Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma (ccRCC) and its association with PD-L1 expression.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4573-4573 ◽  
Author(s):  
Aly-Khan A. Lalani ◽  
Laurence Albiges ◽  
Kathryn P. Gray ◽  
Soumitro Pal ◽  
Jean-Christophe Pignon ◽  
...  

4573 Background: Preclinical models show that c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). The relationship between c-Met and PD-L1 in human ccRCC is not well characterized. We compared c-Met expression between primary and metastatic sites in ccRCC tissues and evaluated the association with PD-L1 expression. Methods: Pairedprimary and metastatic samples from 45 ccRCC patients were included. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab, VARI) and calculated by a combined score (CS, 0-300) as: intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression was previously assessed by IHC (PMID: 26014095). c-Met expression (average c-Met CS) between paired primary and metastatic samples were compared using Wilcoxon signed-rank test. Associations of c-Met expression with PD-L1 expression (+/-) and other clinical features were assessed with Wilcoxon rank-sum tests. Results: Our cohort included 45 primary ccRCCs and 54 corresponding metastases. c-Met expression was higher in metastatic sites compared to primary (c-Met CS: 55 vs. 28, p=0.0003) and was numerically-greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression was associated with higher FNG and T-stage in both primary and metastatic sites (Table). Conclusions: Higher c-Met expression in metastases compared to paired primary tumors in our cohort of ccRCC suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. Although the observation of higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination trials. [Table: see text]


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xiao Lyu ◽  
Xi Zhang ◽  
Li-bin Sun ◽  
Xiao-ming Cao ◽  
Xu-hui Zhang

Background. The SOX gene family has been proven to display regulatory effects on numerous diseases, particularly in the malignant progression of neoplasms. However, the molecular functions and action mechanisms of SOX genes have not been clearly elucidated in clear cell renal cell carcinoma (ccRCC). We aimed to explore the expression status, prognostic values, clinical significances, and regulatory actions of SOX genes in ccRCC. Methods. RNA-sequence data and clinical information derived from The Cancer Genome Atlas (TCGA) database was used for this study. Dysregulated SOX genes between the normal group and ccRCC group were screened using the Wilcoxon signed-rank test. The Kaplan-Meier analysis and univariate Cox analysis methods were used to estimate the overall survival (OS) and disease-specific survival (DSS) differences between different groups. The independent prognostic factors were identified by the use of uni- and multivariate assays. Subsequently, the Wilcoxon signed-rank test or Kruskal-Wallis test and the chi-square test or Fisher exact probability methods were employed to explore the association between clinicopathological variables and SOX genes. Finally, CIBERSORT was applied to study the samples and examine the infiltration of immune cells between different groups. Results. Herein, 12 dysregulated SOX genes in ccRCC were screened. Among them, two independent prognostic SOX genes (SOX6 and SOX12) were identified. Further investigation results showed that SOX6 and SOX12 were distinctly associated with clinicopathological features. Furthermore, functional enrichment analysis revealed that SOX6 and SOX12 were enriched in essential biological processes and signaling pathways. Finally, we found that the SOX6 and SOX12 expression levels were correlated with tumor-infiltrating immune cells (TIICs). Conclusion. The pooled analyses showed that SOX6 and SOX12 could serve as promising biomarkers and therapeutic targets of patients with ccRCC.



2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.



2009 ◽  
Vol 118 (8) ◽  
pp. 581-586 ◽  
Author(s):  
Alessandro de Alarcon ◽  
Susan Baker Brehm ◽  
Lisa N. Kelchner ◽  
Jareen Meinzen-Derr ◽  
Janet Middendorf ◽  
...  

