Preoperative urine sediment chromosomal instability level predicts urothelial cancer prognosis.

PURPOSE: Urothelial carcinomas (UCs) are often characterized by frequent recurrences after surgery, making UC one of the costliest cancers. Chromosomal instability (CIN) has been proven to be a hallmark of UCs and is related to the prognosis of many cancer types. In this study, we evaluated CIN of urine sediments as a prognostic indicator for UCs. METHODS: Patients with UC were prospectively recruited. Preoperative urine samples were collected for whole genome sequencing and urine cytology tests. Patients underwent standard-of-care treatment and were followed up until disease relapse or study ended. Concordance and accuracy of CIN alone or in combination with cytology in predicting disease relapse were assessed. The value of CIN combined with European Organization for Research and Treatment of Cancer (EORTC) model were also analyzed. RESULTS: A total of 137 patients with UCs were included in this study. Median follow-up was 44.2 months and 41.61% patients suffered from cancer relapse. Patients with CIN-high indicated higher relapse rate, and this distinction was significant for patients underwent transurethral resection of bladder tumor (57.89% vs. 34.29%, P = 0.016). Combination of cytology and CIN result could further classified patients into subgroups with distinct relapse risks. Meanwhile, the combination of CIN and EORTC model significantly improved the prediction accuracy compared with EORTC alone (Harrel's C-index: 0.71 vs. 0.65). CONCLUSION: CIN level of preoperative urine exfoliated cells had robust prognostic value for bladder cancer patients underwent TURBT. The prognostic model by combining CIN and EORTC may help in stratifying patients to optimize follow-up regimen.

Enhanced recovery after surgery program alleviates neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients undergoing gynecological surgery.

Background: To evaluate the efficacy of the enhanced recovery after surgery (ERAS) programs on the systemic inflammatory response (SIR) of patients following gynecological surgery, a randomized controlled trial was performed to compare the ERAS programs with the conventional perioperative care programs. Furthermore, novel SIR markers could be identified to evaluate the ERAS programs of gynecological surgery. Methods: Patients undergoing gynecological surgery were randomly allocated to either the ERAS group or the conventional group. The correlations between the elements of ERAS protocols and SIR markers following gynecological surgery were evaluated. Results: A total of 340 patients who underwent gynecological surgery were enrolled (ERAS = 170; conventional = 170). First, we identified whether the ERAS programs after gynecological surgery reduced the perioperative difference between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Interestingly, first flatus time postoperatively, visual analog scale (VAS) score of patients was positively correlated with the perioperative difference NLR or PLR. Moreover, we discovered that the perioperative difference NLR or PLR was correlated with elements of ERAS protocol, including first sips of water, first semifluid diet postoperatively, pelvic drain duration, and out-of-bed time of patients. Conclusion: We originally reveal that certain elements of ERAS programs alleviated SIR to operation. The implementation of ERAS programs enhances postoperative recovery after gynecological surgery via improving system inflammatory status. NLR or PLR could be the novel and inexpensive marker to assess ERAS programs in gynecological surgery.Clinical trial registration:ClinicalTrials.gov, identifier, NCT03629626.

The Safety of Chemotherapy for Ovarian Malignancy during Pregnancy.

