• Title/Summary/Keyword: Diseases Progression

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The Link between Fusobacteria and Colon Cancer: a Fulminant Example and Review of the Evidence

  • Martina King;Hermione Hurley;Kevin R. Davidson;Edward C. Dempsey;Michelle A. Barron;Edward D. Chan;Amy Frey
    • IMMUNE NETWORK
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    • v.20 no.4
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    • pp.30.1-30.10
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    • 2020
  • Systemic infections due to Fusobacterium may originate in the tonsillar/internal jugular veins or from the abdomen. We encountered a patient who presented with bacteremia, fulminant septic shock, and extensive soft tissue pyogenic infection due to Fusobacterium necrophorum. In addition, there was widespread metastatic colon cancer with the unique finding of pre-mortem co-localization of F. necrophorum and cancer cells at a site distant from the colon. We reviewed the literature of the association of F. necrophorum and colon cancer, and discuss the evidence of how each of these 2 distinct entities may mutually augment the development or progression of the other.

The Immune Landscape in Nonalcoholic Steatohepatitis

  • Sowmya Narayanan;Fionna A. Surette;Young S. Hahn
    • IMMUNE NETWORK
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    • v.16 no.3
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    • pp.147-158
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    • 2016
  • The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

Relationship between human immunodeficiency virus infection and periodontal disease; diagnosis and management strategy (Human immunodeficiency virus 감염과 치주 질환의 상관관계, 진단 및 처치에 관한 문헌 고찰)

  • Park, Jung-Chul;Um, Yoo-Jung;Jung, Ui-Won;Kim, Chang-Sung;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan;Choi, Seong-Ho
    • The Journal of the Korean dental association
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    • v.47 no.8
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    • pp.522-533
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    • 2009
  • Purpose: Infection with HIV-1 virus has become a critical worldwide public health problem. The oral complications of HIV infection with its progression of impairment of the host response to combat infection present unique challenges to the periodontists. Material and Methods : Medline research was carried out to find relationship of the progression of HIV infection to the occurrence of oral lesions including the HIV-related periodontal diseases. Results: The linear gingival erythema, necrotizing ulcerative periodontitis, necrotizing ulcerative gingivitis and oral candidiasis are common lesions in HIV-infected individuals. The linear gingival erythema and necrotizing ulcerative periodontitis lesions in HIV-infected subjects were found to have a similar microbiological profile. There are several general considerations in the periodontal management of the HIV-infected patient with or without periodontal disease. The altered immunity and host response in patients with HIV infection may also affect the incidence and severity of other common forms of periodontal disease not associated with HIV infection. Conclusion: Periodontal diseases in HIV-infected individuals present unique challenges in diagnosis, monitoring, treatment and maintenance. Therefore exact HIV staging, geographic location, antiviral and antimicrobial therapies and oral habits should be taken into consideration when treating HIV-infected patients.

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Gene Expression of Intrarenal Renin-angiotensin System in Streptozotocin-induced Diabetic Rats

  • Yang, Eun-Kyoung;Kim, In-Kyeom
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.1
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    • pp.45-53
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    • 1997
  • In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and $AT_1$ subtypes ($AT_{1A}$ and $AT_{1B}$) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and $AT_{1A}$ mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. $AT_1$B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.

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Phase III of Study of R-CHOP-21 vs R-CHOP-14 for Untreated Stage III and IV B-cell Non-Hodgkin's Lymphoma: a Report from Iran

  • Payandeh, Mehrdad;Najafi, Safa;Shojaiyan, Fateme-Zahra;Sadeghi, Masoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1513-1517
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    • 2016
  • Background: A combination of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL patients with Iranian ethnicity. Materials and Methods: In phase III trial, patients with previously untreated stage III and IV indolent and aggressive B-cell NHL were randomly assigned by using a minimization method to receive six to eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14 (administered every 14 days with granulocyte colony-stimulating factor). Results: A total of 143 patients were randomly enrolled in our study (66 patients in R-CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs 89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant correlation for PFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. Conclusions: In our research improved survival was found with CHOP-14 as compared to CHOP-21. It is possible that drug metabolism in different races/ethnicities may be one important factor.

