• Title/Summary/Keyword: cancer severity

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Cisd2 deficiency impairs neutrophil function by regulating calcium homeostasis via Calnexin and SERCA

  • Un Yung Choi;Youn Jung Choi;Shin-Ae Lee;Ji-Seung Yoo
    • BMB Reports
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    • v.57 no.5
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    • pp.256-261
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    • 2024
  • In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

Difference in the Transcriptional Activity of the Interleukin-4 Promoter Haplotypes (Interleukin-4 유전자의 Promoter 일배체형에 따른 전사능의 차이)

  • Choi, Eun Hwa;Kim, Hee Sup;Chanock, Stephen J.;Lee, Hoan Jong
    • Clinical and Experimental Pediatrics
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    • v.48 no.5
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    • pp.495-499
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    • 2005
  • Purpose : Interleukin-4(IL-4) is a critical component of the Th2 cytokine pathway and contributes to severity of respiratory syncytial virus(RSV) bronchiolitis. Previous studies observed an association between severe RSV bronchiolitis in Korean children with a common haplotype of the IL4 promoter. This study was performed to investigate functional differences of the variant IL4 promoter haplotypes. Methods : Genomic DNA was obtained from 20 children from 6 to 48 months of age in the Department of Pediatrics, Seoul National University Bundang Hospital. The IL4 promoter spanning an 1.2 kb region was amplified and haplotype was determined by cloning and the PHASE reconstruction. Transcriptional activity of Jurkat T cells which were transfected with each IL4 haplotype were analyzed by use of luciferase assay. Results : Three haplotypes of the IL4 promoter have been identified with the frequency of GCC(7 percent), TCC(17 percent), and TTT(76 percent). The TTT haplotype demonstrated the highest luciferase values in both unstimulated and PMA-stimulated Jurkat T cells. Increases in transcriptional activity compared to GCC have been shown in TTT(5.3 fold higher) followed by TCC(4.2 fold higher) in unstimulated Jurkat T cells. Conclusion : We provided evidence that increased transcriptional activity of the TTT haplotype of the IL4 promoter, which has previously been over-represented in Korean children with severe RSV bronchiolitis. Therefore, IL-4 could play a potential role in the pathogenesis of RSV infection, possibly via an altered transcriptional activity of the different IL4 haplotypes.

Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

  • Jeng, Jen-Eing;Wu, Hui-Fang;Tsai, Meng-Feng;Tsai, Huey-Ru;Chuang, Lea-Yea;Lin, Zu-Yau;Hsieh, Min-Yuh;Chen, Shinn-Chern;Chuang, Wan-Lung;Wang, Liang-Yen;Yu, Ming-Lung;Dai, Chia-Yen;Tsai, Jung-Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10209-10215
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    • 2015
  • To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

A Case of Non-small Cell Lung Cancer Patient Whose Dermatologic Adverse Reactions Associated with the Epidermal Growth Factor Receptor-inhibitors were Relieved with the Treatment of a Herbal medicine, Samultang-gagambang (비소세포폐암 환자의 표피성장인자 수용체 억제제 치료와 관련된 피부의 이상반응이 사물탕 가감방 투여로 호전된 1례)

  • Park, Hyeong-Jun;Chae, Jean;Lee, Jin-Soo;Jung, Hyun-Sik;Lee, Sang-Hun;Choi, Won-Cheol;Kim, Kyung-Suk
    • Journal of Korean Traditional Oncology
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    • v.16 no.1
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    • pp.55-61
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    • 2011
  • Objectives : Epidermal growth factor receptor-inhibitors have demonstrated improved overall survival in patients with non-small cell lung cancer, but their use is associated with dermatologic adverse reactions that often require symptomatic treatment. Methods : A 44-year-old woman, who started the chemotherapy of Iressa$^{(R)}$ on August 2010, developed cutaneous symptoms such as papulopustular rash, dry skin, and pruritus on her face and scalp after taking Iressa$^{(R)}$ for four weeks. The patient visited our clinic with such symptoms on March 2011 and underwent herebal remedy targeted to alleviate the skin reactions. The severity of dermatologic symptoms was evaluated with the numeric rating scale and the Common Terminology Criteria for Adverse Events version 4.0. Results : Noticeable changes on the skin lesion were observed after the two months of treatment, without any dose modification of the Iressa$^{(R)}$. The cutaneous symptoms as papulopustular rash, dry skin and pruritus were improved and there was no adverse event induced by the treatment with herbal medicine. Conclusions : This case report suggests that the treatment with a herbal medicine, Samultang-gagambang be considered as a useful treatment to relieve EGFR-inhibitor induced dermatologic adverse reactions.

