• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.104-114
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• 2024

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.144-154
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• 2024

Backgrounds/Aims: Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor. Methods: Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio. Results: When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort. Conclusions: Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population-based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.242-250
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• 2007

Background: Abnormal angiogenesis can induce hypoxia within a highly proliferating tumor mass, and these hypoxic conditions can in turn create clinical problems, such as resistance to chemotherapy. However, the mechanism by which hypoxia induces these changes has not yet been determined. Therefore, this study was conducted to determine how hypoxia induces changes in cell viability and extracellular microenvironments in an in vitro culture system using non-small cell lung cancer cells. Methods: The non-small cell lung cancer cell line, A549 was cultured in DMEM or RPMI-1640 media that contained fetal bovine serum. A decrease in the oxygen tension of the media that contained the culture was then induced in a hypoxia microchamber using a $CO_2-N_2$ gas mixture. A gas analysis and an MTT assay were then conducted. Results: (1) The decrease in oxygen tension was checked the anaerobic gas mixture for 30 min and then reoxygenation was induced by adding a 5% $CO_2-room$ air gas mixture to the chamber. (2) Purging with the anaerobic gas mixture was found to decrease the further oxygen tension of cell culture media. (3) The low oxygen tension resulted in a low pH, lactic acidosis and a decreased glucose concentration in the media. (4) The decrease in glucose concentration that was observed as a result of hypoxia was markedly different when different types of media were evaluated. (5) The decrease in oxygen tension inhibited proliferation of A549 cells. Conclusion: These data suggests that tumor hypoxia is associated with acidosis and hypoglycemia, which have been implicated in the development of resistance to chemotherapy and radiotherapy.

• Radiation Oncology Journal
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• v.33 no.3
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• pp.188-197
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• 2015

Purpose: To investigate the patterns of care for patients with nasopharyngeal carcinoma (NPC) in South Korea. Materials and Methods: A multi-institutional retrospective study was performed (Korean Radiation Oncology Group [KROG] 11-06) on a total of 1,445 patients from 15 institutions. Results: Of the 1,445 patients, more than half were stages III (39.9%) and IV (35.8%). In addition to patterns of care, we also investigated trends over time with the periods 1988-1993, 1994-2002, and 2003-2011. The frequencies of magnetic resonance imaging and positron emission tomography-computed tomography were markedly increased in the third period compared to previous 2 periods. Concurrent chemoradiation (CCRT) was performed on 894 patients (61.9%), neoadjuvant chemotherapy on 468 patients (32.4%), and adjuvant chemotherapy on 366 patients (25.3%). Of stage II-IV patients, CCRT performed on 78.8% in 2003-2011 compared to 15.0% in 1988-1993. For patients treated with CCRT, cisplatin was the most commonly used agent in 81.3% of patients. Over the periods of time, commonly used radiotherapy (RT) techniques were changed from 2-dimensional RT (1988-1993, 92.5%) to 3-dimensional RT (2003-2011, 35.5%) or intensity-modulated RT (IMRT; 2003-2011, 56.5%). Median RT doses given to primary tumors, high-risk lymphatics, and low-risk lymphatics were 70.0 Gy, 58.1 Gy, and 48.0 Gy, respectively. Adoption of IMRT increased the dose per fraction and escalated total radiation dose. Conclusion: Assessment of the patterns of care for NPC patients in South Korea demonstrated that management for NPC including diagnostic imaging, treatment regimen, RT techniques and dose schedule, advanced in accordance with the international guidelines.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.160-169
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• 2007

Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/$m^{2}$/day, days 1-4 and 29-32, Cisplatin 60 mg/$m^{2}$/day, days 1 and 29). An esophagectomy was planned in $4{\sim}6$ weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1 % and 53.3%, 41.8%, respectively. By univariate analysis, achieviement of pCR and a clinically uninvolved distant lymph node (cMO) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.259-264
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• 1998

