ABSTRACT
Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Female , Neoplasm Recurrence, Local/genetics , Middle Aged , Aged , Prognosis , Genomics/methods , Adult , Neoplasm Staging , Deep Learning , Disease-Free SurvivalABSTRACT
BACKGROUND: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence. METHODS: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). FINDINGS: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001). INTERPRETATION: Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Prognosis , Retrospective Studies , Biomarkers, Tumor , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Kidney Neoplasms/pathologyABSTRACT
BACKGROUND: For patients with prior intra-abdominal surgery or multiple arteries, the retroperitoneal robot-assisted partial nephrectomy (rRAPN) is a better choice. The renal ventral tumor poses an additional challenge due to poor tumor exposure. This study is determined to assess the feasibility of an internal traction technique (ITT) in rRAPN for the management of renal ventral tumors. METHODS: From November 2019 to March 2021, a total of 28 patients with renal ventral tumor underwent rRAPN. All patients had prior abdominal surgery or multiple arteries. The ITT group (20 patients), which improved the tumor exposure by traction of the kidney with suture, was compared with the traditional technique group (8 patients) in terms of warm ischemia time, estimated blood loss and postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine. Differences were considered significant when P < 0.05. RESULTS: All rRAPN surgeries were successful without conversion to radical nephrectomy or open partial nephrectomy. The warm ischemia time was lower in the ITT group (17.10 min vs. 24.63 min; P < 0.05). Estimated blood loss in the traditional technique group was 324.88 ± 79.42 mL, and in the ITT group, it was 117.45±35.25 mL (P < 0.05). No significant differences with regard to postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine were observed between both groups. Surgical margins were negative and no intraoperative complications occurred in all the patients. After 10 months of follow-up, no recurrence or metastasis occurred in all cases. CONCLUSION: ITT is a feasible, safe, and valid procedure in rRAPN for renal ventral tumors. Application of ITT improved the exposure and reduces warm ischemic time in comparison with the conventional procedure.
Subject(s)
Kidney Neoplasms , Laparoscopy , Robotic Surgical Procedures , Robotics , Creatinine , Humans , Kidney Neoplasms/pathology , Laparoscopy/methods , Nephrectomy/methods , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Traction , Treatment OutcomeABSTRACT
BACKGROUND: Cerebral venous sinus thrombosis (CVST), a rare cause of cerebral infarction, is often unrecognized at initial presentation. We report the case of a patient with bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia. CASE PRESENTATION: A 30-year-old female patient presented with headache, vomiting, and motor aphasia. She was 20 days post-partum and had a lower than normal food intake following a normal vaginal delivery. Brain magnetic resonance images revealed a bilateral corpus callosum and corona radiata infarction. MR venography (MRV) and digital subtraction angiography (DSA) images showed a signal void in the anterior aspect of the superior sagittal sinus and inferior sagittal sinus, ophthalmic vein expansion, and the reversed direction of venous flow. In addition, images showed non-visualization of the left transverse sinus. The left slender sigmoid sinus and small internal jugular vein were also noted. The diagnosis of cerebral venous thrombosis was considered based on the above findings. The patient was managed with anticoagulation therapy, and recovered substantially after treatment. CONCLUSIONS: Bilateral corpus callosum and corona radiata infarction is very rare. However, for patients who clinically show cranial hypertension and neurological deficits during the puerperium period, the possibility of CVST should be considered. Furthermore, DSA plays an important role in the diagnosis of CVST, and should be routinely checked. Early diagnosis is crucial for the patient suffering from CVST.
Subject(s)
Cerebral Infarction/etiology , Sinus Thrombosis, Intracranial/complications , Adult , Aphasia/etiology , Brain/pathology , Cerebral Infarction/pathology , Corpus Callosum/pathology , Female , Headache/etiology , Humans , Postpartum PeriodABSTRACT
BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906â600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.
Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Polymorphism, Single Nucleotide/genetics , Area Under Curve , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Female , Genome, Human/genetics , Genome-Wide Association Study , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Nomograms , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Risk FactorsABSTRACT
We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.
