RESUMO

Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.

RESUMO

BACKGROUND: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. METHODS: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. RESULTS: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. CONCLUSION: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival.

Assuntos

RESUMO

BACKGROUND: Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes. OBJECTIVE: We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie's disease. MATERIAL/METHODS: The study was designed in two phases. To establish an optimal Peyronie's disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages. RESULTS: The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie's disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor ß1 genes and proteins (p > 0.05) in the Peyronie's disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor ß1 genes and proteins (p < 0.05). DISCUSSION: The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor ß1. This study reveals the therapeutic potential for Peyronie's disease involving molecular targets. CONCLUSION: MicroRNA-29b application on the rat's tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie's disease management.

RESUMO

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology.

RESUMO

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.

Assuntos

RESUMO

Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.

RESUMO

ABSTRACT Introduction: The En-bloc Resection of Bladder Tumors (ERBT) is a method that offers more benefits compared to the traditional Transurethral Resection of Bladder Tumor (TURBT) (1, 2). Recent studies have shown that ERBT offers better pathological analysis and oncological outcomes (3-6). Thulium and holmium are the most frequently used lasers for this procedure, with the hybrid laser being a new addition that combines thulium and diode to improve hemostatic properties (5, 7-9). Objective: This report aims to discuss the use of two types of lasers, hybrid and holmium, for ERBT. Material and Methods: Two case studies were conducted. The first case featured a 68-year-old male with two tumors measuring 1.5cm and 2cm. The hybrid laser was used for the procedure. The second case involved a 70-year-old female with a 5cm tumor on the posterior bladder wall, and holmium laser was used with morcellation of the tumor. The quality of histopathological analysis was evaluated. The perioperative data and the entire procedure of the two cases were documented in a step-by-step video. Results: Both lasers demonstrated excellent results without technical difficulties. There was no bleeding, and both patients were discharged with one day of hospitalization. The detrusor muscle was present without artifacts, and the morcellation did not affect the analysis. The first case showed a pT1G3, and the second case showed a pT2 urothelial carcinoma. The hybrid laser exhibited superior hemostatic capacity compared to the holmium laser. Conclusion: ERBT can use hybrid or holmium lasers without affecting histopathological analysis, even with morcellation.

RESUMO

Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.

Assuntos

RESUMO

Oncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.

RESUMO

INTRODUCTION: The En-bloc Resection of Bladder Tumors (ERBT) is a method that offers more benefits compared to the traditional Transurethral Resection of Bladder Tumor (TURBT) (1, 2). Recent studies have shown that ERBT offers better pathological analysis and oncological outcomes (3-6). Thulium and holmium are the most frequently used lasers for this procedure, with the hybrid laser being a new addition that combines thulium and diode to improve hemostatic properties (5, 7-9). OBJECTIVE: This report aims to discuss the use of two types of lasers, hybrid and holmium, for ERBT. MATERIAL AND METHODS: Two case studies were conducted. The first case featured a 68-year-old male with two tumors measuring 1.5cm and 2cm. The hybrid laser was used for the procedure. The second case involved a 70-year-old female with a 5cm tumor on the posterior bladder wall, and holmium laser was used with morcellation of the tumor. The quality of histopathological analysis was evaluated. The perioperative data and the entire procedure of the two cases were documented in a step-by-step video. RESULTS: Both lasers demonstrated excellent results without technical difficulties. There was no bleeding, and both patients were discharged with one day of hospitalization. The detrusor muscle was present without artifacts, and the morcellation did not affect the analysis. The first case showed a pT1G3, and the second case showed a pT2 urothelial carcinoma. The hybrid laser exhibited superior hemostatic capacity compared to the holmium laser. CONCLUSION: ERBT can use hybrid or holmium lasers without affecting histopathological analysis, even with morcellation.

Assuntos

RESUMO

BACKGROUND: Previously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia. METHODS AND RESULTS: In vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 µg/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation. CONCLUSION: Our results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.

Assuntos

RESUMO

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Assuntos

RESUMO

Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.

Assuntos

RESUMO

PURPOSE: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults. METHODS: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density. RESULTS: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively (p = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.032). CONCLUSIONS: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.

Assuntos

RESUMO

Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.

RESUMO

BACKGROUND: The Gleason grading system is an important clinical practice for diagnosing prostate cancer in pathology images. However, this analysis results in significant variability among pathologists, hence creating possible negative clinical impacts. Artificial intelligence methods can be an important support for the pathologist, improving Gleason grade classifications. Consequently, our purpose is to construct and evaluate the potential of a Convolutional Neural Network (CNN) to classify Gleason patterns. METHODS: The methodology included 6982 image patches with cancer, extracted from radical prostatectomy specimens previously analyzed by an expert uropathologist. A CNN was constructed to accurately classify the corresponding Gleason. The evaluation was carried out by computing the corresponding 3 classes confusion matrix; thus, calculating the percentage of precision, sensitivity, and specificity, as well as the overall accuracy. Additionally, k-fold three-way cross-validation was performed to enhance evaluation, allowing better interpretation and avoiding possible bias. RESULTS: The overall accuracy reached 98% for the training and validation stage, and 94% for the test phase. Considering the test samples, the true positive ratio between pathologist and computer method was 85%, 93%, and 96% for specific Gleason patterns. Finally, precision, sensitivity, and specificity reached values up to 97%. CONCLUSION: The CNN model presented and evaluated has shown high accuracy for specifically pattern neighbors and critical Gleason patterns. The outcomes are in line and complement others in the literature. The promising results surpassed current inter-pathologist congruence in classical reports, evidencing the potential of this novel technology in daily clinical aspects.

RESUMO

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.

Assuntos

RESUMO

INTRODUCTION: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. OBJECTIVE: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. METHODS: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. RESULTS: in mRNA, the Ki67 upregulation is associated with cancer tissue (p<0.0001) and worst disease-free survival (p=0.035). The protein upregulation is associated with increase of the ISUP score (p<0.0001), cancer stage (p=0.05), biochemical recurrence (p=0.0006) and metastasis (p<0.0001). We also show a positive correlation between Ki67 expression and ISUP score (r=0.5112, p<0.0001) and disease risk stratification (r=0.3388, p=0.0009). Ki67 expression is a factor independently associated with biochemical recurrence (p=0.002) and metastasis (p<0.0001). Finally, the patients with high Ki67expression shows better survival regarding biochemical recurrence (p=0.008) and metastasis (p=0.056). Patients with high Ki67 expression are 2.62 times more likely to develop biochemical recurrence (p=0.036). CONCLUSION: Ki67 upregulation is associated with prostate cancer aggressiveness.

Assuntos

RESUMO

Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.

RESUMO

METHODS: We present a series of three patients with large hepatocellular adenoma lesions showing a central location, for which the living donor liver transplantation strategy was used as a backup procedure. RESULTS: Hepatocellular adenoma was confirmed by biopsy in all patients. Surgical resection was indicated because of the patients' symptoms and lesion size and growth. All patients had a lesion that was central or in close contact with major vessels. The final decision to proceed with the resection was made intraoperatively. A live donor was prepared for all three patients. Two patients underwent portal vein embolization associated with extended hepatectomy, and a total hepatectomy plus liver transplantation with a living donor was performed in one patient. All patients had good postoperative outcomes. CONCLUSIONS: In the treatment of hepatocellular adenomas for which complex resections are necessary and resectability can only be confirmed intraoperatively, surgical safety can be improved through the use of a living donor backup. Center expertise with living donor liver transplantation is paramount for the success of this approach.