Association Between Thyroid Radiation Dose and Hypothyroidism in Breast Cancer Patients Undergoing Volumetric Modulated Arc Therapy for Regional Nodal Irradiation.

BACKGROUND/AIM: To investigate the association between the thyroid dysfunction and thyroid radiation dose in regional nodal irradiation (RNI) using volumetric modulated arc therapy (VMAT) for breast cancer. PATIENTS AND METHODS: We reviewed medical data of 67 patients with breast cancer who underwent curative surgery followed by adjuvant radiotherapy, including RNI using VMAT, between 2018 and 2021. All patients had normal thyroid functional test results, including thyroid stimulating hormone (TSH), T3, and free-T4. We defined subclinical hypothyroidism as increased TSH with or without decreased levels of free-T4 and T3 after the completion of VMAT. We calculated dose-volume histogram parameters (DVHPs), including the mean dose and relative thyroid volume receiving at least 10, 20, 30, and 40 Gy. RESULTS: The median follow-up time was 23.2 months. The 3-year locoregional failure-free survival, progression-free survival, and overall survival rates were 96.3%, 94.7%, and 96.2%, respectively. The mean thyroid dose was 21.4 Gy (range=11.5-29.4 Gy). Subclinical hypothyroidism was noted in 14 patients (20.9%) and the median time to the event was 4.1 months. Among the DVHPs, the relative volume receiving ≥20 Gy (V20Gy) was associated with subclinical hypothyroidism. The 2-year rates of subclinical hypothyroidism were 24.8% and 59.1% in patients with V20Gy ≤46.3% and >46.3%, respectively. CONCLUSION: A significant proportion of patients with breast cancer developed subclinical hypothyroidism after undergoing VMAT for RNI. Our findings highlight the importance of considering the thyroid as an organ at risk for VMAT planning, and suggest that V20Gy could be a useful dose-volume constraint.

Patterns of locoregional recurrences and suggestion of the clinical target volume in resected perihilar extrahepatic cholangiocarcinoma.

Purpose: To evaluate the patterns of locoregional recurrence (LRR) in patients with perihilar extrahepatic cholangiocarcinoma (PEHC) treated with radical resection and to suggest the optimal target volume for elective nodal irradiation. Methods: Medical records of PEHC patients who underwent radical resection between January 2000 and September 2021 at five institutions were reviewed. Patients who were confirmed with LRR in the follow-up imaging study were included. The LRR sites were mapped onto the corresponding sites in template computed tomography images. The margin around the vascular structure was investigated to generate the clinical target volume (CTV) covering the common sites of regional recurrences. Results: A total of 87 LRRs in 46 patients were identified, 29 (33.3%) of which were local recurrences and 58 (66.7%) were regional recurrences. The most common site of local recurrence was the liver resection margin (n = 16), followed by the anastomosis site (n = 8). Regional recurrences were observed most commonly in the para-aortic area (n = 13), followed by in the aortocaval space (n = 11), portal vein area (n = 11), and portocaval area (n = 9). Nodal CTV was generated by adding an individualized margin around the portal vein, aorta, common hepatic artery, celiac artery, and left gastric artery. Conclusions: The LRR patterns in the resected PEHC were evaluated and specific guidelines for nodal CTV delineation were provided, which may help physicians delineating the target volume in postoperative radiotherapy for PEHC. These findings need further validation in a lager cohort.

Passive exoskeletons alter low back load transfer mechanism.

Previous studies that tested passive back-support exoskeletons focused only on active low-back tissue. Therefore, this study examines the effect from a passive back-support exoskeleton by investigating changes in the load transfer mechanism between active and passive tissue in the low back. Twelve healthy male participants performed a full range of trunk flexion-extension movements under three conditions-FREE (no exoskeleton), the backX, or the CoreBot exoskeleton-while holding 0 kg, 4 kg, and 8 kg loads. Body kinematics and electromyography were recorded. Results showed that the average muscle activity of the lumbar erector spinae (LES) was significantly reduced while wearing the exoskeletons, with a 5.9%MVC reduction with the backX and a 3.3%MVC reduction with the CoreBot. Earlier occurrence of the flexion-relaxation phenomenon induced by the trunk extension moment of exoskeletons played an important role in reducing LES muscle activity because the LES returned to a relaxed state earlier (EMG-Off: a 3.1° reduction with the backX, and a 1.8° reduction with the CoreBot; EMG-On: a 2.3° reduction with the backX, and a 1.4° reduction with the CoreBot). In addition, the maximum lumbar flexion angle (a 2.2° reduction with the backX and a 1.5° reduction with the CoreBot) showed significant decreases compared to the FREE condition, indicating that exoskeleton use can prevent low-back passive tissue from being fully activated. These results suggested the overall effects of passive back-support exoskeletons in reducing loads on both active and passive tissue in the low back.