BACKGROUND: Data on epidemiologic features, treatments and outcomes in women diagnosed with ovarian malignancy during pregnancy are very sparse due to its low incidence. The goal of our study was to summarize the epidemiologic characteristics of pregnant women complicated with ovarian malignancy and investigate the safety and efficacy of chemotherapy during pregnancy. METHODS: We retrospectively analyzed the clinicopathological data of eight patients suffering from ovarian malignancy during pregnancy in our institution from June 2011 to July 2021. Furthermore, a systematic literature search was conducted in PubMed up to 1 September 2021, which identified 92 cases with ovarian malignancy during pregnancy eligible for the analysis. Therefore, we collected the data of 100 pregnant patients complicated with ovarian malignancy, including clinical demographics, tumor characteristics, treatment interventions and outcomes. RESULTS: In total, 100 pregnant patients complicated with ovarian malignancy were investigated and classified into three groups: 34 cases in the epithelial ovarian cancer (EOC) group, 38 cases in the germ cell tumors (GCTs) group and 28 cases in the sex cord-stromal tumors (SCSTs) group. The onset age of pregnant patients with epithelial ovarian cancer was significantly higher than that of other patients. Pelvic mass and abdominal pain were the common clinical presentations of pregnant patients with ovarian malignancy. For distinguishing epithelial ovarian cancer during pregnancy, the area under the curve (AUC) of CA-125 was 0.718 with an optimal cutoff value of 58.2 U/mL. Moreover, 53 patients underwent surgery during pregnancy, the majority of whom underwent unilateral adnexectomy in the second trimester. Furthermore, 43 patients received chemotherapy during pregnancy, and 28 delivered completely healthy newborns at birth; 13 neonates showed transient abnormalities without further complications; and 2 died during the neonatal period. CONCLUSIONS: Our study reveals the safety of chemotherapy for ovarian malignancy during pregnancy. However, large-sample prospective studies are still needed to further explore the safety of chemotherapy in pregnant patients with malignancy to choose the appropriate chemotherapy regimen and achieve the maximum benefit for patients.

Enhanced Recovery After Surgery Impact on the Systemic Inflammatory Response of Patients Following Gynecological Oncology Surgery: A Prospective Randomized Study.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body's response to surgical stress. METHODS: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints. RESULTS: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups. CONCLUSION: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03629626).

Lung neoplasm mimicking as ectopic pregnancy due to paraneoplastic secretion of human chorionic gonadotropin: a case report and literature review.

PURPOSE: The present systematic review aimed to examine the relationship between lung neoplasm and human chorionic gonadotropin (HCG). Especially, women with lung neoplasm mimicking as ectopic pregnancy were explored. METHODS: A rare case of lung neoplasm with high serum ß-HCG, which was initially thought to be ectopic pregnancy, was reported. A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2020. RESULTS: Studies assessed lung neoplasm patients with positive HCG were included. Twenty studies, including 24 patients, were included. These cases illustrate the importance of considering the possibility of paraneoplastic secretion of ß-HCG in patients who have a positive pregnancy test. This may prevent a delay in the diagnosis and treatment of malignancy in young women. Of the 24 cases, only 7 (29.17%) were managed surgically; others were managed conservatively or with chemotherapy or radiation. CONCLUSION: The present systematic review shows the need to re-awaken awareness and high index of suspicion to lung neoplasm diagnosis in patients with positive pregnancy test.

Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA.

PURPOSE: Urothelial carcinoma is a malignant cancer with frequent chromosomal aberrations. Here, we investigated the application of a cost-effective, low-coverage whole-genome sequencing technology in detecting all chromosomal aberrations. EXPERIMENTAL DESIGN: Patients with urothelial carcinomas and nontumor controls were prospectively recruited in clinical trial NCT03998371. Urine-exfoliated cell DNA was analyzed by Illumina HiSeq XTen, followed by genotyping with a customized bioinformatics workflow named Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD). RESULTS: In the discovery phase, urine samples from 126 patients with urothelial carcinomas and 64 nontumor disease samples were analyzed. Frequent chromosome copy-number changes were found in patients with tumor as compared with nontumor controls. A novel diagnosis model, UroCAD, was built by incorporating all the autosomal chromosomal changes. The model reached performance of AUC = 0.92 (95% confidence interval, 89.4%-97.3%). At the optimal cutoff, |Z| ≥ 3.21, the sensitivity, specificity, and accuracy were 82.5%, 96.9%, and 89.0%, respectively. The prediction positivity was found correlated with tumor grade (P = 0.01). In the external validation cohort of 95 participants, the UroCAD assay identified urothelial carcinomas with an overall sensitivity of 80.4%, specificity of 94.9%, and AUC of 0.91. Meanwhile, UroCAD assay outperformed cytology tests with significantly improved sensitivity (80.4% vs. 33.9%; P < 0.001) and comparable specificity (94.9% vs. 100%; P = 0.49). CONCLUSIONS: UroCAD could be a robust urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests. It may be used as a noninvasive approach for diagnosis and recurrence surveillance in urothelial carcinoma prior to the use of cystoscopy, which would largely reduce the burden on patients.