Pemetrexed Continuation Maintenance versus Conventional Platinum-Based Doublet Chemotherapy in EGFR-Negative Lung Adenocarcinoma: Retrospective Analysis

  • Paik, Seung Sook;Hwang, In Kyoung;Park, Myung Jae;Lee, Seung Hyeun
    • Tuberculosis and Respiratory Diseases
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    • v.81 no.2
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    • pp.148-155
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    • 2018
  • Background: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma. Methods: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. Results: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15-0.87). Conclusion: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.

The Effect of the Timing of Dexamethasone Administration in Patients with COVID-19 Pneumonia

  • Lee, Hyun Woo;Park, Jimyung;Lee, Jung-Kyu;Park, Tae Yeon;Heo, Eun Young
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.3
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    • pp.217-225
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    • 2021
  • Background: Despite the proven benefits of dexamethasone in hospitalized coronavirus disease 2019 (COVID-19) patients, the optimum time for the administration of dexamethasone is unknown. We investigated the progression of COVID-19 pneumonia based on the timing of dexamethasone administration. Methods: A single-center, retrospective cohort study based on medical record reviews was conducted between June 10 and September 21, 2020. We compared the risk of severe COVID-19, defined as the use of a high-flow nasal cannula or a mechanical ventilator, between groups that received dexamethasone either within 24 hours of hypoxemia (early dexamethasone group) or 24 hours after hypoxemia (late dexamethasone group). Hypoxemia was defined as room-air SpO2 <90%. Results: Among 59 patients treated with dexamethasone for COVID-19 pneumonia, 30 were in the early dexamethasone group and 29 were in the late dexamethasone group. There was no significant difference in baseline characteristics, the time interval from symptom onset to diagnosis or hospitalization, or the use of antiviral or antibacterial agents between the two groups. The early dexamethasone group showed a significantly lower rate of severe COVID-19 compared to the control group (75.9% vs. 40.0%, p=0.012). Further, the early dexamethasone group showed a significantly shorter total duration of oxygen supplementation (10.45 days vs. 21.61 days, p=0.003) and length of stay in the hospital (19.76 days vs. 27.21 days, p=0.013). However, extracorporeal membrane oxygenation and in-hospital mortality rates were not significantly different between the two groups. Conclusion: Early administration of dexamethasone may prevent the progression of COVID-19 to a severe disease, without increased mortality.

Treatment of Mycobacterium avium Complex Pulmonary Disease

  • Kwon, Yong-Soo;Koh, Won-Jung;Daley, Charles L.
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.1
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    • pp.15-26
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    • 2019
  • The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Current Perspectives on Emerging CAR-Treg Cell Therapy: Based on Treg Cell Therapy in Clinical Trials and the Recent Approval of CAR-T Cell Therapy (장기이식 거부반응과 자가면역질환 치료제로서의 CAR Treg 세포치료제의 가능성: Treg 세포치료제 임상시험 현황과 CAR T 세포치료제 허가 정보를 바탕으로)

  • Kang, Koeun;Chung, Junho;Yang, Jaeseok;Kim, Hyori
    • Korean Journal of Transplantation
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    • v.31 no.4
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    • pp.157-169
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    • 2017
  • Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

Immune Checkpoint Inhibitor Score Predicts Survival Benefit of Immunotherapy in Patients with Non-small Cell Lung Cancer

  • Da Hyun Kang;Chang-Min Choi;Cheol-Kyu Park;In-Jae Oh;Young-Chul Kim;Seong Hoon Yoon;Yoonjoo Kim;Jeong Eun Lee
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.4
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    • pp.483-493
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    • 2024
  • Background: The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs. Methods: This was a prospective multicenter study in patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score. Results: A total of 143 patients from four institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p=0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p<0.001). Conclusion: Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.