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1.
Oncogene ; 37(11): 1472-1484, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29321661

RESUMEN

Members of the CD44 family of transmembrane glycoproteins control cell signaling pathways from numerous cell surface receptors, including receptor tyrosine kinases (RTKs). The decisive factor (ligand, RTKs or both) that controls the recruitment of specific CD44 isoforms is still unknown. We investigated this question by using the EGFR signaling pathway, in which one receptor can be activated by a broad range of ligands. By means of siRNA-mediated downregulation of CD44 expression and blocking experiments, we identified CD44v6 as a co-receptor for EGF- and ER-induced ErbB1 activation and for NRG1-induced ErbB3 and ErbB4 activation. In contrast, TGFα is independent of all CD44 isoforms, even though it addresses the same receptor pairs as EGF. Moreover, the heparin-sulfated CD44v3 isoform is required for HB-EGF-induced EGFR signaling. These data suggest that specific CD44 isoforms are recruited in a ligand-dependent manner as co-receptors in the EGFR signaling pathways and that the specificity is determined by the ligand and not by the receptors themselves. The in vivo relevance of this interplay between CD44 isoforms and EGFR ligands is underlined by the decreased metastatic spreading of mammary carcinomas in mice treated with a CD44v6-specific peptide. Most importantly, we found a clear correlation between the presence of CD44v6/ErbB1 complexes in breast cancer patients and lymph node metastases.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptores de Hialuranos/metabolismo , Proteínas Oncogénicas v-erbB/metabolismo , Animales , Células Cultivadas , Femenino , Células HT29 , Humanos , Receptores de Hialuranos/fisiología , Ligandos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Unión Proteica , Isoformas de Proteínas/metabolismo , Transducción de Señal
2.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-667209

RESUMEN

Objective To study the expression of insulin-like growth factor I(IGF-I)and insulin like growth factor binding protein -3(IGFBP-3)in the colorectal cancer and the relations between them. Methods A case-control study was conducted.We selected 113 patients with a pathologically conformed diagnostic colorectal cancer as the colorectal cancer(CRC)group, 37 patients with colorectal benign diseases as benign control(N-CRC)group, and other 76 healthy subjects as normal control(NC)group. CRC was divided into lymphatic metastasis(M-CRC)subgroup and no lymphatic metastasis(NM-CRC) subgroup and was also categorized by TNM staging.Concentrations of serum IGF-I and IGFBP-3 were measured by chemiluminescence method.SNK test and one-way ANOVA were used for comparison between the two groups and among multi-groups, respectively.Results A slightly decreasing trend of the concentrations of serum IGF-I was observed following the sequences of the NC, N-CRC and CRC groups. Moreover,the concentrations of serum IGF-I in T4 were significantly lower than that in(T1+T2)and T3 (F=6.279,P=0.003).The concentration of serum IGFBP-3 in the CRC group(3.13 ±1.57)μg/ml was significantly lower than that both in the N-CRC(3.42 ±1.32)μg/ml(F=3.04,P=0.09)and the Normal group(4.62 ±1.10)μg/ml(F=10.88,P=0.001).The concentration of serum IGFBP-3 in the M-CRC was higher than that in NM-CRC(F=4.44,P<0.05).The ratio of IGF-I/IGFBP-3 in the CRC group (48.85 ±29.14)was remarkably higher than that both in the N-CRC group(42.38 ±12.58)(F=5.05, P=0.02)and the Normal group(42.46 ±16.24)(F=5.68,P=0.02).The value of diagnosis is general. The area under the ROC curve(AUC)of IGF-I was 0.63(95% CI 0.56 -0.70), the sensitivity and specificity of IGF-I were 85.8%and 40.7%respectively when the critical value was 102.5 μg/ml.The area under the ROC curve(AUC)of IGFBP-3 was 0.72(95%CI 0.64-0.78),the sensitivity and specificity of IGFBP-3 were 78.8%and 62.8%respectively when the critical value was 3.32 μg/ml.Conclusions The concentrations of IGF-I and IGFBP-3 were low expressed in serum of patients with colorectal cancer. Meanwhile,they are correlated with the lymphatic metastasis and TNM staging.

3.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-477314

RESUMEN

Objective Serological characteristic analysis for patients with autoimmune hemolytic anemia(AIHA)who has cold and warm auto‐antibody when undergoing blood type and cross‐matching .Methods Choosed 3 donors of red blood cells of group O to absorb autoantibodies of the patient′s serum(by using the methods of cold absorption) and used 2‐mercaptoethanol(2‐Me) to de‐stroyed the IgM antibody .Results The patient of AIHA blood type was B+ .There was cold and warm auto‐antibody in the pa‐tient′s serum ,and the result of cross‐matching is incompatible .Conclusion The patient′s serum contains cold and warm auto‐anti‐body which interferes blood type and cross‐matching .In emergency ,considering the patients condition ,blood transfusion combined with the drug treatment could achieve good effects .

4.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-482696

RESUMEN

Objective To evaluate the transfusion efficacy and safety of patients with non‐specificity irregular antibodies .Meth‐ods A total of 19 cases of patients with non‐specificity irregular antibodies were analyzed ,then the transfusion efficacy and the in‐cidences of adverse transfusion reactions were investigated .Blood donor samples with the same ABO blood type of patients were randomly collected ,then blood cross‐matching was carried out .And the transfusion efficacy and safety of patients with non‐specific‐ity irregular antibody were evaluated when compatible blood were found by using both micro‐column gel technique and saline meth‐od .Results The non‐specificity irregular antibodies of the 19 cases of patients all were IgG irregular antibodies .The erythrocyte transfusion was carried out in the 19 cases of patients ,the total efficiency rate ,partial efficiency rate and inefficiency rate was 73 .7% ,26 .3% and 0 .0% ,respectively .No delayed hemolytic transfusion reactions were observed in any patient .Conclusion For patients with non‐specificity irregular antibodies ,the blood transfusion could be efficacy and safety when compatible blood samples are confirmed by using both micro‐column gel technique and saline method .

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