The Value of Preoperative Alpha-L-Fucosidase Levels in Evaluation of Malignancy and Differential Diagnosis of Urothelial Neoplasms.

PURPOSE: To evaluate the role of Alpha-L-fucosidase (AFU) in diagnosis and differential diagnosis of pure urothelial carcinoma (UC), urothelial carcinoma with squamous differentiation (UCSD), and squamous cell carcinoma (SqCC). METHODS: A retrospective study was performed for 599 patients who were histologically confirmed with urothelial tumor. Preoperative AFU levels were compared across the distinct subgroups with different clinicopathological parameters. ROC curve analysis and logistic regression analysis were performed to further evaluate the clinical application value of serum AFU levels in diagnosis and differential diagnosis of urothelial tumors. RESULTS: There were no statistically significant differences in the AFU levels between different groups with different malignant degrees (UC versus papilloma and papillary urothelial neoplasm of low malignant potential [PUNLMP], high-grade UC versus low-grade UC, invasive versus noninvasive malignant uroepithelial tumor) and different pathological types (UC, UCSD, and SqCC) (all P > 0.05). ROC curve analysis and logistic regression analysis showed that there was no statistically significant association between AFU levels and the tumor characteristics (all P > 0.05). CONCLUSIONS: Preoperative AFU levels cannot serve as a reliable predictor for malignant degree and differential diagnosis, including pure UC, UCSD, and SqCC of urothelial tumors.

The effect of CPAP and PDE5i on erectile function in men with obstructive sleep apnea and erectile dysfunction: A systematic review and meta-analysis.

Growing evidence has shown that obstructive sleep apnea (OSA) and erectile dysfunction (ED) often coexist. However, the effect of continuous positive airway pressure (CPAP) on erectile function remains controversial. The objective of this review was to clarify the anti-ED effect of CPAP and further compare the efficacy between CPAP, phosphodiesterase type 5 inhibitors (PDE5i) and combination therapy on erectile function in OSA patients concurrent ED. Literature search was performed up to December 1st, 2018 and 26 studies were included in the review. Results showed that CPAP significantly ameliorated the international index of erectile function (IIEF) score, total erectile events (TEE) and nocturnal penile rigidity (NPR), while no significant improvements in nocturnal penile tumescence circumference (NPTC). Moreover, CPAP was inferior to PDE5i in improving IIEF-erectile function, IIEF-intercourse satisfaction, NPTC, successful attempted intercourses rate (SAIR) and erectile dysfunction inventory of treatment satisfaction-question one (EDITS-Q1), while CPAP and PDE5i were of equal efficacy in other domains of IIEF and NPR. Interestingly, CPAP was more effective in improving TEE. Furthermore, CPAP combined with PDE5i was superior to CPAP alone in improving IIEF score, SAIR, and TEE. This review provided promising insights about CPAP-based ED treatment for OSA patients.

MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ.

BACKGROUND: MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. METHODS: Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. RESULTS: Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375. CONCLUSIONS: The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions.

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

MicroRNA-132/212 Upregulation Inhibits TGF-ß-Mediated Epithelial-Mesenchymal Transition of Prostate Cancer Cells by Targeting SOX4.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that are important for embryonic stem cell development and epithelial to mesenchymal transition (EMT). Accumulating evidence indicates that miRNAs play critical roles in prostate cancer (PCa) metastasis and have potential use as therapeutic targets. Although dysregulated miR-132/212 have been suggested to be directly involved in the proliferation and invasion of multiple malignancies, the exact role of miR-132/212 in PCa has not yet been fully understood. METHODS: Real-time quantitative PCR (RT-qPCR) and bioinformatics analysis were used to validate the expression levels of miR-132/212 in PCa cell lines as well as in prostatic tissues. The biological function of miR-132/212 was evaluated by MTS, transwell, and wound healing assays, respectively. RT-qPCR and Western blot were used to study the transcript and protein expression levels. Bioinformatics tools and luciferase reporter assay were utilized to identify the molecular target of miR-132/212. Immunohistochemistry (IHC) was used to detect the expression of SOX4. RESULTS: miR-132 and miR-212 from the same gene cluster are downregulated in human PCa tissues when compared with benign prostatic hyperplasia tissues (both P < 0.05). Functionally, upregulation of miR-132/212 inhibits the migration and invasive capacity of Vcap and Lncap cells by wound-healing and transwell assays, respectively. Notably, overexpression of miR-132/212 could inhibit TGF-ß (transforming growth factor-ß)-induced EMT in Vcap and Lncap cells at both the mRNA and protein expression levels. SOX4 gene, an important EMT regulator of PCa, was identified as the target of miR-132/212 by bioinformatics tools and luciferase reporter assay. Clinically, miR-132/212 expression levels were adversely correlated with Gleason score (P < 0.001) and SOX4 expression by IHC and RT-qPCR in PCa tissues. CONCLUSION: Our data suggested that miR-132/212 may act as tumor suppressors in PCa progression through disrupting EMT process by directly targeting SOX4. Prostate 76:1560-1570, 2016. © 2016 Wiley Periodicals, Inc.

The clinical and biological significance of MICA in clear cell renal cell carcinoma patients.

Major histocompatibility complex class I-related chains A (MICA), a ligand of Natural killer group 2, member D (NKG2D) receptor, is broadly upregulated in epithelial originated tumor cells. MICA plays a critical role in the immune surveillance against tumor cells and is associated with the prognosis of several malignancies. The aim of this study is to evaluate the clinical and biological significance of MICA in clear cell renal cell carcinoma (ccRCC). The expression of MICA was analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Both MICA mRNA and protein levels were upregulated in ccRCC tissues, compared with normal tissues. IHC staining revealed a homogenous pattern of MICA staining within each tumor, which combined both membrane staining and granular cytoplasmic staining. Furthermore, high MICA expression was associated with lymph node metastasis and advanced clinical stage and predicted poor prognosis in patients with ccRCC. Gene set enrichment analysis (GSEA) was performed using RNA-sequencing data from The Cancer Genome Atlas Research Network (TCGA) to elucidate the biological role of MICA in ccRCC and revealed that MICA was significantly associated with the epithelial-to-mesenchymal transition (EMT) gene set, which was further confirmed by qRT-PCR. Our findings contribute to the studies on biomarkers of kidney cancers and the mechanism of renal cancer progression driven by EMT pathway.

Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma.

Eg5 is critical for mitosis and overexpressed in various malignant tumors, which has now been identified as a promising target in cancer therapy. However, the anti-cancer activity of Eg5 inhibitor in renal cell carcinoma (RCC) remains an open issue. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking Eg5 by S-(methoxytrityl)-L-cysteine (S(MeO)TLC) in RCC both in vitro and vivo. The expression of Eg5 was examined in clinical tissue samples and various kidney cell lines, including 293T, 786-0, and OS-RC-2. The anti-proliferative activity of Eg5 inhibitors, (S)-trityl-L-cysteine (STLC) and S(MeO)TLC, was evaluated by a cell viability assay. An apoptosis assay with Hoechst nuclear staining and flow cytometry was applied to investigate the efficacy of the S(MeO)TLC, which is more potent than STLC. Immunofluorescence was used to research the possible mechanism. Furthermore, in vivo studies were performed by using subcutaneous xenograft models, which were used to confirm its role as a potential anti-neoplastic drug. The Eg5 expression was detected in kidney cell lines and RCC tissues, which was low in normal kidney samples. STLC and S(MeO)TLC exhibited their optimal anti-proliferative activity in 72 h, and cells treated with S(MeO)TLC presented characteristic monoastral spindle phenotype in 24 h and apoptotic cells in 48 h. In vivo, S(MeO)TLC effectively suppressed tumor growth in subcutaneous xenograft models. Inhibition of Eg5 represses the proliferation of RCC in vitro and in vivo. All these findings collectively demonstrate that S(MeO)TLC, a potent Eg5 inhibitor, is a promising anti-cancer agent for the treatment of RCC.

The effect of gemcitabine/paclitaxel chemotherapy on the survival of patients with metastatic urothelial cancers.

BACKGROUND: To evaluate the survival benefit of gemcitabine and paclitaxel (GT) chemotherapy for patients with metastatic urothelial cancer (UC), a retrospective analysis was performed to compare the overall survival in two periods: before (group I) and after (group II) the introduction of GT chemotherapy. PATIENTS AND METHODS: Eighty-five patients with metastatic UC were treated with MEC/MVAC (methotrexate, epirubicin, and cisplatin / methotrexate, vinblastine, doxorubicin, and cisplatin) or GT between 1995 and 2007. The response rate, maintenance rate, maintenance duration of each regimen, and the survival times of responding patients in each group were evaluated retrospectively. RESULTS: The median survival of patients in group ΙI (20 months) was significantly longer than that for group I (13 months) (p = 0.03). Especially in patients with a favorable response (CR/PR) to induction chemotherapy, the median survival period was significantly different between group Ι and group II (median 15 and 28 months, respectively; p = 0.02). The rate of the shift to maintenance chemotherapy when using GT chemotherapy was significantly higher than with MEC/MVAC chemotherapy alone (p < 0.05), and the cessation rate due to adverse effects was significantly lower when using GT chemotherapy (26.1%) than MEC/MVAC in group Ι (42.1%). CONCLUSION: Our results demonstrated that the administration of GT chemotherapy may be useful to improve the survival of patients with metastatic UC. This effect was significant, especially among those who were sensitive to the induction course of first-line chemotherapy. The excellent tolerability of GT regimens mean that they may be suitable for maintenance chemotherapy.

Overexpression of Eg5 predicts unfavorable prognosis in non-muscle invasive bladder urothelial carcinoma.

OBJECTIVE: To investigate the relationship between Eg5 expression and prognosis of patients with non-muscle invasive bladder urothelial carcinoma. METHODS: Eg5 expression was examined by immunohistochemistry in non-muscle invasive urothelial carcinoma specimens (grade: G1, 32 cases; G2, 92 cases; and G3, 39 cases. Stage: pTa, 49 cases and pT1, 114 cases). The correlation between clinicopathological characteristics and Eg5 expression was evaluated. The prognostic significance of Eg5 immunoreactivity was analyzed through survival analysis in 163 non-muscle invasive cases that were treated with transurethral resection and adjuvant intravesical instillations. RESULTS: The expression of Eg5 was significantly associated with tumor grade (P = 0.006), with a trend towards significant association with stage (P = 0.057). The 163 patients with non-muscle invasive tumors were regularly followed with the mean of 32.52 (from 6 to 72) months. Univariate analysis showed Eg5 overexpression exhibited a significant unfavorable influence on intravesical recurrence (P = 0.012) while having only a marginal correlation with disease progression (P = 0.070). Subsequent Cox hazard multivariate analysis showed that both grade (P = 0.045) and Eg5 expression (P = 0.029) were independent predictors for early intravesical recurrence. CONCLUSIONS: Overexpression of Eg5 correlates with poor differentiation of bladder cancer, and it represents an independent prognostic factor in predicting early intravesical recurrence in non-muscle invasive bladder carcinoma patients.

A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor.

Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of S-(methoxytrityl)-L-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(MeO)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P<0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer.