Real-world clinical effectiveness of nonsurgical treatments for female with POP-Q stage II cystocele: a retrospective analysis of therapeutic efficacy.

Background: Patients with cystocele of pelvic organ prolapse quantification (POP-Q) stage II and below can be treated conservatively, but there are few reports on non-surgical treatment for these patients. This study aimed to present the real-world clinical effectiveness of nonsurgical treatment, including pelvic floor muscle training (PFMT), PFMT combined with pessary (PFMT + P), or non-ablative radiofrequency (PFMT + RF) for female with POP-Q stage II cystocele. Methods: We retrospectively analyzed females with POP-Q stage II cystocele between January 2020 and January 2022 who received PFMT, PFMT + P, or PFMT + RF treatment and were followed up for 12 months. Clinical parameters including Pelvic Floor Distress Inventory-20 questionnaire (PFDI-20), Persian version urinary incontinence quality of life questionnaire (I-QOL), POP-Q, pelvic floor Glazer evaluation, and trans-labial ultrasound at different time points were analyzed. Results: There were 147 participants enrolled. PFDI-20 and I-QOL scores were improved in all groups, but the mean decrement in the PFDI-20 scores (-14.28±8.57 and -9.78±8.25) was higher in the PFMT + P group than in the PFMT group and PFMT + RF group at both 6 and 12 months (P<0.05), and the mean I-QOL score (3.82±23.43 and 3.47±22.06) was higher in the PFMT + RP group at both 6 months and 12 months (P<0.05). The PFMT + P group also showed higher improvement rate (43.3%, P=0.03) in terms of changing the severity of cystocele (point Ba) and delta bladder neck-symphyseal distance (ΔBSD) (P<0.05) than the other 2 groups at 12 months. No statistical difference was found in the type-I and type-II myofiber function-based Glazer assessment among 3 groups. Conclusions: The combination of 2 treatment strategies seems to be superior to PFMT only for stage-II cystocele. Specific prolapse-related symptoms and objective indicators did improve more in the PFMT + P group, whereas stress urinary incontinence (SUI) symptoms and quality of life were improved in the PFMT + RP group.

OTUB1 Promotes Progression and Proliferation of Prostate Cancer via Deubiquitinating and Stabling Cyclin E1.

Background: Prostate cancer (PCa) is currently the most common cancer among males worldwide. It has been reported that OTUB1 plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis. The aim of this research is to investigate the regulatory effect of OTUB1 on PCa proliferation and the underlying mechanism. Methods: Using the TCGA database, we identified that OTUB1 was up-regulated in PCa, and observed severe functional changes in PC3 and C4-2 cells through overexpression or knock down OTUB1. Heterotopic tumors were implanted subcutaneously in nude mice and IHC staining was performed on tumor tissues. The relationship between OTUB1 and cyclin E1 was identified via Western blotting and immunoprecipitations assays. Results: We found that the expression of OTUB1 in PCa was significantly higher than that in Benign Prostatic Hyperplasia (BPH). Overexpression OTUB1 obviously promoted the proliferation and migration of PC3 and C4-2 cells via mediating the deubiquitinated Cyclin E1, while OTUB1 knockout has the opposite effect. The nude mice experiment further explained the above conclusions. We finally determined that OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabling Cyclin E1. Conclusions: Our findings reveal the critical role of OTUB1 in PCa, and OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabilizing Cyclin E1. Blocking OTUB1/Cyclin E1 axis or applying RO-3306 could significantly repress the occurrence and development of PCa. OTUB1/Cyclin E1 axis might provide a new and potential therapeutic target for PCa.

Correction: Evaluating prognosis by CK7 differentiating renal cell carcinomas from oncocytomas can be used as a promising tool for optimizing diagnosis strategies.

[This corrects the article DOI: 10.18632/oncotarget.10225.].

18F-fluorodeoxyglucose positron emission computed tomography for monitoring tumor response in esophageal carcinoma treated with concurrent chemoradiotherapy.

