scholarly journals Host autophagy mediates organ wasting and nutrient mobilization for tumor growth

2020 ◽  
Author(s):  
Rojyar Khezri ◽  
Petter Holland ◽  
Todd Andrew Schoborg ◽  
Ifat Abramovich ◽  
Szabolcs Takats ◽  
...  
Keyword(s):  
Amino Acids ◽  
Tumor Growth ◽  
Nutrient Recycling ◽  
Critical Role ◽  
Tumor Model ◽  
Nutrient Mobilization ◽  
X Ray ◽  
Support Tumor Growth ◽  
Host Tissues

During tumor growth - when nutrient and anabolic demands are high – autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling1. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids2–4. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster. Micro-computed X-ray tomography and metabolic profiling reveal that RasV12; scrib-/- tumors grow 10-fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, −motility, −feeding and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

Critical role of Bronsted acid in Lewis-acid-catalyzed synthesis of Amadori and Heyns compounds of β-amino acids

2021 ◽  
pp. 1-11
Author(s):  
Debasree Chanda ◽  
Gangothri M. Venkataswamy ◽  
Lagamawwa V. Hipparagi ◽  
Nanishankar V. Harohally
Keyword(s):  
Amino Acids ◽  
Lewis Acid ◽  
Critical Role ◽  
Bronsted Acid ◽  
Brønsted Acid ◽  
Brönsted Acid ◽  
Acid Catalyzed

Diverse Roles of Macrophage Matrix Metalloproteinases in Tissue Destruction and Tumor Growth

1999 ◽  
Vol 82 (08) ◽  
pp. 846-849 ◽  
Author(s):  
Steven Shapiro
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Gene Targeting ◽  
Critical Role ◽  
Human Biology ◽  
Disease Models ◽  
Tumor Growth Inhibition ◽  
Mouse Macrophage ◽  
Tissue Destruction

SummaryIn the mouse, macrophage elastase is critical to macrophage proteolysis. The use of gene-targeting has uncovered both pathological roles, including destructive effects in aneurysm formation and emphysema, and physiological roles, such as tumor growth inhibition and regulation of inflammation. Translation of findings from mouse to human biology depends upon how well the disease models replicate the human conditions and the similarity of enzyme profile between species. We know that human MMP-12 is associated with these diseases, but as opposed to the mouse, other MMPs may also be of importance (MMP-9, and perhaps MMP-7, in particular). Our interpretation is that findings in mice reflect the critical role of macrophage proteolysis in these disease processes.

Critical Role of Capping Layer in Determining Co−Fe−B/MgO Interfacial Magnetism Revealed by X-Ray Magnetic Circular Dichroism

2020 ◽  
Vol 14 (5) ◽  
Author(s):  
James Lourembam ◽  
Xiaojiang Yu ◽  
Maria Patricia Rouelli Sabino ◽  
Michael Tran ◽  
Roslyn Wan Teng Ang ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Magnetic Circular Dichroism ◽  
Critical Role ◽  
Capping Layer ◽  
X Ray ◽  
Circular Dichroïsm

Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for effective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model

2020 ◽  
Vol 69 (6) ◽  
pp. 1001-1014 ◽  
Author(s):  
Jose-Ignacio Rodriguez-Barbosa ◽  
Miyuki Azuma ◽  
Gennadiy Zelinskyy ◽  
Jose-Antonio Perez-Simon ◽  
Maria-Luisa del Rio
Keyword(s):  
Tumor Cells ◽  
Critical Role ◽  
Tumor Model ◽  
Transplantable Mouse

Arginine 595 is duplicated in patients with acute leukemias carrying internal tandem duplications of FLT3 and modulates its transforming potential

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 686-694 ◽  
Author(s):  
Sridhar Vempati ◽  
Carola Reindl ◽  
Seshu Kumar Kaza ◽  
Ruth Kern ◽  
Theodora Malamoussi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Mechanism ◽  
Positive Charge ◽  
Critical Role ◽  
Heterogeneous Group ◽  
Wild Type ◽  
Acute Leukemias ◽  
Juxtamembrane Region ◽  
Tandem Duplications

