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Objective@#Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. @*Methods@#We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. @*Results@#High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). @*Conclusion@#Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.
ABSTRACT
Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.
ABSTRACT
Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.
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OBJECTIVE: In cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN. METHODS: p16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes. RESULTS: A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively). CONCLUSION: p16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.
Subject(s)
Humans , Uterine Cervical Dysplasia , Genotype , Immunohistochemistry , Medical Records , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. METHODS: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. RESULTS: The median follow-up period was 64.3 months. The depth of stromal invasion was 3 mm, but 7 mm in 25 cases. One of the 33 cases that had tumor volumes of 500 mm3 were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p<0.0001). The frequency of pelvic lymph node metastases was significantly higher in the lymphovascular space invasion (LVSI)-positive group than in the LVSI-negative group (p=0.02). No adnexal metastasis or parametrial involvement was noted. CONCLUSION: Assessment of the depth of stromal invasion, tumor volume, and LVSI is critical for selecting an appropriate therapeutic modality. Non-radical methods of management are considered suitable for patients with LVSI-negative adenocarcinoma of the cervix exhibiting a stromal invasion depth of < or =5 mm and a tumor volume of < or =500 mm3.
Subject(s)
Female , Humans , Adenocarcinoma , Cervix Uteri , Conization , Follow-Up Studies , Lymph Nodes , Neoplasm Metastasis , Recurrence , Tumor Burden , Uterine Cervical NeoplasmsABSTRACT
We performed exercise intervention for 12 weeks in young females (22.3±2.5 yrs ; mean±SD) with a %fat value of 30% or more (dual energy X-ray absorptiometry : DXA) despite a body mass index (BMI) of less than 25 kg/m<sup>2</sup>, which indicates hidden obesity, and the following results were obtained.The intensity of exercise was established as the double product break point calculated from heart rate and systolic blood pressure, and the subjects were instructed to exercise for 30 minutes or more for 3 or more times a week. Six weeks after exercise intervention, the BMI, body fat level, and plasma glucose level were lower than those before exercise intervention, and the %fat value was lower 12 weeks after intervention. Furthermore, cardiac autonomic function (CAF) was negatively correlated with changes in Total power and changes in fat (kg), suggesting that exercise-related improvement in CAF is involved in a decrease in %fat.