Objectives We performed a retrospective review to compare a subjective parental proxy-derived voice handicap survey to an observer-derived method of measuring voice perturbation in children who have undergone airway reconstruction. The main outcome measures were the Pediatric Voice Handicap Index (pVHI) total score and the Overall Severity score on the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). Methods The percent Overall Severity CAPE-V score (score divided by 100) and the percent pVHI score (score divided by 92) were calculated. A Wilcoxon signed rank test was used to compare CAPE-V scores with the pVHI total scores. The relationship between the pVHI scores and the CAPE-V scores was investigated with a Spearman correlation. Subgroup analysis was performed to determine the relationship of surgery type to CAPE-V and pVHI scores. Results Fifty subjects with a history of airway surgery who were evaluated between 2005 and 2008 were identified. Forty-two of the 50 subjects had complete data for review. Their median age was 7.1 years (range, 3.3 to 17.9 years). Their pVHI total scores had a median of 30 (range, 1 to 80). Their Overall Severity CAPE-V scores had a median of 50.5 (range, 0 to 98). Their median CAPE-V percent was higher than their median pVHI percent (50.5% versus 32.6%; p = 0.0003). A weak correlation was found between the Overall Severity CAPE-V score and the pVHI total score (rho = 0.41; p = 0.0003). There was a trend toward higher Overall Severity CAPE-V scores in patients who underwent cricotracheal resection. The total number of airway surgeries was significantly correlated with the Overall Severity CAPE-V score (rho = 0.6; p < 0.0001) but not with the pVHI score. Conclusions Children who undergo airway reconstruction often have a resulting voice disturbance that can affect their lives in multiple dimensions. The results of this study revealed a weak-to-fair correlation between the parent-reported pVHI total score and expert ratings of voice quality using the CAPE-V. In this patient population, both of these tools provided important information regarding the relationship of the severity of voice disturbance to its handicapping effects.



2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 474-474 ◽  
Author(s):  
Maria Isabel Carlo ◽  
Nabeela Khan ◽  
Yingbei Chen ◽  
James Hsieh ◽  
A. Ari Hakimi ◽  
...  

474 Background: Non-clear cell renal cell carcinoma (nccRCC) encompasses about 20% of RCC cases and includes a number of subtypes that vary clinically and molecularly. Compared to ccRCC, these tumors have more limited sensitivity to conventional anti-VEGF agents and mTOR inhibitors, and there is clear need for better therapies. Analysis of genomic alterations in potentially targetable pathways may lead to novel therapeutic development strategies. Methods: We retrospectively analyzed tumors from 112 patients with metastatic nccRCC with targeted next-generation sequencing (NGS) across a panel of >340 cancer-relevant genes. Matched tumor and normal was used to facilitate somatic calling. We report on recurrent alterations observed for nccRCC variants. Results: Median age was 53 years (range 12-77), 67% were male; 47% presented with metastatic disease and 53% with localized disease that later metastasized. NGS was performed on tissue from primary tumors (57%) or metastatic sites (43%). Subtype classifications included unclassified (44%), papillary (21%), chromophobe (13%), translocation (12%), and other (9%). The most frequently altered genes by subtype are included in table. 36% of unclassified or papillary tumors had a mutation in a putative driver gene amenable to targeted therapies, including MET, NOTCH1, SMARCB1, TSC1, TSC2, PIK3CA, and FGFR3. 3 chromophobe tumors and 1 translocation tumor had a mutation in a potentially targetable pathway. Conclusions: The mutation profiles of metastatic nccRCC vary by papillary, chromophobe, and translocation subtype, with unclassified tumors most approximating papillary subtype. Unclassified and papillary subtypes harbor frequent mutations in potentially targetable pathways that merit further investigation. [Table: see text]



2015 ◽  
Vol 46 (4) ◽  
pp. 43-52 ◽  
Author(s):  
J. Islam ◽  
S. Sathye ◽  
H. Hu

Previous research has studied the impact of corporate governance on bank performance, but only a few aspects of the impact were reported. The present study develops a unique corporate governance index to provide a comprehensivemeasure of corporate governance and examines the relationship between this comprehensive measure and bank performance. We apply the Wilcoxon signed rank test to examine whether the introduction of the Code of CorporateGovernance in Bangladesh has significantly promoted the improvement of corporate governance practices in Bangladeshi banks. Our results provide support for the hypothesis that corporate governance practices of Bangladeshi banks have been significantly improved since the introduction of the code. Further, the present study adopts regression analysis and reveals that the comprehensive measure of corporate governance is not significantly related to Bangladeshi banks’ performance.



2015 ◽  
Vol 06 (04) ◽  
pp. 511-514 ◽  
Author(s):  
Ayhan Kanat ◽  
Ugur Yazar ◽  
Bulent Ozdemir ◽  
Zerrin O. Coskun ◽  
Ozlem Erdivanli

ABSTRACT Background and Aims: There is no study in the literature that investigates an asymmetric morphological feature of the frontal sinus (FS). Materials and Methods: Four hundred and sixty-nine consecutive direct X-rays of FSs were analyzed for the asymmetry between the right and left sides. When an asymmetry in the height and contour of the FS existed, this difference was quantified. Results: Of the 469 patients, X-rays of 402 patients (85.7%), there was an asymmetry between right and left sides of the FS. Of these 235 (50.1%) were dominant on the left side, whereas 167 (35.6%) were dominant on the right, the sinuses of remaining 67 patients (14.3%) was symmetric. Statistical Analysis: The comparisons between parameters were performed using Wilkinson signed rank test. The relationship between handedness and sinus asymmetry was also examined by two proportions test. There is statistically significant difference between the dominance of left and right FS. Conclusions: Hemispheric dominance may have some effect (s) of on sinus asymmetry of the human cranium. Surgeons sometimes enter the cranium through the FS and knowledge of asymmetric FS is important to minimize surgical complications.



