Comprehensive kinase profiling to classify clear cell (cc)-renal cell carcinoma (RCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 409-409
Author(s):  
Amitkumar N. Mehta ◽  
Christopher Douglas Willey ◽  
Joshua Anderson ◽  
Karim Youssry Welaya ◽  
Dongquan Chen ◽  
...  

409 Background: Comprehensive high throughput functional kinase activity in localized cc-RCC tumors may assist in devising a classification system and help identify potential therapeutic targets. Methods: Patients (pts) with localized tumors undergoing surgery with minimum follow-up of 18 months underwent kinomics of fresh frozen cc-RCC tumors and matched normal renal tissue using the PamStation12 high-content phospho-peptide substrate microarray system (PamGene). The protein tyrosine kinome (PTK) and serine/threonine kinome (STK) PamChips were used to measure global kinase activity. Advanced network modeling of altered phospho-peptides was performed using MetaCore while upstream kinase prediction scoring was based off of phosphonet (phosphonet.ca). Both unsupervised analyses and supervised analyses of kinomics were done guided by tumor recurrence. Kinomics of tumor and matched normal tissue were compared. Results: Of 41 evaluable pts, the median age was 61 and pathologic stage was 1, 2, 3 and 4 in 19, 1, 20 and 1 pts, respectively. Unsupervised clustering analyses of tumor kinomics showed 3 groups: A (N=12), B (N=16), C (N=13). Potential driver kinases implicated were PFTK1, PKG1 and SRC in groups A, B, and C, respectively. Network modeling of these groups identified many Process Mappings including, but not limited to Inflammation pathways (A), translation initiation (B) and immune response and cell adhesion pathways(C). 5 of 9 pts who progressed were classified as Group C, 1 progressor was in Group B, and 3 were in Group A. Supervised analysis showed decreased CDK1, RSK1-4, ERK1-2, PKG2 and AKT2 kinase activity in those who progressed compared to others. 12 tumors showed increased PIM1 and MAPKAPK3, and decreased JNK2 and CDK1 compared to adjacent normal tissue. Conclusions: Comprehensive kinomics of localized cc-RCC was used to classify tumors based on unsupervised clustering, which appeared to confer differential long-term outcomes while supervised analysis also identified potential pathways related to recurrence. Kinases amplified in renal tumors compared to adjacent normal renal tissue were also identified. Significant heterogeneity of kinases was found with no single dominant kinase across all analyses.

2021 ◽  
pp. 039156032098779
Author(s):  
Debansu Sarkar ◽  
Akash Agrawal ◽  
Dilip Kumar Pal

Introduction and objective: Nephrectomy leads to derangement of renal function and various adaptive changes by the remaining kidney over a period of time. This study is performed to evaluate the amount of derangement of renal function in donor and radical nephrectomy, how much the remaining kidney adapts over a period of time and the time taken for stabilisation of renal function. Method: A total of 60 patients who underwent nephrectomy (Radical/Donor) were followed up for 12 months with serial estimation of renal function and was compared with preoperative renal function. Data was analysed with statistical analysis. Result: Patients who underwent radical nephrectomy had 37% initial decline in renal function which was later stabilised at 19% lower than baseline value. Patient who underwent donor nephrectomy had initially 39% decline in renal function which was later stabilised at 24% lower than normal. Conclusion: Removal of functional renal tissue led to reduction of renal function. This decline is more evident in the initial post-operative period and then begin to stabilise over months. The greater is the amount of normal tissue removed, the greater is the reduction of renal function and more time it will take to stabilise, increasing overall morbidity of the patient. This study suggests that even patients with normal GFRs should be followed up postoperatively to determine their ultimate renal functional outcomes.


2012 ◽  
Vol 36 (2) ◽  
pp. 512-520 ◽  
Author(s):  
J. J. Wendler ◽  
M. Porsch ◽  
S. Hühne ◽  
D. Baumunk ◽  
P. Buhtz ◽  
...  

2010 ◽  
Vol 9 (2) ◽  
pp. 120
Author(s):  
K. Barwari ◽  
E. Cauberg ◽  
D.M. De Bruin ◽  
D.J. Faber ◽  
T.G. Van Leeuwen ◽  
...  

2021 ◽  
pp. 039156032110016
Author(s):  
Francesco Chiancone ◽  
Marco Fabiano ◽  
Clemente Meccariello ◽  
Maurizio Fedelini ◽  
Francesco Persico ◽  
...  

