The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.
B7 Antigens ; Humans ; Immune Evasion ; Immunity, Cellular ; Immunotherapy* ; Ligands ; Melanoma ; Prognosis ; Tumor Burden ; Tumor Microenvironment

Hepatocellular carcinoma (HCC) has become an important indication for liver transplantation in Korea. Even though the Milan criteria have been accepted as the gold standard in deceased donor liver transplantation, the acceptable indication for living donor liver transplantation is controversial. This review covers several key issues in liver transplantation for advanced HCC: (1) recent developments and published data on expanded criteria, (2) the role of down-staging, (3) an ethical issue in expanding the criteria in living donor liver transplantation, and (4) post-operative management, including the immunosuppressive regimen and post-transplant adjuvant chemotherapy to improve survival after transplantation for advanced HCC. Biological factors, such as AFP, PIVKA-II, and a PET scan, in addition to tumor size and number, may be helpful in selecting eligible patients for liver transplantation among patients with advanced HCC. Low-level immunosuppression with low exposure of calcineurin inhibitor may reduce HCC recurrence after transplantation.
Biological Factors ; Biomarkers ; Calcineurin ; Carcinoma, Hepatocellular ; Chemotherapy, Adjuvant ; Humans ; Immunosuppression ; Korea ; Liver ; Liver Transplantation ; Living Donors ; Positron-Emission Tomography ; Protein Precursors ; Prothrombin ; Recurrence ; Tissue Donors ; Transplants

To evaluate the effects of kerationocytes on the growth of melanocytes, keratinocyte conditioned media (K-CM) with different molecular weight obtained by dialysis were added to melanocyte growth medium (M-GM). In addition, K-CM only, and K-CM mixed with each component of M-GM, such as TPA(12-tetradecanoyl- phorbol-13-acetate), IBMX(isobutylmethylxanthine) and CT(cholera toxin), were used for the culture of melanocytes. 1) The proliferation of melanocytes was incresased to 2.86 x 10(5)+/-0.87 x 10(5) cells/ well and 2.87 x 10(5)+/-0.71 x 10(5) cells/well in 25% K-CM with a cut-off molecular weight of 2,000 and 25% K-CM with a cut,-off molecular weight between 6000 8000 respectively, as compared to 1.88 x 10(5)+/-0.45 x 10(5) cells/well in the control group (p < 0.05). 2) The amount of melanin was increased to 0.2987+/-0.0830ng/mlin 25% un- dialyzed K-CM, as compared to 0.2264+/-0.0643ng/ml in the control group, but this differnce was not statistically significant. 3) Maximum proliferation of melanocytes was observed in 35% concentration of K-CM with a cut-off molecular weight of 6000 8000. 4) Maximum of melanin production was observed in 35% concentration of undialyzed K-CM 5) As compared to 7.86 x 10+/-1.74 x 10(5) cells/well in M-GM,proliferation of melanocytes in 35% K-CM with a cut-off molecular weight of 6000 8000 was de- creased to 1.38 X 10(5)+/-0.97 X 10(5) cells/well. 6) There was no difference in melanocyte proliferation between 6.81 x 10(5)+/-2.19 x 10(5) cells/well in 35% 6,000 8,000 M.W. cut-off dialyzed K-CM, with IBMX only, and 7.86 x 10(5)+/-1.74 x 10(5) cells/well in M-GM. 7) Compared to 0.2303+/-0.0700ng/well cell in M-GM, the amount of melanin was increased to 0.3227+/-0.0900ng/cell, 0.3624+/-0.0900ng/cell and 0.2928+/-0.0500ng/cell, respectively, when TPA, IBMX, CT was added to 35% undialyzed K-CM. It also increased to 0.3176+/-0.1100 in 35% undialyzed K-CM(p<0.05). In summary, the results proved that cellular activating substances released from keratinocytes affect the proliferation of melanocyte and the synthesis of melain. It is also expected that methods used in this study can be clinically utilized because melanocyte culture is possible on K-CM without adding tumor promotors.
1-Methyl-3-isobutylxanthine ; Culture Media, Conditioned ; Dialysis ; Keratinocytes* ; Melanins ; Melanocytes* ; Molecular Weight

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321–106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus.
Humans ; Liver Function Tests ; Liver Transplantation* ; Liver* ; Patient Safety ; Risk Factors* ; Tacrolimus* ; Transplants

BACKGROUND/AIMS: In the immunological and functional aspects, freshly isolated human hepatocytes are better than animal hepatocytes from other species such as the pig and hepatocytes from human tumor cell lines. Human liver tissue for hepatocyte isolation can be obtained either from surgical specimens of patients with liver disease, such as hepatocellular carcinoma or from donor livers that are not suitable for transplantation. In the latter case, the liver may be preserved in 4 degrees C UW solution. Therefore, studies of the limit on the preservation time to get clinically applicable hepatocytes, and proper isolation techniques improving cell viability are needed. In this study, the authors isolated hepatocytes from a few kinds of the liver with different UW preservation times and different isolation techniques. METHODS: Male Sprague-Dawley rats weighing 200g-250g were used. The hepatocytes were isolated from unpreserved livers(control), livers preserved for 24 hours in UW solution, and livers preserved for 48 hour in UW solution, with a modified Seglen's two step method. To improve cell viability, 5mM glycin was added to the EDTA solution in one group and in another, the pH of the EDTA solution was slowly changed from 6.5 to 7.25. RESULTS: The control group showed 80.0% of cell viability. 53.8% of isolated hepatocytes were viable even after 24 hours of preservation. The cell viability decreased to 36.1% and severe cellular damage was observed after 48 hours preservation. The glycin and pH change showed no protective effect on the isolation of hepatocytes from UW preserved livers. CONCLUSION: After 24 hours preservation in UW solution, many clinically useful hepatocytes were isolated with a modified Seglen's two step method. Further studies concerning the preservation of functions of hepatocytes isolated from UW preserved livers and on the technique of cell culture and cryopreservation are needed.
Animals ; Carcinoma, Hepatocellular ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Survival ; Cryopreservation ; Edetic Acid ; Hepatocytes* ; Humans ; Hydrogen-Ion Concentration ; Liver Diseases ; Liver* ; Male ; Rats* ; Rats, Sprague-Dawley ; Tissue Donors

OBJECTIVES: This study was carried out to survey the prevalence of Helicobacter pylori infection and the incidence of vacuolating toxin producing H. pylori. A further aim of this study was to evaluate the quantitative assay for cell vacuolation on the basis of the rapid uptake of neutral red dye by vaculoes of the cells. METHODS: We studied the gastric biopsy specimens of patients with 154 cases of gastritis, 74 cases of gastric ulcer, and 167 cases of gastric cancer and in 44 cases of healthy persons. One of the biopsy specimen was placed into a CLOtest plate for rapid urease test and the other one of the biopsy spcimen was inoculated on Brain Heart Infusion blood agar for culture. The culture supernatant of isolated H. pylori was serially diluted with BHI broth. After 24 hour incubation of cultured RK-13 cells treated with the culture supernatant of H. pylori, cytoplasmic vacuolation of the cells were observed microscopically. RESULTS: The positivity of urease test and the rate of isolation of H. pylori from urease positive gastric biopsy materials were 34.1% and 93.3% in healthy person, 55.8% and 70.9% in gastritis, 60.8% and 71.1% in gastric ulcer, and 56.3% and 96.8% in gastric cancer. The isolation rate of H. pylori from patients between 20 and 39 years old was 16.8%, for patients between 40 and 59 years old it was 51.9%, and for patients above 60 years old it was 31.2%. The isolation rate of the vacuolating toxin producing H. pylori from gastric biopsy specimens was 66.7% in a healthy person, 76.6% in gastritis, 79.4% in gastric ulcer, and 80% in gastric cancer. CONCLUSIONS: The isolation rate of H. pylori from the patients with gastric diseases is higher than the rate of H. pylori from healthy persons, but the isolation rate of the vacuolating toxin producing H. pylori is not different between the patients with gastric diseases and healthy persons. The titers of vacuolating toxin produced by some H. pylori isolated from the patients with gastric diseases are higher than those from healthy persons.
Adult ; Agar ; Biopsy ; Brain ; Cytoplasm ; Gastritis ; Heart ; Helicobacter pylori* ; Helicobacter* ; Humans ; Incidence* ; Middle Aged ; Neutral Red ; Prevalence ; Stomach Diseases* ; Stomach Neoplasms ; Stomach Ulcer ; Urease

