Evaluating TRAIL and IP-10 alterations in vaccinated pregnant women after COVID-19 diagnosis and their correlation with neutralizing antibodies.

Background: This study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers. Methods: We studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns' blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors. Results: Our study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level. Conclusions: Our study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.

TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

PD-L1 expressed from tumor cells promotes tumor growth and invasion in lung cancer via modulating TGF-ß1/SMAD4 expression.

BACKGROUND: Programmed death ligand-1 (PD-L1) has a known association with the prognosis of human cancers because of its ability to alter tumor immune surveillance via its interaction with PD-1. We questioned whether expression of PD-L1 in tumor cells could directly promote tumor growth and invasiveness in non-small cell lung cancer (NSCLC). METHODS: Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate PD-L1 messenger RNA (mRNA) expression in lung tumors. The prognostic value of PD-L1 mRNA was assessed by Cox regression model. Transcriptional regulation of PD-L1 by human papillomavirus (HPV) 16/18 E6 oncoprotein or by epidermal growth factor receptor (EGFR) mutation in lung cancer cells was examined by Western blot and luciferase reporter assay. The cell growth and invasion were evaluated by colony formation, soft agar growth, and Boyden chamber assay. RESULTS: The PD-L1 mRNA levels showed a positive association with HPV 16/18 E6 oncoprotein and with EGFR mutation in 223 surgically resected NSCLC patients. The prognostic significance of PD-L1 was more commonly observed in patients with high PD-L1/E6 positive and high PD-L1/EGFR mutant tumors. Mechanistically, upregulation of PD-L1 transcription by E6 or mutant EGFR occurred largely through the ERK-C/EBPß-TLR4-NF-κB cascade. PD-L1 promotes the efficacy of colony formation, soft agar growth, and cell invasion. PD-L1 upregulates BAG-1 to reduce transforming growth factor (TGF)-ß1 expression, and the decrease in SMAD4 because of TGF-ß1 occurs through the p53/microRNA (miR)-224 axis. The decreases in TGF-ß1 and SMAD4 are responsible for PD-L1-mediated cell invasiveness. CONCLUSION: Induction of PD-L1 by E6 oncoprotein or mutant EGFR through the ERK-C/EBPß-TLR4-NF-κB cascade may promote tumor growth and invasiveness in NSCLC because of decreasing TGF-ß1 and SMAD4 expression.

Small-volume detection: platform developments for clinically-relevant applications.

Biochemical analysis of human body fluids is a frequent and fruitful strategy for disease diagnosis. Point-of-care (POC) diagnostics offers the tantalizing possibility of providing rapid diagnostic results in non-laboratory settings. Successful diagnostic testing using body fluids has been reported on in the literature; however, small-volume detection devices, which offer remarkable advantages such as portability, inexpensiveness, capacity for mass production, and tiny sample volume requirements have not been thoroughly discussed. Here, we review progress in this research field, with a focus on developments since 2015. In this review article, we provide a summary of articles that have detailed the development of small-volume detection strategies using clinical samples over the course of the last 5 years. Topics covered include small-volume detection strategies in ophthalmology, dermatology or plastic surgery, otolaryngology, and cerebrospinal fluid analysis. In ophthalmology, advances in technology could be applied to examine tear or anterior chamber (AC) fluid for glucose, lactoferrin, interferon, or VEGF. These approaches could impact detection and care for diseases including diabetic mellitus, dry-eye disease, and age-related maculopathy. Early detection and easy monitoring are critical approaches for improving overall care and outcome. In dermatology or plastic surgery, small-volume detection strategies have been applied for passive or interactive wound dressing, wound healing monitoring, and blister fluid analysis for autoimmune disease diagnosis. In otolaryngology, the analysis of nasal secretions and mucosa could be used to differentiate between allergic responses and infectious diseases. Cerebrospinal fluid analysis could be applied in neurodegenerative diseases, central neural system infection and tumor diagnosis. Other small-volume fluids that have been analyzed for diagnostic and monitoring purposes include semen and cervico-vaginal fluids. We include more details regarding each of these fluids, associated collection and detection devices, and approaches in our review.

Association of hOGG1-Cys variants with occurrence of p53 and EGFR deletion mutations in non-small cell lung cancer.

