Objective: 177 Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [ 177 Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60–90) with mCRPC from a phase I study with activity escalation design of single administration of [ 177 Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [ 177 Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion [ 177 Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

No abstract available.
Myxoma

PURPOSE: The purpose of this study was to describe factors affecting body image and sexual life for colorectal cancer patients with stoma. METHODS: A cross-sectional descriptive correlational study was applied to 102 ostomates from June to November in 2015 using self-report questionnaires: the Body image scale (BIS), and the Derogatis interview for sexual functioning self report (DISF-SR). RESULTS: The influencing factors for body image were ‘need for preoperative sexual education and sexual counseling’ (β=−.29, p=.003), and clinical stage II of colorectal cancer (β=−.26, p=.006). The influencing factor for sexual life was educational level (college education or higher) (β=.21, p=.02). CONCLUSION: The results of this study showed that colorectal cancer patients with stoma had a negative body image. The sexual counseling and education for ostomates should be approached by considering gender characteristics.
Body Image* ; Colorectal Neoplasms* ; Counseling ; Education ; Humans ; Self Report ; Surgical Stomas

PURPOSE: The dried body of Scolopendra subspinipes mutilans has long been used as a traditional Korean medicinal food, but little is known about its mechanisms of action. In this study, we investigated the anti-inflammatory activities of Scolopendra subspinipes mutilans and possible mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. METHODS: Cytotoxicity of Scolopendra subspinipes mutilans extract (SSME) was measured by MTT assay, anti-inflammatory activities were analyzed by nitric oxide (NO) production, the expression of inducible NO synthase (iNOS) and the mRNA level of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). Nuclear translocation of nuclear factor-kappa B (NF-κB) p65 subunit and degradation of inhibitory kappa B (IκB) were examined by western blot. RESULTS: SSME inhibited LPS-induced NO production and iNOS expression without cytotoxicity. Up-regulation of LPS-induced pro-inflammatory cytokines, IL-1β and IL-6 was dose dependently attenuated by SSME. Exposure of pyrrolidine dithiocarbamate, an NF-κB specific inhibitor, accelerated the inhibitory effects of SSME on NO production and iNOS expression in LPS-stimulated cells. Moreover, translocation of NF-κB from the cytosol to the nucleus and degradation of IκB were decreased by treatment with SSME in LPS-induced cells. CONCLUSION: These results suggest that the SSME might have the inhibitory effects on inflammation, partly through inhibition of the NF-κB signaling pathway.
Blotting, Western ; Cytokines ; Cytosol ; Inflammation ; Interleukin-6 ; Nitric Oxide ; Nitric Oxide Synthase ; RAW 264.7 Cells* ; RNA, Messenger ; Up-Regulation

PURPOSE: Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected. MATERIALS AND METHODS: In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions. RESULTS: Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. GNAQ/11 mutation showed 100% homogeneity in uveal melanoma patients. CONCLUSION: Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.
Cohort Studies ; Genetic Heterogeneity ; Genotype ; Humans ; Incidence ; Melanoma* ; Phenotype ; Population Characteristics* ; Prognosis

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Peripheral Nervous System Diseases ; Polymers* ; Treatment Outcome

PURPOSE: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. METHODS: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor κB (NF-κB) signaling was examined by nuclear translocation of NF-κB p65 subunit and phosphorylation of IκB. RESULTS: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced NF-κB p65 nuclear translocation and phosphorylation of IκB. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an NF-κB inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. CONCLUSION: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of NF-κB signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.
Alzheimer Disease ; Blotting, Western ; Brain Diseases ; Cell Survival ; Cyclooxygenase 2 ; Microglia ; Neurodegenerative Diseases ; Nitric Oxide ; Nitric Oxide Synthase ; Parkinson Disease ; Phosphorylation

PURPOSE: The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC).METHODS: From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68 ± 9 years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis.RESULTS: The median duration of follow-up period was 5.4 months (interquartile range: 1.45~15.45). FDG PET/CT showed higher sensitivity than conventional imagingmodalities in detection of regional node involvement (74.5 % vs. 61.8 %, p = 0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2 ± 3.1, 6.8 ± 2.5, 4.0 ± 0.8, 192.7 ± 360.5 cm3, and 823.7 ± 1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p = 0.001), higher SUVpeak (≥6.5, HR: 2.333, p = 0.020), higher SUVmean (≥3.9, HR: 2.799, p = 0.004), higher SUVgluc (≥8.1, HR: 2.648, p = 0.012), and higher TLGgluc (≥431.6, HR: 2.186, p = 0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p= 0.005).CONCLUSION: FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.
Cholangiocarcinoma ; Diagnostic Imaging ; Female ; Follow-Up Studies ; Glucose ; Glycolysis ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging ; Male ; Neoplasm Metastasis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; ROC Curve ; Tumor Burden

BACKGROUND: Lentigo maligna melanoma (LMM) is a subtype of melanoma that typically develops on sun-damaged skin. LMM is estimated to comprise 4~15% of melanomas, but the prevalence is known to be relatively lower in the Korean population than in the Caucasian population. OBJECTIVE: To review the clinico-pathologic features and treatment outcomes of Korean patients with LMM. METHODS: Nineteen patients diagnosed with LMM during 2003~2015, in the Yonsei University Health System, were included in this study. The age and sex of the patients, lesion location, thickness (Breslow), stage, treatment methods, BRAF, NRAS, and KIT mutation status, and survival rates were analyzed. RESULTS: Among the 19 Korean patients, 11 were male and 8 were female. The median age was 59.2 years. The most common site was the cheek (47.4%), followed by the scalp, eyelid, nose, forehead, lip, and neck. At the time of diagnosis, 13 patients were in localized stages (5 patients, stage 0; 3 patients, stage I; and 5 patients, stage II) and 6 patients were in advanced stages (3 patients, stage III; and 3 patients, stage IV). Patients in the localized stages showed better overall survival (OS) than those in the advanced stages (p=0.012). Nine patients were treated with a wide excision, and 6 using Mohs micrographic surgery. Three patients received high-dose interferon-α therapy; 6, chemotherapy; and 4, radiotherapy. Two patients in stage 0 were treated with topical ingenol mebutate. Two patients had BRAF V600E mutation; 1, NRAS G12R mutation; and 1, KIT mutation. Median OS of the patients was 40.8 months. CONCLUSION: Our analysis provides additional information about clinical characteristics, treatment, and prognosis of LMM in Korean patients.
Cheek ; Diagnosis ; Drug Therapy ; Eyelids ; Female ; Forehead ; Humans ; Hutchinson's Melanotic Freckle* ; Lentigo* ; Lip ; Male ; Melanoma* ; Mohs Surgery ; Neck ; Nose ; Prevalence ; Prognosis ; Radiotherapy ; Retrospective Studies* ; Scalp ; Skin ; Survival Rate