Subject(s)
Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Reperfusion Injury/drug therapy , Animals , Apoptosis/drug effects , Disease Models, Animal , Male , Medicine, Chinese Traditional , Mitochondria/drug effects , Mitophagy/drug effects , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
This study examined the course of mitophagy following cerebral ischemia with reperfusion and the role of the PTEN-induced kinase 1 (PINK1)/Parkin/p62 signalling pathway. The middle cerebral artery of male Sprague-Dawley rats was occluded for 90â¯min and was followed by different time-points of reperfusion. Cerebral infarct areas were detected by 2,3,5-triphenyl tetrazolium chloride staining, while brain damage was observed by haematoxylin and eosin staining. Levels of LC3, Beclin1 and LAMP-1 were estimated by western blots. LC3B location was observed in various cells in the neurovascular unit. In addition, PINK1 accumulation in damaged mitochondria and Parkin/p62 mitochondrial translocation were investigated by double immunofluorescence staining. Finally, the levels of PINK1, Parkin and p62 expression in mitochondrial fractions were estimated by western blots. Cerebral ischemia with different time-points of reperfusion resulted in infarct in the territory of the middle cerebral artery accompanied by overall brain damage. In addition, we found up-regulation of LC3B, Beclin1, and LAMP-1, as well as mitophagy activation after reperfusion, with peak expression of these proteins at 24â¯h after reperfusion. Electron microscopy and immunofluorescence indicated that LC3B was primarily located in neurons, although lower levels of expression were found in astrocytes and even less in vascular endothelial cells. Moreover, significant increases in PINK1 accumulation in the outer membrane of mitochondria and increased Parkin/p62 mitochondrial translocation were shown at 24â¯h after reperfusion. These ï¬ndings suggest that the PINK1/Parkin/p62 signalling pathway was involved in the pathophysiological processes following ischemia and reperfusion.
Subject(s)
Brain Ischemia/metabolism , Brain/metabolism , Mitophagy/physiology , Reperfusion Injury/metabolism , Animals , Astrocytes/metabolism , Astrocytes/pathology , Autophagy/physiology , Brain/pathology , Brain Ischemia/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Gene Expression , Male , Mitochondria/metabolism , Mitochondria/pathology , Neurons/metabolism , Neurons/pathology , Protein Kinases/metabolism , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Sequestosome-1 Protein/metabolism , Signal Transduction , Time Factors , Ubiquitin-Protein Ligases/metabolismABSTRACT
The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a suitable model for human prostate carcinoma. In this study, we sequenced its complete mitogenome and total length of the genome was 16,310 bp (GenBank Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into prostate adenocarcinoma disease.
Subject(s)
Adenocarcinoma/genetics , Genome, Mitochondrial , Prostatic Neoplasms/genetics , Animals , Base Sequence , Genes, Mitochondrial , Genetic Variation , Male , RNA, Transfer/genetics , RatsABSTRACT
OBJECTIVES: To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating T2 large renal cell carcinoma (RCC). METHODS: Retrospectively analyzed 5 cases (2 males and 3 females, aged 52-73 years) of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1-3 months) and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. RESULTS: During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome (Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD) and medium density (MD) of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. CONCLUSIONS: Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Neoadjuvant Therapy , Niacinamide/analogs & derivatives , Peritoneum/pathology , Peritoneum/surgery , Phenylurea Compounds/therapeutic use , Aged , Carcinoma, Renal Cell/diagnostic imaging , Female , Humans , Kidney Neoplasms/diagnostic imaging , Laparoscopy , Male , Middle Aged , Neoplasm Staging , Niacinamide/therapeutic use , Perioperative Care , Sorafenib , Tomography, X-Ray ComputedABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture attenuates neuronal damages following ischemia. AIM OF THE STUDY: The purpose of the present study was to investigate the beneficial effects of acupuncture on hypoxia-ischemia induced brain damages in neonatal rats. MATERIALS AND METHODS: Male postnatal 7 days rats were randomly divided into 3 groups: sham control (sham), hypoxia-ischemia (HI), and HI plus acupuncture treatment (HI+Acu). The rats in HI and HI+Acu groups were submitted to model of neonatal HI, established by occluding the left common carotid artery followed by a 3.5h period of hypoxia (8% O2-92% N2). At 24h after HI, animals were stimulated by acupuncture treatment once a day and the treatment continued during 4 weeks, 5days/week. Behavioral functions, learning and memory ability, and body weight were observed at different time-points after HI. DNA fragmentation assay were performed with TUNEL staining to evaluate apoptosis and expression levels of mitochondrial Bcl-2, mitochondrial Bax, Cleaved caspase 3, Cleaved caspase 9 in the damaged hippocampus were detected by western blotting 28 days following HI. GDNF, BDNF levels in hippocampus were also determined. RESULTS: The results showed that acupuncture significantly promoted growth and development, improved neurobehavioral function, learning and memory ability after 20 days' treatment. Furthermore, we obtained one interesting finding that acupuncture attenuated cellular apoptosis and up-regulated GDNF and BDNF levels in hippocampus. CONCLUSIONS: All of these results suggest that acupuncture as a potential treatment may exert neuroprotective effects via inhibiting cellular apoptosis, increased GDNF and BDNF expression levels in rat hippocampus experiencing HI.
Subject(s)
Acupuncture Therapy , Apoptosis , Brain-Derived Neurotrophic Factor/biosynthesis , CA1 Region, Hippocampal/metabolism , Glial Cell Line-Derived Neurotrophic Factor/biosynthesis , Hypoxia/metabolism , Hypoxia/therapy , Ischemia/metabolism , Ischemia/therapy , Animals , Animals, Newborn , Behavior, Animal , Body Weight , Brain/pathology , CA1 Region, Hippocampal/blood supply , Hypoxia/complications , Hypoxia/pathology , In Situ Nick-End Labeling , Ischemia/complications , Ischemia/pathology , Male , Rats , Up-RegulationABSTRACT
PURPOSE: Urolithiasis is a rare complication of renal transplantation, and there is limited evidence to guide treatment. Management of stones in the transplanted kidney can be challenging. We present our experience in treating upper urinary tract (UUT) allograft lithiasis using minimally invasive procedures, with the aim of demonstrating their efficacy and safety in renal transplant recipients. METHODS: The records of 1615 patients undergoing kidney transplantation and follow-up in our center between August 2000 and July 2014 were reviewed. The mode of presentation, donor type, onset time, immunosuppression protocol, stone character, therapeutic intervention and outcomes of those with UUT allograft lithiasis were recorded. Extracorporeal shock wave lithotripsy (SWL), flexible ureteroscopy (F-URS) and percutaneous nephrolithotomy (PCNL) were used in the management of these calculi. Stone composition was analyzed after the procedure. RESULTS: Nineteen renal transplant recipients (1.2 %, nine males and ten females) were found to have UUT allograft calculi. Of these, five underwent SWL (26.3 %), four had F-URS combined with lithotomy forceps extraction or holmium laser disruption (21.1 %), six had PNCL (31.6 %), one submitted to F-URS after two failed sessions of SWL (5.3 %), one combined PCNL and F-URS (5.3 %), and two spontaneously of stones (10.5 %). All patients were rendered stone-free with a combination of treatments, and none required a blood transfusion. CONCLUSIONS: The incidence of calculi in the transplanted kidney is low. Minimally invasive procedures are safe and effective means of removing allograft calculi.
