Role of Klotho and N-acetylcysteine in Oxidative Stress Associated with the Vitrification of Ovarian Tissue Cytoprotective Function of Klotho in Cryopreservation

BACKGROUND@#Cryopreservation can cause mechanical and chemical stress, ultimately leading to the formation of reactive oxygen species (ROS) and oxidative stress. ROS inhibits the expression of antioxidant enzymes in cells, resulting in increased DNA fragmentation and apoptosis. In this paper, we used a vitrification method that has the advantage of producing less ice crystal formation, cost-effectiveness, and time efficiency during cryopreservation. The objective of this paper is to evaluate the degree of protection of ovarian tissue against oxidative stress when N-acetylcysteine (NAC) and Klotho proteins are treated in the vitrification process of ovarian tissue. @*METHODS@#The control group and the cryopreservation groups were randomly assigned, and treated NAC, Klotho, or the combination (NAC ? Klotho). The cell morphological change, DNA damage, senescence, and apoptosis of each group after the freeze–thaw process were compared using transmission electron microscopy, immunohistochemistry, and western blot analysis. @*RESULTS@#Both NAC and Klotho were found to be more effective at protecting against DNA damage than the control;however, DNA damage was greater in the NAC ? Klotho group than in the group treated with NAC and Klotho, respectively. DNA damage and cellular senescence were also reduced during the vitrification process when cells were treated with NAC, Klotho, or the combination (NAC ? Klotho). NAC increased apoptosis during cryopreservation, whereas Klotho inhibited apoptosis and NAC-induced apoptosis. @*CONCLUSION@#This study highlights Klotho’s benefits in inhibiting DNA damage, cell senescence, and apoptosis, including NAC-induced apoptosis, despite its unclear role in vitrification.

A Case of Achieving Partial Remission with the Combination of Sorafenib and Nivolumab in a Patient with Hepatocellular Carcinoma Showing Disease Progression after Nivolumab Therapy

Sorafenib is a well-known approved systemic therapeutic agent used in patients with advanced hepatocellular carcinoma (HCC). Regorafenib and nivolumab are approved as second-line therapeutic drugs in patients showing disease progression after sorafenib therapy. However, there is no established third- or fourth-line therapy in patients with progression after regorafenib or nivolumab treatment. Recently, the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs) has been attempted as a first-line treatment strategy in advanced HCC patients based on the hypothesis that combination therapy may overcome resistance in ICPI monotherapy. On the basis of this suggestion, we herein describe the case of an HCC patient demonstrating macrovascular invasion, whereby partial remission was achieved via the combination of sorafenib and nivolumab following disease progression after nivolumab therapy. Further studies on the combination of TKIs and ICPIs are necessary to determine ways to manage HCC patients showing disease progression after ICPI therapy.

Differences in 25-hydroxy vitamin D and vitamin D-binding protein concentrations according to the severity of endometriosis / 대한생식의학회지

OBJECTIVE: To investigate serum 25-hydroxyl vitamin D (25(OH)D) and vitamin D-binding protein (VDBP) concentrations in women with endometriosis according to the severity of disease. METHODS: Women with mild endometriosis (n = 9) and advanced endometriosis (n = 7), as well as healthy controls (n = 16), were enrolled in this observational study. Serum total 25(OH)D concentrations were analyzed using the Elecsys vitamin D total kit with the Cobas e602 module. Concentrations of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using the Human Vitamin D BP Quantikine ELISA kit. Variables were tested for normality and homoscedasticity using the Shapiro-Wilk test and Leven F test, respectively. Correlation analysis was used to identify the variables related to total 25(OH)D and VDBP levels. To assess the effects of total 25(OH)D and VDBP levels in the three groups, multivariate generalized additive modeling (GAM) was performed. RESULTS: Gravidity and parity were significantly different across the three groups. Erythrocyte sedimentation rate (ESR) and CA-125 levels increased as a function of endometriosis severity, respectively (p= 0.051, p= 0.004). The correlation analysis showed that total 25(OH)D levels were positively correlated with gravidity (r = 0.59, p< 0.001) and parity (r = 0.51, p< 0.003). Multivariate GAM showed no significant relationship of total 25(OH)D levels with EMT severity after adjusting for gravidity and ESR. However, the coefficient of total 25(OH)D levels with gravidity was significant (1.87; 95% confidence interval, 0.12–3.63; p= 0.040). CONCLUSION: These results indicate that vitamin D and VDBP levels were not associated with the severity of endometriosis.

