scholarly journals Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 537
Author(s):  
Paula Wróblewska-Łuczka ◽  
Aneta Grabarska ◽  
Magdalena Florek-Łuszczki ◽  
Zbigniew Plewa ◽  
Jarogniew J. Łuszczki
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Type I ◽  
Antiproliferative Effects ◽  
Isobolographic Analysis ◽  
Natural Substances ◽  
Additive Interactions ◽  
Melanoma Cell Lines

(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired. Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on two human melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring coumarins (osthole, xanthotoxin, xanthotoxol, isopimpinellin, and imperatorin). The antiproliferative effects produced by combinations of CDDP with the coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of coumarins were presented by osthole and xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC50) values relative to the FM55P and FM55M2 melanoma cells. Isobolographic analysis showed that for both melanoma cell lines, the combination of CDDP and osthole exerted synergistic and additive interactions, while the combination of CDDP and xanthotoxol exerted additive interactions. Combinations of CDDP with xanthotoxin, isopimpinellin, and imperatorin showed antagonistic and additive interactions in two melanoma cell lines. (4) The combination of CDDP and osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for cancer drugs among natural substances.

scholarly journals Identification and characterization of a low-affinity granulocyte- macrophage colony-stimulating factor receptor on primary and cultured human melanoma cells

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 609-615 ◽  
Author(s):  
GC Baldwin ◽  
DW Golde ◽  
GF Widhopf ◽  
J Economou ◽  
JC Gasson
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Melanoma Cell Lines

Abstract Hematopoietic growth factor receptors are present on cells of normal nonhematopoietic tissues such as endothelium and placenta. We previously demonstrated functional human granulocyte-macrophage colony- stimulating factor (GM-CSF) receptors on small cell carcinoma of the lung cell lines, and others have reported that certain solid tumor cell lines respond to GM-CSF in clonogenic assays. In the current study, we examine human melanoma cell lines and fresh specimens of melanoma to determine whether they have functional GM-CSF receptors. Scatchard analyses of 125I-GM-CSF equilibrium binding to melanoma cell lines showed a mean of 542 +/- 67 sites per cell with a kd of 0.72 +/- 0.14 nmol/L. Cross-linking studies in the melanoma cell line, M14, showed a major GM-CSF receptor species of 84,000 daltons. Under the conditions tested, the M14 cells did not have a proliferative response to GM-CSF in vitro, nor was any induction of primary response genes detected by Northern analysis in response to GM-CSF. Studies to determine internal translocation of the receptor-ligand complex indicated less than 10% of the 125I-GM-CSF internalized was specifically bound to receptors. Primary melanoma cells from five surgical specimens had GM-CSF receptors; Scatchard analysis was performed on one sample, showing 555 sites/cell with a kd of 0.23 nmol/L. These results indicate that human tumor cells may express a low-affinity GM-CSF receptor protein that localizes to the cell surface and binds ligand, but lacks functional components or accessory factors needed to transduce a signal.

Effect of small inhibitors of nuclear export (SINE) on growth inhibition and apoptosis of human melanoma cells.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13549-e13549
Author(s):  
Gregory B. Lesinski ◽  
Jennifer Yang ◽  
Matthew A Bill ◽  
Yosef Landesman ◽  
Sharon Shacham ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Nuclear Export ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Nuclear Accumulation ◽  
Dependent Manner ◽  
Melanoma Cell Lines

e13549 Background: Inhibition of nuclear export can promote re-activation of tumor suppressor pathways. CRM1 (chromosomal regional maintenance 1) or XPO1 (exportin 1) is the major protein that mediates nuclear export. We hypothesized that CRM1 mediated nuclear export represents a novel therapeutic target that can be manipulated to inhibit melanoma cell survival. Methods: The growth inhibitory and pro-apoptotic effects of KPT-185, KPT-276 and KPT-330, small molecules selective inhibitor of nuclear export (SINE) were evaluated in human melanoma cell lines using an MTT assay and Annexin V/PI staining, respectively. Fluorescence microscopy and immunoblots were used to assess nuclear accumulation of tumor suppressor proteins. The trans-isomer of KPT-185 and DMSO (vehicle) were used as a negative controls in all assays. The pharmacokinetic (PK) profile of all compounds was evaluated in mice. Results: CRM1 protein was highly expressed in human melanoma cell lines with diverse molecular profiles (i.e., B-Raf, NRAS, p53). KPT-SINE inhibited melanoma cell growth in a concentration-dependent manner and induced apoptosis at nanomolar concentrations. Importantly, there was no evidence that B-Raf V600 mutational status influenced melanoma cell response to these agents. Nuclear accumulation and/or induction of p53, p21, FOXO3a, STAT1 and BAD, and reduction of MCL-1 occurred in melanoma cells at time points prior to apoptosis as shown by increase in cleaved PARP and caspase 3 levels. PK studies were conducted in mice following oral administration of 10 mg/kg, to guide drug selection for our ongoing efficacy studies in murine melanoma models. KPT-185 showed limited bioavailability and systemic exposure, while KPT-276 and KPT-330 showed >50% bioavailability reaching Cmax >5µM. Conclusions: This study represents the first report of CRM1 inhibition in melanoma. These data indicate that the novel SINE compounds can effectively inhibit CRM1-mediated nuclear export and induce apoptosis in melanoma cells. KPT-330 is currently under development as orally bioavailable, small molecule inhibitors for a human clinical trial.

Recombinant arginase as a novel anti-melanoma agent

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12032-12032 ◽  
Author(s):  
E. C. Hsueh ◽  
S. Knebel ◽  
I. Collier ◽  
M. Kadze ◽  
C. Hsueh ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Large Scale ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Subtilis Strain ◽  
Argininosuccinate Synthetase ◽  
Melanoma Cell Lines

12032 Background: BCT-100 is a recombinant arginase comprised of 329 amino acid residues. Arginase converts arginine to urea and ornithine. Previous studies suggested that melanoma cells were auxotrophic for arginine due to absence of argininosuccinate synthetase (ASS) expression. Thus, we hypothesized that recombinant arginase, BCT-100, is cytotoxic to human melanoma cells and its cytotoxicity correlates with absence of ASS expression. Methods: BCT-100 pegylated recombinant human arginase was manufactured by large scale fermentation of a recombinant B. subtilis strain LLC101 encoded with a human arginase gene. Following fermentation, the recombinant protein was extracted, purified, pegylated, and ultra-dialyzed. Ten established human melanoma cell lines were used. Cells were grown to 90% confluence, harvested, and plated at 104 cells per well in a 96-well plate and co-cultured with increasing concentrations of pegylated BCT-100 for 72 hours. CellTiter 96 Aqueous Non-radioactive Cell Proliferation Assay (Promega, Madison, WI) was used to measure percent viability, with absorbances measured at 490 nm. Total cellular RNA was isolated from established melanoma cell lines converted to cDNA at a concentration of 5 ng/ul. Quantitative real time polymerase chain reaction was performed on a 7300 Real Time PCR System, using Gene Expression Assays for ASS and GAPDH (Applied Biosystems). 10,000 fold standard curves were generated for all samples using GAPDH expression. Results: All ten cell lines demonstrated decreased viability as concentrations of BCT-100 increased. Average IC50 value was 0.11 IU/ml. Eight of the 10 cells lines have IC50 values < 0.1 IU/ml. Of the 8 cell lines with IC50< 0.1 IU/ml, all of them have low or undetectable ASS expression using quantitative RT-PCR. Of the 2cell lines with IC50 > 0.1 IU/ml, ASS expression was detected in 1 of 2. Conclusions: Arginine depletion with recombinant arginase, BCT-100, was cytotoxic to melanoma cells in vitro. The cytotoxic effect of BCT-100 on melanoma cells correlated with expression of argininosuccinate synthetase. BCT-100 is a promising novel agent for treatment of melanoma. Further in vivo experiment with BCT-100 is ongoing. [Table: see text]

Melatonin inhibits human melanoma cells proliferation and invasion via cell cycle arrest and cytoskeleton remodeling

2020 ◽  
Vol 3 (2) ◽  
pp. 194-209 ◽  
Author(s):  
Ana Carolina Ramos Moreno ◽  
Renata de Freitas Saito ◽  
Manoela Tiago ◽  
Renato Ramos Massaro ◽  
Roberta Liberato Pagni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Cell Swelling ◽  
Cycle Arrest ◽  
Cytoskeleton Remodeling ◽  
Melanoma Cell Lines