BACKGROUND: The human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene encodes a DNA glycosylase that removes 8-hydroxy-2-deoxyguanine (8-OH-dG) DNA damage to protect against gene mutations. The association of hOGG1 Ser326Cys polymorphism with lung cancer risk has predicted that hOGG1-Cys variants are less effective at removing 8-OH-dG damage from DNA; therefore, these variants might show an increased occurrence of tumor suppressor gene and oncogene mutations. However, no evidence has yet supported this hypothesis. METHODS: Direct sequencing was performed to examine the mutations of p53 and EGFR genes in lung tumors from patients with non-small cell lung cancer (NSCLC). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine hOGG1 Ser326Cys polymorphism in this study population. RESULTS: A total of 99 p53-mutated and 99 EGFR-mutated patients with NSCLC were selected to explore the possible associations of these mutations with hOGG1 Ser326Cys polymorphism. The p53-mutated and EGFR-mutated patients were divided into nondeletion and deletion subgroups. P53 deletion mutations were more commonly observed in male than in female patients (P = 0.030). However, EGFR exon 19 deletion mutations were more prevalent in female and adenocarcinoma patients than in male and squamous cell carcinoma patients (P = 0.028 for genders, P = 0.017 for tumor histology). Interestingly, p53 and EGFR exon 19 deletion mutations were more frequent in patients with hOGG1 Ser/Cys + Cys/Cys hOGG1-Cys variants than with the hOGG1 Ser/Ser genotype (P = 0.010 for p53, P = 0.032 for EGFR). CONCLUSIONS: We suggest that the association of hOGG1 Ser326Cys polymorphism with lung cancer risk could be partially explained by increases in p53 and EGFR deletion mutations. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: NSCLC patients with hOGG1-Cys variants may have a higher risk of p53 and EGFR deletion mutations than with hOGG1 Ser/Ser genotype. WHAT THIS STUDY ADDS: NSCLC patients with hOGG1-Cys variants might be helpful to predict patients having higher risk of EGFR exon 19 deletion mutations and these patients who were treated with gefitinib or erlotinib could be a higher risk to occur EGFR T790M mutation.

Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression.

NKX2-1 was shown to enhance cisplatin sensitivity in KRAS-mutated cells, but it conferred cisplatin resistance in EGFR-mutated lung adenocarcinoma cells. However, NKX2-1 as a dual role in tumor progression depended on p53 mutational status via modulation of the NF-κB pathway. We hypothesized that NKX2-1 may confer cisplatin resistance in p53-mutated (p53-MT) lung adenocarcinoma cells but may enhance cisplatin sensitivity in wild-type (p53-WT) cells. In the present study, six p53-MT and -p53-WT cell lines were treated with various concentrations of cisplatin to calculate the inhibitory concentration of cisplatin for 50% cell viability (IC50). The IC50 value was positively correlated with NKX2-1 expression in the p53-MT cells but negatively correlated in the p53-WT cells. TNFSF10 was identified in a microarray analysis as a potential candidate responsible for NKX2-1-mediated apoptosis induced by cisplatin. The retrospective study evaluated 97 surgically resected lung adenocarcinoma patients receiving cisplatin-based chemotherapy to explore the possible association between NKX2-1 expression and tumor response. Patients with higher TNFSF10 mRNA levels, as determined by real-time reverse transcription-polymerase Chain Reaction (RT-PCR), typically showed an favorable response when compared with patients with lower TNFSF10 mRNA levels. Additionally, the association of higher TNFSF10 mRNA levels with favorable response was only revealed in p53-WT patients, not in p53-MT patients. Higher NKX2-1 mRNA levels were associated with an unfavorable response in patients with p53-MT tumors but a favorable response in patients with p53-WT tumors. In summary, modulation of TNFSF10 expression by NKX2-1 may be a potential indicator for predicting the response to cisplatin-based chemotherapy in patients with lung adenocarcinomas.

Hepatitis B virus X protein promotes tumor invasion and poor prognosis in hepatocellular carcinoma via phosphorylation of paxillin at Serine 178 by activation of the c-Jun NH2-terminal kinase.

Hepatitis B virus X protein (HBx) plays critical roles in hepatocellular tumorigenesis by activating different signaling pathways, including the c-Jun NH2-terminal kinase (JNK) pathway. Phosphorylation of paxillin (PXN) promotes cell migration via activation of the JNK signaling pathway, but PXN overexpression is not associated with poor outcome in patients with hepatocellular carcinoma (HCC). HBx gene manipulation and Western blotting indicated that phosphorylation of PXN at Serine 178 (pS178-PXN) by HBx may promote invasiveness in HCC cells via HBx-mediated JNK activation. Immunohistochemical analysis indicated a positive correlation between pS178-PXN and HBx expression levels in tumor specimens. The overall survival (OS) and relapse-free survival (RFS) were poorer in patients with high-pS178-PXN expressing or high-HBx expressing tumors than in patients with low-pS178-PXN expressing or low-HBx expressing tumors. In conclusion, phosphorylation of PXN at Serine 178 by HBx-mediated JNK activation may therefore play a critical role in tumor invasiveness and poor prognosis in patients with HBV-infected hepatocellular tumors. The expression levels of pS178-PXN may be a reliable prognostic biomarker to predict the clinical outcomes in patients with HBV-associated HCC.

