A case of gonadoblastoma with dysgerminoma and choriocarcinoma in the right ovary of a 23-year-old woman is reported. A case of gonadoblastoma without a Y chromosome is very rare. She had a 46XX chromosomes, normal genitalia, no history of menstrual irregularities, thereby differing from the other reproted case. The patient had a normal term pregnancy 2 years after surgery and chemotherapy. It is suggested that gonadoblastoma may occur in functionally and morphologically normal gonads. There have been no signs of recurrence or metastasis for 3 years after the first operation.
Choriocarcinoma* ; Drug Therapy ; Dysgerminoma* ; Female ; Genitalia ; Gonadoblastoma* ; Gonads ; Humans ; Karyotype* ; Neoplasm Metastasis ; Ovary* ; Pregnancy ; Recurrence ; Y Chromosome ; Young Adult

OBJECTIVE: To identified whether serum Mullerian inhibiting substance (MIS) level may be used as a predictive marker of menopausal transition. METHODS: Serum MIS level was measured in reproductive women (n=87), in menopausal transition women (n=58), and in menopausal women (n=5) by ELISA. And we examined the immunohistochemical staining of the MIS in the ovarian tissues of 15 reproductive, 15 menopausal transition, and 5 menopausal women. RESULTS: 1. In the reproductive women, mean serum MIS level was 1.73+/-1.07 ng/ml. In the menopausal transition women, mean serum MIS level was 0.18+/-0.11 ng/ml. Serum MIS level did not show any significant fluctuation patterns according to follicular development. In menopausal transition women, serum MIS level was significantly lower than that of reproductive women (P<0.001). The cutoff value of serum MIS level for menopausal transition was 0.5 ng/mg. In the menopausal women, serum MIS level was not detected. 2. Serum MIS level was significantly decreased as patient age was increased. 3. In the reproductive group, the immunohistochemical staining demonstrated strong expression of MIS in the granulosa cells of the primary follicles and the growing follicles, but not in corpus luteum, preovulatory mature follicle, atretic follicle, and corpus luteum. In the menopausal transition women, immunohistochemical staining for MIS was observed in the nearly same pattern as that of thereproductive women, but with weaker expression. In the menopausal women, immunohistochemical staining of the MIS was not observed. CONCLUSION: MIS is a good candidate for predictive marker for ovarian aging and perimenopausal transition.
Aging ; Anti-Mullerian Hormone* ; Corpus Luteum ; Enzyme-Linked Immunosorbent Assay ; Female ; Granulosa Cells ; Humans ; Ovarian Follicle

Purpose: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. Materials and Methods: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. Results: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. Conclusion Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

BACKGROUND: Low back pain (LBP) is known to be the significant reason for absenteeism and can develop long-term disability. So the airline authorities have made an effort to reduce the incidence of LBP by applying their physical standards. As a LBP Prevention Program, Airline A has provided health education, counseling and physical examinations. The purpose of this study is to analyze the relationship between LBP and physical characteristics, age and work duration, and this result will provide basic information for improving the LBP Prevention Program. METHOD: The subjects were the 585 flight attendants who had undergone regular physical check-ups with Airline A Medical Center from October 2000 to September 2001. We reviewed their absence records and physical characteristics, age and work duration. These data were analyzed statistically by the t-test and Lositic regression. RESULT: The LBP history group accounted for 18% of the study group. The male LBP history group had the more thin waist than the no history group. There were no differences (P<0.05) between LBP and other male and female physical characteristics. The age and work duration of male LBP history group was lower than the no history group (P<0.05). But the female comparison revealed that only the work experience in the LBP history group was lower than the No history group (P<0.05). Waist, age, work duration was analyzed statistically by logistic regression. Only female's work experience was significant. The fewer work experience was the more LBP. CONCLUSION: The results of this study suggest LBP is associated with work experience rather than physical characteristics. This is the first step toward improving a LBP Prevention Program for the cabin crew. It will be useful to conduct another review to assess various other reasons, such as psychosocial job factors, duration of work disability and muscle strength, related to LBP.
Absenteeism ; Counseling ; Female ; Health Education ; Humans ; Incidence ; Logistic Models ; Low Back Pain* ; Male ; Muscle Strength ; Physical Examination

PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients.
Colorectal Neoplasms* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lipid Metabolism ; Lymph Nodes ; Mediator Complex Subunit 1* ; Multivariate Analysis ; Neoplasm Metastasis ; Peroxisomes* ; PPAR gamma* ; Prognosis ; Thyroid Gland

