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Raghu Kalluri

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https://www.readbyqxmd.com/read/29766399/consensus-guidelines-for-the-use-and-interpretation-of-angiogenesis-assays
#1
REVIEW
Patrycja Nowak-Sliwinska, Kari Alitalo, Elizabeth Allen, Andrey Anisimov, Alfred C Aplin, Robert Auerbach, Hellmut G Augustin, David O Bates, Judy R van Beijnum, R Hugh F Bender, Gabriele Bergers, Andreas Bikfalvi, Joyce Bischoff, Barbara C Böck, Peter C Brooks, Federico Bussolino, Bertan Cakir, Peter Carmeliet, Daniel Castranova, Anca M Cimpean, Ondine Cleaver, George Coukos, George E Davis, Michele De Palma, Anna Dimberg, Ruud P M Dings, Valentin Djonov, Andrew C Dudley, Neil P Dufton, Sarah-Maria Fendt, Napoleone Ferrara, Marcus Fruttiger, Dai Fukumura, Bart Ghesquière, Yan Gong, Robert J Griffin, Adrian L Harris, Christopher C W Hughes, Nan W Hultgren, M Luisa Iruela-Arispe, Melita Irving, Rakesh K Jain, Raghu Kalluri, Joanna Kalucka, Robert S Kerbel, Jan Kitajewski, Ingeborg Klaassen, Hynda K Kleinmann, Pieter Koolwijk, Elisabeth Kuczynski, Brenda R Kwak, Koen Marien, Juan M Melero-Martin, Lance L Munn, Roberto F Nicosia, Agnes Noel, Jussi Nurro, Anna-Karin Olsson, Tatiana V Petrova, Kristian Pietras, Roberto Pili, Jeffrey W Pollard, Mark J Post, Paul H A Quax, Gabriel A Rabinovich, Marius Raica, Anna M Randi, Domenico Ribatti, Curzio Ruegg, Reinier O Schlingemann, Stefan Schulte-Merker, Lois E H Smith, Jonathan W Song, Steven A Stacker, Jimmy Stalin, Amber N Stratman, Maureen Van de Velde, Victor W M van Hinsbergh, Peter B Vermeulen, Johannes Waltenberger, Brant M Weinstein, Hong Xin, Bahar Yetkin-Arik, Seppo Yla-Herttuala, Mervin C Yoder, Arjan W Griffioen
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation...
May 15, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29686035/a-peek-into-cancer-associated-fibroblasts-origins-functions-and-translational-impact
#2
REVIEW
Valerie S LeBleu, Raghu Kalluri
In malignant tumors, cancer cells adapt to grow within their host tissue. As a cancer progresses, an accompanying host stromal response evolves within and around the nascent tumor. Among the host stromal constituents associated with the tumor are cancer-associated fibroblasts, a highly abundant and heterogeneous population of cells of mesenchymal lineage. Although it is known that fibroblasts are present from the tumor's inception to the end-stage metastatic spread, their precise functional role in cancer is not fully understood...
April 19, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29669940/generation-and-testing-of-clinical-grade-exosomes-for-pancreatic-cancer
#3
Mayela Mendt, Sushrut Kamerkar, Hikaru Sugimoto, Kathleen M McAndrews, Chia-Chin Wu, Mihai Gagea, Sujuan Yang, Elena V Rodriges Blanko, Qian Peng, Xiaoyan Ma, Joseph R Marszalek, Anirban Maitra, Cassian Yee, Katayoun Rezvani, Elizabeth Shpall, Valerie S LeBleu, Raghu Kalluri
Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. Here, we report on a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29664738/pharmacological-induction-of-hypoxia-inducible-transcription-factor-arnt-attenuates-chronic-kidney-failure
#4
Björn Tampe, Désirée Tampe, Gunsmaa Nyamsuren, Friederike Klöpper, Gregor Rapp, Anne Kauffels, Thomas Lorf, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Samy Hakroush, Michael Zeisberg
Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge, because once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury...
April 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29580275/the-emerging-roles-of-exosomes-in-the-modulation-of-immune-responses-in-cancer
#5
Paul Kurywchak, Jena Tavormina, Raghu Kalluri
Exosomes are promising tools for improving cancer care, but conversely may also contribute to tumor progression. Here, we highlight recently discovered roles of exosomes in modulating immune responses in cancer, with emphasis on exosomal surface proteins and on RNA and DNA content. We also discuss how exosomes could be exploited as biomarkers and delivery vehicles in cancer therapy.