Among skin cancers, melanoma has the highest mortality rate. The heterogeneous genetic melanoma background leads to a tumor-propagating capacity particularly important in maintaining therapeutic resistance, and tumor recurrence. The identification of efficient molecules able to control melanoma progress represents an important opportunity for new therapeutic strategies, particularly in combination with the current standard-of-care treatments. In this context, several studies have reported the antitumor effects of melatonin against different types of cancer, including melanoma. Here, we describe the underlying mechanisms associated with melatonin’s activity in human melanoma cell lines, focusing on cell cycle and cytoskeleton remodeling. Interestingly, while melatonin induced melanocyte DNA replication, melanoma cells exhibited cell cycle arrest in the G1-phase. This phenomenon was associated with cyclin-D1 downregulation or p21 overexpression. The efficacy of melatonin on melanoma cells survival and proliferation was detected using the clonogenic assay, with a decrease in both the number and size of colonies. Additionally, melatonin induced a dramatic cytoskeleton remodeling in all melanoma cell lines, leading to a star-like morphology or cell swelling. The role of melatonin on melanoma cytoskeleton was associated with the actin disruption, with thinning and/or broken actin fibers, and weak and/or loss of paxillin along stress fibers. These data support the observed findings that melatonin impairs melanoma invasion in skin reconstructed models. Together, our results suggest that melatonin could be used to control melanoma growth and support basic and clinical studies on melatonin as a promising immunometabolic adjuvant for melanoma therapy.

scholarly journals Identification and characterization of a low-affinity granulocyte- macrophage colony-stimulating factor receptor on primary and cultured human melanoma cells

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 609-615 ◽  
Author(s):  
GC Baldwin ◽  
DW Golde ◽  
GF Widhopf ◽  
J Economou ◽  
JC Gasson
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Melanoma Cell Lines

Hematopoietic growth factor receptors are present on cells of normal nonhematopoietic tissues such as endothelium and placenta. We previously demonstrated functional human granulocyte-macrophage colony- stimulating factor (GM-CSF) receptors on small cell carcinoma of the lung cell lines, and others have reported that certain solid tumor cell lines respond to GM-CSF in clonogenic assays. In the current study, we examine human melanoma cell lines and fresh specimens of melanoma to determine whether they have functional GM-CSF receptors. Scatchard analyses of 125I-GM-CSF equilibrium binding to melanoma cell lines showed a mean of 542 +/- 67 sites per cell with a kd of 0.72 +/- 0.14 nmol/L. Cross-linking studies in the melanoma cell line, M14, showed a major GM-CSF receptor species of 84,000 daltons. Under the conditions tested, the M14 cells did not have a proliferative response to GM-CSF in vitro, nor was any induction of primary response genes detected by Northern analysis in response to GM-CSF. Studies to determine internal translocation of the receptor-ligand complex indicated less than 10% of the 125I-GM-CSF internalized was specifically bound to receptors. Primary melanoma cells from five surgical specimens had GM-CSF receptors; Scatchard analysis was performed on one sample, showing 555 sites/cell with a kd of 0.23 nmol/L. These results indicate that human tumor cells may express a low-affinity GM-CSF receptor protein that localizes to the cell surface and binds ligand, but lacks functional components or accessory factors needed to transduce a signal.

scholarly journals Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression.

1993 ◽  
Vol 120 (5) ◽  
pp. 1281-1288 ◽  
Author(s):  
C Lu ◽  
R S Kerbel
Keyword(s):  
Growth Inhibition ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Growth Inhibitor ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Advanced Stage ◽  
Melanoma Cell Lines

