• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6277-6283
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• 2012

Background: Northern Iran counts as one of the highest prevalence regions for esophageal cancer (EC) worldwide. This study was designed to assess the epidemiologic aspects of EC in north central and northwest Iran over a 10 year period. Materials and Methods: The Guilan cancer registry study (GCRS) is a population-based cancer registry study featuring retrospective (1996-2003) and prospective (2004-2005) phases. A detailed questionnaire based on WHO standards for cancer registratration was applied to gather the required information. Two trained physicians coded information using ICD-O-3 in close coordination with an expert pathologist. Results: A total of 19,936 cases of malignancy (mean age $55.4{\pm}18.0$ years, range: 1-98 years) were registered, including 1,147 cases (670 males, 447 female; mean age: $64.0{\pm}11.5$ years) of EC. In 1996 the male/female ratio among patients with EC was 1.25 which increased to 1.53 in 2005. The lower third of the esophagus still remained the most common site of tumors. The average age-standardized rate (ASR) was 6.9 and 4.1 per $10^5$ men and women, respectively. In 1996, the ASRs were 7.2 and 5.2 per $10^5$ men and women which decreased to 6.9 and 4.1 per $10^5$ in 2004-2005. Squamous cell carcinoma (SCC) was the most prevalent histological subtype of EC accounting over 80% of cases. Conclusions: However the prevalence of adenocarcinoma (ADC) showed an increase to 18.4%. Guilan province may be considered a relatively low incidence region for EC.

• Journal of Chest Surgery
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• 제55권5호
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• pp.397-404
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• 2022

Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.

• Journal of Chest Surgery
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• 제53권4호
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• pp.184-190
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• 2020

Radiation therapy (RT) has improved patient outcomes, but treatment-related complication rates remain high. In the conventional 2-dimensional and 3-dimensional conformal RT (3D-CRT) era, there was little room for toxicity reduction because of the need to balance the estimated toxicity to organs at risk (OARs), derived from dose-volume histogram data for organs including the lung, heart, spinal cord, and liver, with the planning target volume (PTV) dose. Intensity-modulated RT (IMRT) is an advanced form of conformal RT that utilizes computer-controlled linear accelerators to deliver precise radiation doses to the PTV. The dosimetric advantages of IMRT enable better sparing of normal tissues and OARs than is possible with 3D-CRT. A major breakthrough in the treatment of esophageal cancer (EC), whether early or locally advanced, is the use of proton beam therapy (PBT). Protons deposit their highest dose of radiation at the tumor, while leaving none behind; the resulting effective dose reduction to healthy tissues and OARs considerably reduces acute and delayed RT-related toxicity. In recent studies, PBT has been found to alleviate severe lymphopenia resulting from combined chemo-radiation, opening up the possibility of reducing immune suppression, which might be associated with a poor prognosis in cases of locally advanced EC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1397-1401
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• 2014

Aim: To investigate the mechanisms of induction of apoptosis of esophageal cancer cells by esophageal cancer-related gene 2 (ECRG2) in combination with cisplatin (DDP). Methods: Hoechest staining was performed to analyze the effects of single ECRG2 and ECRG2 in combination with DDP on apoptosis of EC9706 cells. The expression levels of p53 and bcl-2 mRNA and protein were determined by RT-PCR and Western blotting, respectively. Results: The number of apoptotic cells after the treatment with ECRG2 in combination with DDP for 24 hours was more than that after the treatment with single ECRG2. RT-PCR and Western blotting showed that the expression levels of bcl-2 mRNA and protein were both down-regulated, while p53 mRNA and protein were both up-regulated in the cells treated with ECRG2 in combination with DDP compared with those given ECRG2 alone. Conclusion: ECRG2 in combination with DDP can enhance the apoptosis of EC9706 cells, possibly by down-regulating bcl-2 expression and up-regulating p53.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4147-4151
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• 2012

The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.139-143
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• 2013

Patients at the same pathological stage of esophageal cancer (EC) that received the same surgical therapy by the same surgeon may have distinct prognoses. The current study aimed to explore the possibility of differentially-expressed microRNAs (miRNAs) underlying this phenomenon. Samples were collected from EC patients at the same tumor node metastasis (TNM) stage but with different prognoses. Paracancerous normal tissues were taken as controls. The specimens were histopathologically analyzed. Differentially-expressed miRNAs were analyzed using real-time quantitative reverse transcription polymerase chain reaction. Compared with patients with poor prognosis, those with good prognosis exhibited 88 two-fold or more than two-fold increased miRNA fragments and 4 half-decreased miRNAs. The most noticeably up-regulated miRNAs included hsa-miR-31, hsa-miR-196b, hsa-miR-652, hsa-miR-125a-5p, hsa-miR-146b, hsa-miR-200c, hsa-miR-23b, hsa-miR-29a, hsa-miR-186, hsa-miR-205, hsa-miR-376a, hsa-miR-410, hsa-miR-532-3p, and hsa-miR-598, whereas the most significantly-downregulated miRNAs were hsa-let-7e, hsa-miR-130b, and hsa-miR-103. EC patients at same TNM stage but with different prognoses show differentially-expressed miRNAs.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2625-2628
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• 2012

Introduction: Fumonisin B1 (FB1) is a toxic and carcinogenic mycotoxin produced in cereals due to fungal infection. This study was conducted to determine FB1 contamination of rice and corn samples and its relationship with the rate of esophageal cancer (EC) in a high risk area in northeastern Iran. Methods: In total, 66 rice and 66 corn samples were collected from 22 geographical subdivisions of Golestan province of Iran. The levels of FB1 were measured for each subdivision by thin layer and high pressure liquid chromatographies. The mean level of FB1 and the proportions of FB1 contaminated samples were compared between low and high EC-risk areas of the province. Results: The mean of FB1 levels in corn and rice samples were 223.64 and 21.59 ${\mu}g/g$, respectively. FB1 contamination was found in 50% and 40.9% of corn and rice samples, respectively. FB1 level was significantly higher in rice samples obtained from high EC-risk area (43.8 ${\mu}g/g$) than those obtained from low risk area (8.93 ${\mu}g/g$) (p-value=0.01). The proportion of FB1 contaminated rice samples was also significantly greater in high (75%) than low (21.4%) EC-risk areas (p-value=0.02). Conclusion: We found high levels of FB1 contamination in corn and rice samples from Golestan province of Iran, with a significant positive relationship between FB1 contamination in rice and the risk of EC. Therefore, fumonisin contamination in commonly used staple foods, especially rice, may be considered as a potential risk factor for EC in this high risk region.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1803-1806
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• 2013

Purpose: Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf-off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. Results: The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ${\leq}$ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Conclusions: Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1693-1697
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• 2012

Objective: To explore the effect on radiosensitivity of arsenic trioxide ($As_20_3$) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of $As_20_3$ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of $IC_{50}$ value and choice of 20% of the $IC_{50}$ as the experimental drug concentration. Blank control, $As_20_3$, hyperthermia, radiotherapy group, $As_20_3$ + hyperthermia, $As_20_3$ + radiotherapy, hyperthermia + radiotherapy and $As_20_3$ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: $As_20_3$ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an $IC_{50}$ of 18.7 ${\mu}mol/L$. After joint therapy of $As_20_3$ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the $G_2$/M phase, and as the ratio of cells in $G_0/G_1$ and S phases decreased, cell death became more pronounced. Conclusion: $As_20_3$ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, $As_20_3$ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.685-689
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• 2013

Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin.