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BACKGROUND: Trastuzumab is a generally safe agent prescribed in the systemic treatment of breast cancer. Tinnitus is not a currently known adverse event related to trastuzumab. Here, we describe a rare case of severe tinnitus and a migraine headache induced by trastuzumab used for adjuvant therapy. CASE SUMMARY: A 37-year-old woman was diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer. After surgery, she was treated with four cycles of epirubicin and cyclophosphamide; she then received docetaxel and a loading dose of trastuzumab plus pertuzumab. Less than half an hour after trastuzumab infusion, the patient complained of severe tinnitus and left-sided migraine headache. Trastuzumab monotherapy was discontinued immediately, and symptoms disappeared after 10 min. Trastuzumab was readministered, and severe tinnitus and migraine headache recurred. Trastuzumab was stopped, and severe tinnitus diminished after 10 min. Pertuzumab and docetaxel therapy was then administered, and no adverse events were observed. Subsequent infusions of trastuzumab every three weeks did not show the same symptoms. CONCLUSION: Although trastuzumab is well-tolerated in most patients, we should pay attention to the risk of severe tinnitus and migraine.
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Coconut pericarp (shell fiber (mesocarp) and shell (endocarp)), the main by-product of coconut production, is often discarded and causing serious environmental pollution. To make better use of coconut pericarp, the extraction process of polyphenols from coconut mesocarp (CM) carefully studied by screening seven solvent systems, optimizing the assisted ultrasonic process by response surface methodology, and comparing the four processes of Ultrasound-Assisted Extraction (UAE), Homogenization-Assisted Extraction (HAE), Homogenization-Ultrasound-Assisted Extraction (HUAE), and Ultrasound-Homogenization-Assisted Extraction (UHAE). The UAE and HAE are considered to be the main methods for efficient extraction of natural active ingredients. The former effectively destroys the cell wall structure and promotes the intermolecular diffusion based on the cavitation, thermal and mechanical effect of ultrasonic, while the latter breaks the material based on strong shear force between the rotor and stator. Their combinations (HUAE and UHAE) enhance the damage to the cell wall of raw materials and improve the extraction efficiency by the synergistic effect. The results showed that using 60% acetone (V : V) as extraction solvent, solid-liquid ratio of 1:5 g mL-1, ultrasonic temperature of 80 â, ultrasonic time of 80 min, ultrasonic power of 225 W, and then homogenizing at 10,000 rpm for 10 min, the total flavonoid content of CM reached the maximum value of 551.99 ± 12.69 mg Rutin g-1 dry weight (dw), while the total phenolic content reached the maximum value of 289.48 ± 4.41 mg GAE g-1 dw at 10,000 rpm for 5 min, which may be related to the oxidative degradation of polyphenols caused by the increase of polyphenol oxidase with the extension of homogenization time. This study provides a technical guarantee for the further utilization of phenolic substances in CM.
Subject(s)
Cocos , Phenols , Plant Extracts , Polyphenols , Solvents , UltrasonicsABSTRACT
BACKGROUND: Accumulating evidences indicate significant alterations in the aerobic glycolysis in clear cell renal cell carcinoma (ccRCC). We aim to develop and validate a glycolysis-related genes signature for predicting the clinical outcomes of patients with ccRCC. METHODS: mRNA expression profiling of ccRCC was obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. The protein expression levels of the core genes were obtained from the Human Protein Atlas database. We used four external independent data sets to verify the predictive power of the model for prognosis, tyrosine kinase inhibitor (TKI) therapy, and immunotherapy responses, respectively. Finally, we explored the potential mechanism of this signature through gene set enrichment analysis (GSEA). RESULTS: Through the GSEA, glycolysis-related gene sets were significantly different between ccRCC tissues and normal tissues. Next, we identified and constructed a seven-mRNA signature (GALM, TGFA, RBCK1, CD44, HK3, KIF20A, and IDUA), which was significantly correlated with worse survival outcome and was an independent prognostic indicator for ccRCC patients. Furthermore, the expression levels of hub genes were validated based on the Human Protein Atlas databases. More importantly, the model can predict patients' response to TKI therapy and immunotherapy. These findings were successfully validated in the external independent ccRCC cohorts. The mechanism exploration showed that the model may influence the prognosis by influencing tumor proliferation, base mismatch repair system and immune status of patients. CONCLUSIONS: Our study has built up a robust glycolysis-based molecular signature that predicts the prognosis and TKI therapy and immunotherapy responses of patients with ccRCC with high accuracy, which might provide important guidance for clinical assessment. Also, clinical investigations in large ccRCC cohorts are greatly needed to validate our findings.
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Background Multiparametric MRI is used for depiction of prostate cancer (PCa) but without consideration of the mechanical alteration of prostatic tissue by cancer. Purpose To investigate the diagnostic performance of stiffness and fluidity quantified with tomoelastography, a multifrequency MR elastography technique, for depiction of PCa compared with multiparametric MRI with Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. Materials and Methods Prospective participants suspected to have PCa and healthy controls (HCs) underwent multiparametric MRI and tomoelastography between March 2019 and July 2020. Tomoelastography maps of shear-wave speed (c) and loss angle (φ) quantified stiffness and fluidity, respectively, for PCa and benign prostatic disease and for the peripheral and transition zones in HCs. Differences between entities and regions were analyzed by using analysis of variance or Kruskal-Wallis test. Diagnostic performance was assessed with area under the receiver operating characteristic curve (AUC) analysis. Results There were 73 participants with PCa (mean age, 72 years ± 7 [standard deviation]), 82 with benign prostatic disease (66 years ± 7), and 53 HCs (41 years ± 14). Mean ± standard deviation of c and φ were higher in PCa (3.4 m/sec ± 0.6 and 1.3 radian ± 0.2, respectively) than in benign prostatic disease (2.6 m/sec ± 0.3 and 1.0 radian ± 0.2, respectively; P < .001) and age-matched HCs (2.2 m/sec ± 0.1 and 0.8 radian ± 0.1, respectively; P < .001). Incorporating c and φ (AUC, 0.95; 95% CI: 0.92, 0.98) improved the diagnostic performance of PI-RADS version 2.1 (AUC, 0.85; 95% CI: 0.80, 0.91; P < .001). Multiparametric MRI combined with c and φ enabled detection of PCa with 95% (78 of 82 non-PCa) specificity, which was significantly higher than with use of multiparametric MRI alone (77% [63 of 82 non-PCa]; P < .001). In regional analysis, c combined with φ enabled differentiation of transition zone PCa from benign prostatic hyperplasia (AUC, 0.91; 95% CI: 0.83, 0.98) and peripheral zone PCa from chronic prostatitis (AUC, 0.94; 95% CI: 0.88, 1.00). Conclusion Use of tomoelastography-quantified stiffness and fluidity improved the diagnostic performance of multiparametric MRI with Prostate Imaging Reporting and Data System version 2.1 in detecting cancer in both the peripheral and transition zones. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Hectors and Lewis in this issue. An earlier incorrect version of this article appeared online. This article was corrected on March 24, 2021.
Subject(s)
Elasticity Imaging Techniques/methods , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms/diagnostic imaging , Adult , Aged , Case-Control Studies , Humans , Male , Middle Aged , Prospective Studies , Prostatic Neoplasms/pathologyABSTRACT
Background: As a transcription factor, Zinc finger protein ZIC2 can interact with various DNAs and proteins. Current studies have shown that ZIC2 plays an oncogene role in various cancers. In this study, we systematically characterize the prevalence and predictive value of ZIC2 expression across multiple cancer types. Methods: We mined several public databases, including Oncomine, the Cancer Genome Atlas (TCGA), cBioPortal, Kaplan-Meier Plotter and PrognoScan to evaluated the differentially expressed ZIC2 between tumor samples and normal control samples in pan-cancner, and then explored the association between ZIC2 expression and patient survival, prognosis and clinicopathologic stage. We also analyzed the relationship between tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, tumor- and immune-related genes and ZIC2 expression. Finally, we explored the potential signaling pathway mechanism through gene set enrichment analysis (GSEA). Results: ZIC2 expression was higher in most cancer tissues compared with adjacent normal tissues. High ZIC2 expression was associated with worse prognosis and a higher clinicopathologic stage. ZIC2 expression was strongly associated with the TMB, MSI, tumor microenvironment and tumor- and immune-related genes. The GSEA revealed that multiple tumor- and immune-related pathways were differentially enriched in ZIC2 high or low expression phenotype. Conclusion: ZIC2 expression may be a potential prognostic molecular biomarker of poor survival in pan-cancer and may act as an oncogene with a strong effect in the processes of tumorigenesis and progression.
