions: Employing existing standards of treatment, comparable survival can be achieved in Pakistani population with major salivary gland malignancies as elsehwere in the world.
The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.
Shin, Yong Soon;Lee, Jeong A;Bae, So Hyun;Lee, Su Youn;Jang, Min Kyeong
Journal of Korean Academy of Fundamentals of Nursing
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v.20
no.2
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pp.147-156
/
2013
Purpose: The study was done to define complementary and alternative medicine (CAM) use among primary brain tumor patients and factors influencing use. Methods: The study was conducted with convenience sampling in 5 neuro-oncology centers in Seoul and Gyeonggi Province. Data were collected using a 25-item questionnaire developed by the researchers. Results: Of 250 patients approached, 231 (92.4%) agreed to participate. Overall, 26.8% of the respondents used CAM and the average cost for CAM use was 300,000 KRW. More than 72% of CAM users did not disclose CAM use to their health care professionals. The most frequently used therapy was natural products including mushrooms. Logistic regression analysis revealed that an education level of university or higher (OR=2.92, 95% CI=1.56-5.44, p=.001), unemployment (OR=1.99, 95% CI=1.04-3.80, p=.037), and WHO grade III & IV tumors (OR=2.18, 95% CI=1.07-4.72, p=.048) were significant factors influencing CAM use. Conclusion: Three out of ten brain tumor patients spend substantial sum of money for CAM. In these situations, health care professionals should be aware of this phenomenon and provide adequate information and consultation to the patients.
Objective : The goals of surgical intervention for metastatic spinal cord compression (MSCC) are prolonging survival and improving quality of life. Non-ambulatory paraplegic patients, either at presentation or after treatment, have a much shorter life expectancy than ambulatory patients. We therefore analyzed prognostic factors for survival and postoperative ambulation in patients surgically treated for MSCC. Methods : We assessed 103 patients with surgically treated MSCC who presented with lower extremity weakness between January 2001 and December 2008. Factors prognostic for overall survival (OS) and postoperative ambulation, including surgical method, age, sex, primary tumor site, metastatic spinal site, surgical levels, Tokuhashi score, and treatment with chemo- or radiation therapy, were analyzed retrospectively. Results : Median OS was significantly longer in the postoperatively ambulatory group [11.0 months; 95% confidence interval (CI), 9.29-12.71 months] than in the non-ambulatory group (5.0 months; 95% CI, 1.80-8.20 months) ($p$=0.035). When we compared median OS in patients with high (9-11) and low (0-8) Tokuhashi scores, they were significantly longer in the former (15.0 months; 95% CI, 9.29-20.71 months vs. 9.0 months; 95% CI, 7.48-10.52 months; $p$=0.003). Multivariate logistic regression analysis showed that preoperative ambulation with or without aid [odds ratio (OR) 5.35; 95% CI 1.57-18.17; $p$=0.007] and hip flexion power greater than grade III (OR 6.23; 95% CI, 1.29-7.35; $p$=0.038) were prognostic of postoperative ambulation. Conclusion : We found that postoperative ambulation and preoperative high Tokuhashi score were significantly associated with longer patient survival. In addition, preoperative hip flexion power greater than grade III was critical for postoperative ambulation.
Loof-Johanson, Margaretha;Brudin, Lars;Sundquist, Marie;Rudebeck, Carl Edvard
Asian Pacific Journal of Cancer Prevention
/
v.17
no.3
/
pp.1507-1512
/
2016
Background: Risk of developing breast cancer increases with short breastfeeding and the use of hormones. The prognosis of breast cancer is better if the tumours are hormone receptor positive. Since breast feeding affects estrogen and progesterone receptors, we wanted to investigate how such reproductive factors as breastfeeding and the use of hormones interact with known prognostic markers and specific tumour characteristics in women with breast cancer. Materials and Methods: A total of 250 women treated for breast cancer from a larger cohort completed a questionnaire on breastfeeding, number and age at births and use of hormones. A logistic regression analysis was made to search for connections between known prognostic markers on the one hand (type of cancer, grade, tumor size, estrogen receptor and progesterone receptor, lymphovascular invasion and DNA-ploidy) and reproductive data, breastfeeding, and hormone use on the other. Results and Conclusions: Hormone use, but not breastfeeding, was significantly associated, also on multivariate analysis, with the prognostic variable lymphovascular invasion, connected to a worse prognosis. No other hormone use or breast feeding correlations with prognostic variables were found.