Subject(s)
Kidney Transplantation/adverse effects , Lithotripsy , Nephrolithiasis/etiology , Nephrolithiasis/therapy , Nephrostomy, Percutaneous , Ureteroscopy , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Nephrolithiasis/diagnosis , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To analyze the safety and clinical outcome of laparoscopic nephroureterectomy (LNUT) for native upper tract urothelial carcinoma (UC) in renal transplant (RT) recipients. METHODS: We conducted a retrospective analysis of 956 RT recipients from January 2003 to December 2010 to evaluate the benefit of LNUT for patients who were diagnosed with de novo UC after renal transplantation. RESULTS: Women predominated (10/11, 91 %) in the 11 patients with upper tract UC who underwent LNUT. Five patients underwent LNUT ipsilateral to the transplanted kidney, 4 patients underwent contralateral LNUT, and 2 patients underwent bilateral LNUT. Nine were operated with LNUT combining resection of bladder cuff, 2 with right ureteral cancer underwent open ureterectomy with bladder cuff due to severe adhesions attached to the lesion. The mean surgical duration was 184.2 min (105-305), the mean blood loss was 182.3 ml (20-500), and the mean hospitalization time was 6.7 days (5-9). The mean levels of preoperative and postoperative serum creatinine were 0.99 mg/dl (0.78-1.16) and 1.01 mg/dl (0.89-1.18), respectively. No intraoperative complications occurred. One patient died of multiple metastases at 13 months after LNUT. The mean follow-up of the remaining 10 patients after diagnosis was 21.7 months (3-48). Two patients had recurrent bladder cancer and underwent transurethral resection of the tumor. Eight patients showed no evidence of disease during the follow-up. CONCLUSIONS: LNUT is a safe and effective approach with low morbidity in transplant recipients, and this therapy provides less trauma, quicker recovery, and acceptable oncological outcomes.
Subject(s)
Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Kidney Transplantation , Nephrectomy , Ureter/surgery , Ureteral Neoplasms/surgery , Aged , Female , Humans , Kidney Failure, Chronic/surgery , Kidney Pelvis , Laparoscopy , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments.
Subject(s)
Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , MicroRNAs/biosynthesis , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Gene Expression , Gene Expression Profiling/methods , Humans , Male , Prostatic Neoplasms/diagnosisABSTRACT
BACKGROUND: Some patients with exophytic renal masses less than 4 cm and suboptimal renal function, or a solitary kidney and bilateral renal tumors are considered for laparoscopic partial nephrectomy (LPN), which is feasible for early-stage renal tumors, although it is still considered technically difficult and time consuming. Shortening the time of the operation and renal warm ischemia are required urgently. In this study, we report our initial experiences of LPN, especially with some improved surgical techniques. METHODS: Between July 2005 and October 2009, 74 patients with T(1a) renal tumor were treated by LPN, 39 using transperitoneal approach and 35 using retroperitoneal approach. In all cases, the tumor was removed with a margin of 0.5 cm. We compared glomerular filtration rate (GFR) preoperatively and postoperatively, and renal warm ischemia time between traditional ligature and Hem-o-lok methods. RESULTS: All operations were completed successfully, and there was no conversion to open surgery. Mean operation time was 76 minutes (range, 68 - 120), mean time of renal warm ischemia was 23 minutes (range, 15 - 32), and mean blood loss was 65 ml (range, 40 - 300). No hemorrhage or urine leak was observed in two cases with the collecting system sewn. Thirteen cases used Hem-o-lok to clamp the suture instead of traditional ligature, and mean time of renal warm ischemia was (16.5 ± 2.3) minutes (range, 12 - 18). Mean postoperative hospital stay was 6.3 days (range, 5 - 12). Sixty-seven cases had renal clear cell carcinoma, six papillary renal cell carcinoma, and one renal collecting duct carcinoma. All the tumor margin specimens were negative. The mean follow-up was 30.6 months (range, 3 - 51), and no recurrence or metastasis was observed. CONCLUSIONS: LPN for pT(1) stage renal tumor was safe and feasible. Hem-o-lok instead of traditional ligature to clamp the suture when sewing the renal wound could shorten the warm ischemia time.
Subject(s)
Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Adult , Aged , Female , Humans , Laparoscopy/adverse effects , Male , Middle Aged , Nephrectomy/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: To investigate whether the retroperitoneal or transperitoneal approach is preferable for right-sided laparoscopic donor nephrectomy (R-LDN). MATERIAL/METHODS: We retrospectively compared the donor and recipient outcomes of R-LDNs performed with a standard transperitoneal approach (n=21) or a semi-open retroperitoneal approach (n=32). RESULTS: Patient demographics were similar between groups. The semi-open retroperitoneal group had shorter operative time (89.5 min vs. 105 min, p<0.001), shorter WIT (102 s vs. 120 s, p<0.001), and longer renal veins (2.5 cm vs. 2.2 cm, p<0.001). No conversions to open procedures occurred. There were no significant differences in the blood loss, length of hospital stay, or donor complication rate between the 2 groups. All grafts functioned adequately, and there were no significant differences in graft function, first-week hemodialysis, and serum creatinine level at discharge between the 2 groups The recipient complication rate was similar between the 2 groups (9.4% vs. 9.5%, p=0.986). CONCLUSIONS: The semi-open retroperitoneal approach is safe and effective for R-LDN. Further study is required to evaluate long-term graft function.