OBJECTIVE: In order to explore Mullerian inhibiting substance (MIS) effects on the ovarian neoplasia, the expression and localization of the MIS type II receptor (MISR II), the growth inhibitory effects of MIS, and the underlying molecular mechanisms were investigated in the ovarian cancer cell lines. METHODS: Expression of MISR II were studied in SKOV-3, OVCAR-3, and OVCAR-8 cell lines by immunohistochemical staining. The antiproliferative effects of MIS in these cell lines were investigated by methylthiazoletetrazolium (MTT) assay, fluorescence-activated cell sorting (FACS) analysis, annexin-V-FITC binding, and western blot analysis. RESULTS: All cell lines showed strong specific staining for MISR II, although staining in OVCAR-8 cells was more intense than that in SKOV-3 and OVCAR-3. Treatment of OVCAR-8 cells with MIS led to a dose- and time-dependent inhibition of cell growth and survival was determined use by MTT assay. But OVCAR-3 cells exhibited growth inhibition at higher doses after 48 hours of treatment and SKOV-3 cells did not demonstrate response. Using FACS analysis, exposure of OVCAR-8 cells to MIS (71 nM) resulted in G1 arrest after 24 hours of treatment. This pattern was changed by time-dependent increase in the percentage of cells with a sub G0G1 DNA content, suggesting apoptosis, after 48 hours of treatment. These results suggested that cell death be preceded by cell cycle arrest. Time-related induction of apoptosis was also observed in this cell line as measured by annexin-V-FITC binding. In OVCAR-8 cells, the growth inhibitory effects of MIS were mediated through specific induction of CDKI p16 protein expression and via regulation of E2F1 in the absence of detectable levels of pRb. We estimated that OVCAR-3 cells were affected by MIS through p16-independent, alternative mechanistic pathways, since the growth inhibitory effects of MIS were minimal. SKOV-3 cells did not express p16 protein. CONCLUSION: We have demonstrated that ovarian cancer cells express the MISR II. Epithelial ovarian cancer cells respond to MIS by growth inhibition. Although the precise mechanisms of MIS mediated inhibition of ovarian cancer cell growth have not been fully defined, these data suggest that MIS has activity against ovarian cancers in vitro and may also be an effective targeted therapy for ovarian cancer.
Anti-Mullerian Hormone* ; Apoptosis ; Blotting, Western ; Cell Cycle Checkpoints ; Cell Death ; Cell Line* ; DNA ; Flow Cytometry ; Humans* ; Immunohistochemistry ; Ovarian Neoplasms*

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
Atherosclerosis ; Diabetes Mellitus ; Diabetic Angiopathies ; Endothelial Cells* ; Fatty Acids, Nonesterified ; Glucose* ; Human Umbilical Vein Endothelial Cells ; Humans* ; Hyperglycemia ; Reactive Oxygen Species ; RNA, Small Interfering ; Transfection

BACKGROUND/AIMS: This study compared the results of cyclooxygenase-2 (COX-2) expression in inflammatory bowel disease and tuberculous colitis as evident by immunochemical staining and real time polymerase chain reaction (PCR). METHODS: Patients with ulcerative colitis (n=18), Crohn's disease (n=7), tuberculous colitis (n=7) and 10 normal controls were included. Biopsied colonic mucosa was simultaneously used for immunohistochemical staining and real time PCR. RESULTS: Patients with inflammatory bowel disease and tuberculous colitis showed high COX-2 expression by both methods compared to the normal controls. In Crohn's disease patients, the real time PCR value correlated well staining grade; this correlation was not evident in ulcerative colitis patients. In real time PCR, grossly normal colonic mucosa in ulcerative colitis also showed higher expression of COX-2 than normal mucosa. CONCLUSIONS: Real time PCR value of COX-2 is more representative of inflammation state in inflammatory bowel disease than the value from immunohistochemical staining.
Colitis ; Colitis, Ulcerative ; Colon ; Crohn Disease ; Cyclooxygenase 2 ; Humans ; Immunohistochemistry ; Inflammation ; Inflammatory Bowel Diseases ; Mucous Membrane ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×10⁶ parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia-induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.
Angiogenesis Inducing Agents ; Animals ; Anoxia ; Blood Vessels ; Blotting, Western ; Erythrocytes ; Fluorescent Antibody Technique ; Immunohistochemistry ; Injections, Intraperitoneal ; Malaria ; Mice ; Mortality ; Parasitemia ; Plasmodium ; Plasmodium berghei ; Vascular Endothelial Growth Factor A

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.