• Journal of Gastric Cancer
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• v.20 no.4
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• pp.421-430
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• 2020

Purpose: Currently, there is no clear evidence to support any specific treatment as a principal therapy for stage IV gastric cancer outlet obstruction (GCOO) patients. This study evaluated the outcomes of palliative gastrectomies and survival prognostic factors in patients with stage IV resectable GCOO. Materials and Methods: We retrospectively reviewed the medical records of 48 stage IV GCOO patients who underwent palliative gastrectomies between June 2010 and December 2019. Palliative gastrectomies were performed only in patients with resectable disease. Early surgical outcomes and prognostic factors were analyzed using univariate and multivariate analyses. Results: There were no specific risk factors for postoperative complications, except for being underweight. Severe postoperative complications developed in five patients, and most of the patients underwent interventional procedures and received broad-spectrum antibiotics for intra-abdominal abscesses. The multivariate survival analysis showed that palliative chemotherapy is a positive prognostic factor, while the specific type of hematogenous and lymphatic metastasis is a negative prognostic factor. Conclusions: We recommend that the treatment method for stage IV GCOO should be selected according to each patient's physical condition and tumor characteristics. In addition, we suggest that palliative gastrectomies can be performed in stage IV resectable GCOO patients without unfavorable prognostic factors (types of hematogenous and lymphatic metastases).

• BMB Reports
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• v.54 no.12
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• pp.608-613
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• 2021

Melanoma, the most serious type of skin cancer, exhibits a high risk of metastasis. Although chemotherapeutic treatment for metastatic melanoma improves disease outcome and patient survival, some patients exhibit resistance or toxicity to the drug treatment regime. OTUB1 is a deubiquitinating enzyme overexpressed in several cancers. In this study, we investigated the effects of inhibiting OTUB1 expression on melanoma-cell proliferation and viability and identified the underlying molecular mechanism of action of OTUB1. We did endogenous OTUB1 knockdown in melanoma cells using short interfering RNA, and assessed the resulting phenotypes via MTT assays, Western blotting, and cell-cycle analysis. We identified differentially expressed genes between OTUB1-knockdown cells and control cells using RNA sequencing and confirmed them via Western blotting and reverse transcription polymerase chain reaction. Furthermore, we investigated the involvement of apoptotic and cell survival signaling pathways upon OTUB1 depletion. OTUB1 depletion in melanoma cells decreased cell viability and caused simultaneous accumulation of cells in the sub-G1 phase, indicating an increase in the apoptotic-cell population. RNA sequencing of OTUB1-knockdown cells revealed an increase in the levels of the apoptosis-inducing protein TRAIL. Additionally, OTUB1-knockdown cells exhibited increased sensitivity to PLX4032, a BRAF inhibitor, implying that OTUB1 and BRAF act collectively in regulating apoptosis. Taken together, our findings show that OTUB1 induces apoptosis of melanoma cells in vitro, likely by upregulating TRAIL, and suggest that approaches targeting OTUB1 can be developed to provide novel therapeutic strategies for treating melanoma.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.146-158
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• 2023

Endoscopic resection (ER) is widely performed for early gastric cancer (EGC) with a negligible risk of lymph node metastasis (LNM) in Eastern Asian countries. In particular, endoscopic submucosal dissection (ESD) leads to a high en bloc resection rate, enabling accurate pathological evaluation. As undifferentiated EGC (UD-EGC) is known to result in a higher incidence of LNM and infiltrative growth than differentiated EGC (D-EGC), the indications for ER are limited compared with those for D-EGC. Previously, clinical staging as intramucosal UD-EGC ≤2 cm, without ulceration, was presented as 'weakly recommended' or 'expanded indications' for ER in the guidelines of the United States, Europe, Korea, and Japan. Based on promising long-term outcomes from a prospective multicenter study by the Japan Clinical Oncology Group (JCOG) 1009/1010, the status of this indication has expanded and is now considered 'absolute indications' in the latest Japanese guidelines published in 2021. In this study, which comprised 275 patients with UD-EGC (cT1a, ≤2 cm, without ulceration) treated with ESD, the 5-year overall survival (OS) was 99.3% (95% confidence interval, 97.1%-99.8%), which was higher than the threshold 5-year OS (89.9%). Currently, the levels of evidence grades and recommendations for ER of UD-EGC differ among Japan, Korea, and Western countries. Therefore, a further discussion is warranted to generalize the indications for ER of UD-EGC in countries besides Japan.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.2
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• pp.61-67
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• 2023

This systematic review aimed to analyze the clinicopathological profile and relevant prognostic factors of head and neck rhabdomyosarcoma in pediatric patients. The search was carried out in the electronic search portals PubMed, Lilacs, Embase, Scopus, and Web of Science. The search yielded studies that were then analyzed regarding study topic, data extraction, and risk of bias using the STROBE (Strengthening the Reporting of Observational Studies) guidelines. Finally, three studies were included for qualitative analysis. Most of the cases involved embryonic and alveolar rhabdomyosarcoma. Expression of MYOD1 was highly correlated with diagnosis of spindle cell/sclerosing rhabdomyosarcoma, which appears to have a poor prognosis in children. Furthermore, tumor size <5 cm and absence of metastasis accompanied by complete resection and administration of adjuvant therapies such as chemotherapy and radiotherapy favored a better prognosis.