Subject(s)
Kidney Transplantation , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adult , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Living Donors , Male , Middle Aged , Nephrectomy/adverse effects , Peritoneum/surgery , Prognosis , Retrospective Studies , Time Factors , Tissue and Organ Harvesting/adverse effectsABSTRACT
OBJECTIVES: To investigate whether androgen receptor (AR) could serve as a potential molecular target for the treatment of bladder cancer. METHODS: Cell proliferation, apoptosis, and migration capacity were determined in human transitional carcinoma cell lines T24 and 253-J treated with small interfering RNA directed against AR, and expression levels of growth- and metastasis-related genes were assessed using quantitative reverse transcriptase-polymerase chain reaction. Tumor cell growth and apoptosis were also evaluated in vivo in T24 tumor-bearing nude mice receiving electroporation-assisted administration of anti-AR small interfering RNA. RESULTS: AR expression knockdown produced increased apoptosis, decreased proliferation, and migration of bladder cancer cells. Cyclin D1, Bcl-x(L), and matrix metallopeptidase-9 gene expression were also reduced with AR knockdown, which might have contributed to the altered biological behavior of cancer cells. In vivo experiments showed that silencing AR expression, by interference aided by electroporation, significantly suppressed AR-positive bladder tumor growth with decreased cell proliferation and increased apoptotic rates. CONCLUSIONS: Downregulation of AR expression inhibits bladder cancer cell growth in vitro and in vivo, implying that its use might be a potential therapeutic target for the treatment of bladder cancer.
Subject(s)
Carcinoma, Transitional Cell/drug therapy , Receptors, Androgen/drug effects , Urinary Bladder Neoplasms/drug therapy , Animals , Drug Delivery Systems , Humans , Mice , Mice, Nude , Tumor Cells, CulturedABSTRACT
BACKGROUND: Laparoscopic dismembered pyeloplasty is technically feasible for ureteropelvic junction (UPJ) obstruction although it is still challenged by its technical difficulty and time-consuming. In this study, we compared the initial results of retroperitoneal laparoscopic pyeloplasty versus a combined laparoscopic dissection and open reconstruction through a small incision in the treatment of UPJ obstruction. METHODS: Sixty-four patients with primary UPJ obstruction underwent pyeloplasty: 32 patients underwent laparoscopic procedure and 32 patients underwent open assisted laparoscopic surgery including two steps, ie, laparoscopic dissection of the UPJ transperitoneally and then pyeloplasty via an extended small incision. The demographic data and intraoperative, postoperative and follow-up conditions of patients were compared between the two groups. RESULTS: Preoperative data were comparable in the patients of the two groups. The operative time was shorter (60.9 minutes vs 157.7 minutes, P < 0.0001) and the complication rate was lower (9.4% vs 31.3%, P < 0.05) in the open assisted group than in the laparoscopic group. The estimated blood loss (42.3 ml vs 47.8 ml), time to have normal diet (37.6 hours vs 33.8 hours), and hospital stay (6.7 days vs 6.2 days) were equivalent. The operative success rate was 97% for the open assisted group and 91% for the laparoscopic group. CONCLUSIONS: The procedure of combined small incision with laparoscopy for UPJ obstruction is technically easy, and the results are promising. It can be used as an alternative to conventional procedures.
