Transforming Growth Factor Beta 1 is Significantly Elevated in Plasma of Patients Suffering from Renal Cell Carcinoma

Junker, U.; Knoefel, B.; Nuske, K.; Rebstock, K.; Steiner, Th.; Wunderlich, Heiko; Junker, Kerstin; Reinhold, Dirk

doi:10.1006/cyto.1996.0105

Cited by 70 publications

(18 citation statements)

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“…Tgfb1 is most frequently upregulated in tumours, and high tumour burden as well as circulating plasma levels of Tgfb1 are associated with enhanced tumour angiogenesis and poor prognosis in several cancers [53,54,55,56,57,58]. In addition, Tgfb1 may also suppress natural killer cell activity and is known to incur tamoxifen resistance in breast cancer cells [59].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Changes in Spleens and Livers of Tumour-Bearing Mice Suggest Delayed Inflammation and Attenuated Cachexia in Response to Oil Palm Phenolics

et al. 2013

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Background/Aim: Plant phenolics can inhibit, retard or reverse carcinogenesis, and may thus help prevent or treat cancer. Oil palm phenolics (OPP) previously showed anti-tumour activities in vivo via a cytostatic mechanism at 1,500 ppm gallic acid equivalent. Here, we report other possible molecular mechanisms by which this extract attenuates cancer, especially those concerning the immune response. Methods: We subcutaneously injected J558 myeloma cells in BALB/c mice and supplemented OPP orally at 1,500 ppm gallic acid equivalent. We observed the physiology parameters of these animals and harvested their spleens and livers after 18 h, 1 week and 4 weeks for microarray gene expression analysis using Illumina MouseRef-8 BeadChips. Results: Time course microarray analysis on spleens after injecting J558 myeloma cells in mice revealed that the immune response of tumour-bearing mice supplemented with OPP was lower compared to controls, thus suggesting delayed inflammation in response to OPP. In livers, cholesterol biosynthesis genes were upregulated while inflammatory genes were downregulated through time, further suggesting attenuation of systemic inflammation and cachexia. These effects correlated with the delayed in vivo development of syngeneic tumours in mice given OPP. Conclusions: This study suggests the possible utilisation of OPP as an anti-tumour and anti-cachexia agent.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Changes in Spleens and Livers of Tumour-Bearing Mice Suggest Delayed Inflammation and Attenuated Cachexia in Response to Oil Palm Phenolics

et al. 2013

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“…Instead, published studies have relied on ELISA or receptor binding assays performed on blood plasma, with widely varying results (0.5 to 25 ng/mL in human plasma) 55 . It has been shown that TGF-β concentrations are significantly higher in plasma samples from cancer patients compared to healthy controls 56 , but the precise level of active TGF- β at tumor local environments remains unknown. Active TGF-β concentrations are expected to be higher at tumor sites than in plasma, as solid tumors are known to secrete TGF-β, and latent forms of TGF-β (produced by either tumor or other cell types) are known to be activated by tumor-associated metalloproteases 57 .…”

Section: Methodsmentioning

confidence: 99%

Rewiring T-cell responses to soluble factors with chimeric antigen receptors

et al. 2018

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Chimeric antigen receptor (CAR)-expressing T cells targeting surface-bound tumor antigens have yielded promising clinical outcomes, with two CD19 CAR-T cell therapies recently receiving FDA approval for the treatment of B-cell malignancies. The adoption of CARs for the recognition of soluble ligands, a distinct class of biomarkers in physiology and disease, could significantly broaden the utility of CARs in disease treatment. In this study, we demonstrate that CAR-T cells can be engineered to respond robustly to diverse soluble ligands, including CD19 ectodomain, GFP variants, and transforming growth factor beta (TGF-β). We additionally show that CAR signaling in response to soluble ligands relies on ligand-mediated CAR dimerization, and that CAR responsiveness to soluble ligands can be fine-tuned by adjusting the mechanical coupling between the CAR’s ligand-binding and signaling domains. Our results support a role for mechanotransduction in CAR signaling and demonstrate an approach to systematically engineer immune-cell responses to soluble, extracellular ligands.

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“…[9] This has been clearly demonstrated in earlier in vitro studies where cells, human or murine, are treated with recombinant TGF-β (rTGFβ1) in culture. Under these conditions, at single cell level or in batch culture, rTGFβ (300 pg/mL, a concentration found in human plasma [27]) reversibly maintains HSPC cells in a quiescent state without inducing apoptosis. [28–30] Likewise, injection of rTGFβ directly to mice is sufficient to suppress HSPC proliferation.…”

Section: The Conundrum Of Tgfβ Signaling: Quiescence or Not Quiescence?mentioning

confidence: 99%

Deconstructing the Complexity of TGFβ Signaling in Hematopoietic Stem Cells: Quiescence and Beyond

Hinge

Filippi

2016

Curr Stem Cell Rep

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The hematopoietic system is highly dynamic and must constantly produce new blood cells every day. Mature blood cells all derive from a pool of rare long-lived hematopoietic stem cells (HSCs) that are mostly quiescent but occasionally divide and self-renew in order to maintain the stem cell pool and continuous replenishment of mature blood cells throughout life. A tight control of HSC self-renewal, commitment to differentiation and maintenance of quiescence states is necessary for lifelong blood supply. Transforming growth factor-β (TGF-β) is a critical regulator hematopoietic cell functions. It is a potent inhibitor of hematopoietic cell growth. However, TGFβ functions are more complex and largely context-dependent. Emerging evidence suggests a role in aging, cell identity and cell fate decisions. Here, we will review the role of TGF-β and downstream signaling in normal HSC functions, in HSC quiescence and beyond.

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Transforming Growth Factor Beta 1 is Significantly Elevated in Plasma of Patients Suffering from Renal Cell Carcinoma

Cited by 70 publications

References 0 publications

Gene Expression Changes in Spleens and Livers of Tumour-Bearing Mice Suggest Delayed Inflammation and Attenuated Cachexia in Response to Oil Palm Phenolics

Gene Expression Changes in Spleens and Livers of Tumour-Bearing Mice Suggest Delayed Inflammation and Attenuated Cachexia in Response to Oil Palm Phenolics

Rewiring T-cell responses to soluble factors with chimeric antigen receptors

Deconstructing the Complexity of TGFβ Signaling in Hematopoietic Stem Cells: Quiescence and Beyond

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