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result(s) for
"Chevinsky, Michael"
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Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection
by
Russo, Paul
,
Jakubowski, Christopher
,
Sander, Chris
in
631/114/2164
,
631/67/589/1588/1351
,
Biology
2017
The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.
Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.
Journal Article
The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling
by
Russo, Paul
,
Sankin, Alexander
,
Ostrovnaya, Irina
in
Biomarker
,
Biomarkers
,
Biomarkers, Tumor - genetics
2014
Primary clear cell renal cell carcinoma (ccRCC) genetic heterogeneity may lead to an underestimation of the mutational burden detected from a single site evaluation. We sought to characterize the extent of clonal branching involving key tumor suppressor mutations in primary ccRCC and determine if genetic heterogeneity could limit the mutation profiling from a single region assessment. Ex vivo core needle biopsies were obtained from three to five different regions of resected renal tumors at a single institution from 2012 to 2013. DNA was extracted and targeted sequencing was performed on five genes associated with ccRCC (von‐Hippel Lindau [VHL], PBRM1, SETD2, BAP1, and KDM5C). We constructed phylogenetic trees by inferring clonal evolution based on the mutations present within each core and estimated the predictive power of detecting a mutation for each successive tumor region sampled. We obtained 47 ex vivo biopsy cores from 14 primary ccRCC's (median tumor size 4.5 cm, IQR 4.0–5.9 cm). Branching patterns of various complexities were observed in tumors with three or more mutations. A VHL mutation was detected in nine tumors (64%), each time being present ubiquitously throughout the tumor. Other genes had various degrees of regional mutational variation. Based on the mutations' prevalence we estimated that three different tumor regions should be sampled to detect mutations in PBRM1, SETD2, BAP1, and/or KDM5C with 90% certainty. The mutational burden of renal tumors varies by region sampled. Single site assessment of key tumor suppressor mutations in primary ccRCC may not adequately capture the genetic predictors of tumor behavior. Single region genomics of primary kidney cancer leads to underestimation of critical tumor suppressor mutations. On average, analysis of a combination of four distinct tumor regions will yield ~90% of accuracy in detecting the detrimental 3p TSG mutations of clear cell renal cell carcinoma.
Journal Article
Dual-frequency setting for urinary stone fragmentation during shock wave lithotripsy: an in vitro study
by
Zafar Affan
,
Han, Christopher S
,
Endicott, Robert
in
Kidney stones
,
Lithotripsy
,
Performance evaluation
2020
Extracorporeal shock wave lithotripsy (SWL) is less invasive compared to the other invasive modalities of stone treatment that are gaining popularity. Hence, methods to improve the efficacy of SWL are desirable. We studied the effectiveness of dual frequency on the efficacy of stone fragmentation, but minimizing treatment time. A phantom 10 mm spherical BegoStone was fragmented in vitro in a kidney model using an electromagnetic lithotripter (Storz MODULITH®SLX-F2). A total of 78 stones were fragmented each with 3000 shocks at 60 Hz or 120 Hz or a dual frequency (DF) of 60–120 Hz. For the DF setting, the first 1000 shocks were delivered at 60 Hz and the next 2000 at 120 Hz. Total weight and number of significant fragments of > 3 mm (TWSF and TNSF, respectively) and also > 2 mm was measured. Results: The mean TWSF was 0.1, 0.16, and 0.08 g for 60 Hz, 120 Hz, and DF 60–120 Hz, respectively. The TWSF of DF 60–120 Hz was significantly lower than that of 120 Hz (p = 0.02), but same as the 60 Hz (p = 0.32). The mean TNSF of > 3 mm was 2.6, 3.0, and 2.0 for 60 Hz, 120 Hz, and DF 60–120 Hz, respectively, without significant differences between each setting. However, increasing trend of TWSF, TW2 mm and TN2 mm was seen in the order of DF, 60 Hz and 120 Hz (p = 0.019, p = 0.004 and 0.017, respectively). Treatment time for 60 Hz, 120 Hz, and DF 60–120 Hz was 50, 25, and 34 min, respectively. Dual-frequency setting produced effective stone fragmentation compared to the recommended 60 Hz, while decreasing treatment time. DF variation is one other factor that may be tailored for effective stone comminution and needs clinical evaluation.
Journal Article
Low yield of surveillance imaging after surgery for T1 kidney cancer
by
Russo, Paul
,
Vargas, Hebert A.
,
Musser, John E.
in
Follow-Up Studies
,
Humans
,
Kidney Neoplasms - diagnostic imaging
2016
Purpose
To examine the mode of relapse detection and subsequent treatment after partial or radical nephrectomy in patients with low-risk (pT1, N0, Nx) kidney cancer.
Methods
Retrospective study on 1404 patients treated with partial or radical nephrectomy for low-risk kidney cancer from the years 2000–2012. Scans for chest imaging (X-ray or CT) and abdominal imaging (CT, MRI, or ultrasound) are tabulated. For those patients with relapse, the site, mode of detection, and symptoms were recorded.
Results
Twenty-one patients relapsed with a median follow-up of 4.1 years for patients who did not relapse. In 17 (81 %) patients, relapse was detected by imaging alone, while 4 (19 %) patients presented with symptoms. Of the patients who relapsed by imaging, 13 (76 %) were treated immediately, while 4 (24 %) continued observation. During the first 3 years of follow-up, 5762 imaging studies were performed to detect 8 relapses, with 6 patients receiving immediate treatment. The median number of imaging studies per patient per year for the first 3 years was 1.7 (interquartile range 1.0, 2.3) including 30 % CT, 3 % MRI, 36 % X-ray, and 31 % ultrasounds.
Conclusion
We found a low yield of surveillance imaging in the first 3 years for pT1 kidney cancer. Nearly 1000 imaging studies were performed to detect one relapse that required treatment. Further studies are needed to evaluate the clinical impact of imaging surveillance according to recent guidelines.
Journal Article
Longitudinal Analysis of Electronic Health Information to Identify Possible COVID-19 Sequelae
by
Giovanni, Jennifer
,
Tao, Guoyu
,
Chevinsky, Jennifer
in
Cardiomyopathy
,
Clinical coding
,
Codes
2023
Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases.
Journal Article
Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping — United States, 2019
2019
Perrine et al examine the characteristics of a multistate outbreak of lung injury associated with electronic cigarette (e-cigarettes) use or vaping in the US in 2019. E-cigarettes, also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, flavorings, and other additives; users inhale this aerosol into their lungs. E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis. E-cigarettes, or vaping products, should never be used by youths, young adults, pregnant women, or by adults who do not currently use tobacco products. Adults who use e-cigarettes because they have quit smoking should not return to smoking combustible cigarettes.
Journal Article
Factors Predictive of the Status of Sentinel Lymph Nodes in Melanoma Patients from a Large Multicenter Database
2011
Background
Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database.
Methods
Seventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed.
Results
Of 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN.
Conclusions
These results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.
Journal Article
Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injuries — United States, October 2019
2019
CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products.
Journal Article