• Korean Journal of Head & Neck Oncology
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• v.39 no.1
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• pp.45-48
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• 2023

Angiosarcoma is a very rare subtype of sarcoma. It mainly occurs in the head and neck, and cutaneous angiosarcoma in this region seems to be a distinctive neoplasm with characteristic clinicopathologic features that differ from those of angiosarcoma in other anatomical locations. The prognosis of angiosarcoma in the head and neck region is poor, and the risk of local recurrence and metastasis is high. We reconstructed an atypical angiosarcoma that presented as a solitary nodule with a shape suggestive of hemangioma on the cheek using a modified bilobed local flap. At a 12-month follow-up visit, the patient in this case showed successful recovery after radiation therapy.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.40-46
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• 2005

Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1：1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.359-366
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• 2005

Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

• Journal of Chest Surgery
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• v.38 no.6 s.251
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• pp.421-427
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• 2005

Complete surgical resection is the most effective treatment for pT1/2N1 non-small cell lung cancer, however 5 year survival rate of these patients is about $40\%$ and the major cause of death is recurrent disease. We intended to clarify the risk factors of recurrence in completely resected pT1/2N1 non-small cell lung cancer. Material and Method: From Jan. f990 to Jul. 2003, total of 117 patients were operated for pT1/2N1 non-small cell lung cancer. The risk of recurrence according to patients characteristics, histopathologic findings, type of resection, pattern of lymph node metastasis, postoperative adjuvant treatment were evaluated retrospectively. Result: Mean age of patients was 59.3 years. There were 14 patients with T1N1 and 103 patients with T2N1 disease. Median follow-up time was 27.5 months and overall 5 year suwival rate was $41.3\%$. 5 year freedom-from recurrence rate was $54.1\%$. Recurrence was observed in $44 (37.6\%)$ patients and distant recurrence developed in 40 patients. 5 year survival rate of patients with recurence was $3.3\%$, which was significantly lower than patients without recurrence $(61.3\%,\;p=0.000).$ In multi-variate analysis of risk factors for freedom-from recurrence rate, multi-station N1 $(hazard\;ratio=1.997,\;p=0.047)$ was a poor prognostic factor. Conclusion: Multi-station N1 is the risk factor for recurrence in completely resected pT1/2N1 non-small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1615-1621
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• 2013

Background: Matrix metalloproteinase 9 (MMP-9) is related to tumor invasion and metastasis. However, the role of MMP-9 expression in breast cancer survival remains controversial. The purpose of this study was to accomplish a more accurate estimation of the association between MMP-9 expression and survival results in breast cancer patients through meta-analysis. Methods: A meta-analysis of published studies investigating the effects of positive MMP-9 expression on both relapse free survival (RFS) and overall survival (OS) was performed. Relevant literature was confirmed by searching electronic databases including PubMed, Ovid, EMBASE and China National Knowledge Infrastructure (CNKI) before November 1, 2012. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs were used to evaluate the strength of the association between positive MMP-9 expression and survival results of breast cancer patients. Funnel plot and Egger's regression tests were used to evaluate publication bias. Heterogeneity and sensitivity analysis was also conducted. All the work was completed using STATA. Results: A total of 2,344 patients from 15 evaluative studies were finally included. Pooled HRs and 95% CIs suggested that MMP-9 overexpression had an unfavorable impact on both OS (HR: 1.70, 95% CI: 1.41-2.04) and RFS (HR: 1.54, 95% CI: 1.17-2.01) in breast cancer patients. There was no significant heterogeneity observed in the studies reported for OS (P=0.360, $I^2$=8.8%), but not RFS (P=0.002, $I^2$=67%). Publication bias was absent among the studies both in OS and RFS cases (t=-0.54, P=0.605 and t=1.71, P=0.131, respectively). Omission of any single study had little effect on the combined risk estimates on sensitivity analysis. Conclusion: The results of this meta-analysis suggest that positive MMP-9 expression confers a higher risk of relapse and a worse survival in patients with breast cancer. Larger prospective studies are now needed to evaluate the clinical utility of MMP-9 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1215-1219
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• 2016

Background: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients. Materials and Methods: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR). Results: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05). Conclusions: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further expel.