2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0037 ◽  
Author(s):  
Rodrigo Pagnano ◽  
Mauro Cesar Mattos E. Dinato ◽  
Miguel Pereira Filho

Category: Arthroscopy Introduction/Purpose: The Posterior Ankle Impingement Syndrome (PAIS) can be treated by the endoscopic technique with posterior portals and patient in prone position. There is discussion whether this would be the best method, given the possible difficulty in learning and applying this technique, risks of complications and prolonged time of surgery. We conducted this retrospective study to assess the time spent to perform the posterior endoscopy along the learning curve and the relationship of the duration of the procedure to the presence of complications. Methods: We evaluated 39 patients undergoing endoscopic treatment through posterior ankle portals technique and prone position, operated by a single surgeon between 2005 and 2014. We divided the patients into four groups of ten subjects according to the chronological sequence of the surgeries. We used the Jonckheere-Terpstra test to compare the surgery time between the four analyzed groups. We used the Mann-Whitney test to compare operative time and the occurrence of complications, and the relationship between surgical procedure time and presence of intraoperative fibrosis. We used the Wilcoxon signed-rank test to compare preoperative and postoperative AOFAS Ankle-Hindfoot Score. For all statistical analysis, p-values <0.05 were considered to be significant. Results: We found a significant decreasing of the surgery duration over time (p=0.0273) (Figure). Figure: Representing surgery time (in minutes) to groups of patients (Groups 1 to 4, being Group 1 patients 1-10, Group 2 patients 11-20, Group 3 patients 21- 30 and Group 4 patients 31-39).There were three complications not related to the duration of the surgery (p=0.6909). The presence of extensive fibrosis had an impact on the operative time (p=0.0387). The AOFAS Score evolved from 64.0±16.9 preoperatively to 93.7±8.9 postoperatively (p<0.0001). Conclusion: The time of the procedure decreased as the surgeon’s experience increased, and our complications showed no relationship with the surgery time.



2018 ◽  
Author(s):  
Marissa Borgese ◽  
Brent Foster ◽  
Robert D. Boutin ◽  
Christopher O. Bayne ◽  
Robert M. Szabo ◽  
...  

ABSTRACTSeveral methods of describing patterns of carpal kinematics from radiographs have emerged due to their potential use in developing personalized treatments for wrist pathologies. Such radiography-derived metrics have been used to infer associations between patterns of scaphoid kinematics and other clinically relevant factors such as sex, but the simultaneous effects of sex and wrist position on scaphoid kinematic metrics has yet to be considered. We sought to investigate the relationship between wrist position in the coronal plane and radiographic measurements of the scaphoid for each sex independently, then identify sex-specific differences in scaphoid measurements and calculated metrics. We retrospectively identified 38 subjects with posteroanterior radial and ulnar deviation radiographs. Radiographic scaphoid measurements were collected and used to calculate five scaphoid kinematic metrics per participant. We used Pearson correlation coefficients to explore the relationships between the degrees of wrist deviation in the coronal plane and radiographic scaphoid measurements for men and women independently. We used the non-parametric Wilcoxon signed-rank test to compare values between sexes. The correlations between degrees of coronal wrist deviation and radiographic measurements of scaphoid inclination were significant only for men. Men also had significantly greater values for all radiographic scaphoid measurements. Our study demonstrated sex-specific differences in the relationship between the degrees of radial and ulnar wrist deviation and scaphoid positioning.Clinical RelevanceOur findings show the importance of stratifying by sex in studies of carpal kinematics, such as scaphoid kinematics, and that investigation of strategies to restore normal carpal function should incorporate sex as a biological variable.



