Search results for " SCID"
showing 10 items of 131 documents
VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells
2014
Abstract Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this met…
Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells.
2011
Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signaling proteins, and the host tissue reaction, among other influencing factors. This paper presents evidence for the significance of pre-seeded osteoblasts for the in vivo vascularization of a biodegradable scaffold. Human osteoblasts, cultured on silk fibroin micronets in vitro, migrated throughout the interconnected pores of the scaffold and produced extensive bone matrix. When these constructs we…
Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells
2004
Hematopoietic (Hem) and endothelial (End) lineages derive from a common progenitor cell, the hemangioblast: specifically, the human cord blood (CB) CD34+KDR+ cell fraction comprises primitive Hem and End cells, as well as hemangioblasts. In humans, the potential therapeutic role of Hem and End progenitors in ischemic heart disease is subject to intense investigation. Particularly, the contribution of these cells to angiogenesis and cardiomyogenesis in myocardial ischemia is not well established. In our studies, we induced myocardial infarct (MI) in the immunocompromised NOD-SCID mouse model, and monitored the effects of myocardial transplantation of human CB CD34+ cells on cardiac function.…
In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent.
2015
International audience; Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor α chain (IL3-Rα or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and …
RASSF1A inhibits estrogen receptor alpha expression and estrogen-independent signalling: implications for breast cancer development
2012
The Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor whose inactivation is implicated in the development of many human cancers, including breast carcinomas. Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors. Here, we show that RASSF1A inhibits breast cancer growth in vivo, and suppresses estrogen receptor (ERα) expression and function. Reconstitution of RASSF1A in MCF7 cells led to decreased ERα levels and reduced sensitivity to estrogen (E2). Concomitantly, we observed decreased expression of Id1 as well as the E2-responsive gen…
Human interleukin-6 facilitates hepatitis B virus infection in vitro and in vivo.
2000
Abstract Background and aim. Research on hepatitis B virus (HBV) infection in vivo has been limited due to the absence of a suitable animal model. We have developed a human–mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and solid tissues. This resulting human–mouse model, which comprises three genetically disparate sources of tissue, is therefore termed Trimera. This study was aimed at assessing the effect of human IL-6 on HBV infection in vivo in Trimera mice. Methods. Trimera mice were transplanted with human liver tissue fragment…
V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…
2010
Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…
Mutant HRAS as novel target for MEK and mTOR inhibitors.
2015
HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an imp…
Engraftment kinetics of human CD34+ cells from cord blood and mobilized peripheral blood co-transplanted into NOD/SCID mice
2004
We have reported short periods of post transplant neutropenia in human patients co-transplanted with cord blood (CB) and low numbers of haploidentical mobilized peripheral blood (MPB) CD34+ cells. To investigate the effect that the proportion of MPB to CB cells may have on engraftment kinetics, we have co-transplanted fixed numbers of human CB CD34+ cells mixed with different numbers of MPB CD34+ cells into NOD/SCID mice. We periodically quantified the proportion of human cells and the relative contribution of MPB and CB cells to the human engraftment on marrow aspirates. At the lowest MPB/CB ratios (5 : 1, 10 : 1), the contribution of CB cells predominated at all time points analyzed, and …
Differential expression of mRNA encoding interleukin-12 p35 and p40 subunitsin situ
1994
Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly st…