Human β-defensin (hBD) 2 is an epithelial antimicrobial peptide. We studied single-nucleotide polymorphisms in the gene of hBD-2 in a Japanese population, and estimated the effect of a polymorphism in the promoter/enhancer region on the transcriptional activity. By sequencing the hBD-2 gene of 50 unrelated individuals, we detected one SNP in exon 2 and nine SNPs in the promoter/enhancer region. The SNP in the coding region at the +1765 position is synonymous [CCC (Pre)→CCT (Pre)]. One SNP in the promoter region (-1029) is located at the consensus sequence for NF-IL6 binding. By luciferase reporter assay and electrophoretic mobility shift assay, the wild-type (G) of -1029 showed significantly lower transcriptional activity than did the variant-type (A). The SNP at position -1029 may influence the hBD-2 expression and cause genetic variations in susceptibility to infectious diseases.

Human β-defensin (hBD) 2 is an epithelial antimicrobial peptide. We studied single-nucleotide polymorphisms in the gene of hBD-2 in a Japanese population, and estimated the effect of a polymorphism in the promoter/enhancer region on the transcriptional activity. By sequencing the hBD-2 gene of 50 unrelated individuals, we detected one SNP in exon 2 and nine SNPs in the promoter/enhancer region. The SNP in the coding region at the +1765 position is synonymous [CCC (Pre)→CCT (Pre)]. One SNP in the promoter region (-1029) is located at the consensus sequence for NF-IL6 binding. By luciferase reporter assay and electrophoretic mobility shift assay, the wild-type (G) of -1029 showed significantly lower transcriptional activity than did the variant-type (A). The SNP at position -1029 may influence the hBD-2 expression and cause genetic variations in susceptibility to infectious diseases.

OBJECTIVE: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. METHODS: Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed. RESULTS: Most patients presented with abnormal genital bleeding including abnormal menstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia and one had endometrial cancer. Serum 17β-estradiol (E2) levels tended to be higher in patients over 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low in all patients irrespective of serum E2 levels. Magnetic resonance imaging revealed a thicker endometrium in older as compared to younger patients (p<0.05). Tumor cells in the majority of cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E2 levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was strongly positive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E2 levels were associated with P450c17-positive cells in the tumor (p<0.05). CONCLUSION: The expression of hormone-synthesizing enzymes divides granulosa cell tumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E2 and related clinical symptoms, while tumors without these cells show symptoms related to FSH suppression by inhibin.
Adult* ; Aromatase ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometrium ; Estrogens ; Female ; Fibroblasts ; Follicle Stimulating Hormone ; Granulosa Cell Tumor* ; Granulosa Cells* ; Hemorrhage ; Humans ; Inhibins ; Lutein ; Magnetic Resonance Imaging ; Menstrual Cycle ; Ovary* ; Retrospective Studies* ; Steroid Hydroxylases ; Theca Cells

OBJECTIVE: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. METHODS: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. RESULTS: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. CONCLUSION: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model.
Cohort Studies ; Cytoreduction Surgical Procedures ; Disease-Free Survival ; Drug Therapy ; Humans ; Methods ; Multivariate Analysis ; Ovarian Neoplasms ; Recurrence ; Retrospective Studies

Objective: The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinumbased chemotherapy in ovarian cancer. Methods: We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results: NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters. Conclusion Serum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.

Objective: The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinumbased chemotherapy in ovarian cancer. Methods: We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results: NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters. Conclusion Serum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.

OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.
Adult ; Aged ; Aged, 80 and over ; Female ; *Groin ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/pathology ; Magnetic Resonance Imaging ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node/*pathology ; Sentinel Lymph Node Biopsy/*methods ; Vulvar Neoplasms/*pathology/surgery

OBJECTIVE: Carcinosarcoma of the uterine corpus has a poor prognosis. Although pathological necrosis is a prognostic factor of endometrial cancer, the clinicopathological influences of an unenhanced region observed on magnetic resonance imaging (MRI) are inconclusive. The aim of our study was to determine the clinicobiological impact of the presence of an unenhanced region on MRI, which can represent necrosis, in uterine carcinosarcoma. METHODS: The clinicopathological factors of 29 patients diagnosed with uterine carcinosarcoma were assessed retrospectively. The percentage of the tumor that was unenhanced on MRI was determined. The clinicopathological factors related to the unenhanced regions were evaluated. The prognostic significance was assessed using the Kaplan-Meier method and Cox regression model. RESULTS: Although the presence of pathological necrosis was not a poor prognostic factor (p=0.704), unenhanced regions on MRI correlated with poor prognosis when the unenhanced regions in the tumor accounted for more than 10% of the total tumor (p=0.019). The percentage of unenhanced regions was positively correlated with stage (p=0.028; r=0.4691) and related to tumor size (p=0.086; r=0.3749). The Cox regression analysis indicated that the presence of lymph node (LN) metastasis and more than 10% of the tumor being unenhanced on MRI were prognostic factors of overall survival in the univariate analyses (p=0.018 and p=0.047, respectively). CONCLUSION: The unenhanced region on MRI, which represents pathological necrosis, reflects tumor progression, and semi-quantification of the region is useful to predict the prognosis in patients with uterine carcinosarcoma.
Carcinosarcoma* ; Endometrial Neoplasms ; Female ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging* ; Methods ; Necrosis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Uterine Neoplasms

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.