scholarly journals Contribution of LAT1-4F2hc in Urological Cancers via Toll-like Receptor and Other Vital Pathways

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 229
Author(s):  
Xue Zhao ◽  
Shinichi Sakamoto ◽  
Maihulan Maimaiti ◽  
Naohiko Anzai ◽  
Tomohiko Ichikawa
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Essential Amino Acids ◽  
Amino Acid Transporter ◽  
Tumor Cell Growth ◽  
Transporter Protein ◽  
Urological Cancers

Tumor cells are known for their ability to proliferate. Nutrients are essential for rapidly growing tumor cells. In particular, essential amino acids are essential for tumor cell growth. Tumor cell growth nutrition requires the regulation of membrane transport proteins. Nutritional processes require amino acid uptake across the cell membrane. Leucine, one of the essential amino acids, has recently been found to be closely associated with cancer, which activate mTOR signaling pathway. The transport of leucine into cells requires an L-type amino acid transporter protein 1, LAT1 (SLC7A5), which requires the 4F2 cell surface antigen heavy chain (4F2hc, SLC3A2) to form a heterodimeric amino acid transporter protein complex. Recent evidence identified 4F2hc as a specific downstream target of the androgen receptor splice variant 7 (AR-V7). We stressed the importance of the LAT1-4F2hc complex as a diagnostic and therapeutic target in urological cancers in this review, which covered the recent achievements in research on the involvement of the LAT1-4F2hc complex in urinary system tumors. In addition, JPH203, which is a selective LAT1 inhibitor, has shown excellent inhibitory effects on the proliferation in a variety of tumor cells. The current phase I clinical trials of JPH203 in patients with biliary tract cancer have also achieved good results, which is the future research direction for LAT1 targeted therapy drugs.

scholarly journals l-Type amino acid transporter 1 inhibitors inhibit tumor cell growth

2010 ◽  
Vol 101 (1) ◽  
pp. 173-179 ◽  
Author(s):  
Koji Oda ◽  
Noriko Hosoda ◽  
Hiroshi Endo ◽  
Kunio Saito ◽  
Kenji Tsujihara ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Tumor Cell ◽  
Amino Acid Transporter ◽  
Tumor Cell Growth ◽  
Acid Transporter

The uptake of amino acids by mouse cells (strain LS) during growth in batch culture and chemostat culture: the influence of cell growth rate

1967 ◽  
Vol 168 (1013) ◽  
pp. 421-438 ◽  
Keyword(s):  
Amino Acids ◽  
Growth Rate ◽  
Amino Acid ◽  
Cell Growth ◽  
Glutamic Acid ◽  
Batch Culture ◽  
Amino Acid Uptake ◽  
Essential Amino Acids ◽  
Growth Yields ◽  
Acid Uptake

The uptake of thirteen essential amino acids by mouse LS cells in suspension culture was determined by bacteriological assay methods. Chemostat continuous-flow cultures were used to determine the effect of different cell growth rates on the quantitative amino acid requirements for growth. The growth yields of the cells ( Y = g cell dry weight produced/g amino acid utilized) were calculated for each of the essential amino acids. A mixture of the non-essential amino acids, serine, alanine and glycine increased the cell yield from the essential amino acids. The growth yields from nearly all the essential amino acids in batch culture were increased when glutamic acid was substituted for the glutamine in the medium. The growth yields from the amino acids in batch culture were much less at the beginning than at the end of the culture. The highest efficiencies of conversion of amino acids to cell material were obtained by chemostat culture. When glutamic acid largely replaced the glutamine in the medium the conversion of amino acid nitrogen to cell nitrogen was 100 % efficient (that is, the theoretical yield was obtained) at the optimum growth rate (cell doubling time, 43 h). The maximum population density a given amino acid mixture will support can be calculated from the data. It is concluded that in several routinely used tissue culture media the cell growth is limited by the amino acid supply. In batch culture glutamine was wasted by (1) its spontaneous decomposition to pyrrolidone carboxylic acid and ammonia, and (2) its enzymic breakdown to glutamic acid and ammonia, but also glutamine was used less efficiently than glutamic acid. Study of the influence of cell growth rate on amino acid uptake rates per unit mass of cells indicated that a marked change in amino acid metabolism occurred at a specific growth rate of 0.4 day -1 (cell doubling time, 43 h). With decrease in specific growth rate below 0.4 day -1 there was a marked stimulation of amino acid uptake rate per cell and essential amino acids were consumed increasingly for functions other than synthesis of cell material.

scholarly journals Analysis of wild-type and mutant p21WAF-1 gene activities.

1996 ◽  
Vol 16 (4) ◽  
pp. 1786-1793 ◽  
Author(s):  
J Lin ◽  
C Reichner ◽  
X Wu ◽  
A J Levine
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Tumor Cell ◽  
Cyclin D1 ◽  
Cyclin E ◽  
Growth Suppression ◽  
Nuclear Antigen ◽  
Tumor Cell Growth ◽  
Amino Acid Residues ◽  
Wild Type