March 26, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29573973/fatty-acid-oxidation-regulates-the-activation-of-endothelial-to-mesenchymal-transition
#6
Sara Lovisa, Raghu Kalluri
The molecular mechanisms underpinning the process of endothelial-to-mesenchymal transition (EndMT) are mostly unknown. Recently Xiong and colleagues explored for the first time the metabolic changes associated with the activation of the mesenchymal program in endothelial cells, and found that reprogramming of fatty acid oxidation pivotally regulates EndMT.
March 21, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29326430/emt-in-cancer
#7
REVIEW
Thomas Brabletz, Raghu Kalluri, M Angela Nieto, Robert A Weinberg
Similar to embryonic development, changes in cell phenotypes defined as an epithelial to mesenchymal transition (EMT) have been shown to play a role in the tumorigenic process. Although the first description of EMT in cancer was in cell cultures, evidence for its role in vivo is now widely reported but also actively debated. Moreover, current research has exemplified just how complex this phenomenon is in cancer, leaving many exciting, open questions for researchers to answer in the future. With these points in mind, we asked four scientists for their opinions on the role of EMT in cancer and the challenges faced by scientists working in this fast-moving field...
February 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29303514/depletion-of-s100a4-stromal-cells-does-not-prevent-hcc-development-but-reduces-the-stem-cell-like-phenotype-of-the-tumors
#8
Jingjing Jiao, Álvaro González, Heather L Stevenson, Mihai Gagea, Hikaru Sugimoto, Raghu Kalluri, Laura Beretta
There is a pressing need for the development of novel approaches to treat and prevent hepatocellular carcinoma (HCC). The S100 calcium-binding protein S100A4 is associated with poor prognosis and metastasis in several human cancers. In addition, a role for S100A4 in modulating cancer-initiating cells stemness properties was recently proposed in head and neck and gastric cancers. Whether S100A4+ stromal cells contribute to tumor onset remains, however, an unanswered question. To address that question, we generated a new mouse model allowing for the depletion of S100A4+ cells in a mouse model of HCC with stemness properties, by crossing mice with hepatic deletion of phosphatase and tensin homolog (PTEN) with mice expressing viral thymidine kinase under the control of S100A4 promoter...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28855213/exosomes-from-glioma-associated-mesenchymal-stem-cells-increase-the-tumorigenicity-of-glioma-stem-like-cells-via-transfer-of-mir-1587
#9
Javier Figueroa, Lynette M Phillips, Tal Shahar, Anwar Hossain, Joy Gumin, Hoon Kim, Andrew J Bean, George A Calin, Juan Fueyo, Edgar T Walters, Raghu Kalluri, Roel G Verhaak, Frederick F Lang
Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28775207/development-of-aggressive-pancreatic-ductal-adenocarcinomas-depends-on-granulocyte-colony-stimulating-factor-secretion-in-carcinoma-cells
#10
Michael W Pickup, Philip Owens, Agnieszka E Gorska, Anna Chytil, Fei Ye, Chanjuan Shi, Valerie M Weaver, Raghu Kalluri, Harold L Moses, Sergey V Novitskiy
The survival rate for pancreatic ductal adenocarcinoma (PDAC) remains low. More therapeutic options to treat this disease are needed, for the current standard of care is ineffective. Using an animal model of aggressive PDAC (Kras/p48(TGFβRIIKO)), we discovered an effect of TGFβ signaling in regulation of G-CSF secretion in pancreatic epithelium. Elevated concentrations of G-CSF in PDAC promoted differentiation of Ly6G(+) cells from progenitors, stimulated IL10 secretion from myeloid cells, and decreased T-cell proliferation via upregulation of Arg, iNOS, VEGF, IL6, and IL1b from CD11b(+) cells...
September 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28607485/exosomes-facilitate-therapeutic-targeting-of-oncogenic-kras-in-pancreatic-cancer
#11
Sushrut Kamerkar, Valerie S LeBleu, Hikaru Sugimoto, Sujuan Yang, Carolina F Ruivo, Sonia A Melo, J Jack Lee, Raghu Kalluri
The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic KrasG12D , a common mutation in pancreatic cancer...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28524163/an-evolving-function-of-dna-containing-exosomes-in-chemotherapy-induced-immune-response
#12
Paul Kurywchak, Raghu Kalluri
Chemotherapy is a predominant strategy to treat cancer and is often associated with toxicities like severe diarrhea that puts patients at additional risk and can hinder treatment strategies. Lian et al. recently explored the immune-mediated mechanisms of Irinotecan-induced diarrhea in colorectal cancer and found that double-stranded DNA in small vesicles can launch inflammation pathways in immune cells through the cytosolic DNA sensor AIM2.