A Case of Achieving Partial Remission with Sequential Treatment of Transarterial Chemoemoblization after Transarterial Radioembolization in Old Patient with Hepatocellular Carcinoma with Multiple Metastasis

The number of older adults with hepatocelluar carcinoma (HCC) has been increasing with longer life expectancy and earlier diagnosis and treatment. However, older patients have lesser function reserve of multiple organ systems, more disability rate. Therefore, the treatment of elderly HCC patients remains a challenge worldwide. Recently, studies suggests that the survival outcome of older patients may be comparable to that of younger patients and active treatment may achieve promising rates of local and systemic control in selected patients. Based on above suggestions, we herein offer our experience of a case achieved partial remission by sequential therapy of transarterial chemoembolization after transarterial radioemoblization in elderly HCC patient with multiple metastasis. Further study, maybe regarding a combination of locoregional and systemic treatment, is necessary on how to manage HCC in elderly patients.

A Case of Achieving Complete Remission with Combination of Sorafenib and Tegafur in Patients with Hepatocellular Carcinoma with Progression of Disease after Sorafenib Therapy

Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.

A Case of Achieving Complete Remission with Stereotactic Body Radiation Therapy in Patients with Hepatocellular Carcinoma with Macrovascular Invasion after Repeated Transarerial Chemoembolization

Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative treatment because of relatively high local recurrence rate. Moreover, many clinicians frequently experience treatment failure (incomplete necrosis or stage progression etc.) after repeated TACE, but no clear guidelines have been recommended about salvage treatment modalities for this situation. Recently, studies for combination of radiation therapy and TACE for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy. Based on above suggestions, we herein offer our experience of a patient with macrovascular invasion developed after repeated TACE that achieve complete remission by stereotactic body radiation therapy. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.

A Case of Achieving Complete Remission with Combination of Stereotac-tic Body Radiation Therapy and Transarterial Chemoemoblization in Pa-tients with 4.8 cm Sized Infiltrative Hepatocellular Carcinoma with Arte-riovenous Shunt

Infiltrative hepatocellular carcinoma (HCC) patients have a poor prognosis because most patients present with advanced disease. Although tumor size is small, ablation therapy is difficult because it is difficult to delineate tumor boundary and tumor often combined vascular invasion. Therefore many clinicians still try locoregional therapy (LRT) such as transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT and sorafenib in this situation. Stereotactic body radiation therapy (SBRT) is new technology providing very highly conformal ablative radiation dose and is expected to salvage modality for HCC showed incomplete response of TACE due to combined arteriovenous (AV) shunts. Based on above suggestions, we herein offer our experience of a complete remission of tumor by combination of SBRT and TACE in a patient with infiltrative HCC. Further study, maybe regarding a combination of locoregional and systemic therapy is necessary on how to manage infiltrative HCC with AV shunts.

Extramedullary Plasmacytoma of the Pancreas Diagnosed Using Endoscopic Ultrasonography-Guided Fine Needle Aspiration

Extramedullary plasmacytoma involves organs outside the bone marrow; however, involvement of the pancreas is rare. We recently experienced a case of extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). EUS-FNA, which has a high diagnostic accuracy and an excellent safety profile, is the modality of choice for establishing tissue diagnosis. We report a case of extramedullary plasmacytoma of the pancreas diagnosed using EUS-FNA.