The Current Trend of Fertility Preservation in Patients with Cervical Cancer.

Although the incidence of most cancers increases with age, a considerable number of patients receive a diagnosis of cancer during their reproductive years. Young women wishing to get pregnant after cancer treatment should be provided consultation for fertility preservation and possible options. In patients with cervical cancer, hysterectomy is often inevitable because the uterus is located too close to the cervix. For young patients with cervical cancer who desire to get pregnant and whose lesion is confined to the cervix, sparing the uterus and, partially, the cervix should be prioritized as much as possible, while simultaneously ensuring favorable oncologic outcomes. In this review, we explore how to choose an adequate fertility-preserving procedure to achieve a balance between favorable oncologic outcomes and fertility and management during pregnancy after a radical trachelectomy in women with early-stage cervical cancer. For patients who require hysterectomy or radiation, evaluation of the ovarian condition and laparoscopic ovarian transposition followed by the use of artificial reproduction techniques and pregnancy by surrogacy should be discussed as options to achieve a successful pregnancy.

Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Case report: Malignant transformation of ovarian endometrioma during long term use of dienogest in a young lady.

Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable.

Maintenance Chemotherapy in Patients with Platinum-Sensitive Relapsed Epithelial Ovarian Cancer after Second-Line Chemotherapy.

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.

Long-term outcome of minimally invasive staging surgery for clinical stage I endometrial cancer: A single institute experience in Taiwan.

BACKGROUND: Endometrial cancer is the most common gynecological cancer in developed countries. With recent advances in equipment and knowledge, minimally invasive surgery (MIS) is widely accepted for the treatment of endometrial cancer. This study had the largest number of cases to date in Taiwan, comparing outcomes between MIS and laparotomy staging surgery using real-world data with long-term follow-up. METHODS: We retrospectively reviewed patients with clinical stage 1 endometrial cancer from 2009 to 2020 in our institute. All patients underwent comprehensive surgical staging procedures by MIS or laparotomy. The safety, morbidity, progression-free survival (PFS), and overall survival (OS) rates of the two groups were compared. Clinical and pathologic factors were compared with Chi-square and Fisher Exact test. PFS and OS were estimated by the Kaplan-Meier method. Differences between survival curves were analyzed using the log-rank test. A p value of <0.05 was considered statistically significant. Using Cox proportional hazards models, all factors found to be significantly associated with risk of recurrence on univariate analyses were then assessed together through multivariable models, resulting in a final oncologic outcome between MIS and laparotomy. RESULTS: A total of 665 cases (412 cases in MIS group and 253 cases in laparotomy group) were enrolled for data analysis. Median operation time was shorter in MIS group (244 and 265 minutes, p < 0.001). Median blood loss was also less (75 and 430 mL, p < 0.001). Median postoperative hospitalization duration was longer in the laparotomy group (2 and 7 days, p = 0.001). After adjusting presurgery risk factors, the PFS and OS were no significant difference in MIS and laparotomy groups. CONCLUSION: Using real-world data with long-term follow-up, we could confirm excellent PFS and OS in selective patients with clinical stage 1 endometrial carcinoma who received MIS, and the surgical time, hospital day, and blood loss were also less.

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma.

Purpose: Uterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma. Materials and methods: This is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen. Results: Fifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events. Conclusion: Use of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.

Xeno-free culture and proliferation of hPSCs on 2D biomaterials.

Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.

Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?

Objective: This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests. Methods: A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples. Results: The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively. Conclusion: HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.

Early-Stage, BRCA-Associated Ovarian Cancer Detected by Papanicolaou Smear: A Case Report.

Historically known as a "silent killer", ovarian cancer is often diagnosed at an advanced stage. We describe an unusual case of stage I, ovarian, high-grade serous carcinoma detected by a routine Papanicolaou (PAP) smear, with no abnormal physical, imaging, or laboratory findings. A 53-year-old woman with newly diagnosed triple-negative breast cancer received a screening Pap smear, which showed malignant cells not coming from the breast or uterine cervix. Pelvic examination, cervical biopsy, and gynecologic ultrasonography found no abnormality. Endometrial curettage yielded free-floating adenocarcinoma cells. The immunohistochemical stain result indicated ovary or fallopian tube cancer. Complete cytoreductive surgery was performed, and high-grade serous carcinoma of bilateral ovaries, FIGO stage IB, was diagnosed. Although extremely rare, when malignant cells not originating from the uterine cervix are detected on a Pap smear, it may lead to an early diagnosis of ovarian cancers, and this warrants further comprehensive workup.

Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation.

Human cells, especially stem cells, need to communicate and interact with extracellular matrix (ECM) proteins, which not only serve as structural components but also guide and support cell fate and properties such as cell adhesion, proliferation, survival and differentiation. The binding of the cells with ECM proteins or ECM-derived peptides via cell adhesion receptors such as integrins activates several signaling pathways that determine the cell fate, morphological change, proliferation and differentiation. The development of synthetic ECM protein-derived peptides that mimic the biological and biochemical functions of natural ECM proteins will benefit academic and clinical application. Peptides derived from or inspired by specific ECM proteins can act as agonists of each ECM protein receptor. Given that most ECM proteins function in cell adhesion via integrin receptors, many peptides have been developed that bind to specific integrin receptors. In this review, we discuss the peptide sequence, immobilization design, reaction method, and functions of several ECM protein-derived peptides. Various peptide sequences derived from mainly ECM proteins, which are used for coating or grafting on dishes, scaffolds, hydrogels, implants or nanofibers, have been developed to improve the adhesion, proliferation or differentiation of stem cells and to culture differentiated cells. This review article will help to inform the optimal choice of ECM protein-derived peptides for the development of scaffolds, implants, hydrogels, nanofibers and 2D cell culture dishes to regulate the proliferation and direct the differentiation of stem cells into specific lineages.

Improved Progression-Free Survival Associated with Tumor-Infiltrating Lymphocytes in High-Grade Endometrial Cancer.

Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients' information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

Long-Term Efficacy and Toxicity of Intensity-Modulated Radiotherapy in Bulky Cervical Cancer.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

Automatic ovarian tumors recognition system based on ensemble convolutional neural network with ultrasound imaging.

BACKGROUND: Upon the discovery of ovarian cysts, obstetricians, gynecologists, and ultrasound examiners must address the common clinical challenge of distinguishing between benign and malignant ovarian tumors. Numerous types of ovarian tumors exist, many of which exhibit similar characteristics that increase the ambiguity in clinical diagnosis. Using deep learning technology, we aimed to develop a method that rapidly and accurately assists the different diagnosis of ovarian tumors in ultrasound images. METHODS: Based on deep learning method, we used ten well-known convolutional neural network models (e.g., Alexnet, GoogleNet, and ResNet) for training of transfer learning. To ensure method stability and robustness, we repeated the random sampling of the training and validation data ten times. The mean of the ten test results was set as the final assessment data. After the training process was completed, the three models with the highest ratio of calculation accuracy to time required for classification were used for ensemble learning pertaining. Finally, the interpretation results of the ensemble classifier were used as the final results. We also applied ensemble gradient-weighted class activation mapping (Grad-CAM) technology to visualize the decision-making results of the models. RESULTS: The highest mean accuracy, mean sensitivity, and mean specificity of ten single CNN models were 90.51 ± 4.36%, 89.77 ± 4.16%, and 92.00 ± 5.95%, respectively. The mean accuracy, mean sensitivity, and mean specificity of the ensemble classifier method were 92.15 ± 2.84%, 91.37 ± 3.60%, and 92.92 ± 4.00%, respectively. The performance of the ensemble classifier is better than that of a single classifier in three evaluation metrics. Moreover, the standard deviation is also better which means the ensemble classifier is more stable and robust. CONCLUSION: From the comprehensive perspective of data quantity, data diversity, robustness of validation strategy, and overall accuracy, the proposed method outperformed the methods used in previous studies. In future studies, we will continue to increase the number of authenticated images and apply our proposed method in clinical settings to increase its robustness and reliability.

Outcomes of "sandwich" chemoradiotherapy compared with chemotherapy alone for the adjuvant treatment of FIGO stage III endometrial cancer.