Sulforaphane Decrease of SERTAD1 Expression Triggers G1/S Arrest in Breast Cancer Cells.

Studies have identified the potential of chemopreventive effects of sulforaphane (SFN); however, the underlying mechanisms of its effect on breast cancer require further elucidation. This study investigated the anticancer effects of SFN that specifically induces G1/S arrest in breast ductal carcinoma (ZR-75-1) cells. The proliferation of the cancer cells after treatment with SFN was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA content and cell cycle status were analyzed through flow cytometry. Our results demonstrated the inhibition of growth in ZR-75-1 cells upon SFN exposure. In addition, SERTAD1 (SEI-1) caused the accumulation of SFN-treated G1/S-phase cells. The downregulation of SEI-1, cyclin D2, and histone deacetylase 3 suggested that in addition to the identified effects of SFN against breast cancer prevention, it may also exert antitumor activities in established breast cancer cells. In conclusion, SFN can inhibit growth of and induce cell cycle arrest in cancer cells, suggesting its potential role as an anticancer agent.

RV-59 suppresses cytoplasmic Nrf2-mediated 5-fluorouracil resistance and tumor growth in colorectal cancer.

Our previous studies indicated that tumor invasion and 5-flurouracil (5-FU) resistance in colorectal cancer (CRC) was more affected by cytoplasmic localization of expressed Nrf2 (cNrf2) than by nuclear localization (nNrf2), indicating a need for novel antitumor agents to overcome 5-FU resistance and improve outcomes in patients with CRC. In the present study, 20 nitrogen-substituted anthra[1,2-c][1,2,5] thiadiazole-6,11-dione derivatives were collected to verify the compound most able to suppress cell growth in nuclear location sequence (NLS)-mutated Nrf2-transfected shNrf2-HCT116 stable clones that have high cNrf2 expression. The MTT assay indicated that these high-cNrf2-expressing shNrf2-HCT116 stable clones exhibited the lowest percentage survival when treated with RV-59 than with the other 19 compounds. As expected, the high-cNrf2-expressing cells also showed a higher value for the inhibitory concentration of 50% cell survival (IC50) for 5-FU when compared with Nrf2-knockdown HCT116 stable clones (17.74 µM vs. 5.34 µM). Interestingly, a lower RV-59 IC50 value was seen in the high-cNrf2-expressing stable clones than in the Nrf2-knockdown stable clones (3.55 µM vs. 16.81 µM). A similar low RV-59 IC50 value was observed in high-cNrf2-expressing NLS-mutated Nrf2-transfected shNrf2-HCT116 stable clones and p53 null (-/-) HCT116 cells (4.2 µM vs. 4.4 µM), whereas the IC50 value was 17.6 µM in normal colon FHC epithelial cells. Colony-forming assays confirmed that RV-59 treatment inhibited colony formation in NLS-mutated Nrf2-transfected shNrf2-HCT116 stable clones and in p53-/- HCT116 cells. Annexin-V/PI staining showed an involvement of apoptosis in the inhibitory effect of RV-59 on cell viability. A nude mouse xenograft tumor model showed that RV-59 efficiently suppressed tumor growth induced by transplanted NLS-mutated Nrf2-transfected shNrf2-HCT116 stable clones without affecting the body weight of the nude mice over the 37 day experimental period. These results strongly suggest that RV-59 may be a novel antitumor agent for suppression of 5-FU resistance and may have therapeutic potential for improving outcomes in patients with cNrf2-expressing tumors.

Correlation Between IL-20 and De Quervain's Disease Severity.