Alzheimer’s Disease Prediction Using Attention Mechanism with Dual‑Phase 18 F‑Florbetaben Images / 대한핵의학회잡지

Materials and Methods@#A total of 264 patients (74 CN and 190 AD), who underwent FBB imaging test and neuropsychological tests, were retrospectively analyzed. Early- and delay-phase FBB images were spatially normalized with an in-house FBB template. The regional standard uptake value ratios were calculated with the cerebellar region as a reference region and used as independent variables that predict the diagnostic label assigned to the raw image. @*Results@#AD positivity scores estimated from dual-phase FBB showed better accuracy (ACC) and area under the receiver operating characteristic curve (AUROC) for AD detection (ACC: 0.858, AUROC: 0.831) than those from delay phase FBB imaging (ACC: 0.821, AUROC: 0.794). AD positivity score estimated by dual-phase FBB (R: −0.5412) shows a higher correlation with psychological test compared to only dFBB (R: −0.2975). In the relevance analysis, we observed that LSTM uses different time and regions of early-phase FBB for each disease group for AD detection. @*Conclusions@#These results show that the aggregated model with dual-phase FBB with long short-term memory and attention mechanism can be used to provide a more accurate AD positivity score, which shows a closer association with AD, than the prediction with only a single phase FBB.

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.

BACKGROUND/AIM: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). PATIENTS AND METHODS: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. RESULTS: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. CONCLUSION: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.

Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer.

We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.

Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

As the SARS-CoV-2 pandemic remains uncontrolled owing to the continuous emergence of variants of concern, there is an immediate need to implement the most effective antiviral treatment strategies, especially for risk groups. Here, we evaluated the therapeutic potency of nirmatrelvir, remdesivir, and molnupiravir and their combinations in SARS-CoV-2-infected K18-hACE2 transgenic mice. Systemic treatment of mice with each drug (20 mg/kg) resulted in slightly enhanced antiviral efficacy and yielded an increased life expectancy of only about 20-40% survival. However, combination therapy with nirmatrelvir (20 mg/kg) and molnupiravir (20 mg/kg) in lethally infected mice showed profound inhibition of SARS-CoV-2 replication in both the lung and brain and synergistically improved survival times up to 80% compared to those with nirmatrelvir (P= 0.0001) and molnupiravir (P= 0.0001) administered alone. This combination therapy effectively reduced clinical severity score, virus-induced tissue damage, and viral distribution compared to those in animals treated with these monotherapies. Furthermore, all these assessments associated with this combination were also significantly higher than that of mice receiving remdesivir monotherapy (P= 0.0001) and the nirmatrelvir (20 mg/kg) and remdesivir (20 mg/kg) combination (P= 0.0001), underscored the clinical significance of this combination. By contrast, the nirmatrelvir and remdesivir combination showed less antiviral efficacy, with lower survival compared to nirmatrelvir monotherapy, demonstrating the inefficient therapeutic effect of this combination. The combination therapy with nirmatrelvir and molnupiravir contributes to alleviated morbidity and mortality, which can serve as a basis for the design of clinical studies of this combination in the treatment of COVID-19 patients. IMPORTANCESince SARS-CoV-2 spread rapidly with the emergence of new variants of concerns, it is necessary to develop effective treatment strategies to treat elderly individuals and those with comorbidities. Antiviral therapy using a combination of drugs is more effective in eradicating viruses and will undoubtedly improve the clinical outcome and survival probability of hospitalized SARS-CoV-2 patients. In the current study, we observed three FDA-approved antivirals nirmatrelvir, remdesivir, and molnupiravir have therapeutic significance with moderate survival for their monotherapies against SARS-CoV-2 infected K18-hACE2 mouse model. The combination of nirmatrelvir and molnupiravir showed significant antiviral activity and a higher survival rate of approximately 80%, providing in vivo evidence of the potential utility of this combination. In contrast, nirmatrelvir and remdesivir combination showed less antiviral potency and emphasized the ineffective significance with less survival. The current study suggests that the nirmatrelvir and molnupiravir combination is an effective drug regimen strategy in treating SARS-CoV-2 patients.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Interobserver variability in clinical target volume delineation in anal squamous cell carcinoma.

