ABSTRACT
Precipitation patterns are commonly concentric rings forming in a Petri dish or parallel bands appearing in a test tube (Liesegang phenomenon). The rings frequently consist of a number of convex segments that are separated from each other by spaces devoid of precipitate resulting in small gaps (dislocations). Along these gaps, the so-called zig-zag structures can form, which connect one side of a gap with its opposite side. We observe that the occurrence of zig-zags requires a minimum thickness of the reactive layer (≥ 0.8 mm). This fact together with microscopic evidence indicates their three-dimensional character. One finds that at the very beginning of the precipitation reaction a curling process starts in the corresponding contour lines. These observations suggest structures of a helicoid with the axis perpendicular to the plane of the reaction-diffusion front to pass through the layer. Zig-zags are not parallel to the reaction plane, i.e., they are not formed periodically, but evolve continuously as a rotating spiral wave. Thus, their topology is closely related to helices in a test tube.
ABSTRACT
BACKGROUND: The APLNR (apelin receptor) has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure. The aim of this study is to investigate the expression of APLN (apelin) and APLNR in patients with renal cell carcinoma (RCC), and its association with clinicopathological parameters and survival. METHODS: Three well-characterised patient cohorts with RCC were used: Study cohort 1 (clear-cell RCC; APLN/APLNR mRNA expression; n = 166); TCGA validation cohort (clear-cell RCC; APLN/APLNR mRNA expression; n = 481); Study cohort 2 (all RCC subtypes; APLNR protein expression/immunohistochemistry; n = 300). Associations between mRNA/protein expression and clinicopathological variables/patients' survival were tested statistically. RESULTS: While APLN showed only very weak association with tumour histological grade (TCGA cohort), APLNR/mRNA protein expression correlate significantly with ccRCC aggressiveness. APLNR is expressed in tumour vasculature and tumour cells at different levels, and these expression levels associate with tumour aggressiveness in opposing directions. APLNR expression was negatively correlated with PD-L1 expression by tumour cells in a subset of patients with ccRCC. APLNR expression in either compartment is an independent prognostic factor for survival of patients with ccRCC. CONCLUSION: The APLNR/APLN-system appears to play an important role in ccRCC, warranting further clinical investigation.
Subject(s)
Apelin Receptors/biosynthesis , Apelin/biosynthesis , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , Apelin/genetics , Apelin Receptors/genetics , B7-H1 Antigen/biosynthesis , B7-H1 Antigen/genetics , Carcinoma, Renal Cell/blood supply , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Kidney Neoplasms/blood supply , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Microvessels/pathology , Neoplasm Grading , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Tissue Array AnalysisABSTRACT
BACKGROUND: Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as 'foreign') cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. METHODS: During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. RESULTS: No significant differences regarding the patients' survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. CONCLUSIONS: In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.
Subject(s)
Genital Neoplasms, Female/ethnology , Genital Neoplasms, Female/mortality , Head and Neck Neoplasms/ethnology , Head and Neck Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Genital Neoplasms, Female/therapy , Germany/ethnology , Head and Neck Neoplasms/therapy , Humans , Kaplan-Meier Estimate , Male , Matched-Pair Analysis , Middle Aged , Progression-Free Survival , Retrospective Studies , White People , Young AdultABSTRACT
PURPOSE: PIWI-interacting RNAs (piRNAs) have been suggested to serve as biomarkers in cancer. In this study, we validated the expression profile of two piRNAs derived from mitochondria, piR-34536 and piR-51810, in tissue and serum of a cohort of clear cell renal cell carcinoma (ccRCC) patients. METHODS: Tissue and serum samples of patients with ccRCC were collected prospectively in our biobank. Total RNA was isolated from 118 ccRCC tissues, 75 normal renal tissues as well as 30 serum samples from patients with ccRCC, and 15 serum samples from patients with non-malignant diseases. The expression of piRNAs was determined using quantitative real-time PCR. RESULTS: Both piR-34536 and piR-51810 were downregulated in ccRCC compared to non-malignant renal tissue. Decreased tissue piRNA levels were significant and independent predictors of shortened progression-free, cancer-specific and overall survival of ccRCC patients. The piRNA levels in serum did not differ in ccRCC patients and control subjects. CONCLUSIONS: The expression of piR-34536 and piR-51810 in ccRCC tissues may be used as prognostic biomarkers in ccRCC.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/chemistry , Kidney Neoplasms/blood , Kidney Neoplasms/chemistry , RNA, Mitochondrial/analysis , RNA, Small Interfering/analysis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Prospective StudiesABSTRACT
OBJECTIVE: To analyze the expression of mitochondrial respiratory chain protein subunits in clear cell renal cell carcinoma. METHODS: Possible prognostic candidates were determined using The Cancer Genome Atlas database (n = 605). The database provided valid messenger ribonucleic acid expression data for 93 genes encoding for the subunits. Selected subunits were further investigated at the messenger ribonucleic acid and protein level by real-time polymerase chain reaction, western blot and immunohistochemistry with the cohorts of the University Hospital Bonn. RESULTS: The Cancer Genome Atlas messenger ribonucleic acid expression data indicated univariate and multivariate prognostic impact for seven subunits (NDUFS8, NDUFS7, COX5B, COX6B1, SDHD, COX15 and COX19). Using real-time polymerase chain reaction, significant downregulation (P < 0.05, n = 74) could be shown for COX5B, COX6B1, NDUFS7 and NDUF8 in clear cell renal cell carcinoma tissue. Survival analysis of polymerase chain reaction data showed a non-significant relationship (P = 0.067) of high COX5B expression and poor overall survival. Western blot (n = 8) and immunohistochemistry analysis (n = 167) confirmed significant COX5B downregulation on the protein level. Immunohistochemistry analysis identified COX5B as a prognostic marker for overall (P = 0.017) and cancer-specific survival (P = 0.042). CONCLUSIONS: The present study findings suggest downregulation of additional subunits of mitochondrial respiratory chain proteins in clear cell renal cell carcinoma. Remarkably, COX5B, a subunit of the respiratory chain complex IV, can be identified as a novel prognostic marker.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/mortality , Electron Transport Complex IV/metabolism , Kidney Neoplasms/mortality , Protein Subunits/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Down-Regulation , Electron Transport Complex IV/analysis , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Kidney/pathology , Kidney/surgery , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Nephrectomy , Prognosis , Protein Subunits/analysis , Tissue Array AnalysisABSTRACT
PURPOSE: In various malignancies RNA fragments are dysregulated. Our study was designed to determine the expression of 4, 5'-tRNA halves in the tissue and serum of patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Tissue and serum samples of patients with clear cell renal cell carcinoma and nonmalignant disease were collected prospectively in our biobank. We isolated total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13 with nonmalignant urological disease. To specifically determine the expression of 5'-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3' end of the tRNA halves. The expression levels of 4, 5'-tRNA halves (5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG and 5'-tRNA-Lys-TTT) were then measured by TaqMan® based quantitative reverse transcription-polymerase chain reaction. RESULTS: All studied 5'-tRNA halves were down-regulated in clear cell renal cell carcinoma tissues, indicating a potential role as a tumor suppressor. Furthermore, we noted decreased expression of 5'-tRNA halves in patients with adverse clinicopathological parameters. All 5'-tRNA halves were expressed at lower levels in nonorgan confined clear cell renal cell carcinoma. The 5'-tRNA-Lys-TTT halves inversely correlated with ISUP (International Society of Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves circulated at lower levels than in control subjects, indicating relevance as noninvasive biomarkers. CONCLUSIONS: In patients with clear cell renal cell carcinoma 5'-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , RNA, Transfer/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Case-Control Studies , Down-Regulation , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Male , Middle Aged , Prognosis , Prospective Studies , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