De Quervain's disease is a stenosing tenosynovitis of the first dorsal compartment of the wrist. Histopathological studies have reported that the thickening of the first dorsal retinaculum is characterized by degeneration rather than inflammation. However, significant infiltration of mast cells and macrophages was noted in a torn tendon study, which suggested that innate immune pathways are part of the mechanism that mediates early tendinopathy. Recently, Interleukin-20 (IL-20) has been reported to provoke potent inflammation and regulate angiogenesis and chemotaxis, which are important for the pathogenesis of inflammatory diseases. The main purpose of our study was to investigate the correlation between IL-20 and tumor necrosis factor (TNF-α) and clarify the potential predictor of tendinopathy progression. Hematoxylin and eosin (H & E) and immunohistochemistry (IHC) staining were used to score and analyze the clinical outcome. TNF-α, IL-20 and related inflammation cytokines were examined. Moreover, the tenocytes were cultured with a stimulator and were used to examine inflammatory cytokine secretions. A real-time polymerase chain reaction (Real-time PCR) was used to detect the gene expression profile. The IHC data showed that TNF-α is up-regulated in grade III de Quervain's. The analysis data showed that IL-20 is positively correlated with TNF-α and disease severity. The real-time PCR showed that the inflammation stimulator enhanced the expression of IL-20 mRNA expression. Inflammation cytokines such as TNF-alpha, transforming growth factor-ß (TGF-ß) and IL-1 have been used as predictors of de Quervain's; IL-20 is a new predictor based on this study. In the future, IL-20 expression's involvement in the molecular mechanism of the severity of de Quervain's should be further investigated.

Inducement of apoptosis by cucurbitacin E, a tetracyclic triterpenes, through death receptor 5 in human cervical cancer cell lines.

Cervical cancer is the most common malignancy in women, for which conization or hysterectomy are the main therapy. Curcubitacin E (Cu E) is a natural compound-based drug which from the Guadi (climbing stem of Cucumic melo L). Previously shown to be an anti-tumor as well as a potent chemopreventive agent against several types of tumors. The present study, investigated anti-proliferation and apoptosis induced by Cu E in cervical cancer cell lines (HeLa and Ca Ski). The results indicate that the cytotoxicity is associated with accumulation in apoptosis but not necrosis. Cu E produced apoptosis as well as the up-regulation the expression of death receptor 5 (DR5). In addition, the DR5 gene activation in apoptosis, both effects increased proportionally with the dose of Cu E; however, mitosis delay was also dependant on the amount of Cu E treatment in the cancer cells. These results indicate that Cu E may delay cancer cell growth by apoptosis via upregulation of DR5 gene expression.

LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells.

The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region. In addition, PVT1 could competitively bind with miR-195. MiR-195 overexpression suppressed PVT1 expression in the cancer cells. Both PVT1 and miR-195 could inhibit paclitaxel (PTX) induced epithelial-to-mesenchymal transition (EMT) and also sensitize CaSki cells to PTX. Based on these findings, we infer that PVT1 could decrease miR-195 expression via enhancing histone H3K27me3 in the miR-195 promoter region and also via direct sponging of miR-195. In addition, the PVT1/miR-195 axis can modulate responses of the cancer cells to PTX via regulating EMT.

MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer.

High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR.

MiR-148a and miR-152 reduce tamoxifen resistance in ER+ breast cancer via downregulating ALCAM.

Activated leukocyte cell adhesion molecule (ALCAM), also called CD166 is a 105-kDa transmembrane glycoprotein of the immunoglobin superfamily. In this study, we studied the association between ALCAM expression and tamoxifen resistance in ER + breast cancer and further investigated how ALCAM is regulated in the cancer cells. IHC staining data showed that the tumor tissues from non-responders (N = 20) generally had significantly stronger ALCAM staining than that from tamoxifen responders (N = 16). In vitro cell assay also confirmed ALCAM upregulation in tamoxifen resistant (TamR) MCF-7 cells than in tamoxifen sensitive (TamS) MCF-7 cells. ALCAM overexpression significantly alleviated 4-Hydroxytestosterone (4-OHT) induced cell viability inhibition and cell apoptosis in TamS MCF-7 cells, while ALCAM knockdown remarkably enhanced 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. Demethylation reagent treatment significantly restored miR-148a and miR-152 expression in TamR MCF-7 cells. MiR-148a and miR-152 can directly target ALCAM 3'UTR and decrease ALCAM expression. MiR-148a overexpression had similar effect as ALCAM siRNA on enhancing 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. MiR-152 overexpression alone caused growth inhibition and increased cell apoptosis in TamR MCF-7 cells. It also enhanced the effect of 4-OHT. Simultaneous inhibition of miR-148a and miR-152 significantly protected TamS MCF-7 cells from 4-OHT induced cell viability inhibition and cell apoptosis. Based on these findings, we infer that MiR-148a and miR-152 can sensitize TamR MCF-7 cells to tamoxifen at least via downregulating ALCAM.

Clinical effects of transobturator tape procedure with porcine small intestine submucosa for female stress urinary incontinence.