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PURPOSE: To explore the possibility of intraoperative transrectal ultrasound (TRUS)-based dose verification in transperineal brachytherapy (BT) with iodine-125 (125I) seeds for prostate cancer. MATERIAL AND METHODS: Fifteen patients with prostate cancer were treated using BT with 125I seeds. Post-implant TRUS and computed tomography (CT) images were imported into treatment planning system (TPS) for dosimetry. Dosimetry parameters, including minimum dose received by 90% of the volume (D90), percentage of the volume receiving 100% of prescribed dose (V100), and percentage of the volume receiving 200% of prescribed dose (V200) were calculated based on TRUS and CT images, separately. The D90 value of TRUS-based dosimetry was transformed to its expected value. Comparisons of the dosimetric parameters between post-operative verification and preoperative plans were made by paired t-test. One-way ANOVA model was used to assess the differences in preoperative plans. Agreements were evaluated between the preoperative planning and post-operative actual dose parameters using Bland-Altman analysis. RESULTS: In total, 825 of 125I seeds were implanted successfully in 15 patients. In TRUS-based dosimetry, 674 seeds (81%) were identified clearly in TRUS-based images, and the expected value of D90 parameter showed no significant differences compared with the preoperative planning and CT post-operation results (p > 0.05). In CT-based dosimetry, 810 seeds (98%) were identified clearly in CT-based images, and there was good consistency of D90, V100, and V200 values (p > 0.05). Post-implant CT-based dosimetry indicated that 125I seed implantation had fulfilled the expected plan. CONCLUSIONS: Intraoperative TRUS can be used for dosimetric verification of BT for prostate cancer.
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In this study, we performed bioinformatics analysis to identify the competing endogenous RNAs (ceRNAs) that regulate bladder cancer (BCa) progression. RNA-sequencing data analysis identified 2451 differentially expressed mRNAs, 174 differentially expressed lncRNAs, and 186 microRNAs (miRNAs) in BCa tissues (n=414) compared to the normal urothelial tissues (n=19) from the TGCA database. CeRNA network analysis of the differentially expressed lncRNAs and mRNAs showed strong positive correlation between lncRNA MAGI2-AS3 and Tensin 1 (TNS1) mRNA in BCa tissues. Bioinformatics analysis also showed that both MAGI2-AS3 and TNS1 mRNA sequences contain miR-31-5p binding sites. Furthermore, we observed significantly lower MAGI2-AS3 and TNS1 mRNA expression and higher miR-31-5p expression in the BCa tissues and cell lines (T24 and J82) compared with their corresponding controls. Functional and biochemical experiments in BCa cell lines including luciferase reporter assays showed that MAGI2-AS3 upregulated TNS1 by sponging miR-31-5p. Transwell assays showed that the MAGI2-AS3/miR-31-5p/TNS1 axis regulated migration and invasion ability of BCa cell lines. Moreover, immunohistochemical staining of paired BCa and normal urothelial tissues showed that low expression of TNS1 correlated with advanced tumor (T) stages and lymph node metastasis in BCa. In conclusion, our study demonstrates that the MAGI2-AS3/miR-31-5p/TNS1 axis regulates BCa progression.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Gene Expression Regulation, Neoplastic/genetics , Guanylate Kinases/genetics , MicroRNAs/genetics , Tensins/genetics , Urinary Bladder Neoplasms/pathology , Adult , Aged , Computational Biology/methods , Disease Progression , Female , Humans , Male , Middle Aged , RNA, Long Noncoding , Tensins/biosynthesis , Urinary Bladder Neoplasms/geneticsABSTRACT
To evaluate whether the addition of biomarkers to traditional clinicopathological parameters may help to increase the accurate prediction of prostate re-biopsy outcome. A training cohort with 98 patients and a validation cohort with 72 patients were retrospectively recruited into our study. Immunohistochemical analysis was used to evaluate the immunoreactivity of a group of biomarkers in the initial negative biopsy normal-looking tissues of the training and validation cohorts. p-STAT3, Mcm2, and/or MSR1 were selected out of 10 biomarkers to construct a biomarker index for predicting cancer and high-grade prostate cancer (HGPCa) in the training cohort based on the stepwise logistic regression analysis; these biomarkers were then validated in the validation cohort. In the training cohort study, we found that the biomarker index was independently associated with the re-biopsy outcomes of cancer and HGPCa. Moreover supplementing the biomarker index with traditional clinical-pathological parameters can improve the area under the receiver operating characteristic curve of the model from 0.722 to 0.842 and from 0.735 to 0.842, respectively, for predicting cancer and HGPCa at re-biopsy. In the decision-making analysis, we found the model supplemented with the biomarker index can improve patients' net benefit. The application of the model to clinical practice, at a 10% risk threshold, would reduce the number of biopsies by 34.7% while delaying the diagnosis of 7.8% cancers and would reduce the number of biopsies by 73.5% while delaying the diagnosis of 17.8% HGPCas. Taken together, supplementing the biomarker index with clinicopathological parameters may help urologists in re-biopsy decision-making processes.