PURPOSE: Prostate specific membrane antigen is expressed by the endothelium of many tumors. The aim of the study was to find a rationale for prostate specific membrane antigen based imaging and investigate the prognostic role of vascular prostate specific membrane antigen expression in patients with renal cell carcinoma. MATERIALS AND METHODS: A total of 257 patients with renal cell carcinoma were included in study with a median followup exceeding 10.0 years. Prostate specific membrane antigen expression on tumor vessels was detected by immunohistochemistry. Vascular expression of FOLH1 gene (prostate specific membrane antigen) mRNA was investigated in clear cell carcinoma and papillary renal cell carcinoma using TCGA (The Cancer Genome Atlas) data. RESULTS: Endothelial prostate specific membrane antigen protein expression was higher in clear cell than in papillary and chromophobe renal cell carcinoma. Higher grade and stage, metastatic and lethal clear cell renal cell carcinoma showed higher prostate specific membrane antigen expression in tumor vessels. On univariate and multivariate analysis the intensity of positive vs negative endothelial prostate specific membrane antigen protein expression was significantly associated with overall survival. TCGA based analyses confirmed the prognostic role of vascular expression of FOLH1 mRNA. The analyses also supported the usefulness of prostate specific membrane antigen based imaging in cases of clear cell but not papillary renal cell carcinoma. CONCLUSIONS: We provide a rationale for further development of prostate specific membrane antigen targeted imaging in patients with clear cell renal cell carcinoma. The prognostic role of prostate specific membrane antigen was determined at the protein level in clear cell renal cell carcinoma and at the mRNA level in clear cell and papillary renal cell carcinoma.
Subject(s)
Antigens, Surface/metabolism , Biomarkers, Tumor/metabolism , Blood Vessels/metabolism , Carcinoma, Renal Cell/metabolism , Glutamate Carboxypeptidase II/metabolism , Kidney Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Female , Follow-Up Studies , Humans , Immunohistochemistry , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
OBJECTIVE: To study the expression of YRNAs (Ro-associated Y), a novel class of non-coding RNAs, in prostate cancer (PCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival PCA (prostate adenocarcinoma, n = 56), normal (n = 36) and benign prostatic hyperplasia (BPH; n = 28) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for biochemical recurrence-free survival were analysed. RESULTS: All YRNAs were significantly downregulated in PCA tissue compared to normal tissue (all YRNAs) and to BPH tissue (RNY4 and RNY5; RNY1 and RNY3 as trend). Among tumor ISUP grade groups, the most prominent differences in the expression were evident between groups 1 and 2 (RNY1, RNY3 und RNY4; all p < 0.05). Discrimination ability for normal/BPH tissue versus tumor tissue in ROC analysis (area under curve) was ranging from 0.658 (RNY1) to 0.739 (RNY4). Higher RNY5 expression was associated with poor prognosis (biochemical recurrence-free survival). CONCLUSION: The expression of YRNAs is altered in PCA and associated with poor prognosis (RNY5). Possible diagnostic role of YRNAs in prostate cancer should be investigated in further studies.
Subject(s)
Autoantigens/metabolism , Prostatic Neoplasms/metabolism , RNA, Small Cytoplasmic/metabolism , Ribonucleoproteins/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor , Disease-Free Survival , Humans , Male , Middle Aged , Prognosis , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/mortality , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/mortality , Transurethral Resection of ProstateABSTRACT
BACKGROUND: Renal fungal bezoars are remarkably rare and mostly occur in immunodeficient patients. Only a small number of cases with immunocompetent patients have been published so far. The published treatment approaches comprised systemic antimycotic therapy and surgical or minimal invasive removal of the fungal balls. In some cases irrigation of the renal duct system with amphotericin B was performed. By obstruction of the urinary tract bezoars can lead to infected hydronephrosis and severe urosepsis with high lethality. Fungaemia can cause fungal colonization in different distant organs. Fulminant chorioretinitis and irreversible visual impairment can be the consequence of ocular fundus colonization. The following report highlights that a co-operation between urologists and ophthalmologists is absolutely indispensible in case of fungaemia. CASE PRESENTATION: Hereinafter we describe a case of an immunocompetent 56 years old woman, presenting with flank pain and shivering. The diagnosis turned out to be difficult due to initially negative urine culture. The fungaemia caused by obstructive nephropathy led to bilateral candida chorioretinitis. The patient was treated with intravenous amphotericin b and the bezoar was removed by percutaneous "nephrolitholapaxy". After two months, a follow up revealed the patient felt well, chorioretinal lesions regressed and urine culture did not show any fungal growth. CONCLUSION: To the best of our knowledge, this is the first case reporting on obstructive renal bezoars, which lead to haematogenous fungus spread and bilateral chorioretinitis. It points out that extensive ophthalmologic examination should be performed in case of fungaemia even if the patient is not suffering from any visual impairment.