June 2017: Cell Research
https://www.readbyqxmd.com/read/28447602/spatial-computation-of-intratumoral-t-cells-correlates-with-survival-of-patients-with-pancreatic-cancer
#13
Julienne L Carstens, Pedro Correa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P Allison, Valerie S LeBleu, Raghu Kalluri
The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28424339/discovery-of-double-stranded-genomic-dna-in-circulating-exosomes
#14
REVIEW
Raghu Kalluri, Valerie S LeBleu
It is becoming increasingly clear that small vesicles released from cells (extracellular vesicles [EVs]) represent a heterogeneous population implicated in cell-to-cell communication. The classifications and nomenclature of EVs are evolving as enrichment strategies and specific characteristics are being unraveled. At present, physical properties of EVs-namely, size, shape, and density-are often used to identify subpopulations of EVs. A distinct group of EVs, termed exosomes, largely defined by their small size (∼40-150 nm) and proposed subcellular origin, has been extensively studied in several aspects of cancer biology...
2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28424335/a-conversation-with-raghu-kalluri
#15
(no author information available yet)
No abstract text is available yet for this article.
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28334208/morphologically-constrained-spectral-unmixing-by-dictionary-learning-for-multiplex-fluorescence-microscopy
#16
Murad Megjhani, Pedro Correa de Sampaio, Julienne Leigh Carstens, Raghu Kalluri, Badrinath Roysam
Motivation: Current spectral unmixing methods for multiplex fluorescence microscopy have a limited ability to cope with high spectral overlap as they only analyze spectral information over individual pixels. Here, we present adaptive Morphologically Constrained Spectral Unmixing (MCSU) algorithms that overcome this limitation by exploiting morphological differences between sub-cellular structures, and their local spatial context. Results: The proposed method was effective at improving spectral unmixing performance by exploiting: (i) a set of dictionary-based models for object morphologies learned from the image data; and (ii) models of spatial context learned from the image data using a total variation algorithm...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28121262/detection-of-mutant-kras-and-tp53-dna-in-circulating-exosomes-from-healthy-individuals-and-patients-with-pancreatic-cancer
#17
Sujuan Yang, Sara P Y Che, Paul Kurywchak, Jena L Tavormina, Liv B Gansmo, Pedro Correa de Sampaio, Michael Tachezy, Maximilian Bockhorn, Florian Gebauer, Amanda R Haltom, Sonia A Melo, Valerie S LeBleu, Raghu Kalluri
Pancreatic cancer presents with a dismal mortality rate and is in urgent need of methods for early detection with potential for timely intervention. All living cells, including cancer cells, generate exosomes. We previously discovered double stranded genomic DNA in exosomes derived from the circulation of pancreatic cancer patients, which enabled the detection of prevalent mutations associated with the disease. Here, we report a proof-of-concept study that demonstrates the potential clinical utility of circulating exosomal DNA for identification of KRASG 12 D and TP53R 273 H mutations in patients with pancreas-associated pathologies, including pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP) and intraductal papillary mucinous neoplasm (IPMN), and in healthy human subjects...
March 4, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27692563/low-dose-hydralazine-prevents-fibrosis-in-a-murine-model-of-acute-kidney-injury-to-chronic-kidney-disease-progression
#18
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
January 2017: Kidney International
https://www.readbyqxmd.com/read/27550820/the-biology-and-function-of-fibroblasts-in-cancer
#19
REVIEW
Raghu Kalluri
Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells...
August 23, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27372267/partial-epithelial-to-mesenchymal-transition-and-other-new-mechanisms-of-kidney-fibrosis
#20
REVIEW
Sara Lovisa, Michael Zeisberg, Raghu Kalluri
Kidney fibrosis is the unavoidable consequence of chronic kidney disease irrespective of the primary underlying insult. It is a complex phenomenon governed by the interplay between different cellular components and intricate networks of signaling pathways, which together lead to loss of renal functionality and replacement of kidney parenchyma with scar tissue. An immense effort has recently been made to understand the molecular and cellular mechanisms leading to kidney fibrosis. The cellular protagonists of this process include myofibroblasts, tubular epithelial cells, endothelial cells, and immune cells...
October 2016: Trends in Endocrinology and Metabolism: TEM
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