PURPOSE: Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1). MATERIALS AND METHODS: We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases. RESULTS: Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK. CONCLUSION: Increased MKP-1 expression levels could be the cause of the high resistance to conventional chemotherapeutics in human GBM. Therefore, MKP-1 is an attractive target for overcoming drug resistance in this highly refractory malignancy.
Apoptosis ; Camptothecin ; Cell Death ; Dacarbazine ; Deoxycytidine ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple ; Dual Specificity Phosphatase 1 ; Epirubicin ; Etoposide ; Fluorouracil ; Gene Expression ; Glioblastoma ; Humans ; JNK Mitogen-Activated Protein Kinases ; Lipids ; Mitomycin ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; RNA, Small Interfering

PURPOSE: Nipple sparing mastectomy provides good cosmetic results and low local recurrence rates for breast cancer patients. However, there is a potential risk of leaving an occult tumor within the nipple, which could lead to cancer relapse and poor prognosis for the patient. The objective of this study was to investigate the occult nipple involvement rate in mastectomy specimens, and to identify preoperative magnetic resonance imaging (MRI) findings and the clinicopathological characteristics of the primary tumor that may correlate with nipple invasion. METHODS: Four hundred sixty-six consecutive mastectomy samples with grossly unremarkable nipples were evaluated. Demographic and clinicopathological data were collected. Nipple involvement was evaluated using serial histological sections. The tumor size and tumor-nipple distance were measured using preoperative MRI images. RESULTS: Thirty-six of the 466 therapeutic mastectomy specimens (7.7%) were found to have occult nipple involvement. In univariate analysis, tumor size, tumor-nipple distance, lymph node status, p53 mutation, and lymphovascular invasion (LVI) were found to influence the likelihood of nipple involvement. Multivariate logistic regression analysis, adjusted by lymph node status, p53 mutation, and LVI, showed that tumor size and tumor-nipple distance were predictive factors indicating nipple involvement. With regard to tumor location, only tumors in the central area of the breast showed a significant association with nipple involvement. CONCLUSION: In this study, a statistically significant association was found between occult nipple involvement and tumor size, tumor-nipple distance, axillary lymph node status, LVI, and p53 mutation. A cutoff point of 2.2 cm for tumor size and 2 cm for tumor-nipple distance could be used as parameters to predict occult nipple involvement.
Breast ; Breast Neoplasms* ; Humans ; Logistic Models ; Lymph Nodes ; Magnetic Resonance Imaging* ; Mastectomy ; Nipples* ; Prognosis ; Recurrence

There are several dimensions of academic burnout experienced by medical and health science college students. The purpose of this study was to examine the effects of academic relationships on academic burnout. Data was collected from 476 Eulji University students using an online survey over 4 days in April of 2018. Of the 264 respondents, 111 studied medicine (42.0%), 105 studied nursing (39.8%), and 48 studied clinical pathology (18.1%). The questionnaire was composed of the following sections: demographics (four questions), general life characteristics (seven questions), academic enthusiasm (eight questions), academic relationships (15 questions), and academic burnout sub-dimensions (partially revised Maslach Burnout Inventory-Student Survey Scale) (11 questions). T-tests and one-way analysis of variance were performed to illustrate the differences among the three departments. The effects of academic relationships and academic enthusiasm on academic burnout were analyzed using linear regression. Comparing the three departments, academic burnout was not found to be statistically significant (p=0.296). However, medical students' academic enthusiasm was significantly lower (p<0.001) and academic relationships were significantly higher (p<0.001) than nursing and clinical pathology students. The difference in academic burnout among the three departments was not significant. However, medical students have stronger academic relationships, while nursing and clinical pathology students were more focused on academics. Relationships and academic enthusiasm contribute to reducing academic burnout. Therefore, strategies need to be developed to deal with academic burnout considering relationship factors.
Demography ; Education, Premedical ; Health Occupations ; Humans ; Linear Models ; Nursing ; Pathology, Clinical ; Professionalism ; Students, Medical ; Students, Nursing ; Surveys and Questionnaires

Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM patient-derived cells. Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo experiments. Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investigated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accelerated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLCinduced increases in the invasiveness of GBM TSs. Conclusion Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.

Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.