Subject(s)
Bezoars/diagnostic imaging , Candidiasis/diagnostic imaging , Chorioretinitis/diagnostic imaging , Fungemia/diagnostic imaging , Kidney Diseases/diagnostic imaging , Antifungal Agents/administration & dosage , Bezoars/complications , Bezoars/therapy , Candidiasis/complications , Candidiasis/therapy , Chorioretinitis/etiology , Chorioretinitis/therapy , Combined Modality Therapy/methods , Female , Fungemia/etiology , Fungemia/therapy , Humans , Kidney Diseases/complications , Kidney Diseases/therapy , Middle Aged , Nephrolithotomy, Percutaneous/methodsABSTRACT
BACKGROUND: The mediator complex consists of 33 subunits and plays a central role in transcription. Studies have already described the involvement of individual subunits, especially in carcinogenesis. With regard to the subunit MED30, this has, so far, only been confirmed in gastric and breast carcinoma. The role of MED30 in urological tumours is unknown. MATERIALS AND METHODS: First, a database analysis using cBioPortal was performed for the mRNA expression and survival analysis of MED30 in clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). The immunohistochemical analysis (IHC) against MED30 was performed on tissue microarrays (TMA), with benign, ccRCC, pRCC samples, and ccRCC-metastases. Intensity evaluation was performed using the IRS (Immunoreactive Score). The ccRCC cell lines ACHN and A-498 were used for the functional investigation of proliferation, migration, and invasion after the knockdown of MED30 by siRNA. RESULTS: In a database analysis by cBioPortal, it was shown that mRNA overexpression of MED30 in the pRCC was significantly associated with a poorer overall survival and progression-free survival. In the IHC, pRCC showed the highest level of MED30 expression, unfortunately without significant results in the survival analysis. The knockdown of MED30 resulted in a significant decrease in proliferation, migration, and invasion in ccRCC. CONCLUSION: In summary, MED30 seems to be involved in the progression of the RCC.
Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Mediator Complex/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Disease-Free Survival , Female , Gene Knockdown Techniques , Humans , Immunohistochemistry , Kidney Neoplasms/pathology , Male , Mediator Complex/metabolism , Middle Aged , Neoplasm Invasiveness/genetics , Survival Analysis , Tissue Array AnalysisABSTRACT
INTRODUCTION: The prevalence of urinary incontinence is increasing. Two major risk factors are overweight and age. We present objective and subjective cure rates of elderly and overweight patients treated with an adjustable single-incision sling system (AJUST™, C.R. BARD, Inc.). MATERIALS AND METHODS: Between 04/2009 and 02/2012 we treated 100 female patients with the single incision sling. Patients were retrospectively evaluated by Stamey degree of incontinence, cough test, pad use, and overall satisfaction. The primary outcomes of the study were objective and subjective cure rates, secondary outcomes were the safety profile of the sling and complications. RESULTS: The overall success rate in this population was 84.6% with a mean follow-up of 9.3 months. The average usage of pads per day decreased from 4.9 to 1.6 and was significantly lower in patients with a BMI <30 (p=0.004). Postoperative residual SUI was also lower in patients with a BMI <30 (p=0.006). Postoperative satisfaction was better in patients with a lower BMI, but this difference did not reach a level of significance (p=0.055). There were no complications such as bleeding, bladder injury, or tape infection. CONCLUSIONS: In elderly and obese patients a considerable success rate is achievable with this quick and minimal invasive procedure. However, the success rate shows a clear trend in favor of a lower body-mass-index. The cut-off point has been identified at a BMI of 30. The AJUST™ system can be regarded as safe and beneficial for elderly and obese patients.