Subject(s)
Biomarkers, Tumor , Biomarkers , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/diagnosis , Aged , Biopsy , Clinical Decision-Making , Decision Trees , Disease Management , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Prostatic Neoplasms/etiology , Prostatic Neoplasms/therapy , ROC Curve , Reproducibility of ResultsABSTRACT
BACKGROUND: The enhanced recovery after surgery (ERAS) and fast track surgery (FTS) protocols have been applied to a variety of surgeries and have been proven to reduce complications, accelerate rehabilitation, and reduce medical costs. However, the effectiveness of these protocols in minimally invasive radical prostatectomy (miRP) is still unclear. Thus, this study aimed to evaluate the impact of ERAS and FTS protocols in miRP. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases to collect randomized and observational studies comparing ERAS/FTS versus conventional care in miRP up to July 1, 2019. After screening for inclusion, data extraction, and quality assessment by two independent reviewers, the meta-analysis was performed with the RevMan 5.3 and STATA 15.1 software. Results were expressed as risk ratio (RR) and weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: In total, 11 studies involving 1,207 patients were included. Pooled data showed that ERAS/FTS was associated with a significant reduction in length of stay (LOS) (WMD: -2.41 days, 95% CI: -4.00 to -0.82 days, P=0.003), time to first anus exhaust (WMD: -0.74 days, 95% CI: -1.14 to -0.34 days, P=0.0003), and lower incidence of postoperative complications (RR: 0.70, 95% CI: 0.53 to 0.92, P=0.01). No significant differences were found between groups for operation time, estimated blood loss, postoperative pain, blood transfusion rate, and readmission rate (P>0.01). CONCLUSIONS: Our meta-analysis suggests that the ERAS/FTS protocol is safe and effective in miRP. However, more extensive, long-term, prospective, multicenter follow-up studies, and randomized controlled trials (RCTs) are required to validate our findings.
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BACKGROUND: A high prevalence of osteoblastic bone metastases is characteristic of prostate cancer. Prostate-specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serological marker for prostate cancer. However, whether PSA modulates the osteogenic process remains largely unknown. In this study, we explored the effect of PSA on modulating the osteoblastic differentiation of mesenchymal stem cells (MSCs). In this study, we used flow cytometry, CCK-8 assay, Alizarin red S (ARS) staining and quantification, alkaline phosphatase (ALP) activity and staining, Western blotting, and quantitative real-time PCR (qRT-PCR) to explore the effect of PSA on osteogenic differentiation of MSCs. RESULTS: We first demonstrated that although PSA did not affect the proliferation, morphology, or phenotype of MSCs, it significantly promoted the osteogenic differentiation of MSCs in a concentration-dependent manner. Furthermore, we demonstrated that PSA promoted the osteogenic differentiation of MSCs by elevating the expression of Cadherin 11 in MSCs and, thus, activating the Akt signaling pathway. CONCLUSIONS: In conclusion, we demonstrated that PSA could promote the osteogenesis of MSCs through Akt signaling pathway activation by elevating the expression of cadherin-11 in MSCs. These findings imply a possible role of PSA in osteoblastic bone metastases in prostate cancer.