We evaluated the inter-physician variability in the target contouring of the radiotherapy for anal squamous cell carcinoma (ASCC). Clinical target volume (CTV) of three patients diagnosed with ASCC was delineated by seven experienced radiation oncologists from multi-institution. These patients were staged as pT1N1a, cT2N0, and cT4N1a, respectively, according to 8th edition of the American Joint Committee on Cancer staging system. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). The maximum distance from the boundaries of the STAPLE generated volume with confidence level of 80% to those of the contour of each CTV in 6 directions was compared. CTV of pelvis which includes primary tumor, perirectal tissue and internal/external iliac lymph node (LN) area (CTV-pelvis) and CTV of inguinal area (CTV-inguinal) were obtained from the seven radiation oncologists. One radiation oncologist did not contain inguinal LN area in the treatment target volume of patient 2 (cT2N0 stage). CTV-inguinal displayed moderate agreement for each patient (overall kappa 0.58, 0.54 and 0.6, respectively), whereas CTV-pelvis showed substantial agreement (overall kappa 0.66, 0.68 and 0.64, respectively). Largest variation among each contour was shown in the inferior margin of the CTV-inguinal. For CTV-pelvis, anterior and superior margin showed the biggest variation. Overall, moderate to substantial agreement was shown for CTV delineation. However, large variations in the anterior and cranial boarder of the CTV-pelvis and the caudal margin of the CTV-inguinal suggest that further studies are needed to establish a clearer target volume delineation guideline.

Neutrophil-to-Lymphocyte Ratio After Definitive Concurrent Chemoradiotherapy Predicts Survival in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio represent systemic immune-inflammatory responses. We evaluated the association between immune-inflammatory cell ratios and prognosis in esophageal squamous cell carcinoma (ESCC) patients who underwent definitive concurrent chemoradiotherapy (dCCRT). PATIENTS AND METHODS: Medical records of 68 ESCC patients in three institutions who underwent dCCRT between 2006 and 2017 were reviewed. The immune-inflammatory cell ratios were calculated before and after dCCRT. RESULTS: The median follow-up time was 11.4 months. The 3-year overall survival (OS) rate was 21.6%. Among the immune-inflammatory cell ratios, lower post-dCCRT neutrophil-to-lymphocyte ratio (NLRpost) was associated with better OS (median 15.2 vs. 9.7 months, p=0.030). Patients with lower NLRpost had more improved OS when adjuvant chemotherapy was administered following dCCRT (median 16.6 vs. 4.8 months, p<0.001). CONCLUSION: NLRpost may be useful in predicting OS in ESCC patients after dCCRT. Furthermore, NLRpost might play a role in establishing adjuvant therapy plans following dCCRT.

The predictive value of serum myeloma protein in solitary plasmacytoma.

PURPOSE: To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. MATERIALS AND METHODS: Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. RESULTS: At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. CONCLUSION: Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

Adjuvant Chemotherapy and Dose Escalation in Definitive Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: To validate the effect of treatment intensification on survival in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive concurrent chemoradiotherapy (dCCRT). PATIENTS AND METHODS: We reviewed the medical records of 73 ESCC patients who underwent dCCRT between 2006 and 2017 in 3 institutions. RESULTS: The median follow-up time was 13.3 months. The median overall survival (OS) and locoregional recurrence-free survival (LRFS) were 13.3 and 11.2 months, respectively. The median radiotherapy dose was 55.8 Gy, and the median biologically effective dose (BED) was 65.8 Gy. Chemotherapy was given in all patients during dCCRT, and adjuvant chemotherapy was administered in 56 patients (76.7%). Adjuvant chemotherapy improved OS (3-year, 24.2% vs. 11.8%, p=0.004). Higher BED ≥70 Gy improved LRFS (3-year, 41.7% vs. 23.6%, p=0.035). CONCLUSION: The addition of chemotherapy after dCCRT improves OS. A higher radiotherapy dose improved LRFS, but not OS. Adjuvant chemotherapy should be considered after dCCRT for better outcomes.