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BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. METHODS: In order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3. RESULTS: Differential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death. CONCLUSION: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Blotting, Western , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Dopamine Plasma Membrane Transport Proteins/blood , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunohistochemistry , Kidney Neoplasms/metabolism , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Sertraline/pharmacologyABSTRACT
PURPOSE: Rupture of renal artery aneurysm during pregnancy is a severe complication with high mortality and morbidity for mother and fetus, and diagnosis is difficult. The clinical presentation is easily confused with more common conditions like placental abruption, and most of the cases are diagnosed with timely delay. METHODS: We present the case of a patient with spontaneous rupture of an aneurysm of the left renal artery during late pregnancy and summarize the previous reports of ruptured renal artery aneurysm during pregnancy and early postpartum period. RESULTS: Regarding all published cases up to now (n = 32), 65.6% of mothers and 40.6% of fetuses survived. The rupture occurred in 68.7% in the third trimester and in 6.3% shortly postpartum. In our case, the increase of maternal serum lactate in a hemodynamically stable patient lead to diagnosis. CONCLUSIONS: Ruptured renal artery aneurysm should be included in the differential diagnosis for pregnant or peripartum patients presenting with flank pain. Early diagnosis and immediate intervention are important for achieving better outcomes for mother and fetus. Careful surveillance and laboratory results like serum lactate may lead to diagnosis even in hemodynamically stable patients.
Subject(s)
Aneurysm, Ruptured/diagnosis , Pregnancy Complications, Cardiovascular/diagnosis , Renal Artery , Adult , Aneurysm, Ruptured/etiology , Aneurysm, Ruptured/surgery , Diagnosis, Differential , Female , Humans , Peripartum Period , Pregnancy , Pregnancy Complications, Cardiovascular/etiology , Pregnancy Complications, Cardiovascular/surgery , Pregnancy Outcome , Pregnancy Trimester, Third , Rupture, SpontaneousABSTRACT
PURPOSE: Classic serum tumor markers (human chorionic gonadotropin, α1-fetoprotein and lactate dehydrogenase) have an important role in managing testicular germ cell tumor. Since only 60% of all patients with testicular germ cell tumor have elevations of these markers, there is a need for new biomarkers with greater sensitivity/specificity. miRNAs are deregulated in cancer and could serve as noninvasive serum biomarkers. We explored the role of serum miRNAs as a novel biomarker in patients with testicular germ cell tumor. MATERIALS AND METHODS: Total RNA was isolated from serum. miRNA levels were quantified by quantitative real-time polymerase chain reaction. We assessed the miRNAs miR-302a-3p, 302b-3p, 302c-3p, 367-3p, 371a-3p, 372-3p and 373-3p in a subcohort of 30 patients with testicular germ cell tumor and 18 healthy subjects. Validation was performed in 76 patients treated with inguinal exploration due to suspicion of testicular germ cell tumor, of whom 59 had cancer and 17 had benign disease, and in 84 healthy male subjects. RESULTS: Serum miR-367-3p, 371a-3p, 372-3p and 373-3p levels were significantly increased in patients with testicular germ cell tumor compared to healthy individuals and patients with nonmalignant testicular disease. In particular miR-371a-3p allowed for sensitive (84.7%) and specific (99%) identification of patients with testicular germ cell tumor, thus, outperforming human chorionic gonadotropin or α1-fetoprotein testing. Furthermore, miR-367-3p was increased in nonseminoma compared to seminoma cases. Serum miRNA levels were increased in patients with advanced local stage and metastasis. In 9 patients with localized (clinical stage 1A) testicular germ cell tumor serum miR-371a-3p levels decreased postoperatively, indicating tumor specific release. CONCLUSIONS: miR-371a-3p allows for better identification of testicular germ cell tumor than α1-fetoprotein and human chorionic gonadotropin. It could be helpful for clinically managing testicular germ cell tumor, especially for monitoring surveillance therapy and residual disease after chemotherapy.
Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/blood , Neoplasms, Germ Cell and Embryonal/blood , Testicular Neoplasms/blood , Humans , Male , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/pathologyABSTRACT
UNLABELLED: Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is associated with heterogeneous functional and oncological outcomes. The aim of this study was to generate trifecta and pentafecta criteria to optimize outcome reporting after RC. METHODS: We interviewed 50 experts to consider a virtual group of patients (age ≤ 75 years, ASA score ≤ 3) undergoing RC for a cT2 UCB and a final histology of ≤pT3pN0M0. A ranking was generated for the three and five criteria with the highest sum score. The criteria were applied to the Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary logistic regression analyses were used to evaluate the impact of clinical and histopathological parameters on meeting the top selected criteria. RESULTS: The criteria with the highest sum score were negative soft tissue surgical margin, lymph node (LN) dissection of at least 16 LNs, no complications according to Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR-BT with detection of muscle-invasive UCB and RC <3 months and the absence of local UCB-recurrence in the pelvis ≤12 months. The first three criteria formed trifecta, and all five criteria pentafecta. A total of 334 patients qualified for final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria, respectively. Multivariable analyses showed that the relative probability of meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and 3.3 %, p = 0.042) per year, respectively. CONCLUSIONS: Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.
Subject(s)
Carcinoma/surgery , Cystectomy , Urinary Bladder Neoplasms/surgery , Urothelium , Age Factors , Aged , Carcinoma/pathology , Cohort Studies , Female , Humans , Logistic Models , Male , Risk Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathologyABSTRACT
The effect of acetone on temporal oscillations and spatio-temporal patterns occurring in the ruthenium-catalyzed Belousov-Zhabotinsky (BZ) reaction was investigated in a closed batch system. The periods of temporal oscillations and waves significantly decrease with increasing acetone concentration. At low concentrations of acetone (0.01-0.05 M), regular wave patterns are observed with prolonged lifetimes of both temporal oscillations and waves. However, for higher concentrations (0.10-1.00 M acetone), the lifetime is shortened and irregular patterns are formed. The photosensitivity of waves of the Ru(bpy)3(2+)-catalyzed BZ reaction remains the same for all acetone concentrations. The results are discussed in terms of the proposed reaction mechanism.
ABSTRACT
Labyrinth-like Turing patterns are investigated under the influence of an electric field. The patterns form in the ferroin-catalyzed Belousov-Zhabotinsky reaction embedded in the sodium-bis (2-ethylhexyl) sulfosuccinate (AOT) water-in-oil microemulsion. For two different values of the droplet fraction above and below the percolation transition of the system, the electric field induced drift of the patterns is different. Above the percolation transition, a linear increase of the drift velocity with increasing electric field strength is found. However, below the percolation transition, this increase shows an exponential behavior. The patterns are also observed to reorient under high electrical field strength, such that they are arranged perpendicular with respect to the field lines.
Subject(s)
Emulsions/chemistry , Succinates/chemistry , Algorithms , Diffusion , Electric Conductivity , Electricity , Fourier Analysis , Glass , Linear Models , Nonlinear Dynamics , Oils/chemistry , Solvents/chemistry , Surface-Active Agents/chemistry , Water/chemistryABSTRACT
OBJECTIVES: To identify the prognostic impact of venous tumour thrombus (VTT) in locally advanced renal cell carcinomas (RCCs). To further differentiate the clinical course of patients with VTT who have similar clinicopathological characteristics. PATIENTS AND METHODS: We determined the VTT consistency (solid vs friable) in a retrospective cohort of 200 patients with RCC who had undergone nephrectomy between 1994 and 2011. We examined the correlation of VTT consistency in these patients with clinical and pathological variables. RESULTS: A total of 65% of the patients had solid VTT and 35% had friable VTT, which has a significantly lower amount of cell-cell adhesion molecules and connective tissue than solid VTT. We found that friable VTT was associated with advanced pT stage, higher VTT level, papillary RCC subtype and a lower age. Patients with friable VTT had a significantly shorter median overall survival than those with solid VTT (29 vs 89 months), but VTT consistency was not found to be an independent predictor of patients' survival in the multivariate Cox analysis. We found that VTT consistency was an independent significant predictor of overall survival in patients without evidence of distant and nodal metastases (N = 119). CONCLUSIONS: The VTT consistency is caused by the tumour and not by different surgical handling. Friable VTT is an important adverse prognostic predictor of overall survival in patients with non-metastatic RCC.
Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Nephrectomy/statistics & numerical data , Renal Veins/pathology , Vena Cava, Inferior/pathology , Venous Thrombosis/pathology , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/therapy , Female , Germany/epidemiology , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Regression Analysis , Retrospective Studies , Risk Factors , Survival Rate , Time Factors , Venous Thrombosis/mortalityABSTRACT
PURPOSE: Recent studies indicate that circulating microRNAs in serum/plasma are a novel class of non-invasive biomarkers with diagnostic and prognostic information. So far, circulating microRNAs have not been analyzed in patients with bladder cancer. METHODS: We collected serum from patients with non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and non-malignant urological disease. Total RNA was isolated from 400 µl of serum using the mirVana PARIS Kit; the artificial cel-miR-39 was spiked-in prior to RNA isolation to control different RNA isolation efficiencies. Quantitative real-time PCR was applied to measure the levels of 22 microRNAs upregulated in BCA tissue (miR-15a, miR-18a, miR-21, miR-93, miR-96, miR-103, miR-130b, miR-135b, miR-141, miR-182, miR-183, miR-190, miR-191, miR-200b, miR-422b, miR-425, miR-449b, miR-601, miR-639, miR-644, miR-649 and miR-1233) in the marker identification cohort (NMIBC, n = 11, MIBC, n = 10; controls, n = 10). The most promising serum microRNAs were tested in a validation cohort (NMIBC, n = 65, MIBC, n = 61; controls, n = 105). RESULTS: The RNA recovery was similar in patients with NMIBC, MIBC and control subjects. The analysis of serum microRNA levels in the marker identification cohort indicated that serum miR-141 and miR-639 levels were increased in bladder cancer patients compared to CTRL. The analysis of these miR-141 and miR-639 in the validation cohort demonstrated that microRNA levels were similar in bladder cancer patients and control subjects. Furthermore, microRNA levels were not correlated with clinicopathological parameters (pT-stage, metastasis, grading). CONCLUSIONS: The analysis of serum miR-141 and miR-639 levels does not seem to be helpful in the diagnosis or prognosis of BCA.
Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/blood , Urinary Bladder Neoplasms/blood , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Case-Control Studies , Cohort Studies , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Real-Time Polymerase Chain Reaction , Urinary Bladder Neoplasms/geneticsABSTRACT
INTRODUCTION: To evaluate the meaning of urodynamic parameters in patients with pouch incontinence. MATERIALS AND METHODS: Thirteen urodynamic studies in patients with an ileal nipple as the efferent segment of an ileocecal pouch or ileum/ileocecal-augmented bladder were performed. The recorded parameters included pouch capacity, leak point pressure/volume, maximum pouch pressure, compliance, static and dynamic closure pressure, and functional length. Three patients suffered from urinary incontinence. RESULTS: In all cases of incontinent patients, no functional length or static or dynamic closure pressure could be revealed. In 8 of 10 cases of continent patients, a positive functional length as well as static and/or dynamic closure pressure were measured (mean value in continent patients: 15.9 mm, 14.5 cm H2O and 26.5 cm H2O, respectively). In 2 of 3 cases of incontinent patients, the pouch compliance was restricted (21 and 37 ml/cm H2O). The pouch capacity of continent patients was greater than the capacity of incontinent patients (377.4 vs. 185.7 ml). CONCLUSIONS: Positive functional length, static and dynamic closure pressures, and a high pouch capacity with an unrestricted compliance are predictive for pouch continence. They may individually not determine continence, but combining them can. However, the meaning of urodynamic studies in pouch incontinence is not the same as with the urinary bladder.