Abstract FLT3–internal tandem duplications (FLT3-ITDs) comprise a heterogeneous group of mutations in patients with acute leukemias that are prognostically important. To characterize the mechanism of transformation by FLT3-ITDs, we sequenced the juxtamembrane region (JM) of FLT3 from 284 patients with acute leukemias. The length of FLT3-ITDs varied from 2 to 42 amino acids (AAs) with a median of 17 AAs. The analysis of duplicated AAs showed that in the majority of patients, the duplications localize between AAs 591 to 599 (YVDFREYEY). Arginine 595 (R595) within this region is duplicated in 77% of patients. Single duplication of R595 in FLT3 conferred factor-independent growth to Ba/F3 cells and activated STAT5. Moreover, deletion or substitution of the duplicated R595 in 2 FLT3-ITD constructs as well as the deletion of wild-type R595 in FLT3-ITD substantially reduced the transforming potential and STAT5 activation, pointing to a critical role of the positive charge of R595 in stabilizing the active confirmation of FLT3-ITDs. Deletion of R595 in FLT3-WT nearly abrogated the ligand-dependent activation of FLT3-WT. Our data provide important insights into the molecular mechanism of transformation by FLT3-ITDs and show that duplication of R595 is important for the leukemic potential of FLT3-ITDs.

scholarly journals Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer

2019 ◽  
Vol 20 (24) ◽  
pp. 6342
Author(s):  
Teizo Yoshimura ◽  
Kaoru Nakamura ◽  
Chunning Li ◽  
Masayoshi Fujisawa ◽  
Tsuyoshi Shiina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Cancer Progression ◽  
Critical Role ◽  
Gm Csf ◽  
4T1 Cells

We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whether 4T1 cell-derived GM-CSF contributes to the expression of these genes by 4T1tumors, and their subsequent progression. Intraperitoneal injection of anti-GM-CSF neutralizing antibody did not decrease the expression of Mcp-1, Ccl17 or Rankl mRNA by 4T1 tumors. To further examine the role of cancer cell-derived GM-CSF, we generated GM-CSF-deficient 4T1 cells by using the Crisper-Cas9 system. As previously demonstrated, 4T1 cells are a mixture of cells and cloning of cells by itself significantly reduced tumor growth and lung metastasis. By contrast, GM-CSF-deficiency did not affect tumor growth, lung metastasis or the expression of these chemokine and cytokine genes in tumor tissues. By in-situ hybridization, the expression of Mcp-1 mRNA was detected in both F4/80-expressing and non-expressing cells in tumors of GM-CSF-deficient cells. These results indicate that cancer cell-derived GM-CSF is dispensable for the tuning of the 4T1 tumor microenvironment and the production of MCP-1, CCL17 or RANKL in the 4T1 tumor microenvironment is likely regulated by redundant mechanisms.

Barium accumulation in rat pancreatic B cells

1976 ◽  
Vol 22 (2) ◽  
pp. 455-465
Author(s):  
S.L. Howell ◽  
M. Tyhurst
Keyword(s):  
B Cells ◽  
Cyclic Amp ◽  
Divalent Cations ◽  
Critical Role ◽  
Frozen Sections ◽  
X Ray ◽  
Pancreatic B Cells ◽  
Acetate Accumulation ◽  
Rat Islets Of Langerhans

Barium has been used as an electron-opaque substitute for calcium in a study of the distribution of divalent cations between organelles in homogenates or intact rat islets of Langerhans. These were incubated in the presence of barium acetate. Accumulation of electron-opaque deposits was stimulated during incubation of islets in the presence of high glucose concentrations and was diminished in conditions in which intracellular cyclic AMP levels were raised. Mitochondria were found to be the principal sites of accumulation of electron-opaque deposits. Addition of dinitrophenol to homogenates or intact islets abolished mitochondrial barium accumulation. X-ray microanalysis of the deposits in frozen sections showed them to consist predominantly of barium and phosphate. These experiments serve to emphasize further the critical role of mitochondria in the regulation of divalent cation accumulation in B cells, and to confirm that a direct effect on intracellular distribution of divalent cations may represent one important mechanism of action of cyclic AMP in regulating insulin secretion.

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