Occurrence and Expression of Human Papillomavirus Type 16 Genes in Uterine Cervical Carcinomas

The detection of human papillomavirus (HPV) type 16 early genes: E7, E5, and the late gene: L1 was attempted in 42 uterine cervical neoplasia (35 cervical carcinomas and 7 cervical dysplasias) using the polymerase chain reaction (PCR) method. Consequently, E7 gene was detected in 19 (54.3%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, E5 gene was detected in 7 (20.0%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, L1 gene was detected in 18 (51.4%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, respectively.　　 In order to elucidate the transcriptional pattern of HPV type 16 in each of the clinical stages, the expression of mRNA for E7, E5 and L1 genes was examined in HPV DNA positive cases using the reverse transcriptase polymerase chain reaction (RT-PCR) method. E7 gene mRNA was detected in 18 (94.7%) of 19 cervical carcinomas, whereas E5 and L1 genes mRNAs were detected in only 4 (57.1 %) of 7 and in one (5.6%) of 18 carcinomas respectively. In cervical dysplasias, E7, E5 and L1 genes mRNA were detected in all cases. E7, E5 and L1 genes were transcriptionally active in all dysplasias, whereas E5 and L1 genes were not always transcriptionally active in carcinomas.　　 These results suggest that the HPV type 16 early gene E7 is present preferentially as integrated form and transcriptionally active in the carcinoma cell, and plays an important role in the development of malignancy. On the other hand, E5 and L1 genes are present and transcribed in the dysplasia cell but their transcriptional activity is less frequent in the carcinoma cell.This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan (No. 01579833).The outline of this paper was reported at the 50th Annual Meeting of the Japanese Cancer Association (Tokyo, 1991) and at the 44th Annual Meeting of Japan Society of Obstetrics and Gynecology (Chiba, 1992)

An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia

The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets

Adult granulosa cell tumors of the ovary: A retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes

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

Application of Convolutional Neural Networks in the Diagnosis of Helicobacter pylori Infection Based on Endoscopic Images

Background and aims: The role of artificial intelligence in the diagnosis of Helicobacter pylori gastritis based on endoscopic images has not been evaluated. We constructed a convolutional neural network (CNN), and evaluated its ability to diagnose H. pylori infection. Methods: A 22-layer, deep CNN was pre-trained and fine-tuned on a dataset of 32, 208 images either positive or negative for H. pylori (first CNN). Another CNN was trained using images classified according to 8 anatomical locations (secondary CNN). A separate test data set (11, 481 images from 397 patients) was evaluated by the CNN, and 23 endoscopists, independently. Results: The sensitivity, specificity, accuracy, and diagnostic time were 81.9%, 83.4%, 83.1%, and 198 s, respectively, for the first CNN, and 88.9%, 87.4%, 87.7%, and 194 s, respectively, for the secondary CNN. These values for the 23 endoscopists were 79.0%, 83.2%, 82.4%, and 230 ± 65 min (85.2%, 89.3%, 88.6%, and 253 ± 92 min by 6 board-certified endoscopists), respectively. The secondary CNN had a significantly higher accuracy than endoscopists (by 5.3%; 95% CI, 0.3-10.2). Conclusion: H. pylori gastritis could be diagnosed based on endoscopic images using CNN with higher accuracy and in a considerably shorter time compared to manual diagnosis by endoscopists

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer

Purpose/Objective: To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). Methods and Materials: We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. Results: Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%.0 The 2-year local control rate was 85.7%.0 Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. Conclusions: Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed