scholarly journals mRNA EXPRESSION OF PD-1, PD-L1, AND IMMUNOTHERAPY IN BLADDER CANCER

2021 ◽  
Vol 28 (2) ◽  
pp. 164-167
Author(s):  
Muhammad Puteh Mauny ◽  
Raden Danarto ◽  
Didik Setyo Heriyanto

Objective: This study aims to investigate mRNA expression of PD-1 and PD-L1 in patients with bladder cancer. Material & Methods: In this study, we examined 30 samples from paraffin embedded tissue blocks, samples were divided into two groups, 15 were NIMBC, and 15 were MIBC according to their histopathological result. mRNA expression of PD-1 and PD-L1 were conducted using Real Time-Polymerase Chain Reaction (qRT-PCR) and statistical significance was set at a p-value < 0.05. Results: Statistical analysis using the Mann-Whitney test found a significant difference in mRNA expression of PD-1 and PD-L1 in NMIBC compared to MIBC groups. Conclusion: mRNA expression of PD-1 and PD-L1 were higher in MIBC compared to NMIBC. PD-1 and  PD-L1 as immune checkpoints are potential immunotherapy for patients with advance stage bladder cancer. Immunotherapy could be a substitute or combined with other treatments such as chemotherapy or radiotherapy.

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3795-3800 ◽  
Author(s):  
Zhirong Zhan ◽  
Victor A. Sandor ◽  
Erick Gamelin ◽  
Joanna Regis ◽  
Bruce Dickstein ◽  
...  

Abstract Previous work investigating the role of MDR-1 overexpression in relapsed and refractory lymphoma led us to investigate a possible role for multidrug resistance-associated protein (MRP) as a cause of resistance in patients who did not overexpress MDR-1. A quantitative polymerase chain reaction (PCR) method for measuring MRP expression was validated. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein levels. MRP levels were found to be independent of sample tumor content by immunophenotyping, suggesting that the presence of normal cells had no significant impact on measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH). Pre- and post-EPOCH samples were available from 15 patients. MRP levels were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No significant difference in MRP mRNA expression was noted between pre- and post-EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not significantly different from either pre- or post-EPOCH groups. Two of 15 paired pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that MRP overexpression is not responsible for non–P-glycoprotein (Pgp)–mediated drug resistance in the majority of these patients, although it may be important in a subset of patients. Defining this subset prospectively could aid in the development of clinical trials of MRP modulation in drug-resistant lymphoma.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3795-3800 ◽  
Author(s):  
Zhirong Zhan ◽  
Victor A. Sandor ◽  
Erick Gamelin ◽  
Joanna Regis ◽  
Bruce Dickstein ◽  
...  

Previous work investigating the role of MDR-1 overexpression in relapsed and refractory lymphoma led us to investigate a possible role for multidrug resistance-associated protein (MRP) as a cause of resistance in patients who did not overexpress MDR-1. A quantitative polymerase chain reaction (PCR) method for measuring MRP expression was validated. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein levels. MRP levels were found to be independent of sample tumor content by immunophenotyping, suggesting that the presence of normal cells had no significant impact on measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH). Pre- and post-EPOCH samples were available from 15 patients. MRP levels were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No significant difference in MRP mRNA expression was noted between pre- and post-EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not significantly different from either pre- or post-EPOCH groups. Two of 15 paired pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that MRP overexpression is not responsible for non–P-glycoprotein (Pgp)–mediated drug resistance in the majority of these patients, although it may be important in a subset of patients. Defining this subset prospectively could aid in the development of clinical trials of MRP modulation in drug-resistant lymphoma.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Yang Zhang ◽  
Chunyang Dai ◽  
Huiyan Wang ◽  
Yong Gao ◽  
Tuantuan Li ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is posing a serious threat to global public health. Reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. Due to technical limitations, the reported positive rates of qRT-PCR assay of throat swab samples vary from 30 to 60%. Therefore, the evaluation of alternative strategies to overcome the limitations of qRT-PCR is required. A previous study reported that one-step nested (OSN)-qRT-PCR revealed better suitability for detecting SARS-CoV-2. However, information on the analytical performance of OSN-qRT-PCR is insufficient. Method In this study, we aimed to analyze OSN-qRT-PCR by comparing it with droplet digital PCR (ddPCR) and qRT-PCR by using a dilution series of SARS-CoV-2 pseudoviral RNA and a quality assessment panel. The clinical performance of OSN-qRT-PCR was also validated and compared with ddPCR and qRT-PCR using specimens from COVID-19 patients. Result The limit of detection (copies/ml) of qRT-PCR, ddPCR, and OSN-qRT-PCR were 520.1 (95% CI: 363.23–1145.69) for ORF1ab and 528.1 (95% CI: 347.7–1248.7) for N, 401.8 (95% CI: 284.8–938.3) for ORF1ab and 336.8 (95% CI: 244.6–792.5) for N, and 194.74 (95% CI: 139.7–430.9) for ORF1ab and 189.1 (95% CI: 130.9–433.9) for N, respectively. Of the 34 clinical samples from COVID-19 patients, the positive rates of OSN-qRT-PCR, ddPCR, and qRT-PCR were 82.35% (28/34), 67.65% (23/34), and 58.82% (20/34), respectively. Conclusion In conclusion, the highly sensitive and specific OSN-qRT-PCR assay is superior to ddPCR and qRT-PCR assays, showing great potential as a technique for detection of SARS-CoV-2 in patients with low viral loads.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1624
Author(s):  
Christos G. Gavriel ◽  
Neofytos Dimitriou ◽  
Nicolas Brieu ◽  
Ines P. Nearchou ◽  
Ognjen Arandjelović ◽  
...  

The clinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes the assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insight into patient prognosis. In this paper, we apply multiplex immunofluorescence to MIBC tissue sections to capture whole-slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1. We propose a machine-learning-based approach for the prediction of 5 year prognosis with different combinations of image, clinical, and spatial features. An ensemble model comprising several functionally different models successfully stratifies MIBC patients into two risk groups with high statistical significance (p value < 1×10−5). Critical to improving MIBC survival rates, our method correctly classifies 71.4% of the patients who succumb to MIBC, which is significantly more than the 28.6% of the current clinical gold standard, the TNM staging system.


2021 ◽  
Author(s):  
Yong Hao ◽  
Yingpeng Tong ◽  
Yanhong Guo ◽  
Xiaoe Lang ◽  
Xinxin Huang ◽  
...  

Abstract Background Metabolism disturbances are common in patients with depression. The drug metformin has been reported to exhibit antidepressant activity. The purpose of this study was to investigate metabolism disturbances induced by corticosterone (CORT) and determine if metformin can reverse these effects and their accompanying depression-like behaviors. Methods Rats were exposed to corticosterone with or without metformin administration. Depression-like behaviors were tested. Gene expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. In addition, the metabolites were quantified by LC-MS/MS analysis. Results Metformin attenuated the depression-like behaviors induced by CORT. Furthermore, metformin reversed disturbances in body weight, serum glucose, and triglyceride levels, as well as hepatic TG levels induced by CORT. Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1α, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT. Metabolomic analysis showed that metformin reversed the effects of CORT on 11 metabolites involved in the pathways of the tricarboxylic acid cycle, glycolysis, and gluconeogenesis (3-phospho-D-glycerate, β-D-fructose 6-phosphate, D-glucose 6-phosphate, and pyruvate). Conclusion Our findings suggest that metformin can attenuate metabolism disturbances and depression-like behaviors induced by CORT mediating the glucose metabolism pathway.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S162-S163
Author(s):  
Jennifer B Radics-Johnson ◽  
Daniel W Chacon ◽  
Li Zhang

Abstract Introduction Burn camps provide a unique environment and activities for children that have experienced a burn-injury. Positive outcomes from attending burn camp include increased self-esteem, decreased feelings of isolation and a greater sense of self-confidence. In a 3-year retrospective review of camper evaluations from one of the largest and longest running week-long burn camps in the nation for ages 5–17, we aimed to assess if a child’s gender, age, TBSA or ethnicity affected the impact that burn camp had on a child. Methods A 3-year retrospective review of a Burn Camp’s camper evaluation forms was conducted for campers that attended burn camp between 2017–2019. Camp rosters were reviewed to determine the camper gender, age, TBSA and ethnicity. Camper self-evaluation forms completed at the end of each camp session were reviewed to record camper responses to questions regarding their opinions on the impact camp had on them as well as how camp will impact their lives once they return home. Categorical variables were summarized as frequency and percentage, and continuous variables were described as median and range. To check the relationship between two categorical variables, Chi-square test was used. To compare the continuous variable among groups, Kruskal-Wallis ANOVA was used. Statistical significance was declared based on a p value&lt; 0.5. Results Within 2017–2019, there were 413 camper records. Participants’ demographic characteristics are summarized in Table 1. There were 208 males (50.3%) and 205 females (49.6%). The median age of campers were 11.86, 12.44 and 12.45 for 2017–2019, with the range from 5.16 years to 17.96 years. The median TBSA were 20, 20 and 18 for 2017–2019, with the range from 0.08 to 90. Collectively there were 47.7% Hispanic (n= 197); 24.2% Whites (n=100); 13.1% Black (n= 54); 4.6% Asian (n=19) and 7.7% Other (n=32). There were 395 camper self-evaluation forms submitted. Results of three questions there we were interested in are summarized collectively in Table 2. 57% of campers responded, “Yes, Definitely” to the question “After going to this event, will you feel more comfortable being around your classmates or friends?” 54% responded, “ Yes, Definitely” to the question “Do you feel more confidents in sharing your burn story with others when returning home?” and 51% responded “Yes, Definitely” to “Did you learn anything that will help you when you return home?” Conclusions In analyzing the camper responses, there was no statistically significant difference in responses comparing gender, age, TBSA or ethnicity.


2016 ◽  
Vol 52 (1) ◽  
pp. 163-169 ◽  
Author(s):  
Flaviane Granero Maltempe ◽  
Vanessa Pietrowski Baldin ◽  
Mariana Aparecida Lopes ◽  
Vera Lúcia Dias Siqueira ◽  
Regiane Bertin de Lima Scodro ◽  
...  

ABSTRACT Leprosy is a neglected tropical disease and an important public health problem, especially in developing countries. It is a chronic infectious disease that is caused by Mycobacterium leprae, which has a predilection for the skin and peripheral nerves. Although it has low sensitivity, slit-skin smear (SSS) remains the conventional auxiliary laboratory technique for the clinical diagnosis of leprosy. Polymerase chain reaction (PCR) is a molecular biology technique that holds promise as a simple and sensitive diagnostic tool. In the present study, the performance of two PCR methods, using different targets, PCR-LP and PCR-P, were compared with SSS with regard to leprosy diagnosis in a reference laboratory. M. leprae DNA was extracted from 106 lymph samples of 40 patients who had clinical suspicion of leprosy. The samples were subjected to both PCR techniques and SSS. Amplification of the human b-globin gene was used as PCR inhibitor control. The specificity of both PCR techniques was 100%, and sensitivity was 0.007 and 0.015 µg/ml for PCR-LP and PCR-P, respectively. No significant difference was found between either the PCR-LP or PCR-P results and SSS results (p > 0.05). Although PCR is not yet a replacement for SSS in the diagnosis of leprosy, this technique may be used as an efficient auxiliary tool for early detection of the disease, especially in endemic regions. This strategy may also be useful in cases in which SSS results are negative (e.g., in paucibacillary patients) and cases in which skin biopsy cannot be performed.


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