The aim of the present study was to explore the value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in monitoring the early tumor response of esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). A total of 48 patients with pathologically proven ESCC were retrospectively analyzed. All patients underwent two serial 18F-FDG PET scans at baseline (pre-CRT) and 40 Gy/4 weeks of starting radiation therapy (inter-CRT). All patients received intensity-modulated radiotherapy (with a total radiation dose of 59.6 Gy) concurrently with cisplatin-based chemotherapy. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) were measured using 18F-FDG PET. The percentage changes (Δ) in SUVmax and MTV between two serial scans were calculated and were revealed to be associated with the objective tumor response (oTR), according to the Response Evaluation Criteria in Solid Tumors 1.1. Among the 48 patients, 20.8% achieved a complete response, 68.8% exhibited a partial response and the oTR rate was 89.6%. On the pre-CRT PET scans, the mean SUVmax and MTV were 14.1±5.8 and 58.2±25.4 cm3, respectively. Following 40 Gy irradiation over 4 weeks, the mean SUVmax and MTV significantly decreased to 4.3±3.5 and 19.0±12.1 cm3, respectively (P<0.001). A significantly higher ΔSUVmax and ΔMTV was observed in the responders compared with that in the non-responders [0.71±0.16 vs. 0.51±0.26 (P=0.015); and 0.64±0.13 vs. 0.42±0.09 (P=0.001), respectively]. Univariate analysis revealed that ΔSUVmax and ΔMTV were significantly associated with oTR (P=0.010 and P=0.001, respectively). ΔMTV was used as a predictor and a cut-off value of 54% discriminated responders from non-responders with a sensitivity of 69.8% and a specificity of 100% (P=0.001). The area under the receiver operating characteristic curve was 0.837 (95% confidence interval, 0.702-0.928). The results of the present study indicated that interim 18F-FDG PET scans may provide early prognostic value for determining oTR in patients with ESCC undergoing treatment with CRT.

New applications of the acridine orange fluorescence staining method: Screening for circulating tumor cells.

The aim of the present study was to explore use of the acridine orange fluorescence (AO-F) staining method for screening of circulating tumor cells (CTCs) in renal cell carcinoma (RCC) patients. The AO-F positive staining rate of live and dead tumor cells was calculated. The positive staining rate in the live group was 93.4±3.0%, while the dead group failed to emit specific fluorescence. A known number of tumor cells were added to peripheral blood, and the detection sensitivity of the four groups (50, 100, 200 and 500 cells/tube) was 10.2±3.8, 9.2±2.3, 10.8±2.6 and 10.5±1.9%, respectively. The average detection sensitivity of the four groups was 10.16±2.73%. There was a positive correlation between the number of cells that was positively stained with AO-F and the total number cells in the system (χ2=0.959; P<0.001). Subsequently, the AO-F staining method was used to detect positive staining cells in 8 healthy volunteers (control group), and 112 non-metastatic and 27 metastatic RCC patients. The positive staining rate was 13.67% (19/139) in RCC patients, while none of the control group was positive. The AO-F positive staining rate was not significantly different between the metastatic and non-metastatic patients according to age, gender, the pathological pattern, T2/3 (according to the Tumor-Node-Metastasis classification) or Fuhrman grade, while there was a significant difference according to T1. The positive staining rate was 8.93% (10/112) for non-metastatic patients and 33.33% (9/27) for metastatic patients, which showed a significant difference (P<0.05). In 112 non-metastatic and 27 metastatic patients, the positive staining rate was not significantly associated with gender, age, tumor size, the pathological pattern, T classification, Fuhrman grade, the presence of a lesion or metastasis to the lungs. The present study demonstrated that the method of CTC staining with AO-F, which has high reproducibility and specificity, was feasible for identifying CTCs and warrants further study.

Matrix metalloproteinase 9 and prostate cancer risk: a meta-analysis of 1059 participants.