The ability to penetrate the dermal basement membrane and subsequently proliferate in the underlying mesenchyme is one of the key steps in malignant progression of human melanomas. We previously undertook studies aimed at assessing how normal dermal fibroblasts (one of the main cellular components of mesenchyme) may affect the growth of human melanoma cells and facilitate the overgrowth of malignant subpopulations (Cornil, I., D. Theodorescu, S. Man, M. Herlyn, J. Jambrosic, and R. S. Kerbel. 1991. Proc. Natl. Acad. Sci. USA. 88:6028-6032). We found that melanoma cell lines from early-stage (metastatically incompetent) lesions were growth inhibited whereas those from advanced-stage (metastatically competent) lesions were stimulated under the same conditions by co-culture with fibroblasts; conditioned medium from such cells gave the same result. Subsequent studies using biochemical purification and neutralizing antibodies revealed the inhibitory activity to be identical to interleukin-6 (IL-6). We now report that addition of purified recombinant human IL-6 resulted in a growth inhibition in vitro by G1/G0 arrest of early, but not advanced stage melanoma cells. Despite this alteration in response there was no significant difference in melanoma cell lines of varying malignancy in respect to their expression of genes encoding the IL-6 receptor, or gp130, the IL-6 signal transducer. Scatchard analysis also revealed similar [125I]IL-6 binding activities in both IL-6 sensitive and resistant groups. However, studies of IL-6 production indicated that five out eight IL-6 melanoma cell lines known to be resistant to exogenous IL-6-mediated growth inhibition constitutively expressed mRNA for IL-6; they also secreted bioactive IL-6 into culture medium. To assess the possible role of this endogenous IL-6 in melanoma cell growth, antisense oligonucleotides to the IL-6 gene were added to cultures of melanoma cells. This resulted in a significant growth inhibition only in cell lines that produced endogenous IL-6. In contrast, neutralizing antibodies to IL-6 were ineffective in causing such growth inhibition. This indicates that endogenous IL-6 may behave as a growth stimulator by an intracellular ("private") autocrine mechanism. Thus, a single cytokine, IL-6, can switch from behaving as a paracrine growth inhibitor to an autocrine growth stimulator within the same cell lineage during malignant tumor progression. Such a switch may contribute to the growth advantage of metastatically competent melanoma cells at the primary or distant organ sites and thereby facilitate progression of disease.

scholarly journals 598 Reversal of epigenetic silencing of cGAS and STING in melanoma enhances the activity of tumor infiltrating lymphocytes

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A633-A633
Author(s):  
Rana Falahat ◽  
James Mulé ◽  
Anders Berglund ◽  
Patricio Perez- Villarroel ◽  
Ryan Putney ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Promoter Hypermethylation ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Infiltrating Lymphocytes ◽  
Melanoma Cell Lines

BackgroundIt is becoming more evident that STING activity in tumor cells can have a functional role in mediating antitumor immune responses. We have recently shown that activation of STING signaling in human melanoma cell lines enhances their antigenicity and susceptibility to lysis by human melanoma tumor infiltrating lymphocytes (TIL) through the augmentation of MHC class I molecules.1 However, the frequent impairment of this pathway through loss of cGAS and/or STING expression in melanoma cell lines limits their antigen presentation and subsequently their sensitivity to cytotoxic T cell mediated killing. In this study, we asked if this suppression is, in part, epigenetically regulated and if it is indeed a driver of melanoma resistance to T cell-based immunotherapies.MethodsTo determine the role of DNA methylation in melanoma STING and cGAS silencing, we performed genome-wide DNA methylation profiling across a panel of 16 human melanoma cell lines. We subjected melanoma cell lines that indicated STING and/or cGAS promoter hypermethylation to treatment with 5-aza-2’-deoxycytidine (5AZADC) and evaluated their protein expression by immunoblot. We next assessed phosphorylation of IRF3 and induction of IFN-β and CXCL10 in 5AZADC-treated melanoma cells following their stimulation with dsDNA or 2’3’-cGAMP. We also co-cultured 5AZADC-pretreated melanoma cell lines with their HLA-matched human melanoma TIL in the presence or absence of dsDNA or 2’3’-cGAMP and assessed TIL production of IFN-γ.ResultsUsing whole genome methylation profiling, we identified a distinct correlation between promoter hypermethylation and loss of STING and cGAS expression in human melanoma cell lines. Reconstitution of STING and cGAS expression through DNA demethylation reinstated functional STING signaling in at least half of the examined cell lines as indicated by STING-dependent phosphorylation of IRF3, induction of CXCL10 (~300 pg/ml, P < 0.0001) and IFN-β (~900 pg/ml, P < 0.0001) and upregulation of MHC class I. We also observed up to a 8-fold increase in TIL production of IFN-γ in co-culture studies using 5AZADC-pretreated melanoma cells compared to untreated controls in the presence of dsDNA or 2’3’-cGAMP (~2,000 pg/ml, P < 0.001).ConclusionsWe provide evidence that methylation silencing of cGAS and STING is not only a notable mechanism of STING signaling dysfunction in melanoma, but also plays a role in tumor antigen presentation and recognition by TIL. Collectively, these observations argue that targeting epigenetic loss of STING signaling in melanomas should be considered as a strategy to improve the efficacy of clinical interventions using T cell-based immunotherapies.AcknowledgementsFunding: NCI P50 CA168536, Cindy and Jon Gruden Fund, Chris Sullivan Fund, V Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.ReferenceFalahat R, Perez-Villarroel P, Mailloux AW, Zhu G, Pilon-Thomas S, Barber GN, Mulé JJ. STING signaling in melanoma cells shapes antigenicity and can promote antitumor T-cell activity. Cancer Immunology Research 2019; 7(11):1837–48.

