This study was carried out to assess the efficacy of urinary hepatoma up-regulated protein (
HURP
) RNA in bladder cancer diagnosis and its relation to bilharziasis. Voided urine samples and blood ...were collected from 344 consecutive participants: 211 patients diagnosed with bladder cancer, 71 patients with benign urological disorders and 62 healthy volunteers. Serologic assessment of schistosomiasis antibody in sera, urine cytology and estimation of
HURP
RNA by reverse transcription polymerase chain reaction in urothelial cells was carried out in all samples.
HURP
RNA expression showed a significant difference among the three investigated groups. The best cutoff point for
HURP
RNA was determined as 0.0132 at 78.67 % sensitivity and 94 % specificity. The sensitivity of urine cytology was improved when combined with
HURP
RNA in detection of early stage (77.3 %), low grade (85.3 %) and bilharzial bladder cancer (78.1 %). Detection of urinary
HURP
RNA is a useful non-invasive test for early detection of bladder cancer and bilharzial bladder cancer and it improves sensitivity of urine cytology up to 91 %.
We identified and validated novel urinary autophagy markers in diabetic kidney disease (DKD) based on bioinformatics analysis and clinical validation.
We retrieved three novel autophagy genes related ...to DKD from public microarray databases, namely; microtubule-associated protein light chain (MAP1LC3A), WD Repeat Domain, Phosphoinositide Interacting 2 (WIPI2), and RB1-Inducible Coiled-Coil 1 (RB1CC1). Secondly we assessed the expression of the chosen autophagy transcript in urine sediment of 86 patients with DKD and 74 (age and sex matched) controls by reverse transcription quantitative real-time PCR.
The urinary expression levels of MAP1LC3A, WIPI, RB1CC1 were significantly lower in DKD than control group (P<0.001).The receiver-operating characteristic curve (ROC) analyses that each urinary autophagy transcript showed high sensitivity and specificity for distinguishing DKD from control (MAP1LC3A, 81.4% and 81.1%; WIPI, 74.4% and 67.6%, and RB1CC1, 81.4%,70.3%, respectively). Notably, a negative correlation was found between these autophagy markers, serum creatinine and urinary albumin creatinine ratio. The sensitivity and specificity of this urinary autophagy based panel reached 90.6% and 60% in diagnosis of DKD.
We identified and validated a novel diagnostic urinary autophagy based panel with high sensitivity and moderate specificity representing a vital player in the pathogenesis of DKD.
•Recent studies documented autophagy genes as key player in development of diabetic kidney disease (DKD).•We identified for the first time a urinary autophagy transcripts (MAP1LC3A,WIPI, RPPIC mRNA) in DKD cases.•This panel showed higher sensitivity and specificity than that of the commonly used non-invasive diagnostic assays for DKD.
Autophagy is a highly conserved pathway. Impairment of autophagy is implicated in the pathogenesis of diabetic nephropathy. The current study applied a bioinformatics analysis to retrieve promising ...autophagy biomarker relevant diabetic nephropathy. Urinary expression of Microtubule-associated protein 1 light-chain 3B (LC3B) RNA was assessed. Urine samples of 86 type II diabetic kidney disease Egyptian patients (albuminuria group) were provided to quantify urinary expression of LC3B. A group of 30 healthy volunteers were also enrolled in addition to non-albuminuria group including 44 patients. Our study revealed a cut-off value for urinary LC3B expression level that was calculated by receiver-operating characteristic curve as 0.866. Sensitivity and specificity of LC3B were 83.7 and 78.4% respectively. The positivity rate of urinary LC3B expression level was significantly lower in diabetic nephropathy patients than control group. LC3B has great clinical value as promising biomarker in diabetic nephropathy assessment.
An overview on precision therapy in bladder cancer Sayed, Ahmed; Munir, Malak; Eweis, Noor ...
Expert review of precision medicine and drug development,
09/02/2020, 2020-09-02, Letnik:
5, Številka:
5
Journal Article
Recenzirano
Bladder cancer is a common global cause of morbidity and mortality, with many patients not responding to -or not tolerating- traditional chemotherapeutic regimens. Recent studies have allowed us to ...utilize the genetic profile of tumors to better target therapy as is required, as well as innovate novel therapeutic interventions usable when more traditional options prove futile.
The development of novel interventions in bladder cancer, particularly immune checkpoint inhibitors, as well as using genetic markers to guide both traditional and novel therapeutic interventions. We also discuss the utility of these markers in diagnosing and prognosticating bladder cancer patients.
Biomarker-guided therapy could revolutionize bladder cancer care in several ways: not only do novel therapeutic agents provide alternate treatment options for more difficult cases, but it can also increase the efficacy of more traditional treatment options. In addition, it may have a role in the early diagnosis and detection of bladder cancer, as well as predicting the course and prognosis of these patients. Unresolved challenges include how to best optimize therapy with novel agents as regarding duration and patient selection, as well as investigations as to whether using gene-guidance results in clinically improved patient outcomes.
Expression of the human telomerase reverse transcriptase (hTERT) gene, which codes for the catalytic subunit of telomerase is considered an important tumor marker used for bladder cancer detection ...being found in the majority of cancer cells. Scatter Factor (SF) is a secretory protein produced by fibroblasts and smooth muscles and induces scattering of the epithelial cells. The aim of the current study was to evaluate the potential usefulness of hTERT and SF measurement as urinary markers for bladder cancer diagnosis.
Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (malignant group: n = 60), urological patients without urothelial carcinoma (benign group: n = 25), and healthy volunteers (control group: n = 20). All cases underwent urine cytology, serological schistosomiasis antibody assay and detection of urinary hTERT mRNA using RT-PCR and SF using ELISA.
