Novel Patient Metastatic Pleural Effusion-Derived Xenograft Model of Renal Medullary Carcinoma Demonstrates Therapeutic Efficacy of Sunitinib

BackgroundRenal medullary carcinoma (RMC) is a rare but aggressive tumor often complicated by early lung metastasis with few treatment options and very poor outcomes. There are currently no verified RMC patient-derived xenograft (PDX) mouse models established from metastatic pleural effusion (PE) available to study RMC and evaluate new therapeutic options.MethodsRenal tumor tissue and malignant PE cells from an RMC patient were successfully engrafted into 20 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. We evaluated the histopathological similarity of the renal tumor and PE PDXs with the original patient renal tumor and PE, respectively. We then evaluated the molecular integrity of the renal tumor PDXs between passages, as well as the PE PDX compared to two generations of renal tumor PDXs, by microarray analysis. The therapeutic efficacy of sunitinib and temsirolimus was tested in a serially-transplanted generation of 27 PE PDX mice.ResultsThe pathologic characteristics of the patient renal tumor and patient PE were retained in the PDXs. Gene expression profiling revealed high concordance between the two generations of renal tumor PDXs (RMC-P0 vs. RMC-P1, r=0.865), as well as between the first generation PE PDX and each generation of the renal tumor PDX (PE-P0 vs. RMC-P0, r=0.919 and PE-P0 vs. RMC-P1, r=0.843). A low number (626) of differentially-expressed genes (DEGs) was seen between the first generation PE PDX and the first generation renal tumor PDX. In the PE-P1 xenograft, sunitinib significantly reduced tumor growth (p<0.001) and prolonged survival (p=0.004) compared to the vehicle control.ConclusionsA metastatic PE-derived RMC PDX model was established and shown to maintain histologic features of the patient cancer. Molecular integrity of the PDX models was well maintained between renal tumor and PE PDX as well as between two successive renal tumor PDX generations. Using the PE PDX model, sunitinib demonstrated therapeutic efficacy for RMC. This model can serve as a foundation for future mechanistic and therapeutic studies for primary and metastatic RMC.

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Cytology of metastatic renal medullary carcinoma in pleural effusion: A study of two cases

Diagnostic Cytopathology ◽

10.1002/dc.21111 ◽

2009 ◽

Vol 37 (11) ◽

pp. 843-848 ◽

Cited By ~ 8

Author(s):

Carla L. Ellis ◽

Frances Burroughs ◽

Claire W. Michael ◽

Qing Kay Li

Keyword(s):

Pleural Effusion ◽

Medullary Carcinoma ◽

Renal Medullary Carcinoma

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Renal Medullary Carcinoma: A Recently Described Highly Aggressive Renal Tumor in Young Black Patients

The Journal of Urology ◽

10.1016/s0022-5347(01)64734-7 ◽

1997 ◽

Vol 157 (6) ◽

pp. 2246-2247 ◽

Cited By ~ 17

Author(s):

Judi C. Herring ◽

Mark A. Schmetz ◽

Amalia B. Digan ◽

Stephanie T. Young ◽

Naida B. Kalloo

Keyword(s):

Renal Tumor ◽

Medullary Carcinoma ◽

Renal Medullary Carcinoma ◽

Black Patients

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748: Gene Expression Profiling of Renal Medullary Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)37997-7 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 198-199 ◽

Cited By ~ 1

Author(s):

Ximing J. Yang ◽

Jun Sugimura ◽

Maria S. Tretiakova ◽

Bin T. Teh

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Medullary Carcinoma ◽

Renal Medullary Carcinoma

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Parental breeding age effects on descendants’ longevity interact over two generations in matrilines and patrilines

10.32942/osf.io/mnx8h ◽

2019 ◽

Author(s):

Zac Wylde ◽

Foteini Spagopoulou ◽

Amy K Hooper ◽

Alexei A Maklakov ◽

Russell Bonduriansky

Keyword(s):

Maternal Age ◽

First Generation ◽

Age Effects ◽

Population Variation ◽

Paternal Age ◽

Interactive Effects ◽

Competitive Environment ◽

Larval Diet ◽

Negative Effects ◽

Two Generations

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does, and that breeding age effects can interact over two generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over two generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grandparental ages at breeding on descendants’ mortality rate and lifespan in both matrilines and patrilines. These breeding age effects were not modulated by grandparental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intra-population variation in mortality and longevity.

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Establishment of a Patient-Derived Xenograft Model of Colorectal Cancer in CIEA NOG Mice and Exploring Smartfish Liquid Diet as a Source of Omega-3 Fatty Acids

Biomedicines ◽

10.3390/biomedicines9030282 ◽

2021 ◽

Vol 9 (3) ◽

pp. 282

Author(s):

Helle Samdal ◽

Lene C Olsen ◽

Knut S Grøn ◽

Elin S Røyset ◽

Therese S Høiem ◽

...

Keyword(s):

Colorectal Cancer ◽

Fatty Acid ◽

Fish Oil ◽

Fatty Acid Content ◽

Xenograft Model ◽

Liquid Diet ◽

Lymphoid Cells ◽

Omega 3 ◽

Pdx Model ◽

Nog Mice

Cancer patient-derived xenografts (PDXs) better preserve tumor characteristics and microenvironment than traditional cancer cell line derived xenografts and are becoming a valuable model in translational cancer research and personalized medicine. We have established a PDX model for colorectal cancer (CRC) in CIEA NOG mice with a 50% engraftment rate. Tumor fragments from patients with CRC (n = 5) were engrafted in four mice per tumor (n = 20). Mice with established PDXs received a liquid diet enriched with fish oil or placebo, and fatty acid profiling was performed to measure fatty acid content in whole blood. Moreover, a biobank consisting of tissue and blood samples from patients was established. Histology, immunohistochemistry and in situ hybridization procedures were used for staining of tumor and xenograft tissue slides. Results demonstrate that key histological characteristics of the patients’ tumors were retained in the established PDXs, and the liquid diets were consumed as intended by the mice. Some of the older mice developed lymphomas that originated from human Ki67+, CD45+, and EBV+ lymphoid cells. We present a detailed description of the process and methodology, as well as possible issues that may arise, to refine the method and improve PDX engraftment rate for future studies. The established PDX model for CRC can be used for exploring different cancer treatment regimes, and liquid diets enriched with fish oil may be successfully delivered to the mice through the drinking flasks.

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Conservation or change? Exploring trends in Modern Hebrew in light of new spoken corpora of the first two generations of speakers

Folia Linguistica ◽

10.1515/flih-2020-0004 ◽

2020 ◽

Vol 54 (s41) ◽

pp. 89-115

Author(s):

Einat Gonen

Keyword(s):

Early Modern ◽

First Generation ◽

Linguistic Features ◽

The Feminine ◽

Two Generations ◽

Modern Hebrew ◽

Small Set ◽

Diachronic Study ◽

The 1950S

Abstract This paper presents a diachronic study of Modern Hebrew agreement between numerals and their quantified nouns. This research is possible thanks to the discovery of two rare collections of recordings from the 1950s and 1960s, which document four generations of speakers and have become important sources of spoken Early Modern Hebrew. On the basis of these two corpora, I compare numeral agreement in the first two generations of speakers with present-day usage and analyze trends of change and conversation in Modern Hebrew. The study shows that the first generation of speakers (“Gen1”) largely acquired the gender distinction of cardinals. However, in contrast to other agreement issues that educated Gen1 speakers realized fully, numeral use showed variation and absence of agreement in a small set of cases. Moreover, some linguistic features of Gen1 Hebrew found in this study no longer characterize Present-Day Hebrew; among these features is prosodic conditioning, which led to a Gen1 tendency to use the feminine form of the numeral ‘four’ with masculine nouns more frequently than was the case with other numerals.

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