• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3009-3013
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• 2012

Background: The clinical course of individual chronic lymphocytic leukemia (CLL) is highly variable and clinical staging systems do not help us to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. Recently, several important observations related to other prognostic factors including lymphocyte doubling time (LDT), ${\beta}_2$-microglobulin (${\beta}_2$-MG), and percent of smudge cell in peripheral blood smears, cytogenetic and molecular analysis have been made. The aim of this study was to evaluate a range of prognostic factors in our CLL patients. Design and methods: Seventy patients with CLL were enrolled. Prognostic factors of disease including Binet staging, LDT, ${\beta}_2$-MG, ESR, LDH, percent of smudge cell in peripheral blood smear, absolute lymphocyte count, and conventional cytogenetic (CC) analysis were evaluated at diagnosis, and the patients were followed up to determine their outcome. We compared factors with each other and with Binet staging and prognosis. Results: Enrolled patients aged 37-85 years at diagnosis or during follow up. There was no relationship between serum LDH level (P=0.3), ESR (P=0.11), percent of smudge cells in peripheral blood smear (P=0.94), and absolute lymphocyte count (P=0.18) with the stage of disease and prognosis, but the ${\beta}_2$ macroglobulin level (p<0.0001), LDT (p<0.001) had direct and significant relation with staging and outcome. In 19% of patients cytogenetic alteration were seen. Conclusion: The detection of cytogenetic alteration only using the CC method is not sufficient and we need to use FISH, but because FISH study is an expensive method not available in all areas, instead we believe that ${\beta}_2$ MG can be applied in its place as a good prognostic factor for CLL at diagnosis and during follow up. We suggest to add it to Binet staging for prognostic subgrouping of CLL.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8847-8853
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• 2014

The aim of this study was to establish the expression and localization of E-cadherin and ${\beta}$-catenin in oral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevant histopathological variables. E-cadherin and ${\beta}$-catenin expression in normal oral epithelia and in oral squamous cell carcinomas was examined immunohistochemically, and associations with histopathological differentiation and prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiated and (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade (p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, with no correlation to the histological grade (p=0.106). ${\beta}$-Catenin expression was found in 87% of the squamous cells of well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expression was significantly associated with histological grade (p=0.000). the nuclear ${\beta}$-Catenin expression appeared in 3.3% of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells ${\beta}$-Catenin localized in the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression of ${\beta}$-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closely linked to ${\beta}$-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structural association and the role of both in tumor progression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8843-8846
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• 2014

Background: Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. Materials and Methods: This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). Results: The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression-free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Conclusions: Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3561-3566
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• 2014

Background: Recurrent nasopharyngeal carcinoma (NPC) after previous radiotherapy is challenging. There is no standard approach for salvage treatment. Here we present toxicity and treatment results for recurrent NFC patients who underwent fractionated stereotactic radiotherapy (FSRT) as second line radiotherapy (RT). Materials and Methods: Between April 2009 and July 2012, 24 patients, with a male to female ratio of 3:1, were treated with CykerKnife$^{(R)}$ FSRT for recurrent NFC in our institution. Seven out of 24 patients had metastatic recurrent disease. Median age was 53 years (range, 20-70 years). Initial RT dose was 70Gy. The time period between initial RT and FSRT was a median of 33.2 months. The median prescription dose for FSRT was 30Gy (range, 24-30 Gy) in a median of 5 fractions (range, 4-6). Results: The median follow-up for all patients was 19.5 months (IQR: 12.2.-29.2 months). The locoregional control; progression free survival and overall survival (OS) rates for 1-, 2- and 3-year were 64%, 38%, 21%; 60%, 30%, 17% and 83%, 43%, 31%, respectively. Median OS for the entire cohort was 22 months (95% CI: 16.5-27.5). On multivariate analysis recurrent tumor stage was the only prognostic factor for OS (p=0.004). One patient exhibited grade III temporal lobe necrosis. One died because of grade IV mucositis and overlapping infection. Conclusions: The treatment of recurrent NPC is controversial. Fractionated stereotactic radiotherapy is promising. However, the published trials are heterogeneous with respect to the selection criteria and treatment details. Prospective studies with long term follow-up data are warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3065-3070
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• 2014

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5651-5655
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• 2013

Objective: Major histocompatibility complex class I chain-related A (MICA) is a stress-inducible glycoprotein that can be shed as a soluble protein. This study was conducted to determine the expression of MICA in renal cell carcinoma (RCC) and examine the clinical relevance of soluble MICA (sMICA) in this disease. Methods: Immunohistochemistry and real-time PCR analyses were performed to assess the expression of MICA in 48 pairs of RCC and adjacent normal renal tissues. Serum levels of sMICA were measured in 48 RCC patients, 12 patients with benign renal tumors, and 20 healthy individuals. The correlations between sMICA levels and clinicopathological parameters were analyzed and the diagnostic performance of sMICA in RCC was evaluated. Results: RCCs exhibited elevated expression of MICA compared to adjacent normal tissues. Serum concentrations of sMICA were significantly greater in RCC patients ($348.5{\pm}32.5pg/ml$) than those with benign disease ($289.3{\pm}30.4pg/ml$) and healthy controls ($168.4{\pm}43.2pg/ml$) and significantly correlated with advanced tumor stage, lymph node metastasis, distant metastasis, vascular invasion, and higher histological grade. Using a cut-off point of 250 pg/ml, sMICA demonstrated a specificity and sensitivity of 63.2% and 75.6%, respectively, in distinguishing between RCC and benign renal tumors. Conclusion: MICA expression is upregulated in RCC and increased serum sMICA levels predict aggressive tumor behavior. However, the applicability of sMICA alone is limited in distinguishing RCC from benign renal tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5281-5285
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• 2016