scholarly journals Overcoming genetically based resistance mechanisms to PD-1 blockade.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2584-2584 ◽  
Author(s):  
Davis Yuri Torrejon ◽  
Gabriel Abril-Rodriguez ◽  
Jennifer Tsoi ◽  
Ameya Champhekar ◽  
Anusha Kalbasi ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Resistance Mechanisms ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Type I ◽  
Ifn Gamma ◽  
Melanoma Cell Lines ◽  
Biased Agonist

2584 Background: Mechanism-based strategies to overcome resistance to anti-PD1 therapy are urgently needed. Using CRISPR/Cas9 genome editing tools, we developed acquired resistant models through JAK1/2 and B2M loss of function (LoF) mutations in human melanoma cell lines and in the murine MC38 colon carcinoma, known for high mutational load and good response to anti-PD-1. We hypothesized that the downstream activation of the IFN-receptor pathway or the activation of natural killer (NK) cells would overcome this resistance. Methods: We studied signaling changes in four human cell lines (parental and LoFs) exposed to IFN-gamma using RNAseq. In addition, we analyzed the in-vivo antitumor activity in MC38 variants with anti-PD1 and characterized the tumor microenvironment using mass cytometry (CyTOF). Finally, we tested strategies to overcome resistance mechanisms with SD-101 (TLR-9 agonist) and bempegaldesleukin (NKTR-214, CD-122 biased agonist) with the extent of CD8 and NK1.1 depletion. Results: RNAseq differential gene expression analysis showed that the IFN-gamma induced increased expression of antigen presenting machinery, IFN-gamma signaling and chemokines (CXCL9/10) was lost in JAK1/2-LoF human melanoma cell lines. The significant antitumor activity of anti-PD-1 against MC38 parental cell line was lost in JAK1/2 and B2M LoF sublines, and CyTOF analysis revealed that anti-PD-1 therapy was unable to increase tumor CD8+ T-effectors in these LoF tumors. The intratumoral administration of SD-101 (50 μg/injection q4dx3wks) was able to overcome local resistance even in non-injected sites in JAK1/2 and IFNAR-type-I LoF tumors, and systemic administration of bempegaldesleukin (0.8 mg/kg, q9dx2, i.v.) was able to overcome resistance in B2M LoF with significantly increased survival (Table). Depletion studies showed complete abrogation of anti-tumor response with anti-NK1.1 in JAK1 LoF and B2M LoF, and partial abrogation with anti-NK1.1 or anti-CD8 in JAK2 LoF tumors. Conclusions: Even in the extreme setting of genetic resistance to PD-1 blockade by JAK1/2 LoF, resistance can be overcome by SD-101, a TLR9 agonist, while resistance of B2M LoF can be overcome by bempegaldesleukin (NKTR-214), a CD-122 biased agonist. Our findings support the testing of these rational mechanistic strategies in patients with a-PD1 resistance. [Table: see text]

scholarly journals DR (Ia-like) antigens on human melanoma cells. Serological detection and immunochemical characterization.

1979 ◽  
Vol 149 (3) ◽  
pp. 658-668 ◽  
Author(s):  
B S Wilson ◽  
F Indiveri ◽  
M A Pellegrino ◽  
S Ferrone
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Chain Structure ◽  
Human Melanoma ◽  
Lymphoid Cells ◽  
Beta Chain ◽  
Serological Detection ◽  
B Lymphoid ◽  
Melanoma Cell Lines

11 cultured human melanoma cell lines were tested for the expression of DR antigens by using specific allo- and xenoantisera in an indirect rosette microassay. Four of these melanoma cell lines expressed DR antigens, but in lower amounts than expressed on cultured human B-lymphoid cells. Rabbits injected with the DR-positive melanoma cells produced antibodies that were serologically and immunochemically reactive with B-cell-derived DR antigens. Immunochemical studies indicate that melanoma cell-derived DR antigens have a two-chain structure with 34,000 and 27,000 mol wt components. The melanoma cell-derived DR beta-chain at 27,000 mol wt is slightly smaller than that of the Victor cell DR beta-chain whose mol wt is 29,000.

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