INTRODUCTION: Numerous studies have evaluated the association between the matrix metalloproteinase 9 (MMP-9) and prostate cancer (PCa) risk. However, these studies have yielded conflicting results. EVIDENCE ACQUISITION: A comprehensive search was conducted through researching MEDLINE, PubMed, Web of Science, and EMBASE, and a total of 10 studies including 1059 cases were included on the basis of inclusion criteria. EVIDENCE SYNTHESIS: A meta-analysis was performed to obtain a summary of estimated odds ratios (ORs) and 95% confidence intervals (CIs) of MMP-9 for PCa, with attention to study quality and publication bias. MMP-9 by immunohistochemistry was significantly associated with increased diagnosis of PCa (OR=7.91; 95% CI: 5.27-11.89; P<0.00001). Subgroup-analysis showed that findings did not substantially change when only Caucasians or Asians (OR=5.87; 95% CI: 3.38-10.20; P<0.00001) or (OR=11.80; 95% CI: 6.60-21.08; P<0.00001) were considered. There was also no significant publication bias observed. CONCLUSIONS: Our findings provide further evidence that the expression of MMP-9 contribute to PCa risk. MMP-9 protein overexpression was found in prostate cancers, low expression in any of the normal tissues or in benign prostatic tissue. MMP-9 is potentially an important prostate tumor marker.

Evaluating prognosis by CK7 differentiating renal cell carcinomas from oncocytomas can be used as a promising tool for optimizing diagnosis strategies.

Renal Oncocytomas and renal cell carcinomas (RCCs) share a common phenotype. This makes it very difficult to differentiate between the two tumors. Here, this study was to confirmed and expanded the findings that CK7 as a promising tool differentiate RCC from Oncocytomas across various geographic regions. A systematic search of databases was carried out and other relevant articles were also identified. Then the meta-analyses were conducted for 1,711 participants according to the standard guidelines. A total of 21 studies were included on the basis of inclusion criteria. CK7 by IHC was significantly associated with increased diagnosis of RCC (OR=10.64; 95% CI, 7.44-15.23; P=0.0001). Subgroup-analysis showed that findings didn't substantially change when only Caucasians or Asians (OR=10.58; 95% CI, 6.97-16.07; P<0.01 or OR=10.83; 95% CI, 5.39-21.74; P=0.004) were considered. There was also no significant publication bias observed. Our findings provide further evidences that the expression of CK7 contribute to differentiate RCC from Oncocytomas. CK7 protein overexpression was found in RCC, low expression in any of Oncocytomas. CK7 is potentially an important renal tumor marker.

ZFX is a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma.

BACKGROUND: This study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients. MATERIAL AND METHODS: The expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis. RESULTS: The qRT-PCR result showed that the ZFX was significantly up-regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033-24.180). CONCLUSIONS: Our findings show that ZFX could be considered as a predictor for prognosis of RCC patients.

[Expression and gene mutation of cluster of differentiation 9 in lung cancer cells induced by mineral powder in Gejiu].

OBJECTIVE: To investigate the expression and gene mutation of cluster of differentiation 9 (CD9) in the pathway of the mineral powder induced malignant transformation in immortalized human bronchial epithelial cells (BEAS-2B) in Gejiu. METHODS: BEAS-2B cells served as the control group and its malignant transformation cells induced by mineral powder in Gejiu were considered as experiment group. The expression of CD9 protein in 20 bottles of BEAS-2B cells and 20 bottles of malignant transformation cells was evaluated by immunocytochemistry. The mRNA expression of CD9 in 10 bottles of BEAS-2B cells and 10 bottles of malignant transformation cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR). Gene mutation was detected in the products of RT-PCR by DNA sequencing. RESULTS: There was significant difference between the expression of CD9 protein in BEAS-2B cells (100%, 20/20) and that in its malignant transformation cells (35%, 7/20 P < 0.01). The expression of CD9 mRNA in BEAS-2B cells 0.91 +/- 0.09 was significantly higher than that in its malignant transformation cells (0.34 +/- 0.14) (P < 0.01). Two point mutation of CD9 gene was detected in the malignant transformation cells of BEAS-2B by DNA sequencing. The change of G-->T in the base of 231 led to the change of Gln-->His in the amino acids of 40. The change of T-->A in the base of 119 led to the change of Val-->Asp in the amino acids of 3. CONCLUSION: The absence or down-regulation of CD9 expression and point mutation in the malignant transformation cells of BEAS-2B may play a considerable role in the pathway of the malignant transformation in the BEAS-2B cells induced by mineral powder in Gejiu.