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BACKGROUND: To determine the efficacy and safety of a periprostatic nerve block combined with perineum subcutaneous anaesthesia and intrarectal lidocaine gel for transrectal ultrasound-guided transperineal prostate biopsy (TPBx) through a prospective randomised controlled trial. METHODS: In total, 216 patients from May 2018 to November 2018 were randomly assigned to the experimental group and the control group at a ratio of 1:1. The experimental group received a periprostatic nerve block combined with subcutaneous perineal anaesthesia and intrarectal lidocaine gel. The control group received total intravenous anaesthesia. A visual analogue scale (VAS) score (0-10) was used to evaluate pain at different stages. The operative time, duration of hospitalisation, intraoperative vital signs, perioperative complications and clinicopathological features were recorded. RESULTS: The overall detection rate of prostate cancer was 40.74%, and the median Gleason score was 8 for all patients diagnosed with prostate cancer. No significant differences in terms of detection rates, Gleason scores and ISUP/WHO Grade Groups were found between the two groups (P > 0.05). The experimental group had no pain or just met the criteria for mild pain during the biopsy, which was significantly alleviated after the biopsy, and had a shorter operation time compared with that of the control group (P < 0.05). Compared with the control group, the experimental group had more stable haemodynamics and respiratory status and fewer surgical complications (P < 0.05). CONCLUSIONS: In multiple aspects, a periprostatic nerve block combined with subcutaneous perineal anaesthesia and intrarectal lidocaine gel is a safer and more efficient approach to local anaesthesia for TPBx that can almost replace total intravenous anaesthesia and is worthwhile applying in the clinical setting.
Subject(s)
Anesthesia, Local , Autonomic Nerve Block , Image-Guided Biopsy/methods , Prostatic Neoplasms/diagnosis , Ultrasound, High-Intensity Focused, Transrectal , Anesthesia, Local/adverse effects , Anesthesia, Local/methods , Autonomic Nerve Block/adverse effects , Autonomic Nerve Block/methods , Disease Management , Humans , Length of Stay , Male , Operative Time , Pain/diagnosis , Pain/etiology , Pain Management , Postoperative Complications , Ultrasound, High-Intensity Focused, Transrectal/methodsABSTRACT
While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERß in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERß expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERß signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERß/Bcl-2 signalling by either an shRNA targeting ERß or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERß/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance.
Subject(s)
Drug Resistance, Neoplasm , Estrogen Receptor beta/metabolism , Insulin-Like Growth Factor I/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Urinary Bladder Neoplasms/pathology , Animals , Apoptosis/drug effects , Cancer-Associated Fibroblasts/cytology , Cancer-Associated Fibroblasts/metabolism , Cell Line , Cisplatin/pharmacology , Cisplatin/therapeutic use , Estrogen Receptor beta/antagonists & inhibitors , Estrogen Receptor beta/genetics , Female , Humans , Insulin-Like Growth Factor I/immunology , JNK Mitogen-Activated Protein Kinases/metabolism , Kaplan-Meier Estimate , Mice , Mice, Nude , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction/drug effects , Urinary Bladder/cytology , Urinary Bladder/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/mortalityABSTRACT
BACKGROUND: Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and is involved in various microtubule-dependent processes. We previously showed that CLASP2 is involved in the epithelial-to-mesenchymal transition of bladder urothelial cancer. This research aimed to explore the significance of CLASP2 expression as a prognostic marker for muscle-invasive bladder urothelial cancer (MIBC) patients after radical cystectomy-pelvic lymph node dissection (RC-PLND). METHODS: CLASP2 expression was analyzed in 76 benign bladder tissues and 160 MIBC tissues by tissue immunohistochemistry. Survival analysis and multiple regression analysis following propensity score matching were performed to investigate the correlation between high CLASP2 expression and MIBC patients' survival. RESULTS: CLASP2 expression was increased in MIBC patients, especially those with high-stage tumors or lymph node metastasis. In the follow-up of MIBC patients after propensity score matching, whether MIBC patients received adjuvant chemotherapy after RC-PLND, high CLASP2 expression was significantly associated with a poor prognosis. MIBC patients with low CLASP2 expression who received adjuvant chemotherapy tended to have an improved survival prognosis. CONCLUSION: CLASP2 expression is correlated with malignant progression of MIBC. High CLASP2 expression predicted a poor prognosis for MIBC patients after RC-PLND.