Post-operative radiation therapy with or without chemotherapy for anal squamous cell carcinoma incidentally discovered after local excision: a propensity score matched analysis of retrospective multicenter study.

OBJECTIVE: To evaluate the results of post-operative radiation therapy (RT) for anal squamous cell carcinoma (ASCC) incidentally detected after excision, and compare these outcomes with those of definitive RT without excision for exploring the possibility of treatment de-intensification. METHODS AND MATERIALS: A total of 25 patients with T1-2N0-1 ASCC who underwent RT following incidental tumor resection were selected from multicenter retrospective database. And, we selected one-to-one matched 25 patients receiving definitive RT from the same database using propensity score matching method, and the outcomes were compared. RESULTS: Median age was 60 years (range, 30-76), and 18 patients (72%) were female. 19 patients (76%) had T0/1 tumors and four patients (16%) had regional lymph node metastases. Hemorrhoidectomy was performed in eight patients (32%) and the others underwent local excision. 12 patients (48%) had microscopic or gross residual diseases. Median RT dose to the primary lesion was 50.4 Gy (range, 40-60). Concurrent chemotherapy was delivered to 23 patients (92%). Median follow-up period was 71 months (range, 4.5-203.1 months). None of the patients showed recurrence during follow-up. However, one patient died after 6 months due to the chemotherapy-related hematologic toxicity. When compared with those patients receiving definitive RT, clinicopathological variables were well-balanced between the two groups. While matched paired patients treated with definitive RT received a higher median RT dose of 54 Gy (range, 45-61.2) and concurrent chemotherapy was given to 22 patients (88%), overall survival was not significantly different (p = 0.262). CONCLUSION: Patients treated with RT for early stage ASCC after local excision showed favorable treatment outcomes. Further study is warranted to justify the de-intensification of the treatment for these patients. ADVANCES IN KNOWLEDGE: Post-operative RT can achieve favorable treatment outcomes in incidental ASCC with residual diseases after local excision.

The predictive value of serum myeloma protein in solitary plasmacytoma

Purpose@#To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. @*Materials and Methods@#Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. @*Results@#At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. @*Conclusion@#Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

Enzyme-treated date plum leave extract ameliorates atopic dermatitis-like skin lesion in hairless mice

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Seven-week-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract. Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4-dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin (IL)-4, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzyme-hydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4,and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes and HMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

Patterns of Care After Surgery for Elderly Patients With Malignant Brain Tumors: Data from the National Health Insurance Service in South Korea.

BACKGROUND/AIM: To analyze patterns of care and overall survival for elderly patients with malignant brain tumors. MATERIALS AND METHODS: The database from the National Health Insurance Service was searched January 2008-December 2016. A total of 1,607 patients aged 65-year-old or more with malignant brain tumors who underwent surgery or biopsy were extracted. Treatment performed in 180 days after surgery was divided into no treatment (N=522), radiotherapy (RT) (N=351), chemotherapy (N=69), and chemotherapy plus RT (N=665). Survival was recorded at 3, 6, 9, 12, 18, and 24 months after surgery. RESULTS: Patients were divided into groups by age: 65-69, 70-74, 75-79, and ≥80 years. Chemotherapy plus RT was most commonly used in all age groups except those aged 80 years and more. Treatment modality after surgery or biopsy was significantly prognostic (p<0.001) in univariate analysis. CONCLUSION: Adjuvant treatment can be recommended for elderly patients with malignant brain tumors based on data from the National Health Insurance Service.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro.

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Fabrication of additive manufacturing interim denture and comparison with conventional interim denture: A case report / 대한치과보철학회지

With development of digital dentistry, the 3-dimensional (3D) manufacturing industry using computer-aided design and computer-aided manufacturing (CAD/CAM) has grown dramatically in recent years. Denture fabrication using digital method is also increasing due to the recent development of digital technology in dentistry. The 3D manufacturing process can be categorized into 2 types: subtractive manufacturing (SM) and additive manufacturing (AM). SM, such as milling is based on cutting away from a solid block of materal. AM, such as 3D printing, is based on adding the material layer by layer. AM enables the fabrication of complex structures that are difficult to mill. In this case, additive manufacturing method was applied to the fabrication of the resin-based complete denture to a 80 year-old patient. During the follow-up periods, the denture using digital method has provided satisfactory results esthetically and functionally.