Renal Lymph: Vital for the Kidney and Valuable for the Physiologist

Pinter, G. G.

doi:10.1152/physiologyonline.1988.3.5.189

Cited by 10 publications

(9 citation statements)

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“…As such, transplantable tumor lines, akin to those presented here, were not developed. One of the major advantages of SRC grafting over traditional subcutaneous grafting is the high tumor take rate (94%) and success rate of transplantable tumor line development (44%); largely due to the vascularization of the kidney (40,41). The abundant supply of nutrients, hormones, growth factors, and oxygen to transplanted cells and tissues (before they become vascularized) at the SRC site is likely instrumental to the success of the engraftment, and the conservation of patient tumor properties (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

High Fidelity Patient-Derived Xenografts for Accelerating Prostate Cancer Discovery and Drug Development

et al. 2014

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Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development. Xenografts preserved the histopathology, genome architecture, and global gene expression of donor tumors. Moreover, their aggressiveness matched patient observations, and their response to androgen withdrawal correlated with tumor subtype. The panel includes the first xenografts generated from needle biopsy tissue obtained at diagnosis. This advance was exploited to generate independent xenografts from different sites of a primary site, enabling functional dissection of tumor heterogeneity. Prolonged exposure of adenocarcinoma xenografts to androgen withdrawal led to castration-resistant prostate cancer, including the first-in-field model of complete transdifferentiation into lethal neuroendocrine prostate cancer. Further analysis of this model supports the hypothesis that neuroendocrine prostate cancer can evolve directly from adenocarcinoma via an adaptive response and yielded a set of genes potentially involved in neuroendocrine transdifferentiation. We predict that these next-generation models will be transformative for advancing mechanistic understanding of disease progression, response to therapy, and personalized oncology. Cancer Res; 74(4); 1272-83. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

High Fidelity Patient-Derived Xenografts for Accelerating Prostate Cancer Discovery and Drug Development

et al. 2014

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“…39 Consequently, there is an exceptionally high fluid circulation within the extracellular space of the kidney. 40 This provides high graft perfusion, and the abundant supply of nutrients, hormones, growth factors and oxygen to transplanted cells and tissues (before they become vascularized) is likely instrumental to the success of the engraftment. 41 42 43 44 45 Access to the graft site is relatively easy via a small incision into the back of the host.…”

Section: Src Grafting Of Prostatic Tissuesmentioning

confidence: 99%

Next generation patient-derived prostate cancer xenograft models

et al. 2014

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There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients’ tumor tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer.

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“…These clustered regions occupy only a limited surface area of the peritubular capillary wall (14,15). We have suggested that plasma proteins leak out through these limited regions of the peritubular capillary wall, distinct from the reabsorbing surfaces that comprise the major part of the capillary wall where the bulk of the tubular reabsorbate enters the capillary (16). We have further estimated that, under normal conditions, the reflexion coefficient of the reabsorbing surfaces is high (>0.99) and that virtually none of the extravasated protein caught up in the reabsorbtive stream will reenter the capillaries; almost all of the extravasated plasma proteins will drain from the interstitium through the lymph (11).…”

Section: Plasma Protein Circulation Through Kidney Cortical Interstitiummentioning

confidence: 99%

Role of Postglomerular Microvessels in Pathophysiology of Diabetic Nephropathy: Assessment and Hypothesis

Pinter

Atkins²

1991

Diabetes

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Although glomerular damage plays a well-established and important role in the pathomechanism of diabetic nephropathy, it alone does not fully explain the progression of renal complications in long-term diabetes mellitus. We discuss experimental evidence showing involvement of the postglomerular microvessels (peritubular capillaries and venules) in diabetic microangiopathy. This involvement is manifest in increased permeability of these vessels to plasma proteins and in highly augmented lymphatic drainage of the extravasated proteins from the renal interstitium. We suggest that in the advanced phase of diabetic nephropathy, proteinuria (corresponding to excess leakage of proteins through the glomerular capillary wall) indicates the probability that postglomerular microvessels have also allowed leakage of plasma proteins. As long as lymphatic drainage is capable of removing the increased quantity of extravasated plasma proteins from the interstitium, renal function should not be deleteriously affected. However, if the excess amount of extravasated proteins exceeds the capacity of lymphatic drainage, increases in interstitial volume and pressure are unavoidable with detrimental consequences for glomerular filtration and tubular reabsorption. Under these conditions, a potential positive-feedback loop can be visualized that involves increased extravasation of plasma proteins leading to increased interstitial pressure that through dilation of the afferent and efferent arterioles results in a further increase in protein extravasation. These conditions combined with glomerular damage should lead to the eventual collapse of renal function.

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Renal Lymph: Vital for the Kidney and Valuable for the Physiologist

Cited by 10 publications

References 0 publications

High Fidelity Patient-Derived Xenografts for Accelerating Prostate Cancer Discovery and Drug Development

High Fidelity Patient-Derived Xenografts for Accelerating Prostate Cancer Discovery and Drug Development

Next generation patient-derived prostate cancer xenograft models

Role of Postglomerular Microvessels in Pathophysiology of Diabetic Nephropathy: Assessment and Hypothesis

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