Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). Conclusion This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

The Clinical Research Center for Dementia of South Korea (CREDOS), a nation-wide clinical dementia research group, has prepared clinical practice guidelines (CPG) for dementia tailored to the Korean population. In this article, a summary of the CREDOS CPG is presented with the Korean and English version of full report included in the appendix. The CREDOS CPG in intended not only for psychiatrists and neurologists, but also internists, family physicians, and other primary care physicians involved in the prevention and early diagnosis of dementia. While our CPG for dementia mainly covers Alzheimer's disease (AD) and vascular dementia (VaD), it also includes mild cognitive impairment (MCI) and vascular MCI, which are currently known to be the preclinical stages of AD or VaD, respectively, with emphasis placed on early diagnosis. The CREDOS CPG aims to achieve the following goals by developing CPG for dementia: to establish evidence-based, objective and clear clinical standards for dementia; to improve the clinical decision-making process for patients with dementia; to provide scientific and systematic scales to aid in the work of dementia specialists; to suggest comprehensive and systematic healthcare services tailored to each dementia subtype. The CREDOS CPG focuses on diagnosis and evaluation of clinical practice available domestically, and provides useful concepts of dementia. Its emphasis is on etiologies and epidemiology, diagnostic criteria and evaluation, neuropsychological tests, behavioral and psychological symptoms, the activities of daily living, laboratory tests, and brain imaging.
Activities of Daily Living ; Alzheimer Disease ; Appendix ; Delivery of Health Care ; Dementia ; Dementia, Vascular ; Early Diagnosis ; Humans ; Mild Cognitive Impairment ; Neuroimaging ; Neuropsychological Tests ; Physicians, Family ; Physicians, Primary Care ; Psychiatry ; Republic of Korea ; Weights and Measures

We here report two cases of combined liver-kidney transplantation in patients with both end stage renal disease and hepatitis B related liver cirrhosis. The first case was a 55-year-old man with hepatitis B related liver cirrhosis and chronic renal failure, who received cadaveric liver and kidney transplantation. Immunosuppressants were cyclosporine, prednisolone, and mycophenolate mofetil. Clinical course was uneventful except for hemolytic anemia due to alloimmunization that occurs after ABO-mismatched solid organ transplantation. Hemoglobin level became stable after plasmapheresis. His renal and hepatic function is maintained up to the present time. The second case was a 42-year-old man with nephrotic syndrome and liver cirrhosis. The patient underwent living related-combined liver-kidney transplantation. Donors were his son and brother. Blood type of the patient and donors were identical and the result of HLA crossmatch was negative. On the 14th postoperative day, stenosis at anastomotic site of hepatic artery was detected. After balloon angioplasty hepatic function was normalized. At 8 months after the transplantation, the patient is stable without adverse events.
Adult ; Anemia, Hemolytic ; Angioplasty, Balloon ; Cadaver ; Constriction, Pathologic ; Cyclosporine ; Hepatic Artery ; Hepatitis B* ; Hepatitis* ; Humans ; Immunosuppressive Agents ; Kidney Failure, Chronic ; Kidney Transplantation ; Liver Cirrhosis* ; Liver* ; Middle Aged ; Nephrotic Syndrome ; Organ Transplantation ; Plasmapheresis ; Prednisolone ; Siblings ; Tissue Donors ; Transplants

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.
Adult ; Age Distribution ; Biopsy ; Child ; Female ; Glomerulonephritis/pathology ; Glomerulonephritis/epidemiology ; Glomerulosclerosis, Focal/pathology ; Glomerulosclerosis, Focal/epidemiology ; Human ; Kidney/pathology* ; Kidney Diseases/pathology* ; Kidney Diseases/epidemiology* ; Korea ; Male ; Middle Age ; Prevalence ; Sex Distribution

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured

No abstract available
Drug Therapy ; Glioma* ; Humans ; Nimustine* ; Radiotherapy*

To search for the more effective amblyopia treatment, we prospectively compared the results of initial group and alternative group with use of Min's glasses. Initial and alternative groups consisted of 18 and 64 patients. 15 patients (83.3%) of initial group were compliant with the treatment while 50 patients(78.1%) of alternative group were. No significant differences existed between them based on age, sex, causes of amblyopia and initial visual acuity (P>0.05). Average visual acuity improvements were 2.13 +/- 1.81 lines in initial group, compared to 2.51 +/- 1.50 lines in alternative group and no significant differences existed between them according to age, causes of amblyopia and initial visual acuity (P>0.05), However, in cases of female, there was significant visual acuity improvement in alternative group in comparision with initial group (P=0.034). In conclusion, Min's glasses were effective not only in initial treatment group but also in alternative treatment group, and in female patients who previously failed with conventional occlusion therapy the effect was more pronounced than male patients.
Amblyopia ; Child* ; Compliance ; Eyeglasses* ; Female ; Glass* ; Humans ; Male ; Prospective Studies ; Visual Acuity

Functioning adrenal cortical tumors are originated form a distinct zone(zonna glomerulosa, zonna fasciculata or zonna reticularis) or the transitonal zone of adrenal gland. Each zone of the gland is regulated by their specific hormons or cytokines, and their signal transduction systems are different. The oncogenes of many endocrine tumors were mutated proteins involved in signal transduction, however gip is the only reported oncogene in adrenal cortical tumors. Therefore we decided to reevaluate whether gsp might be detected as an oncogene in several different functioning adrenal tumors, and we also tested whether CREB protein is a tentative oncogene or not. In our study, gsp was not detected in 13 patients, however gip was not also detected unexpectedly. There were no mutations in the phosporylation site of CREB("P" box) in adrenal cushing syndrome. We concluded that gip was not a oncogene detected frequently in adrenal cortical tumor, and CREB protein was not considered as a tentative oncogen, because there might be no amplification of the signals due to its extreme distal component of PKA or PKC system.
Adrenal Glands ; Cushing Syndrome ; Cyclic AMP Response Element-Binding Protein ; Cytokines ; Humans ; Oncogenes ; Signal Transduction

No abstract available.
Astrocytoma ; Brain* ; Drug Therapy ; Glioblastoma ; Glioma* ; Humans ; Nimustine* ; Radiotherapy*