The Journal of the Korean bone and joint tumor society
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v.16
no.1
/
pp.14-20
/
2010
Purpose: To investigate prognostic factors influencing on local recurrence, distant metastasis and event-free survival of liposarcomas. Materials and Methods: Fifty-two patients managed for liposarcomas since 1993 were analyzed respectively in the view of prognostic influence of patient age, tumor size, location, histologic type, histologic grade, resection type, surgical margin, chemotherapy and radiation therapy on local recurrence, distant metastasis and event-free survival. The mean follow up period was 39 months. The univariate and multivariate regression analysis were performed for statistical evaluation. Results: The local recurrences occurred in 11 patients (21.2%) and distant metastasis in 4 patients (8%), Event-free survival rate at 4 year follow up was 67%. In univariate analysis, histologic grade, surgical margin, chemotherapy and radiation therapy were significant prognostic factors on local recurrence (p<0.05). However, histologic grade lost its significance in muitivariate analysis. Trunk location revealed higher rate of distant metastasis than extremity location. In univariate analysis on event-free survival. histologic grade and chemotherapy were significant factors (p<0.05). No factor remained significant in multivariate analysis. Conclusion: Considering selection bias, positive surgical margin was negative prognostic factor on local recurrence. Liposarcomas arisen in trunk revealed higher rate of distant metastasis. There was no independent prognostic factor on event-free survival of patients with liposarcomas.
Kim, Won-Taek;Ki, Yong-Kan;Nam, Ji-Ho;Kim, Dong-Hyun;Cho, Kyu-Sup;Lee, Jin-Choon;Lee, Byung-Joo;Kim, Dong-Won
Radiation Oncology Journal
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v.27
no.2
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pp.55-63
/
2009
Purpose: This study was performed to objectively evaluate the rate of tumor response to hypofractionated radiotherapy for advanced squamous cell carcinomas of the head and neck. Materials and Methods: Thirty-one patients with advanced squamous cell carcinoma of the head and neck, who were treated by hypofractionated radiotherapy with 3 Gy per fraction for palliative purpose between 1998 and 2008, were reviewed retrospectively. Every tumor-volume was measured and evaluated from CT (computed tomography) images obtained before and 2~3 months after radiotherapy. The radiation toxicity was assessed during and after radiotherapy. A statistical analysis was performed to investigate overall survival, progressionfree survival, and the prognostic factors for survival and response. Results: The median age of the study patients was 70 years. In addition, 85% of the patients were in stage 4 cancer and 66.7% had an ECOG performance status of 1~2. The mean tumor-volume was 128.4 cc. Radiotherapy was administered with a total dose of 24~45 Gy (median: 36 Gy) over 10~25 days. Twenty-nine patients were treated with 30 Gy or more. The observed complete response rate was 12.9% and the partial response rate was 61.3%. Median survival time was 8.9 months and the 1-year progression-free survival rate was 12.9%. The treatment response rate was confirmed as a prognostic factor in the rate of survival. The primary site, stage, tumor-volume, radiotherapy field and overall radiation-dose showed a significant relationship with survival and treatment response. No grade 4 toxicity was observed during and after radiotherapy. Conclusion: There was an objective tumor-regression in about 74% of patients treated by hypofractionated radiotherapy. Further evaluation is needed to select the appropriate fraction-size and patient who may require the additional radiotherapy.
In the analysis of competing risks data, some of covariates may not be fully observed for some subjects. In such cases, excluding subjects with missing covariate values from the analysis may result in biased estimates and loss of efficiency. In this paper, we studied multiple imputation and the augmented inverse probability weighting method for regression parameter estimation in the cause-specific proportional hazards model with missing covariates. The performance of estimators obtained from multiple imputation and the augmented inverse probability weighting method is evaluated by simulation studies, which show that those methods perform well. Multiple imputation and the augmented inverse probability weighting method were applied to investigate significant risk factors for the risk of death from breast cancer and from other causes for breast cancer data with missing values for tumor size obtained from the Prostate, Lung, Colorectal, and Ovarian Cancer Screen Trial Study. Under the cause-specific proportional hazards model, the methods show that race, marital status, stage, grade, and tumor size are significant risk factors for breast cancer mortality, and stage has the greatest effect on increasing the risk of breast cancer death. Age at diagnosis and tumor size have significant effects on increasing the risk of other-cause death.
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