• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3875-3879
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• 2015

Background: The neutrophil/lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. Inflammation has been implicated in the initiation and progression of thyroid cancer. The aim of this study was to examine the relationship of NLR with papillary thyroid cancer (PTC) and different benign thyroid pathologies like multinodular goiter (MNG) and lymphocytic thyroiditis (LT). Materials and Methods: We retrospectively evaluated the neutrophil, lymphocyte counts and NLR calculated from these parameters of 232 patients with histologically confirmed as multinodular goiter (group MNG) (n=70), lymphocytic thyroiditis (group LT) (n=97), LT with PTC (group LT-PTC) (n=25) and PTC (group PTC) (n=40). The optimal cut-off value for NLR was determined. Results: NLR level was significantly higher in groups LT-PTC and PTC as compared to groups MNG and LT (p<0.05). NLR of LT subgroups according to TSH levels were not different (p>0.05). When we grouped the patients as benign and malignant according to PTC presence, the optimum NLR cut-off point obtained from ROC analysis was 1.91 (sensitivity 89.0% and specificity 54.5%). Conclusions: Since NLR was significantly elevated in group LT-PTC and group PTC, NLR value may give an opinion as a potential marker in differentiation of benign and malign thyroid disorders. For this purpose a cut-off value of 1.91 for NLR may be accepted.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3827-3833
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• 2015

Background: Positive para-aortic lymph node (PALN) at diagnosis in cervical cancer patients confers an unfavorable prognosis. This study reviewed the outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with extended field RT (CCEFRT) in patients with positive PALN at diagnosis. Materials and Methods: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed. Results: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed. Conclusions: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1365-1370
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• 2012

The high mobility group box-1 (HMGB1) protein and NALP3 inflammasome have been identified to play important roles in inflammation and cancer pathogenesis, but the relationships between the two and cancer remain unclear. The current study investigated the relationship between HMGB1 and the NALP3 inflammasome in THP-1 macrophages. HMGB1 was found unable to activate the NALP3 inflammasome and failed to induce the release of the IL-$1{\beta}$ and IL-18 in THP-1 macrophages. HMGB1 was also found significantly enhanced the activity of ATP to induce IL-$1{\beta}$ and IL-18 by the induction of increased expression of pro-IL-$1{\beta}$ and pro-IL-18. This process was dependent on activation of RAGE, MAPK p38 and NF-${\kappa}B$ signaling pathway. These results demonstrate that HMGB1 promotes the synthesis of pro-IL-$1{\beta}$ and pro-IL-18 in THP-1 macrophages by the activation of p38 MAPK and NF-${\kappa}B$ through RAGE. HMGB1 likely plays an important role in the first step of the release of the IL-$1{\beta}$ and IL-18, preparing for other cytokines to induce excessive release of IL-$1{\beta}$ and IL-18 which promote inflammation and cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1177-1182
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• 2012

Protein kinase C (PKC) has been implicated in carcinogenesis and displays variable expression profiles during cancer progression. Studies of dietary phytochemicals on cancer signalling pathway regulation have been conducted to search for potent signalling regulatory agents. The present study was designed to evaluate any suppressive effect of maslinic acid on PKC expression in human B-lymphoblastoid cells (Raji cells), and to identify the PKC isoforms expressed. Effects of maslinic acid on PKC activity were determined using a PepTag$^{(R)}$ assay for non-radioactive detection of PKC. The highest expression in Raji cells was obtained at 20 nM PMA induced for 6 hours. Suppressive effects of maslinic acid were compared with those of four PKC inhibitors (H-7, rottlerin, sphingosine, staurosporine) and two triterpenes (oleanolic acid and ursolic acid). The $IC_{50}$ values achieved for maslinic acid, staurosporine, H-7, sphingosine, rottlerin, ursolic acid and oleanolic acid were 11.52, 0.011, 0.767, 2.45, 5.46, 27.93 and $39.29\;{\mu}M$, respectively. Four PKC isoforms, PKC ${\beta}I$, ${\beta}II$, ${\delta}$, and ${\zeta}$, were identified in Raji cells via western blotting. Maslinic acid suppressed the expression of PKC ${\beta}I$, ${\delta}$, and ${\zeta}$ in a concentration-dependent manner. These preliminary results suggest promising suppressive effects of maslinic acid on PKC activity in Raji cells. Maslinic acid could be a potent cancer chemopreventive agent that may be involved in regulating many downstream signalling pathways that are activated through PKC receptors.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6481-6486
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• 2013

Background: Our previous study demonstrated cytotoxicity of a crude extract from Patrinia heterophylla Bunge (PHEB). In the present study, we aimed to investigate the effects of isovaltrate acetoxyhydrin (IA) isolated from PHEB on the gastric cancer cell SGC-7901, in order to explore a potential treatment for gastric cancer. Methods: MTT assays were employed to determine the effects of IA on cell vitality and proliferation, with monitoring of cell morphology changes and examination of apoptosis with Annexin V-PI staining. Flow cytometry was used to assess cell cycle progression and mitochondrial membrane potential. The activity of caspase 3, 9 was evaluated by spectrophotometry, and the protein levels of Bax, Bcl2 and Cyclin B1 were analyzed with Western blotting of total proteins extracted from cultured cells. Results: The results demonstrated direct toxicity of IA towards SGC-7901 cells. Evidence of apoptosis included blebbing and chromatin condensation. Annexin V-PI assays revealed early apoptosis, involving rapid depolarization of mitochondrial membranes and activity of caspase 3, 9 signaling pathways. Western blotting showed that Bcl2 and Bax proteins was down- and up-regulated, respectively, and cyclin B1 was up-regulated. Cell cycle analysis further indicated that IA could induce G2/M phase arrest in SGC-7901 cells. Conclusions: In conclusion, we believe that IA induces apoptosis of SGC-7901 cells, therefore providing a potential therapeutic agent for treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5687-5690
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• 2015

Background: Factors predictive of survival have been identified in Western patients with metastatic clear cell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictive of survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients with mCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46 consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemical markers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniand multivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associated with poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International Metastatic RCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations (p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorer PFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in response to sunitinib was significantly higher in patients with normal (${\leq}0.5mg/dl$) than elevated baseline CRP (p<0.001). Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treated with first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response to sunitinib treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6001-6006
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• 2015

Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. Materials and Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. Results: 101 patients were found to be eligible. Mean age was $56.7{\pm}12.8years$, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. Conclusions: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6149-6154
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• 2015

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5343-5348
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• 2014

Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti- HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six randomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publication bias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4711-4715
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• 2013

Aim: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensitymodulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. Methods: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. Results: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ${\geq}$ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival ($X^2$ = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). Conclusions: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.