[Generation of specific cytotoxicity T lymphocytes induced by tumor-derived heat shock protein 90-peptide complexes in vitro].

OBJECTIVE: To investigate the specific induction of cytotoxic lymphocyte (CTL) by tumor-derived heat shock protein 90-peptide complexes (HSP90-PC). METHODS: Heat shock protein 90-peptide complex (HSP90-PC) was isolated and purified by liquid chromatography after precipitation by 50% - 70% (NH4) 2SO4 saturation from 10 specimens of renal carcinoma resected from 10 patients aged 40 - 60 during operation. The component containing HSP90-PC was filtered and sterilized. The molecular weight and the identity of the purified HSP90-PC were confirmed by SDS-PAGE and Western blotting. 10 - 15 ml peripheral blood was extracted from these patients. T cells were amplified. Flow cytometry was used to detect the phenotype of dendritic cells (DCs). The DCs in the experimental group were cultured for 5 days and then HSP90-PC and tumor necrosis factor (TNF)-alpha was added into the culture. The HSP90-PC pulsed DCs were collected and co-cultured with auto-T cells for 72 hours. Flow cytometry was used to detect the content of CD8(+) T cells. The DC of the control group were mixed directly with auto-T cells and the content of CD8(+) T cells was examined by flow cytometry. RESULTS: The proliferation of T cells co-cultured with the HSP90-PC pulsed DCs was significantly remarkable and the content of CD8(+) CTLs was significantly more in comparison with the control DC (P < 0.01). CONCLUSION: HSP90-PC prepared from tumor tissues has strong immunogenicity and the DC sensitized thereby effectively induces the proliferation of CTL. Application of HSP90-PC provides a new approach in tumor immunotherapy.

[Study on the attenuation of graft versus host disease by methoxy polyethylene glycol modification of donor lymphocytes].

AIM: To find out why mPEG modification of donor's lymphocytes can attenuate the occurrence of graft versus host disease(GVHD), but not affect the hemopoietic reconstitution of stem/progenitor cells after transplanting the mPEG-modified mononuclear cells from human cord blood into the SCID mice. METHODS: The followings were observed: (1) Changes of CD4(+) and CD8(+) T cells and the ratio of CD4(+)/CD8(+) T cells were examined by flow cytometry before and after mononuclear cells from human cord blood were modified with mPEG. (2) The difference in forming the CFU-GM in-vitro between the mPEG modified-stem/progenitor cell group and non-modified cell group was observed. (3) The time of appearance of GVHD and the survival of the SCID mice were observed after the pre- and post-modification mononuclear cells were transplanted. (4) The number of humanized CD45(+) cells in the mouse's bone marrow was detected about 7 weeks after transplantation. RESULTS: (1) mPEG nearly completely covered up the CD4 and CD8 antigens on T cells, while the number of CFU-GM did not show any obvious change between the modified and non-modified cell groups. (2) GVHD appeared later in the modified mononuclear cell group than in the non-modified group, and the survival rate was elevated in the modified group than in the non-modified group. (3) Humanized CD45 cells were found in mouse's bone marrow at the 47th day after transplantation of both mPEG-modified and non-modified mononuclear cells. CONCLUSION: After CD4 and CD8 antigens were covered up with mPEG, the graft's immune response against host was weakened, but the proliferation and differentiation of transplanted hemopoietic stem/progenitor cells were not affected.