The p21WAF-1 gene is positively regulated by the wild-type p53 protein. p21WAF-1 has been shown to interact with several cyclin-dependent kinase complexes and block the activity of G1 cyclin-dependent kinases (cdks). Mutational analysis with the p21WAF-1 gene localized a site, at amino acid residues 21 and 24 in the amino terminus of the protein, for p21WAF-1 binding to cyclins D and E. This region of the protein is conserved (residues 21 to 26) in other p21WAF-1 family members, p27kip-1 and p57kip-2. The same p21WAF-121,24 mutant also fails to bind to cyclin D1-cdk 4 or cyclin E-cdk 2 complexes in vitro, suggesting that amino acid residues 21 and 24 are important for p21WAF-1-cdk-cyclin trimeric complex interactions. The p21WAF-1 wild-type protein will suppress tumor cell growth in culture while p21WAF-1 mutant proteins with defects in residues 21 and 24 fail to suppress tumor cell growth. The overexpression of cyclin D or E in these cells will partially overcome the growth suppression of wild-type p21WAF-1 protein in cells. These results provide evidence that p21WAF-1 acts through cyclin D1-cdk4 and cyclin E-cdk2 complexes in vivo to induce the growth suppression. The p21WAF-1 binding sites for cyclins (residues 21 to 26), cdk2 (residues 49 to 71), and proliferating-cell nuclear antigen (residues 124 to 164) have all been mapped to discrete sites on the protein.

scholarly journals Mathematical Modelling of the Dynamics of Tumor Growth and its Optimal Control

2020 ◽  
Author(s):  
Jannatun Irana Ira ◽  
Md. Shahidul Islam ◽  
Jagadish Chandra Misra
Keyword(s):  
Optimal Control ◽  
Cell Growth ◽  
Tumor Growth ◽  
Mathematical Modelling ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Treatment Process ◽  
Tumor Cell Growth ◽  
Growth Of Tumor ◽  
Over Time

The dynamics of tumor cell growth and its treatment process is discussed in this paper. We analyze some simple mathematical models and generalized models to understand the growth of tumor cells. A couple of diffusion models are discussed to explain how the tumor cells spread and become more dangerous as well as the treatment process of cancer and how cancer cell behaves in the presence of different therapy and drugs. The optimal control of chemotherapy has been discussed. It has also been explained how much the model is effective in reducing tumor cells over time.

The stimulation of tumor cell growth by a substance produced by normal and tumor cells

1969 ◽  
Vol 73 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Yasuo Ichikawa ◽  
Michael Paran ◽  
Leo Sachs
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Cell Growth ◽  
Stimulation Of

Lung Laminin-332 Deficiency Enhances Engraftment of Tumor Cells into the Lung but Retards Tumor Cell Growth

2012 ◽  
Vol 9 (2) ◽  
pp. 83-83
Author(s):  
Tracy L. Adair-Kirk ◽  
Michelle J. Meyer ◽  
Haris G. Vikas ◽  
Jay W. Tichelaar ◽  
Erin N. Jackson ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Cell Growth ◽  
Laminin 332

Gene Transfer of CD40-Ligand to Human Dendritic Cells Induces Growth Arrest and Apoptosis of Tumor Cells Mediated by Up-Regulated TRAIL and its Receptors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3454-3454
Author(s):  
Kei Tomihara ◽  
Kazunori Kato ◽  
Yukari Masuta ◽  
Makoto Noguchi ◽  
Hiroyoshi Hiratsuka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Growth ◽  
Natural Killer Cells ◽  
Gene Transfer ◽  
Cell Surface ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Growth Arrest ◽  
Tumor Cell Growth

Abstract Interaction of CD40 and its ligand CD40L is essential for the activation of dendritic cells (DC) followed by the induction of antigen-specific T-cell responses. Recent studies have also indicated that ligation of CD40 on tumor cells directly modulate tumor cell growth. In this study we examined whether gene transfer of CD40L to DC could exhibit direct anti-tumor effect on CD40-expressing tumors. First, we constructed a modified adenoviral vector driving human CD40L gene with CA promoter/enhancer and incorporating the integrin-binding motif, RGD, in the H1 loop of the fiber knob (AxCAhCD40L-F/RGD). At the same multiplicity of infection, cell surface expression of human CD40L on DC after infection with AxCAhCD40L-F/RGD (CD40L-DC) was induced to express superior higher levels of T-cell costimulatory molecules (CD80, CD86, and CD54), DC maturation markers (CD25 and CD83), MHC molecules and the production of IL-12 than soluble CD40L or TNF-a treated DC. In addition to the phenotypic alternation of CD40L-DC, we found that cultivation of tumor cells (including lymphoma, leukemia, glioma, head and neck carcinoma) with CD40L-DC significantly inhibited the expression of phospho-AKT and tumor cell growth in vitro. Importantly, these tumor cells in transwell cocultured with CD40L-DC, but not with TNF-a-treated DC or immature DC, were significantly induced to express apoptosis-inducing death receptors such as TRAIL-R1, TRAIL-R2 and Fas. The ability of CD40L-DC to inhibit tumor-cell growth and TRAIL receptor induction could not be abrogated by neutralizing antibodies specific for CD40L, IFN-b, IFN-g, and IL-12, indicating that these factors were not involved. Additionally, natural killer cells cocultured with CD40L-DC displayed marked up-regulation of TRAIL on their cell surface. To confirm the biological function of TRAIL and its receptors, we assessed the cytotoxic activity of NK cells to various tumors that were stimulated with CD40L-DC. Tumor cells stimulated with CD40L-DC were susceptible to apoptosis by recombinant TRAIL protein and natural killer cells expressing TRAIL. Overall, these results reveal that CD40L-transfected DC could induce direct tumor cell growth arrest mediated by AKT pathway and susceptibility of apoptosis by TRAIL, indicating that CD40L-DC have potential therapeutic implications which we were currently exploring.

Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3133-3138 ◽  
Author(s):  
Jasmine Zain ◽  
Yao-Qi Huang ◽  
XueSheng Feng ◽  
Mary Lynn Nierodzik ◽  
Jian-Jun Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Calf Serum ◽  
Annexin V ◽  
Tumor Cell Growth ◽  
Diisopropyl Fluorophosphate ◽  
General Caspase Inhibitor

Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume12 greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G2M and increased pre-GoDNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.

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