Effectiveness of a Health Educational Program Based on Self-Efficacy and Social Support for Preventing Liver Fluke Infection in Rural People of Surin Province, Thailand

  • Kaewpitoon, Soraya J;Thanapatto, Sirisuda;Nuathong, Wimonya;Rujirakul, Ratana;Wakkuwattapong, Parichart;Norkaew, Jun;Kujapun, Jirawoot;Padchasuwan, Natnapa;Kaewpitoon, Natthawut
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1111-1114
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    • 2016
  • Opisthorchiasis is a major problem in Thailand particularly in northeast region which also has a high incidence of cholangiocarcinomas. Since health modification is needed, this quasi-experimental study aimed to assess the effectiveness of a health education program based on self-efficacy and social support in Tha Tum district, Surin province, Thailand. A total of 70 participants were purposive selected with a history of opisthorchiasis. Participants were divided into experimental and control groups, each with 35 subjects. The experimental group received a health education program composed of: (1) knowledge improvement, lectured with multimedia, demonstration, brochure, and handbook; (2) group discussion about their health beliefs, sharing their ideas and experience; and (3) social support from village health volunteers (VHV), heads of villages (HV), friends, and members of families, and public health officer (PHO). Follow-up was by PHO/VHV/HV, with provision of certificates and flasg for household that did not eat raw fish. Data were collected by predesigned questionnaires after implementation of the program for 3 months. Comparative data was analyzed by paired simple t-test and independent t-test. The results revealed that the experimental group had mean score of knowledge higher more than before the experiment (mean difference=3.1, t=3.915, 95%CI-3.3, -1.8 p-value=0.001), and the control group (mean difference=2.5, t=4.196, 95%CI=1.4, 3.6, p-value=0.001) with statistical significance. The mean scores of practice were higher than before the experiment (mean difference=4.6, t=4.331, 95%CI-5.3, -3.1, p-value=0.001), and control group (mean difference=4.4, t=6.142, 95%CI=4.2, 7.9, p-value=0.001). The mean scores of perceived susceptibility and perceived severity of opisthorchiasis, al well as perceived benefits and perceived barriers to prevention of opisthorchiasis, were also higher than before the experiment and in the control group (p-value <0.001). In conclusion, this was a successful health education program for liver fluke avoidance. Therefore, it may useful for further behavior modification in the other epidemic areas.

Risk Factors Related to Development of Delirium in Hospice Patients (호스피스 병동의 암환자에서 섬망 발생 위험 요인)

  • Ko, Hae Jin;Youn, Chang Ho;Chung, Seung Eun;Kim, A Sol;Kim, Hyo Min
    • Journal of Hospice and Palliative Care
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    • v.17 no.3
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    • pp.170-178
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    • 2014
  • Purpose: Delirium is a common and serious neuropsychiatric complication among terminally ill cancer patients. We investigated risk factors related to the development of delirium among hospice care patients. Methods: Between May 2011 and September 2012, we included patients who were mentally alert and had no psychiatric disease or drug addiction at the hospice ward of two local hospitals. Among them, participants who had been diagnosed with delirium by two doctors according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-4th edition) criteria were grouped as Delirium Group. We analyzed results of psychometric and other laboratory tests performed at the time of patient's admission - psychometric tests included cognitive function (mini-mental status examination, MMSE), depression (Beck Depression Inventory, BDI), anxiety, and insomnia (Insomnia Severity Index, ISI). Logistic regression analysis was used to compare delirium and the related factors. Cox's proportional hazard model was performed using significant factors of logistic regression analysis. Results: Of the 96 patients who met the inclusion criteria, 41 (42.7%) developed delirium. According to the logistic regression analysis, primary cancer site, cognitive impairment (MMSE < 24), depression ($BDI{\geq}16$), and insomnia ($ISI{\geq}15$) were significant factors related to delirium. Among the four factors, depression (OR 5.130; 95% CI, 2.009~13.097) and cognitive impairment (OR 5.130; 95% CI, 2.009~13.097) were found significant using Cox's proportional hazard model. Conclusion: The development of delirium was significantly related to depression and cognitive impairment among patients receiving hospice care. It is necessary to carefully monitor depression and cognitive function in hospice care.

Aideo-Assisted Thoracic Surgery in Pleural Adhesion (늑막유착을 동반한 질환에서의 비디오 흉부수술)

  • Seong, Suk-Hwan;Kim, Hyeon-Jo;Lee, Chang-Ha;Kim, Ju-Hyeon
    • Journal of Chest Surgery
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    • v.29 no.8
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    • pp.916-922
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    • 1996
  • In patients with pleural adhesion, video-assisted thoracic surgery (VATS) has been regarded as a contra- indication. When such adhesions were found during a thoracoscopic trial, the thoracotomy proceeded with for fear of parenchymal Injury and bleeding. We had a question whether or not thoracoscopic surgery should be done in such pleural adhesions. Of the 226 consecutive thoracoscopic surgeries from Jul. 1992 through Sep. 1995, pleural adhesions were detected intraoperatively in 50 cases (22.1%): a detailed breakdown is as follows: pneumothorax (16 cases), pleural disease (15), benign pulmonary nodule(7), mediastinal mass(5), hyperhidrosis (2), diffuse parenchymal or interstitial lung disease (2), bronchiectasis(2), and primary lung cancer(1). We classified pleural adhesions according to their extent and severity. Extent is categorized as the involved area of the lung: degree 1, II, or III; severity is given one of four grades: mild, moderate, severe, or ve y severe. In cases of very severe severity requiring decortication, the possibility of VATS was excluded. Of the 50 cases, mild adhesions were detected in 15 cases(30.0%), moderate in 29 (58.0%), and severe in 6 (12.0%). As for the extent of the adhesions, 8 cases (16.0%) were categorized as degree 1, 32 cases (64. 0%) as degree II, and 10 cases (20.0%) as degree III. For patients with pleural adhesions, the operation time, the chest tube indwelling time, and the postoperative hospital stay were all longer than for patients in the non-adhesion group. Postoperative complications, namely prolonged air-leakage and pleural drain- age, were more common (18.0% and 6.0%, respectively) than in the non-adhesion group (5.1% and 1.7%, respectively). Only two bronchiectatic patients (4%) were converted to an open thoracotomy because of in- ability to control bleeding. Although complications were encountered more frequently in the group with adhesions, patients were still able to enjoy the benefi s of thoracoscopic surgery. It is advisable to proceed with thoracoscopic surgery even in cases of unpredicted pleural adhesions.