Introduction: The aim of this study was to compare laparoscopic and open partial nephrectomy (PN) for renal tumors of high surgical complexity (PADUA score ⩾10). Methods: We retrospectively evaluated 93 consecutive patients who underwent PN at our department from January 2015 to September 2019. 21 patients underwent open partial nephrectomy (OPN) (Group A) and 72 underwent laparoscopic partial nephrectomy (LPN) (Group B). All OPNs were performed with a retroperitoneal approach, while all LPNs were performed with a transperitoneal approach by a single surgical team. Post-operative complications were classified according to the Clavien-Dindo system. Results: The two groups showed no difference in terms of patients’ demographics as well as tumor characteristics in all variables. Group A was found to be similar to group B in terms of operation time ( p = 0.781), conversion to radical nephrectomy ( p = 0.3485), and positive surgical margins ( p = 0.338) while estimated blood loss ( p = 0.0205), intra-operative ( p = 0.0104), and post-operative ( p = 0.0081) transfusion rates, drainage time ( p = 0.0012), pain score at post-operative day 1 (<0.0001) were significantly lower in Group B. The rate of enucleation and enucleoresection/polar resection was similar ( p = 0.1821) among the groups. Logistic regression analysis indicated that preoperative factors were not independently associated with the surgical approach. There was a statistically significant difference in complication rate (<0.0001) between the two groups even if no significant difference in terms of grade ⩾3 post-operative complications ( p = 0.3382) was detected. Discussion: LPN represents a feasible and safe approach for high complex renal tumors if performed in highly experienced laparoscopic centers. This procedure offers good intraoperative outcomes and a low rate of post-operative complications.


1998 ◽  
Vol 26 (2) ◽  
pp. 117-121 ◽  
Author(s):  
Sirpa Rintala ◽  
Teuvo L. J. Tammela ◽  
Risto Tuimala

Author(s):  
Vishwajeet Singh ◽  
P K Berwal ◽  
T C Saini ◽  
Narender Mishra

Background: This study was carried out to compare the efficacy and outcome of albumin with fresh frozen plasma (FFP) in the treatment of diuretic resistant edema in nephrotic syndrome Methods: Sixty patients with idiopathic NS were enrolled in this prospective analytic study. Patients with moderate to severe edema with serum albumin <1.5 gm/dl were given albumin and FFP dividing into two groups. Group-A, received intravenous albumin- 1 gm/kg/day and Group-B intravenous FFP 15ml/kg/day. Total number of albumin and FFP infusion were determined by edema reduction. Results: Diagnosis of NS and biochemical parameters were same in both groups. Dry weight was achieved in Group-A in 6.62± 3.15 days and in Group-B 6.65 ± 3.18 days. In GroupA the number of albumin infusion required was 1.42±0.62 and Group-B FFP infusion required was 3.11± 1.05 (p=0.0001). No significant complications were observed in both the groups. Conclusion: FFP cost half than albumin and same duration required to reduce edema but with double number of infusion and it is safe in pediatric patients with NS presenting with moderate to severe edema. Keywords: NS, Oedema, FFP, Albumin


Processes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 448
Author(s):  
Alessandro Tonacci ◽  
Alessandro Dellabate ◽  
Andrea Dieni ◽  
Lorenzo Bachi ◽  
Francesco Sansone ◽  
...  

Nowadays, psychological stress represents a burdensome condition affecting an increasing number of subjects, in turn putting into practice several strategies to cope with this issue, including the administration of relaxation protocols, often performed in non-structured environments, like workplaces, and constrained within short times. Here, we performed a quick relaxation protocol based on a short audio and video, and analyzed physiological signals related to the autonomic nervous system (ANS) activity, including electrocardiogram (ECG) and galvanic skin response (GSR). Based on the features extracted, machine learning was applied to discriminate between subjects benefitting from the protocol and those with negative or no effects. Twenty-four healthy volunteers were enrolled for the protocol, equally and randomly divided into Group A, performing an audio-video + video-only relaxation, and Group B, performing an audio-video + audio-only protocol. From the ANS point of view, Group A subjects displayed a significant difference in the heart rate variability-related parameter SDNN across the test phases, whereas both groups displayed a different GSR response, albeit at different levels, with Group A displaying greater differences across phases with respect to Group B. Overall, the majority of the volunteers enrolled self-reported an improvement of their well-being status, according to structured questionnaires. The use of neural networks helped in discriminating those with a positive effect of the relaxation protocol from those with a negative/neutral impact based on basal autonomic features with a 79.2% accuracy. The results obtained demonstrated a significant heterogeneity in autonomic effects of the relaxation, highlighting the importance of maintaining a structured, well-defined protocol to produce significant benefits at the ANS level. Machine learning approaches can be useful to predict the outcome of such protocols, therefore providing subjects less prone to positive responses with personalized advice that could improve the effect of such protocols on self-relaxation perception.


2005 ◽  
Vol 29 (6) ◽  
pp. 747-754 ◽  
Author(s):  
Brian F Skinnider ◽  
Andrew L Folpe ◽  
Randolph A Hennigar ◽  
So Dug Lim ◽  
Cynthia Cohen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document