Objective: To analyze and compare outcomes of adjuvant chemoradiotherapy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial cancer (EC) patients using the "Sandwich" sequence and chemotherapy (CT) alone. Methods: From, 2005 to, 2019, we retrospectively reviewed 80 patients with FIGO stage III EC who received treatment at our institute. We analyzed 66 patients who had undergone complete surgical staging followed by adjuvant treatment with sandwich chemoradiotherapy (39 patients) and CT alone (27 patients). The 5-year overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Additional prognostic factors were analyzed using Cox proportional hazards regression. Results: Herein, the analysis was conducted using 66 patients with a median follow-up period of 50 and 85 months in the sandwich and CT-alone arms. Comparing the sandwich sequence and CT-alone groups, the 5-year OS and PFS were 87% vs. 70% (p = 0.097) and 77% vs. 65% (p = 0.209), respectively. The sandwich therapy conferred an improved 5-year DSS (92% vs. 70%, p = 0.041) and a lower local recurrence rate (0% vs. 11%, p = 0.031). In multivariable analyses, grade 3 histology and deep myometrial invasion were independent risk factors for 5-year OS and DSS. The sandwich sequence was a positive predictor for 5-year DSS (hazard ratio [HR] = 0.23, p = 0.029). The sandwich arm demonstrated higher acute hematologic toxicity than the CT-alone arm. CT dose delay/reduction and treatment completion rates were similar in both groups. Conclusion: For patients with stage III EC, postoperative sandwich chemoradiotherapy appears to offer a superior 5-year DSS and local control with tolerable toxicity when compared with CT alone.

Endometrial Cancer Detection Using a Cervical DNA Methylation Assay (MPap) in Women with Abnormal Uterine Bleeding: A Multicenter Hospital-Based Validation Study.

BACKGROUND: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. METHODS: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. RESULTS: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. CONCLUSIONS: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

Real-World Efficacy of Bevacizumab in Patients With Recurrent Epithelial Ovarian Cancer.

Background: Bevacizumab in combination with chemotherapy prolonged the progression-free survival (PFS) of patients with recurrent epithelial ovarian cancer (EOC) in large-scale randomized controlled trials. However, real-world data for the use of bevacizumab in Asian patients with EOC is lacking. This study investigated the efficacy of adding bevacizumab to chemotherapy and compared it with that of chemotherapy alone in patients with recurrent EOC using real-world data from an Asian population. Method: We conducted a retrospective cohort study using data from a tertiary medical center in central Taiwan. Patients who had EOC with first relapse between 2011 and 2019 were enrolled. Patients' medical histories, medication treatment, and relevant information were collected. The outcomes were PFS and overall survival (OS). The Kaplan-Meier plot was used to generate a survival curve for OS and PFS. Cox proportional hazard analysis was used to determine the associations of Bevacizumab treatment with OS and PFS with adjustment of relevant variables. Subgroup analyses were conducted to determine if there was a significant variation in the aforementioned associations. Results: After a median follow-up of 23 months, 67% of patients in the Bevacizumab group and 81% of patients in the non-Bevacizumab group had disease progression or death. There was no significant between-group difference in OS (p = 0.475). The median duration of PFS was 18.9 and 9.6 months, respectively, favoring those who were treated with Bevacizumab. After multivariate adjustment, treatment with Bevacizumab was associated with a lower risk of disease progression (hazard ratio 0.33, 95% CI 0.13-0.85, p = 0.021). The improvement in PFS was consistent in the subgroups of different histological types, different disease stages at diagnosis, different treatment-free intervals, those undergoing or not undergoing secondary cytoreductive surgery, diverse chemotherapy regimens. Conclusion: Our findings provided crucial insights into the efficacy of bevacizumab for the treatment of recurrent EOC in the real-world setting.

The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo.

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.

Laminin-511 and recombinant vitronectin supplementation enables human pluripotent stem cell culture and differentiation on conventional tissue culture polystyrene surfaces in xeno-free conditions.

Human pluripotent stem cells (hPSCs) are typically cultivated on extracellular matrix (ECM) protein-coated dishes in xeno-free culture conditions. We supplemented mixed ECM proteins (laminin-511 and recombinant vitronectin, rVT) in culture medium for hPSC culture on conventional polystyrene dishes. Three hPSC cell lines were successfully cultivated on uncoated polystyrene dishes in medium supplemented with optimal conditions of laminin-511 and rVT. Excellent colony shape and colony size as well as high expansion fold of hPSCs were found under these conditions, whereas the colony size was small and poor expansion fold was found solely on L-511-coated dishes. A small portion of L-511 in the culture medium supported hPSC adhesion and prevented the adhesion from being too strong on the uncoated dishes, and rVT in the culture medium further supported adhesion of hPSCs on the dishes by maintaining their pluripotency. Having the optimal composition of L-511 and rVT in the culture medium was important for generating good hPSC colony shapes and sizes as well as a high expansion fold. After long-term culture of hPSCs on uncoated dishes supplemented with the mixed proteins, the hPSCs successfully showed pluripotent markers and could differentiate into a specific lineage of cells, cardiomyocytes, with high efficiency.

