• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3849-3856
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• 2015

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7997-8002
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• 2015

Gene amplification is an important mechanism in the development and progression of cancer. Currently, gene amplification status is generally determined by in situ hybridization (ISH). Multiplex ligation-dependent probe amplification (MLPA) is a PCR-based method that allows copy number detection of up to 50 nucleic acid sequences in one reaction. The aim of the present study was to compare results for HER2, CCND1, MYC and ESR1 gene amplification detected by MLPA with fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) as clinically approved methods. Tissue samples of 170 invasive breast cancers were collected. All were ER positive. Tissue samples had previously been tested for HER2 using immunohistochemistry. Amplification of the selected genes were assessed using MLPA, FISH and CISH and results were compared. HER2 MLPA and ISH results were also compared with HER2 immunohistochemistry (IHC) which detects protein overexpression. Amplification of HER2, CCND1, MYC and ESR1 by MLPA were found in 9%, 19%, 20% and 2% of samples, respectively. Amplification of HER2, CCND1, MYC and ESR1 by FISH was noted in 7%, 16%, 16% and 1% of samples, respectively. A high level of concordance was found between MLPA/FISH (HER2: 88%, CCND1: 88%, MYC: 86%, ESR1: 92%) and MLPA/CISH (HER2: 84%). Of all IHC 3+ cases, 91% were amplified by MLPA. In IHC 2+ group, 31% were MLPA amplified. In IHC 1+ group, 2% were MLPA amplified. None of the IHC 0 cases were amplified by MLPA. Our results indicate that there is a good correlation between MLPA, IHC and ISH results. Therefore, MLPA can serve as an alternative to ISH for detection of gene amplification.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7859-7863
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• 2015

Purpose: To compare the efficacy and toxicity of gemcitabine versus docetaxel in a second-line setting of nonsmall cell lung cancer (NSCLC) patients previously treated with platin-based combination chemotherapy. Materials and Methods: We retrospectively evaluated the medical records of 57 patients treated with single agent gemcitabine or docetaxel in second-line setting of advanced NSCLC who received one prior platinum-based therapy. Results: The mean age was $56.7{\pm}8.39$ years with 55 (96.5%) males and two (3.5%) females. Forty of them received docetaxel and 17 gemcitabine. The mean number of chemotherapy cycles was $6.8{\pm}4.0$ in the gemcitabine group, while it was $4.6{\pm}3.0$ in the docetaxel group. Overall response rates were 8% and 12% (P=0.02) for gemcitabine and docetaxel, respectively. The median survival time was 22 versus 21 months for gemcitabine and docetaxel, respectively. The median times to progression were 8 and 5 months. There was no difference between the two groups in terms of incidence of adverse affects (40% vs 47.1%). All of the hematological side effects were grade 1/2. No major toxicity was encountered necessitating stopping the drug for either group. Conclusions: Treatment with gemcitabine demonstrated clinically equivalent efficacy with a significantly improved safety profile compared with those receiving docetaxel in the second-line setting for advanced NSCLC in this study. Based on these results, treatment with gemcitabine should be considered a standard treatment option for second-line NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6221-6225
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• 2012

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7453-7457
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• 2014

Objective: To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Methods: Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel $125mg/m^2$ on day 1 and day 8, cisplatin $75mg/m^2$ on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Results: Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Conclusion: Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotheraphy for stage III/IV squamous NSCLC, and its adverse effects are tolerable.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7271-7275
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• 2014

Background: The aim of the present study was to evaluate the presentation, clinical course and outcome between children and young adults with differentiated thyroid cancer (DTC) treated in our hospital. Materials and Methods: The medical records of 145 patients with DTC who underwent surgery followed by radioiodine and thyroid hormone (TSH) suppression were retrospectively reviewed. The follow up was between January 2006 and June 2012. These patients consisted of 38 children (age${\leq}18y$) and 107 young adult patients (age${\leq}30y$). The clinical characteristics and outcome were analyzed and compared, and the progression-free survival (PFS) was evaluated using the Kaplan-Meier method. Results: At initial diagnosis, a greater degree of extra thyroidal extension was found in children than adults patients (p<0.001). However, there was no significant difference between the two groups with regard to the tumor size and the presence of lymph node or distant metastasis (p=0.172, p=0.050 and p=0.068, respectively). The extent of surgery and the cumulative or mean dose of radioiodine were similar in both groups. During the follow up, the overall survival rate was 100% for both groups, and the PFS rate was similar in children and in young adults group (log rank test, ${\chi}^2$=0.126, p=0.723). Conclusions: In comparison to the young adult patients, DTC in children presents with more aggressive behavior, but outcomes are similar between the two groups after the intensive management of surgery followed by radioiodine and TSH suppression therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1581-1584
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• 2014

Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$, day 1) and cisplatin ($75mg/m^2$, day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6267-6271
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• 2013

Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.314-317
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• 2008

We report the patient presented with a left-sided pleural effusion. Pleural fluid analysis revealed lymphocyte-dominant exudates with lower level of adenosine deaminase and negative cytologic malignancy. Thoracoscopic examination and histologic examination revealed metastatic nodules on pleurae, proven to be from the papillary thyroid cancer. There were no other sites of distant metastases. Though papillary thyroid cancer is characterized with slow progression and relatively good prognosis, metastatic pleural effusion as an initial manifestation of undiagnosed papillary thyroid cancer can be considered.