Purpose : This study was to evaluate the effectiveness of preoperative radiotherapy in maxillary sinus cancer. Materials and Methods : A retrospective analysis was done for 42 patients with maxillary sinus cancer who were treated with radiation with or without surgery from April 1986 to September 1996. There were 27 male and 15 female patients. Patients' age ranged from 24 to 75 years (median 56 years). Stage distribution showed 2 in T2, 19 in T3, and 21 in T4 lesions The histologic type was squamous cell carcinoma in 38, undifferentiated carcinoma in 1, transitional cell carcinoma in 1, and adenoid cystic carcinoma in 2 patients. All patients were treated with radiation initially with a dosage range of 50.4-70.2 Gy (median 70.2 Gy) before further evaluation of remnant disease. Eleven patients were given induction chemotherapy (2cycles of 5-fluorouracil and cisplatin) concurrently with radiotherapy. Six to eight weeks after radiotherapy with or without chemotherapy computerized tomography (CT) of paranasal sinus was taken to evaluate remnant disease. If the CT finding showed remnant disease, a Caldwell-Luc procedure was done to get the specimen of suspicious lesions. A radical maxillectomy was done if the specimen was proven to contain malignancy. In contrast periodic follow-up examination was done without any radical surgery if the tissue showed only granulation tissue. Follow-up period ranged from 3 to 92 months with a median 16 months. Results : Nine (21.4$\%$) patients showed complete response (CR) and 33 patients (78.6$\%$) showed persistent disease (PER) to initial radiotherapy. Among the 9 CR patients, 7 patients had no evidence of disease (NED), 1 patient had local failure, and 1 patient had regional failure. Among 33 PER patients, salvage total maxillectomy was done in 10 patients, and the surgery was not feasible or refused in 23 patients. Following the salvage radical surgery, 2 patients were NED and 8 patients were PER status. Overall and disease- free survival rate at 5 years was 23.1$\%$ and 16.7$\%$, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (P<0.01). Conclusion : The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4$\%$) so as to preserve their facial integrity.

• Journal of Chest Surgery
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• v.40 no.6 s.275
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• pp.428-434
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• 2007

Background: Recent studies have suggested that UFT may be an effective adjuvant therapy for completely resected IB (pT2N0) non-small cell lung cancer (NSCLC). We designed this study to clarify the feasibility of performing adjuvant chemotherapy with UFT for completely resected IB nor-small cell lung cancer, Material and Method: We randomly assigned patients suffering with completely resected IB non-small cell lung cancer to receive either UFT 3g for 2 year or they received no treatment. All patients had to be followed until death or the cut-off date (December 31 2006). Result: From June 2002 through December 2004, 64 patients were enrolled. Thirty five patients were assigned to receive UFT (the UFT group) and 29 patients were assigned to observation (the control group). A follow-up surrey on the 3 year survival rate was successfully completed for all the patients. The median follow-up time for all the patients was 32.8 months. In the UFT group, the median time of administration was 98 weeks (range: $2{\sim}129$ weeks). The rate of compliance was 88.2% at 6 months, 87.5% at 12 months, 80.6% at 18 month and 66.7% at 24 months. Seven recurrences (24.1%) occurred in the control group and six (17.1%) occurred in the UFT group (p=0,489). The three-year disease free survival rate was 71.3% for the control group and 82.0% for the UFT group (p=0.331). On the subgroup analysis, the three-year disease free survival rate for the patients with adenocacinoma was 45.0% for the control group and 75.2% for the UFT group (p=0.121). The three-year disease free survival rate for the patients with non-adenocarcinoma was 88.1% for the control group and 88.9% for the UFT group (p=0.964), Conclusion: Postoperative oral administration of UFT was well-tolerated. Adjuvant chemotherapy with UFT for completely resected pT2N0 adenocarcinoma of the lung could be expected to improve the disease free survival, but this failed to achieve statistical significance. A prospective randomized study for a large number of patients will be necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10445-10449
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• 2015