BACKGROUNDS/AIMS: In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. METHODS: We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. RESULTS: Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. CONCLUSIONS: Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2).
Bile Ducts* ; Bile* ; Bilirubin ; Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; Joints ; Medical Records ; Mortality ; Multivariate Analysis ; Pathology ; Recurrence ; Retrospective Studies ; Risk Factors ; Seoul

PURPOSE: Ocular sparganosis has not been reported in Korea and 5 cases have been reported sporadically worldwide. Among these, 2 cases were found under the conjunctiva. We reported the first Korean case of ocular sparganosis manifesting as a subconjunctival mass. CASE: A 29-year-old man was presented to remove sunconjunctival mass in his left eye for cosmetic purpose. His ocular findings were normal except 0.5 x 0.5 mm sized subconjunctival mass. The surgically excised mass was suspected to have a parasite grossly. Sparganum was identified under microscopic examination after hematoxylin-eosin staining. CONCLUSIONS: The morphologic state of mumified parasite under microscope was plerocercoid phase of spargaum. His ocular movement and visual acuity remained normal after excision of the mass.
Adult ; Conjunctiva ; Humans ; Korea* ; Parasites ; Sparganosis* ; Sparganum ; Visual Acuity

PURPOSE: To evaluate the usefulness of stereoscopic localization of nonpalpable breast lesions. MATERIALS AND METHODS: The authors retrospectively analyzed 60 cases of stereotactic localization performed for lesions whichwere mammographically visible but not palpable. Each case was reviewed for chief complaint, indication oflocalization on a mammograph, location of the lesion, pathological diagnosis, and complications during and afterthe procedure. RESULTS: Most patients(75%) had no specific complaint. Among the 60 cases, microcalcification,mass and combined lesions were found in 34(57%), 12(20%), and 14 cases(23%), respectively. The most commonlocation of the lesion was the upper outer quadrant(29 cases). A histopathologic report was available in 56 of 60cases. Among 43 benign cases(76.8%), fibrocystic disease was most common(38 cases, 67.9%), while among 13malignant cases, ductal carcinoma was most common(9 cases, 16.1%). In four of 56 cases(7.1%), failure to removethe target lesion was identified. Retrospective analysis suggests that movement of the patient during theprocedure is the most likely cause of failure. There were no major complications. CONCLUSION: Stereotacticlocalization is simple and accurate, and compared with the conventional method, requires less experience on thepart of the practitioner. Movement of the patient during the procedure may be the major cause of failure.
Breast* ; Carcinoma, Ductal ; Diagnosis ; Humans ; Retrospective Studies

BACKGROUND/AIMS: There are many reports in which perioperative transfusion was closely related to the survival of cancer. The long-term survival rate of patients with hepatocellular carcinoma undergoing hepatectomy has improved, and it may be related to the reduction of intraoperative transfusion. The aim of this study is to evaluate the effect of intraoperative transfusion on the prognosis in the hepatectomized hepatocellular carcinoma patients and the relationship between the survival improvement and reduction of intraoperative transfusion. METHODS: From 1988 Jan. to 1995 Dec., 507 cases in which the amount of intraoperative transfusion was known were reviewed. Operative transfusion of whole blood or packed red cells was included in this study. The clinical, operative, and pathological factors were analyzed to identify factors that affected long-term survival and disease free survival. RESULTS: By multivariate analysis, Child classification, the extent of resection, portal vein invasion, and blood transfusion(more than 7 units) were shown to be independent factors in overall survival. Child classification, the number of tumors, portal vein invasion, and blood transfusion(more than 7 units) were shown to be independent factors in disease free survival. CONCLUSION: Operative blood transfusion affects the long-term survival and the disease free survival. Therefore, the intraoperative transfusion should be reduced if possible. Through the improvement of surgical technique and instrument, surgeon can reduce the intraoperative bleeding, and this reduction of intraoperative bleeding may contribute the improvement of survival through the reduction of intraoperative transfusion.
Blood Transfusion ; Carcinoma, Hepatocellular* ; Child ; Classification ; Disease-Free Survival ; Hemorrhage ; Hepatectomy ; Humans ; Multivariate Analysis ; Portal Vein ; Prognosis* ; Survival Rate