Subject(s)
Kidney Pelvis/surgery , Laparoscopy/methods , Ureteral Obstruction/surgery , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retroperitoneal Space , Urologic Surgical ProceduresABSTRACT
BACKGROUND: Prostate cancer is one of the most common urogenital tumors in the world with an increasing incidence in China. Androgen deprivation therapy is the major therapeutic option for advanced prostate cancer. However, the role of androgen receptor (AR) in hormone-refractory prostate cancer still remains unclear. This work aimed to investigate the role of AR in an androgen independent prostate cancer cell line by in vitro and in vivo studies. METHODS: The role of AR in the proliferation and invasion/metastasis ability of PC3-AR9 (a PC3 stable clone expressing human AR driven by natural human AR promoter) were examined with MTT assay, soft agar assay, chamber invasion assay, wound healing assay, and also with orthotopic xenograft mouse model. RESULTS: Restoring androgen receptor in PC3 cells resulted in decreased proliferation and invasion/metastasis ability in MTT, soft agar, chamber invasion and wound healing assay. In the mouse orthotopic xenograft model, PC3-AR9 resulted in smaller primary tumors and metastasis tumors, with a lower proliferation rate and higher apoptosis rate. CONCLUSION: The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo.
Subject(s)
Prostatic Neoplasms/prevention & control , Receptors, Androgen/physiology , Tumor Suppressor Proteins/physiology , Animals , Cell Line, Tumor , Humans , Male , Mice , Neoplasm Transplantation , Prostatic Neoplasms/pathology , Receptors, Androgen/analysis , Transplantation, HeterologousABSTRACT
OBJECTIVE: To report initial experience with laparoscopic radical cystectomy in 43 patients with invasive bladder carcinoma. METHODS: From December 2003 to October 2006, 29 men and 14 women underwent laparoscopic radical cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=40), adenocarcinoma (n=2) and squamous cell arcinoma (n=1). We report the specific technical details and present initial results of our series. RESULTS: The mean operative time of laparoscopic radical cystectomy with pelvic lymph node dissection was 195.4 min, the mean blood loss 273.7 ml, and the transfusion rate 6.9%. Two procedures converted to open techniques. Lymphadenectomy detected lymph node metastasis in three patients. CONCLUSIONS: We demonstrate that the combination of laparoscopic radical cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. The laparoscopic surgery with extracorporeal urinary reconstruction is emerging as a viable alternative to open radical cystectomy while characterized by less trauma, short recovery time and low complications. Intermediate oncologic outcomes are encouraging and comparable to those of open series. To determine the oncologic outcome long-time follow-up will be necessary.
Subject(s)
Cystectomy/methods , Laparoscopy , Urinary Bladder Neoplasms/surgery , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Treatment Outcome , Urinary Diversion/methodsABSTRACT
PURPOSE: To present our experience in laparoscopic radical cystectomy with extracorporeal urinary diversion for treatment of Chinese bladder cancer patients. METHODS: Between January 2003 and November 2005, 41 men and 5 women with organ-confined muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with the Bricker-type urinary diversion. The age range was 36-71 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using five fan-shaped ports by a transperitoneal approach. An ileal conduit diversion was created through the site of specimen retrieval which was the second port at the region of the right pararectus. RESULTS: 46 radical cystectomies with Bricker-type ileal conduits were performed. No conversion to open surgery was necessary. Mean operating time was 220 min (range 120-249 min) for laparoscopic radical cystectomy and 75 min (range 65-120 min) for creating the ileal conduits. Mean estimated blood loss was 276 ml (range 155-567 ml). Two of the 46 patients needed blood transfusion (400 ml each). Mean days to ambulation and oral intake was 4.1 (range 3-5 days) and 3.5 (range 3-6 days), respectively. Mean hospital stay was 17.6 days (range 12-35 days). Mean follow-up was 6.1 months (range 3-19 months). Histopathological examination of the specimens revealed stage T2N0M0 in 18 cases, T3aN0M0 in 14, T3bN0M0 in 9 and T3bN1M0 in 5 (TNM staging). WHO grading: G1 in 2 cases, G2 in 26 cases and G3 in 18 cases. Pelvic metastases appeared in one case and 44 patients are alive and free of disease. Intravenous pyelogram at 3 weeks postoperatively shows no evidence of upper urinary obstruction in 45 patients. CONCLUSION: Despite technical difficulties, laparoscopic radical cystectomy with Bricker-type urinary diversion is feasible. With more experience in the surgical technique, laparoscopic radical cystectomy with extracorporeal urinary diversion can become an alternative treatment of choice in the selected patients with organ- confined bladder cancer in China.