Objective: To observe treatment effects and safety of fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain. Methods: Patients confirmed pathologically with cancer and complicated with moderate to severe pain, were divided into control and experimental groups. Oxycodone prolonged-release tablets, with or without fluvoxamine, were administrated to all study patients until pain relief. Degree of pain relief, dose of oxycodone prolonged-release tablets, side effects and quality of life were compared before and after treatment. Results: In total, 120 patients were recruited. No statistically significant difference was detected regarding age, gender, types of cancer, KPS between two groups of patients (P>0.05). Baseline pain score of patients with moderate pain in treatment and control group was $4.9{\pm}0.8$ and $5.1{\pm}0.8$, respectively; and decreased to $1.8{\pm}1.1$ and $1.2{\pm}1.1$ after treatment, respectively. Pain intensity was significantly reduced in the treatment group (P=0.028). Average daily consumption of oxycodone prolonged-release tablets was ($54.0{\pm}19.6$) mg and ($44.7{\pm}18.7$) mg respectively, which is lower in treatment grpup than in control group, but the difference was not statistically significant (P=0.065). Baseline pain score of patients with severe pain in treatment and control groups were $8.3{\pm}1.1$ and $8.3{\pm}1.1$, respectively; and pain intensity after treatment decreased to $2.9{\pm}1.0$ and $2.3{\pm}1.0$. Pain intensity was significantly reduced in the treatment group, with statistical significance (P=0.026). Average daily consumption of oxycodone prolonged-release tablets was ($132.0{\pm}42.2$) mg and ($110.7{\pm}33.9$) mg, respectively, which is lower in treatment group than in control group, and the difference was statistically significant (P=0.035). In terms of quality of life, patients in treatment group had better performance status, daily activity, mood, and sleep than that in control group (P < 0.05). Patients in two groups had similar side effects, eg., constipation, nausea/vomiting, lethargy, dizziness, itchy skin, dysuria, and ataxia. Lower incidence of nausea/vomiting, lethargy, was obtained from patients in treatment than in control group, while significant low constipation was observed in treatment than in control group (35.0% vs 49.2%, P=0.026). Conclusion: Fluvoxamine combined with oxycodone prolonged-release tablets could be more effective in treating patients with cancer pain, and could reduce the dosage of oxycodone prolonged-release tablets and thus be associated with lower side effects, and improved quality of life.

• Korean Journal of Psychosomatic Medicine
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• v.21 no.1
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• pp.11-17
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• 2013

Objectives : This study was designed to investigate the prevalence of depressive symptoms in patients with breast cancer and to identify demographic variables and clinical characteristics impact on depressive symptoms and health related quality of life in patients with breast cancer in a university hospital. Methods : Fourty-one patients with breast cancer were selected, who had visited the department of General surgery of the Wonkwang University hospital with a diagnosis of breast cancer regularly during the period November, 2010-May, 2011. All of subjects were evaluated for the depression, anxiety and the health related quality of life with Beck Depression Inventory(BDI), anxiety subscale of Personality Assessment Inventory(PAI) and Short-Form 36 Health Survey-Korean version(SF-36-K). Patients were divided into depressive symptoms and non-depressive symptoms group according to the BDI score. We compared SF-36-K between two groups, and analized multiple regression with depression and health related quality of life as criterion variables and demographic and clinical characteristics. Results : The prevalence of depression in patients with breast cancer in a University hospital was 36.4%. Compared to the non-depression, depressed patients with breast cancer appeared significantly lower mean scores on six subscales in SF-36-K : Physical function(p<.01), Role-physical(p<.001), General health(p<.05), Social function(p<.001), Role-emotional(p<.001) and Mental health(p<.001). But there was no significant difference between two groups in Vitality and Bodily pain. Anxiety, level of education and presence of enforcement of chemotherapy(63.6%) were significant explanation variables for depressive symptoms. And type of surgery and age(55.8%) were significant explanation variables for health related quality of life. Conclusions : The prevalence of depressive symptoms in patients with breast cancer in a University hospital was 36%. The depressive symptoms had not only negative impact on the health related quality of life but also important explanation variable for health related quality of life. These results suggest that depressive symptoms in patients with breast cancer should be evaluated and treated for improving patient's health related quality of life.