2019 ◽  
Vol 3 (1) ◽  
pp. 25
Author(s):  
Dewi Nurhanifah ◽  
Desy Noor Latifah Sari ◽  
Rahmawati Rahmawati

Salah satu masalah kesehatan yang sering dialami adalah penyakit gastritis. Gejala yang sering dikeluhkan oleh penderita gastritis adalah mual. Salah satu penatalaksanaan keperawatan yang dapat mengurangi rasa mual adalah tirah baring. Penelitian ini bertujuan untuk mengetahui pengaruh tirah baring terhadap penurunan rasa mual pada klien gastritis di Pelayanan Kesehatan. Metode penelitian menggunakan eksperimental dengan bentuk penelitian one group pretest-posttest design. Populasi dan sampel adalah klien yang mengalami mual di Wilayah Kerja Puskesmas  yang berjumlah 15 orang. Sampel diambil dengan teknik purposive sampling. Alat pengumpul data menggunakan observasi. Analisa data melalui uji Wilcoxon Signed Rank Test. Hasil penelitian menujukkan klien gastritis sebelum tirah baring mengalami mual ringan sebanyak 7 orang (46,7%), sesudah tirah baring mengalami tidak mual sebanyak 7 orang (46,7%). Ada pengaruh tirah baring terhadap penurunan rasa mual pada klien gastritis di Pelayanan Kesehatan (ρ value = 0,001).



2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Ferawato Ferawati

ABSTRAKReumatoid Artritis (RA) merupakan penyakit muscoloskelektal yang sering terjadi pada usia lanjut. Gangguan pada system muscoloskelektal yang ditandai dengan munculnya nyeri sendi dan kekakuan yang mengakibatkan penurunan kemampuan fisiologis atau kualitas hidup lansia. Dampak dari Reumatoid Artritis dapat menimbulkan beberapa keluhan dan dapat menyebabkan kelumpuhan. Untuk menganalisis efektifitas kompres jahe merah hangat dan kompres serai hangat terhadap penurunan intensitas nyeri artitris remauthoid pada lanjut usia.Metode Penelitian: Jenis penelitian adalah quasy experimental dengan two group pre – post test design. Subjek adalah sebagian lansia yang penderita Arthritis Remathoid di Desa Sumberagung Kecamatan Dander Kabupaten Bojonegoro. Subjek dibagi menjadi dua kelompok yaitu kelompok I (n=15) diberi perlakuan kompres jahe hangat dan II (n=15) diberi perlakuan kompres serai hangat. Analisis yang digunakan uji Mann Whitney U Test dan Wilcoxon Signed Ranks Test dengan ingkat kemaknaan α = 0,05.Hasil uji Wilcoxon Signed Rank Test, didapat keduanya mempunyai nilai kemaknaan yaitu ρ value = 0,000. Nilai ρ = 0,031 pada kelompok kompres serai hangat dan kelompok kompres jahe merah ρ value = 0,165. Hasil uji Mann Withney U Test pada Post perlakuan kedua terapi diperoleh selisih nilai nyeri pada kompres jahe ρ= 0,003 dan selisih nilai nyeri kompres serai ρ value = 0,001.Penggunaan kompres jahe merah lebih efektif dibandingkan dengan kompres serai terhadap penurunan intensitas nyeri arthritis remathoid. Kata Kunci: usia lanjut, Reumatoid Artritis (RA), jahe merah, serai, perbedaan efektifitas.    ABSTRACTReumatoid Artritis (RA) is a musculoskeletal which frequently occurs in the elderly. The disorders in the musculoskeletal system are noted by the occurrence of pain in the joints and stiffness which reduces the physiological abilities or life quality of the elderly. The disease causes many such complaints and  consequences of the disease rheumatoid arthritis may experience paralysis. The aims of this study is to analyze the effect of warm red ginger compress therapy and warm lemongrass compress therapy against of  Decreased pain intensity in  the elderly  with  artitris remauthoid. The study was Queasy experimental with two group pre – post test design. Subjects were some elderly people with Arthritis Remathoid in Sumberagung Village, Dander Sub District, Bojonegoro District. Subjects were divided into two groups: group I (n-15) with warm ginger compress therapy, and II (n=15) with warm lemongrass compress therapy. The analyses used in this study were the Mann Whitney U Test and Wilcoxon Signed Ranks Test with α of 0.05. Results of Wilcoxon Signed Rank Test obtained Both have meaning p value of  0.000. ρ value = 0,031 in a warm lemongrass compress therapy group and obtained of warm ginger compress therapy group ρ value = 0,165. The results of Mann Withney U Test on Post treatment second therapy, obtained difference of warm ginger compress therapy with ρ value= 0,003 and difference of warm lemongrass compress therapy with ρ value = 0,001.The use of warm ginger compresses therapy are more effective than a warm lemongrass compress therapy against decreased pain intensity in  the elderly  with  artitris remauthoid.  Keywords: elderly, artitris remauthoid, red ginger, lemongrass, differences in effectiveness



Sign in / Sign up

Export Citation Format

Share Document