A Comparison of In-flight and Ground-Based Emergency Medical Events on the Clinical Demand for Outreach Medical Services at Taoyuan International Airport, Taiwan.

Background: Limited information is available covering all medical events managed by the airport-based outreach medical service. This study explores the clinical demand for emergency medical outreach services at Taoyuan International Airport (TIA), Taiwan. Methods: Electronic medical records collected from TIA medical outreach services from 2017 to 2018, included passengers' profiles, flight information, events location, chief complaints, diagnosis (using ICD-9 -CM codes), and management outcomes. Medical events distribution was stratified by location and ages, and were compared statistically. Results: Among 1,501 eligible records, there were 81.8% ground-based emergency medical events (GBME), 16.9% in-flight medical events (IFME) managed after scheduled landing, and 1.3% IFME leading to unscheduled diversion or re-entry to TIA. The top three GBME diagnoses were associated with neurological (23.3%), gastrointestinal (21.2%), and trauma-related (19.3%) conditions. The top three IFME diagnosis that prompted unscheduled landings via flight diversion or re-entry were neurological (47.4%), psychological (15.8%), and cardiovascular (10.5%). The chief complaints that prompted unscheduled landings were mostly related to neurological (42.1%), cardiovascular (26.3%), and out-of-hospital cardiac arrest (OHCA) (10.5%) symptoms. A higher frequency of IFME events due to dermatologic causes in patients aged ≤ 18 years compared with adults and older adults (19 vs. 1.5% and 0, respectively); and a higher frequency of IFME due to cardiovascular causes in adults ≥ 65 years compared with patients aged ≤ 65 (15.1 vs. 9%). Among all IFME patients, six out-of-hospital deaths occurred among passengers from scheduled landings and two deaths occurred among 18 IFME passengers who were transferred to local hospitals from flight diversion or re-entry. A statistically significant difference in outcomes and short-term follow-up status was found between patients with IFME and those with GBME (p < 0.001). Conclusion: Ground-based emergency medical events exceeded in-flight medical events at TIA. The most frequent events were related to neurological, gastrointestinal symptoms, or trauma. Results of this study may provide useful information for training medical outreach staff and preparing medical supplies to meet the clinical demand for airport medical outreach services.

Transient characteristics of universal cells on human-induced pluripotent stem cells and their differentiated cells derived from foetal stem cells with mixed donor sources.

INTRODUCTION: It is important to prepare 'hypoimmunogenic' or 'universal' human pluripotent stem cells (hPSCs) with gene-editing technology by knocking out or in immune-related genes, because only a few hypoimmunogenic or universal hPSC lines would be sufficient to store for their off-the-shelf use. However, these hypoimmunogenic or universal hPSCs prepared previously were all genetically edited, which makes laborious processes to check and evaluate no abnormal gene editing of hPSCs. METHODS: Universal human-induced pluripotent stem cells (hiPSCs) were generated without gene editing, which were reprogrammed from foetal stem cells (human amniotic fluid stem cells) with mixing 2-5 allogenic donors but not with single donor. We evaluated human leucocyte antigen (HLA)-expressing class Ia and class II of our hiPSCs and their differentiated cells into embryoid bodies, cardiomyocytes and mesenchymal stem cells. We further evaluated immunogenic response of transient universal hiPSCs with allogenic mononuclear cells from survival rate and cytokine production, which were generated by the cells due to immunogenic reactions. RESULTS: Our universal hiPSCs during passages 10-25 did not have immunogenic reaction from allogenic mononuclear cells even after differentiation into cardiomyocytes, embryoid bodies and mesenchymal stem cells. Furthermore, the cells including the differentiated cells did not express HLA class Ia and class II. Cardiomyocytes differentiated from transient universal hiPSCs at passage 21-22 survived and continued beating even after treatment with allogenic mononuclear cells.