• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.363-368
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• 2014

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.

• Radiation Oncology Journal
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• 제29권3호
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• pp.156-163
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• 2011

Purpose: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. Materials and Methods: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Results: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. Conclusion: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3451-3454
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• 2012

Background: Esophageal cancer in Iran is the sixth most common cancer and is particularly important in east Azerbaijan. The aim of this study was to calculate survival rates and define prognostic factors in esophageal cancer patients. Methods: In this study, all patients with esophageal cancer registered in the Radiation Therapy Center, during March 2006 to March 2011, were analyzed and followed up for vital status. Data were analyzed using the Kaplan-Meier method and the Cox proportional hazard models. Results: Out of 532 patients, survival information was available for 460, including 205 (44/ 5%) females and 255 (55/4%) males. The mean age was $65.8{\pm}12.2$, ranging from 29 to 90 years at the time of diagnosis. 1-, 3- and 5-year survival rates after diagnosis were 55%, 18% and 12%, respectively, with a median survival time of $13.2{\pm}.7$ (CI 95% =11.8-14.6) months. In the univariate analysis, age (P=0/001), education (P=0/001), smoking status (P= 0/001), surgery (P= 0/001), tumor differentiation (P= 0/003) and tumor stage (P= 0/001) were significant prognostic factors. Tumor morphology, sex, place of residence, tumor histology and tumor location did not show any significant effects on the survival rate. In multivariate analysis, age (P = 0/003), smoking (P= 0/01) and tumor stage (P= 0/001) were significant independent predictors of survival. Conclusion: In summary, prognosis of esophageal cancer in North West of Iran is poor. Therefore, reduction in exposure to risk factors and early detection should be emphasized to improve survival.

• Korean Journal of Head & Neck Oncology
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• 제19권2호
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• pp.127-132
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• 2003

Objectives: The best treatment for the malignant parotid tumor still remains to be defined, and a better knowledge about the tumor features that predict the treatment result is needed. The aim of this study is to evaluate the treatment outcomes and to suggest the optimal treatment modality for the parotid cancer. Materials and Methods: The clinicopathologic characteristics of 113 patients who were treated for parotid cancer from January 1990 to December 2002 were retrospectively analysed. Univalate analyses were performed to establish the prognostic influence of pateint age, gender, tumor size, histologic grade and lymph node metastasis. Results: The mean age was 46.4 years old (15-81 years) and. The male to female ratio was 1 : 1.1. The chief complaint was a palpable mass in 85%, pain was in 12.4% and facial nerve palsy was accompanied with 2.7%. The mean tumor size was 3.5cm in diameter. The most common malignant tumor was mucoepidermoid carcinoma (33.6%), followed by acinic cell carcinoma (15%), adenoid cystic carcinoma (11%), carcinoma expleomorhpic adenoma (11%), basal cell carcinoma (7%). The most common operative procedure was total parotidectomy (47.8%) and various types of cervical lymph node dissection were added in 69.9%. Postoperative radiotherapy was done in 61.1 %. Postoperative complications developed in 54 cases (47.8%), including 46 cases (40.7%) of facial nerve palsy and 9 cases (8%) of Frey's syndrome. Recurrences developed in 21 cases (18.6%) and deaths in 15 (13.3%). Cumulative survival at 5 year was 75.4%. Univariate analysis of clinical factors showed that histologic grade and positive cervical lymph node significantly influenced survival (p<0.05). Conclusion: These results suggests that the radical resection with lymph node dissection and postopertaive XRT would be necessary to improve the survival of the patients with high grade cancer or positive lymphnode metastasis.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1110-1118
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• 2018

Objective: To perform a meta-analysis to quantitatively assess functional magnetic resonance imaging (MRI) in the diagnosis of locally recurrent prostate cancer. Materials and Methods: A comprehensive search of the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted from January 1, 1995 to December 31, 2016. Diagnostic accuracy was quantitatively pooled for all studies by using hierarchical logistic regression modeling, including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) curves (AUCs). The Z test was used to determine whether adding functional MRI to T2-weighted imaging (T2WI) results in significantly increased diagnostic sensitivity and specificity. Results: Meta-analysis of 13 studies involving 826 patients who underwent radical prostatectomy showed a pooled sensitivity and specificity of 91%, and the AUC was 0.96. Meta-analysis of 7 studies involving 329 patients who underwent radiotherapy showed a pooled sensitivity of 80% and specificity of 81%, and the AUC was 0.88. Meta-analysis of 11 studies reporting 1669 sextant biopsies from patients who underwent radiotherapy showed a pooled sensitivity of 54% and specificity of 91%, and the AUC was 0.85. Sensitivity after radiotherapy was significantly higher when diffusion-weighted MRI data were combined with T2WI than when only T2WI results were used. This was true when meta-analysis was performed on a per-patient basis (p = 0.027) or per sextant biopsy (p = 0.046). A similar result was found when $^1H$-magnetic resonance spectroscopy ($^1H$-MRS) data were combined with T2WI and sextant biopsy was the unit of analysis (p = 0.036). Conclusion: Functional MRI data may not strengthen the ability of T2WI to detect locally recurrent prostate cancer in patients who have undergone radical prostatectomy. By contrast, diffusion-weight MRI and $^1H$-MRS data may improve the sensitivity of T2WI for patients who have undergone radiotherapy.

• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1444-1452
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• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4487-4491
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• 2014

Objective: To explore the clinical manifestations and imaging characteristics of gliomatosis cerebri to raise the awareness and improve its diagnostic accuracy for patients. Materials and Methods: Clinical data, imaging characteristics and pathological examination of 12 patients with GC from Jan., 2008 to Jan., 2012 were analyzed retrospectively. Results: Patients with GC were clinically manifested with headache, vomiting, repeated seizures, fatigue and unstable walking, most of whom had more than 2 lesions involving in parietal lobe, followed by temporal lobe, frontal lobe, periventricular white matter and corpus callosum. Magnetic resonance imaging (MRI) showed diffuse distribution, T1-weighted images (T1WI) with equal and low signals and T2-weighted images (T2WI) with bilateral symmetrical high diffuse signals. There was no reinforcement by enhancement scanning and signals were different in diffusion-weighted images (DWI). The higher the tumor staging, the stronger the signals. Pathological examination showed neuroastrocytoma in which tumor tissues were manifested by infiltrative growth in blood vessels and around neurons. Conclusions: In clinical diagnosis of GC, much attention should be paid to the diffuse distribution of imaging characteristics, incomplete matching between clinical and imaging characteristics and confirmation by combining with histopathological examination.

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.660-664
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• 2005

Infantile hemangioendothelioma(IHE) of the liver is the most common vascular tumor in infants before the age of 6 months. It is a histologically benign tumor with potentially life-threatening complications. The clinical manifestations are variable, ranging from asymptomatic forms to intractable high-output heart failure. In addition, abdominal mass, intraperitoneal hemorrhage due to rupture of mass, respiratory distress, hematologic abnormalities and jaundice can occur. Diagnostic work-up is through doppler ultrasound sonography, computed tomography scan, magnetic resonance imaging and angiography. Treatment consists of medical treatment, interventional therapy, surgical resection and liver transplantation. We experienced symptomatic IHE in a premature neonate who presented with high output heart failure and respiratory distress. Initial medical treatment and steroid therapy failed to improve his condition. Coil embolization of left hepatic artery resulted in improvement of respiratory symptoms. However, a left lobectomy was performed because the mass size was not decreased with development of collateral vessels. The infant was well, after a successful discharge from the hospital.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.15-20
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• 2013

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.