Subject(s)
Microtubule-Associated Proteins/biosynthesis , Urinary Bladder Neoplasms/metabolism , Aged , Female , Humans , Male , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Middle Aged , Prognosis , Propensity Score , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Prostate cancer (PCa) is a prevalent and deadly cancer worldwide. Considering the malignant progression and therapeutic resistance of PCa, further dissection of the underlying mechanisms and exploration of novel therapeutic targets for PCa are urgently needed. The long noncoding RNA HOTTIP has recently been revealed as an oncogenic regulator in different cancers; however, whether HOTTIP is involved in PCa remains poorly understood. Here, we examined the crucial roles of HOTTIP in the proliferation and chemoresistance of PCa. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the HOTTIP messenger RNA (mRNA) levels in PCa samples from patients and PCa cells. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell cycle and flow cytometry assays were performed to investigate the proliferation and cisplatin-resistance of PCa cells with silenced HOTTIP compared with a negative control. We applied Western blotting, qRT-PCR and a TOP/FOP assay to explore the relevant mechanisms. RESULTS: In this study, we found that the HOTTIP mRNA levels were increased in the PCa patient samples and PCa cell lines compared with the controls. The knockdown of HOTTIP not only inhibited the proliferation of PCa cells but also facilitated cell cycle arrest and chemosensitivity to cisplatin. Furthermore, the qRT-PCR, Western blotting, TOP/FOP assays, MTT assay, and flow cytometry revealed that Wnt/ß-catenin signaling was related to the regulation of HOTTIP in cell proliferation, cell cycle arrest, and chemoresistance to cisplatin in PCa. CONCLUSION: Taken together, our findings suggest that HOTTIP may be a potent therapeutic target for PCa, and HOTTIP inhibitors might be regarded as effective strategies for PCa therapy.
Subject(s)
Cisplatin/pharmacology , Drug Resistance, Neoplasm , Prostatic Neoplasms/genetics , RNA, Long Noncoding/genetics , Wnt Signaling Pathway/drug effects , Case-Control Studies , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Male , PC-3 Cells , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Up-RegulationABSTRACT
PURPOSE: PB is one of the most severe complications of late stage prostate cancer and negatively impacts patient quality of life. A major challenge for the treatment of cancer bone metastasis is the management of efficient drug delivery to metastatic bone lesion. We aimed to explore the use of aptamers as promising tools to develop a targeted drug delivery system for PBs. MATERIALS AND METHODS: In vivo SELEX was applied to identify bone targeting aptamer in a mouse model with PBs. RESULTS: The aptamer (designated as "PB") with the highest bone targeting frequency in mice bearing PC3 PB was selected for further analysis. The PB aptamer specifically targeted modulated endothelial cells in response to cancer cells in the bones of mice bearing PC3 PBs. The targeting efficiency of the PB aptamer conjugated to gold particles was verified in vivo. CONCLUSION: This investigation highlights the promise of in vivo SELEX for the discovery of bone targeting aptamers for use in drug delivery.
Subject(s)
Aptamers, Nucleotide/metabolism , Bone Neoplasms/secondary , Prostatic Neoplasms/pathology , SELEX Aptamer Technique/methods , Animals , Bone Marrow/pathology , Cell Line, Tumor , Disease Models, Animal , Drug Delivery Systems , Endocytosis , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Lysosomes/metabolism , Male , Mice, NudeABSTRACT
BACKGROUND: To compare the efficacy of patients undergoing esophagectomy for cancer in video-assisted thoracoscopic surgery (VATS) versus traditional open surgery (TOS) in the perioperative period, along with the advantages and disadvantages of each. METHODS: A retrospective analysis of 108 patients, who underwent esophagectomy between September 2011 and February 2012 in our department, was performed. Patients were divided into two groups based on operative technique (VATS vs. TOS), with 50 patients in the VATS group and 58 patients in the TOS group. Operative duration, intraoperative blood loss, intraoperative blood transfusion, number of lymph nodes harvested, postoperative pain score, period of time requiring chest tube drainage, complications, hospital stay, and hospital costs, were all statistically analyzed between the two groups. RESULTS: There was no statistical difference between the two groups with regard to operative duration or number of lymph nodes harvested. The VATS group had significantly less intraoperative blood loss, intraoperative blood transfusion, postoperative pain, earlier ambulation, shorter postoperative hospital stay, and a shorter period of time requiring chest tube drainage. The amount of drainage was significantly lower in the TOS group (P < 0.05). Pulmonary complication (pneumonia and pleural effusion) was less prevalent among the VATS group. CONCLUSION: Compared with TOS, VATS-assisted esophagectomy is less traumatic with lower intraoperative blood loss, faster recovery, and a better overall outcome.