Positivity rate of hTERT mRNA was markedly higher in malignant versus benign or control cases (86.67%, 8%, and 0%, respectively, p-value < 0.001). Combining hTERT and cytology increased the sensitivity of cytology to 95%. According to a cut-off value of urinary SF (> or = 410 ng/mg protein), 57 (95%) of the patients with bladder carcinoma, 10 (40%) with benign lesions, and non of the control individuals were positive and the difference between the 3 groups was statistically significant (p < 0.001). The sensitivity of cytology was increased to 98.33% when combined with the SF assay. When associating the two urinary markers with different clinicopathological factors of the bladder cancer group, only SF exerted a significantly higher positivity rate at the invasive stage (100%) than the superficial stage (88.46%) as well as in transitional cell carcinoma (100% thansquamous cell carcinoma type (87.5%).
hTERT and SF can be considered potential useful markers for detection of bladder cancer.
Schistosomiasis (SCH) is the second only to malaria among the parasitic diseases affecting humans regarding the prevalence of infection worldwide. In this nonsystematic review, we summarize the ...existing data on commercially available and promising investigational urine markers for the detection of SCH and its associated bladder cancer (BC). We searched PubMed, Scopus and Cochran without time limits. We reviewed the recent literatures on urine-based markers for SCH and its associated BC. Many studies identified several urine biomarkers of Schistosoma haematobium and Schistosoma mansoni worms and their associated BC using automated, inexpensive, quantitative assays in urine. These markers may aid in early detection of bladder carcinoma and have the potential to reduce the number of follow-up cystoscopy, thus reducing healthcare costs and patient discomfort, at the same time. Nevertheless, clinical evidence is insufficient to warrant the substitution of the cystoscopic follow-up scheme by any of the currently available urine marker tests.
Purpose New, noninvasive methods are needed for the diagnosis, followup and screening of patients with bladder cancer. Three methods of detecting telomerase were evaluated in this aspect. Materials ...and Methods This study included 200 patients diagnosed with bladder carcinoma, 85 with benign bladder lesions and 30 healthy individuals who served as the control group. All underwent serological schistosomiasis antibody assay in serum, urine cytology and estimation of relative telomerase activity by telomeric repeat amplification protocol, human telomerase RNA by reverse transcriptase-polymerase chain reaction and human telomerase reverse transcriptase by real-time reverse transcriptase-polymerase chain reaction in urothelial cells from voided urine. Results The concordance between the positive rates of telomerase detected by the 3 methods was high (90% to 95%). Results were significantly higher in the malignant group than in the benign and control groups. There was a significant difference among the results of the 3 methods in relation to different clinicopathological factors. Overall the sensitivity of human telomerase reverse transcriptase for detecting bladder cancer was the highest compared to that of human telomerase RNA, relative telomerase activity and urine cytology (96%, 92%, 75% and 75%, respectively). Combinations of telomerase results with urine cytology were not useful except in cases of relative telomerase activity. Conclusions Detection of human telomerase reverse transcriptase in urine by real-time polymerase chain reaction, followed by human telomerase RNA by reverse transcriptase-polymerase chain reaction, improves sensitivity and specificity for the diagnosis of bladder cancer. However, regarding cost-effectiveness, human telomerase RNA is superior.
With the introduction of integrated approach in the medical curriculum, there is a need to teach basic sciences in a way relevant to real clinical scenarios. The aim of this study is to investigate ...the feasibility of case-based learning (CBL) for teaching of medical biochemistry to a large number of medical students. It also evaluates both the students’ and faculty members’ perception of this approach. CBL was introduced in teaching medical biochemistry in the Neuroscience block for the second-year medical students. This study’s students were from two consecutive academic years (n = 721 and 769). Four clinical cases were prepared. Students were divided into subgroups, each having one CBL session every 2 weeks. Students were encouraged to work together to understand the given clinical scenario by building on past knowledge obtained through other teaching modalities and new knowledge acquired during the session. A pretest was administered at the beginning of the session, and an identical posttest administered at the end of the session. Perception of both the students and facilitators of the CBL-teaching approach was evaluated using end-of-block questionnaires. In both studied academic years, students got higher scores in posttest compared to pretest scores with a statistically significant difference of the paired scores (P < 0.001). Analysis of the students’ questionnaire demonstrated that most students positively perceived the CBL approach, with a feeling that CBL has helped them learning the biochemistry concepts. Likewise, analyzing staff questionnaire revealed staff’s positive attitude toward the impact of CBL in teaching biochemistry on the students and on themselves. The current work suggests that CBL is both feasible and efficient to be applied for teaching medical biochemistry on a large scale. It is positively perceived by both students and teaching staff. Future work is still needed to solve certain challenges such as increasing work load on the faculty members and to test the impact of this teaching modality on long-term retention of knowledge.
Diagnosis of bladder cancer is done by cystoscopy and cytology. In the last decade, many urine-based tests for bladder cancer have been developed and tested in different populations. Hence, it was ...relevant to assess the diagnostic significance of urinary hyaluronidase RNA and its enzyme activity in bladder cancer. Seventy patients with bladder cancer, 56 patients with benign bladder lesions, and 49 healthy controls were enrolled in this study. Voided urine samples from all subjects were used for estimation of urinary HAase RNA by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and determination of its enzymatic activity by zymography. There was a significant difference in the mean ranks and positivity rates of HAase RNA expression (
P
< 0.01) and its enzymatic activity among the three investigated groups: malignant, benign, and normal (
P
< 0.01). In detecting bladder cancer, the sensitivity of urine cytology (42.83 %) was improved to 100 % when combined with urinary Hyal RNA or Hyal enzyme activity. Detection of urinary Hyal RNA and its enzyme activity is promising noninvasive tests with high sensitivities and specificities for detection of bladder cancer.
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