• Journal of Preventive Medicine and Public Health
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• v.40 no.1
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• pp.23-28
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• 2007

Objectives : Chronic infections with hepatitis B or C and alcoholic cirrhosis are three well-known major risk factors for liver cancer. Diabetes has also been suggested as a potential risk factor. However, the findings of previous studies have been controversial in terms of the causal association. Therefore, the aim of this study was to evaluate the association between serum glucose levels and liver cancer development in a Korean cohort. Methods : Thirty-six liver cancer cases were identified in the Korean Multi-Center Cancer Cohort (KMCC). Baseline information on lifestyle characteristics was obtained via questionnaire. Serum glucose levels were measured at the study's enrollment. Relative risks (RRs) were estimated using a Cox proportional hazard regression model. The adjusting variables included age, gender, smoking history, alcohol consumption, body mass index, and hepatitis B surface antigen (HBsAg) seropositivity. Results : The RRs of serum glucose for liver caner were 1.20 (95% CI = 0.48-2.99) for the category of 100 to 125 mg/dL of serum glucose and 2.77 (95% CI = 1.24-6.18) for the >126 mg/dL serum glucose category (both compared to the <100 mg/dL category). In a subgroup analysis, the RR of serum glucose among those who were both HBsAg seronegative and non-drinkers was 4.46 (95% CI = 1.09-18.28) for those with glucose levels >100 mg/dL. Conclusions : The results of this study suggest that a high level of serum glucose can increase liver cancer risk independently of hepatitis infection and drinking history in Koreans. This study implies that glucose intolerance may be an independent risk factor for liver cancer.

• The Journal of Internal Korean Medicine
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• v.41 no.1
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• pp.1-13
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• 2020

Objectives: Osteoarthritis (OA) is a chronic and degenerative joint disease characterized by progressive degeneration of articular cartilage. Inflammation is a recognized and important factor of OA progression. The present study was designed to investigate the protective effect of Corni Fructus water extract (CFW) on a monosodium iodoacetate (MIA)-induced rat model of OA. Methods: Osteoarthritis was induced by injection of MIA (50 µL; 80 mg/mL) into the knee joint cavity of rats. After an adaptation period for seven days, the rats were divided into 4 groups (n=8/group): normal, control, indomethacin-treated (5 mg/kg), and CFW-treated (200 mg/kg) groups. The rats were treated orally for 14 days. Pain was evaluated by determining hind paw weight distribution. For biochemical analyses, we measured the changes in reactive oxygen species (ROS) and peroxynitrite (ONOO^-) in the knee joint. The presence of anti-oxidant proteins and inflammatory proteins was determined by western blotting. Results: The administration of CFW significantly improved the hind paw weight distribution. The ROS and ONOO^- levels of knee joint were significantly decreased in the CFW group. CFW inhibited the production of inflammatory mediators, such as COX-2, and inflammatory cytokines, including IL-6 and IL-1β, via the NF-κB signaling pathway. The expression of anti-oxidant enzymes, such as catalase and GPx-1/2 also increased significantly. Conclusions: The findings indicate that CFW has a therapeutic and protective effect on OA by suppression of inflammation. Therefore, CFW could represent a potential and effective candidate for OA treatment.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.306-311
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• 2001

Purpose : In this retrospective study, we attempted to evaluate the treatment outcome and the prognostic factors of thymoma treated with surgery, radiotherapy and chemotherapy. Methods and materials : Between 1979 and 1998, 55 patients with thymoma were treated at the Seoul National University Hospital. Of these, 11 patients underwent surgery only, 33 patients received post-operative radiotherapy and 11 patients received radiotherapy only. Twenty-three patients had gross total resection and 21 patients subtotal resection. For postoperative radiotherapy, the radiation dose consisted of $41.4\~55.8\;Gy$. The average follow-up was 64 months, and ranged from 2 to 160 months. The sex ratio was 1:1 and the median age was 48 years $(15\~74\;years)$. Overall survival and disease-free survival were determined via the Kaplan-Meier method, and the log-rank was employed to evaluate for differences in prognostic factor. Results : The five- and 10-year survivai rates were $87\%\;and\;65\%$ respectively, and the median survival was 103 months. By univariate analysis, only stage (p=0.0017) turned out to be significant prognostic factors of overall survival. Also, stage (p=0.0007) was significantly predictive for overall survival in mutivariated analysis. Conclusion : This study showed the stage was found to be important prognostic factors, which influenced survival. Especially, as incomplete resection is related with poor results, complete resection is important to cure the invasive thymoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6111-6116
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• 2015

Background: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. Materials and Methods: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. Results: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. Conclusions: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1545-1551
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• 2015

Purpose: Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low-frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Patients and Methods: Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Results: Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (p<0.05) and fluorouracil-based adjuvant chemotherapy (p<0.001), the 3 factors were attributed to a favorable survival status independently. Among 201 patients who did not receive adjuvant chemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p<0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). It was implied that female patients had better survival than male. Conclusion: Survival status after anterior resection of rectal carcinoma is related to the microsatellite instability status, adjuvant chemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite-instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite-instable have a better 5-year rate of DFS than those with microsatellite-stable or low microsatellite-instable, and female patients have a better survival as well.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2101-2107
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• 2012

Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.707-712
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• 2014

Purpose: Anastomotic leakage (AL) is associated with high morbidity and mortality, high reoperation rates, and increased hospital length of stay. Here we investigated the risk factors for AL after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Data for 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2003 to 2007 were prospectively collected. All patients experienced a total mesorectal excision (TME) operation. Clinical AL was defined as the presence of leakage signs and confirmed by diagnostic work-up according to ICD-9 codes 997.4, 567.22 (abdominopelvic abscess), and 569.81 (fistula of the intestine). Univariate and logistic regression analyses of 20 variables were undertaken to determine risk factors for AL. Survival was analysed using the Cox regression method. Results: AL was noted in 35 (7.6%) of 460 patients with rectal cancer. :Median age of the patients was 65 (50-74) and 161 (35%) were male. The diagnosis of AL was made between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate and multivariate analysis, age (p=0.004), gender (p=0.007), tumor site (p<0.001), preoperative body mass index (EMI) (p<0.001), the reduction of TSGF on 5th POD less than 10U/ml (p=0.044) and the pH value of pelvic dranage less than or equal to 6.978 on 3rd POD (p<0.001) were selected as 6 independent risk factors for AL. It was shown that significant differences in survival of the patients were AL-related (p<0.001), high ASA score related (p=0.036), high-level EMI related (p=0.007) and advanced TNM stage related

• Journal of Korean Neurosurgical Society
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• v.54 no.5
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• pp.399-404
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• 2013

Objective : The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS). Methods : Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan- Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors. Results : Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ${\geq}70$ (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were $89.5{\pm}4.5%$ and $70.5{\pm}6.9%$ at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (${\leq}3$) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival. Conclusion : The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5219-5223
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• 2013

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT, pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.354-360
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• 2020

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.