The aim of this study was to evaluate the efficacy of the transobturator tape (TOT) procedure using porcine small intestine submucosa (SIS) for the treatment of female stress urinary incontinence (SUI). Forty-two consecutive patients with SUI who underwent the TOT procedure with porcine SIS were enrolled. The surgical outcomes, and data of urodynamic study and a questionnaire prior to and after surgery were collected and analyzed retrospectively. SUI was reported subjectively cured in 34 of the 42 patients (81.0%) 1 year after surgery, and declined to the rate of 66.7% at 5 years postoperatively. The subjective symptoms of frequency and nocturia also improved significantly (p < 0.01). Graft-versus-host disease (GVHD) developed in four patients, but without major complications. Despite the bladder volume at first desire to void increased significantly after surgery (p < 0.01), the remaining urodynamic parameters did not differ in a significant manner. In conclusion, the long-term cure rate of the TOT procedure with SIS is lower than with synthetic materials, but with relatively lower morbidity.

Human umbilical cord matrix-derived stem cells expressing interferon-ß gene inhibit breast cancer cells via apoptosis.

Human umbilical cord mesenchymal stem cells (hUCMSCs) derived from the umbilical cord matrix have been reported to be used as anti-tumor gene carrier for attenuation of tumor growth, which extends the half-life and lowers the unexpected cytotoxicity of the gene in vivo. Interferon-ß (IFNß) is known to possess robust anti-tumor effects on different types of cancer cell lines in vitro. The present study was aimed to investigate the anti-tumor effect of IFNß gene-transfected hUCMSCs (IFNß-hUCMSCs) on breast cancer cells with emphasis on triple negative breast carcinoma. Our findings revealed that the co-culture of IFNß-hUCMSCs with the human triple negative breast carcinoma cell lines MDA-MB-231 or Hs578T significantly inhibited growth of both carcinoma cells. In addition, the culture medium conditioned by these cells also significantly suppressed the growth and induced apoptosis of both carcinoma cells. Further investigation showed that the suppressed growth and the apoptosis induced by co-culture of IFNß-hUCMSCs or conditioned medium were abolished by pretreating anti-IFNß neutralizing antibody. These findings indicate that IFNß-hUCMSCs triggered cell death of breast carcinoma cells through IFN-ß production, thereby induced apoptosis and suppressed tumor cell growth. In conclusion, we demonstrated that IFNß-hUCMSCs inhibited the growth of breast cancer cells through apoptosis. With potent anti-cancer activity, it represents as an anti-cancer cytotherapeutic modality against breast cancer.

Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs.

Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G1 phase due to the down-regulation of CDK 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer.

Comparison of clinical outcomes using "elevate anterior" versus "Perigee" system devices for the treatment of pelvic organ prolapse.

OBJECTIVE: This study aims to compare clinical outcomes using the Perigee versus Elevate anterior devices for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and forty-one women with POP stages II to IV were scheduled for either Perigee (n = 91) or Elevate anterior device (n = 50). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about quality of life and urinary symptoms. RESULTS: Despite postoperative point C of Elevate group being significantly deeper than the Perigee group (median: -7.5 versus -6; P < 0.01), the 1-year success rates for two groups were comparable (P > 0.05). Apart from urgency incontinence, women with advanced POP experienced significant resolution of irritating and obstructive symptoms after both procedures (P < 0.05), generating the improvement in postoperative scores of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) (P < 0.01). On urodynamics, only the residual urine decreased significantly following these two procedures (P < 0.05). Women undergoing Perigee mesh experienced significantly higher visual analogue scale (VAS) scores and vaginal extrusion rates compared with the Elevate anterior procedure (P < 0.05). CONCLUSIONS: With comparable success rates, the Elevate procedure has advantages over the Perigee surgery with lower extrusion rate and postoperative day 1 VAS scores.

Clinical and urodynamic effects of tolterodine in women with an overactive bladder.

OBJECTIVE: The aim of this study was to compare the changes in urinary symptoms and urodynamic parameters after administration of tolterodine in women with an overactive bladder (OAB). MATERIALS AND METHODS: Thirty-eight women diagnosed with OAB and treated with tolterodine were reviewed. Urinalysis, pelvic examination, 3-day bladder diary, urodynamic study, and a personal interview to identify urinary symptoms prior to and 3 months after treatment were recorded and interpreted. RESULTS: Most of our patients were menopausal (76.3%; mean age 55.7 years) and multiparous (mean parity 3.3) women. Urinary symptoms such as urinary frequency, urgency, urge incontinence, and nocturia were decreased significantly (p < 0.05). All urodynamic parameters did not change significantly except for the maximum cystometric capacity (p < 0.05), showing a significant increase after 3 months of medication. CONCLUSIONS: Tolterodine, at a recommended dose, improves the symptoms of OAB syndrome without causing urine retention, as proved by the changes of urodynamic parameters.