Background: Brachytherapy is the most commonly used conservative treatment for the uveal melanoma. The aim of this study was to evaluate therapeutic results of Ruthenium-106 plaque brachytherapy in the management of localized uveal melanoma cases. Methods: We reviewed retrospectively the clinical records of all patients treated in our department for an uveal melanoma, undergoing Ruthenium-106 plaque brachytherapy, from January 1996 to December 2015. We focused on clinical features, therapeutic characteristics, local and distant tumor control and side effects. Results: Nineteen patients were enrolled in our study. Mean age was 56.2 years (28-79) and the sex ratio was 1.37:1 males to females. Diagnosis was made on the basis of ophthalmological clinical examination, angiography, ultrasound and/or magnetic resonance. Median tumor diameter was 9.7 mm (6-13) and median thickness 4.4 mm (2.5-8). The dose of Ruthenium-106 plaque brachytherapy prescribed to the apex of each tumor was 70 Gy in all cases. The median radiation dose to the sclera surface was 226.4 Gy (range: 179.6-342.3) and the median total application time 115.2 hours (range: 27 to 237). After a median follow-up of 61.5 months, local control was achieved in 17 patients (89%): 16 demonstrated a partial tumor response and 1 tumor stabilization. Two patients suffered local progression leading to enucleation, one dying of hepatic metastasis. Radiation-induced complications were cataracts in 3 cases and vitreal hemorrhage in 2. Conclusion: Ruthenium-106 plaque brachytherapy is an efficient treatment for localized uveal melanoma, offering good local control with low toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2145-2150
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• 2016

Background: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. Materials and Methods: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. Results: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. Conclusions: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2027-2030
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• 2016

Objective: To investigate the effect of peripheral blood CD4 + CD25 + regulatory T cell on postoperative immunotherapy in patients with renal carcinoma. Methods: 38 patients with renal cell carcinoma were recruited, and 20 patients from the operation group purely underwent the radical nephrectomy therapy, 18 patients from the combined group successively underwent the radical nephrectomy therapy and IFN-${\alpha}$ adjuvant immunotherapy. Additionally, 12 healthy subjects were recruited in the same period of time and regarded as the control group. Flow cytometry was used to detect CD4 +, CD8 +, CD4 + CD25+ T lymphocyte subset content and the ratio of all parts in the pre-operative period, in the first post-operative week and in the third post-operative month, compare and analyze its variation trend. Results: The CD4+CD25+ T lymphocyte subset content of individual renal carcinoma patients was significantly higher than that of the control group, also increases with the progression in the tumor stage (P<0.05). The post-operative CD4 + CD25+T lymphocytes of individual operation group and combined group patients showed different degrees of increment, but the increment of the combined group was significantly lower than that of the operation group (P<0.05). For the combined group patients with less pre-operative CD4 + CD25+T lymphocytes, their levels would increase after the immunotherapy, while the pre-operative patients with more CD4 + CD25+ T lymphocytes were the opposite situation. Conclusion: The detection of peripheral blood CD4+CD25+ regulatory T lymphocyte subset can reflect the anti-tumor immune status of renal cell carcinoma patient body. It can contribute to predict the prognosis of immunotherapy and provide reference for the choice of renal carcinoma post-operative adjuvant immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1609-1613
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• 2015

Purpose: To determine the rate of lymph node metastasis, oncologic and pregnancy outcomes in apparent early-stage malignant ovarian germ cell tumor (MOGCT). Materials and Methods: Medical records of apparent early-stage MOGCT patients undergoing primary surgical treatment at Siriraj Hospital, Bangkok, Thailand, between January 2006 and December 2013, were retrospectively reviewed. Results: Thirty-eight patients had apparent stage I-II MOGCT. The mean age was $22.1{\pm}7.7years$ (median, 20.8 years; range, 7.7-35.6 years). The mean tumor size was $17.8{\pm}6.5cm$ with a median of 20 (range 4-30) cm. Three most common histopathologies were dysgerminoma (12 patients, 31.6%), immature teratoma (12 patients, 31.6%), and endodermal sinus tumor (6 patients, 15.8%). Twenty-seven of 38 patients underwent lymphadenectomy; 13 patients (48.2%) were stage IA and 8 patients (29.6%) were stage IC. The rate of retroperitoneal nodes metastasis was 7.4% (2/27 patients). At 26.1 months of median follow-up time (range 1.9-88.5 months), 9 patients retained fertility functions, with uneventful pregnancies in 3 of these. Only one patient (2.6%) had progression of disease at 4.9 months after surgery. The 5-year survival rate was 97.4%. Conclusion: As the rate of pelvic or para-aortic node metastasis in MOGCT is considerable, lymphadenectomy should be incorporated in surgical staging procedures.