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Patient Satisfaction with Cancer Pain Management (암성통증관리 만족도)

  • Lee, So-Woo;Kim, Si-Young;Hong, Young-Seon;Kim, Eun-Kyung;Kim, Hyun-Sook
    • Journal of Hospice and Palliative Care
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    • v.6 no.1
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    • pp.22-33
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    • 2003
  • Purpose : The purpose of this study was to evaluate the present status of patients' satisfaction and the reasons for any satisfaction or dissatisfaction in cancer pain management Methods : A cross-sectional survey was used to obtain the feedback about pain management. The results of the survey were collected from 59 in- or out-patient who had cancer treatment at two of the teaching hospitals in Seoul from July, 2002 to November, 2002. The data was obtained by a structured questionnaire based on the American Cancer Society Patient Outcome Questionnaire(APS-POQ) and other previous research. The clinical information for all patients were compiled by reviewing their medical records. Resuts : 1) The subjects' mean score of the worst pain was 6.77, the average pain score was 3.80, and the pain score after management was 2.93 for the past 24 hours. The mean score of total pain interference was $25.03{\pm}12.82$. Many of the subjects had false beliefs about pain such as 'the experience of pain is a sign that the illness has gotten worse', 'pain medicine should be 'saved' in case the pain gets worse' and 'people get addicted to pain medicine easily'. 2) 66.1% of the subjects were properly medicated with analgesics. 33.9% of the subjects reported use of various methods in controlling pain other than the prescribed medication. Only 33.9% of the subjects had a chance to be educated about pain management by doctors or nurses. 3) The mean score of patients' satisfaction with pain management was $4.19{\pm}1.14$. 72.9% of the subjects answered 'satisfied' with pain management. The reasons for dissatisfaction were 'the pain was not relieved even after the pain management', 'I was not quickly and promptly treated when I complained of pain', 'doctors and nurses didn't pay much attention to my complaints of pain.', and 'there was no appropriate information given on the methods of administration, effect duration and side effects of pain medicine.' The reasons for satisfaction were: 'the pain was relieved after the pain management.', 'doctors and nurses quickly and promptly controlled my pain.', 'doctors and nurses paid enough attention to my complaints of pain.' and 'trust in my physician'. 4) In pain severity or pain interference, no significant difference was found between the satisfied group and dissatisfied group. On the belief 'good patients avoid talking about pain', a significant difference was found between the satisfied group and dissatisfied group. Conclusions : The patients' satisfaction with cancer pain management has increased over the years but still about 30% of patients reported to be 'not satisfied' for various reasons. The results of this study suggest that patients' education should be done to improve satisfaction in the pain management program.

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The Study of Normal Tissue Complication Probability(NTCP) for Radiation Pneumonitis by Effective Volume Method (유효체적 방법과 임상분석을 통한 방사선에 의한 정상 폐조직의 부작용 확률에 관한 연구)

  • Ahn Seung Do;Choi Eun Kyung;Yi Byong Yong;Chang Hyesook
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.243-249
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    • 1997
  • Purpose : In radiation therapy, NTCF is very importart indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. Materials and Methods : From August 1993 to December 1994, thirty six patients with locally advanced non=small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutlc agents were mitomycin C. vinblastion, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of raniation pneumonitis by CT scan, chest x-rar and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumanitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung, Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. Results : Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients , 6 had grade I severity and 2 had grade II. The average NTCP value cf the patients who showed radiation pneumonitis was significantly higher than that uf the patients without pneumonitis $(66\%\;vs.\;26.4\%)$. But the results of pulmonary function test was not correlated with NTCP. Conclusion : NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to anaiyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.

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Radiotherapy Results of Uterine Cervix Cancer Stape IIB : Overall Survival, Prognostic factors, Patterns of Failure and Late Complications (자궁경부암 병기 IIB에서의 방사선 치료 성적: 생존율 및 예후인자, 치료 후 실패양상, 만성 합병증)

  • Kim Eun-Seog;Choi Doo-Ho;Huh Seung-Jae
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.51-61
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    • 1998
  • Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

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