1,721,039 research outputs found
Implication of von Willebrand factor as a regulator of tumor cell metastasis: potential perioperative use of desmopressin and novel peptide analogs
Letter to the EditorFil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Re: Effect of ADAM28 on carcinoma cell metastasis by cleavage of von willebrand factor
I read with great interest the elegant work by Mochizuki et al. ( 1 ) providing novel experimental evidence for the crucial role of von Willebrand factor (VWF), a prominent plasma protein associated with blood coagulation, in resistance to metastasis. The authors found that aggressive human breast and non-small cell lung carcinoma cells expressing high levels of ADAM28 are able to avoid VWF-induced apoptosis at metastatic sites. ADAM28 binds and cleaves VWF, thus enhancing metastasis by favoring cancer cell survival within the blood vessels. I completely agree with the authors in the sense that ADAM28 can be a potential molecular target for cancer therapy, and the development of selective inhibitors of the proteinase is expected. However, another strategy could be to raise the levels of VWF by a pharmacological intervention to stimulate a natural defense against metastasis formation.Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Repurposing of host-based therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19): a link between antiviral and anticancer mechanisms?
Drug repurposing, also called repositioning or rediscovering, refers to the process of developing a known drug for a novel use that is different from its original clinical indication. This concept has focused great attention on the search for viable treatments in the context of the current coronavirus disease 2019 (COVID-19) pandemic.Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Reciprocal interactions between tumor and endothelial cells: Effects of selective vasopressin V2 receptor peptide agonists
Recent experimental evidence suggested that the synthetic peptide desmopressin (DDAVP) interferes tumor angiogenesis by inducing the formation of angiostatin. It is also known that DDAVP stimulates the endothelial release of von Willebrand factor, a key element in resistance to metastasis. Vasopressin V2 receptor agonists such as DDAVP seem to evoke dual angiostatic and antimetastatic effects, breaking cooperative interactions of tumor and endothelial cells during tumor progression.Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Impact of Perioperative Blood Transfusion on Survival Among Women With Breast Cancer: Potential Benefits of Blood-Saving Agent Desmopressin Use During Surgery
Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentin
Editorial. Anti-idiotype antibodies in cancer treatment.
Anti-idiotype antibodies (anti-Id Abs) are antibodies to idiotopes that are located in the variable region, including the antigen binding site, of another antibody. When the last is the case, these anti-Id Abs can act as surrogates of the original antigen. The capability of anti-Id Abs to modulate the immune response has been the basis for the development of anti-Id vaccines against different antigens, including tumor-associated antigens. Over the years, its use in cancer has been demonstrated as effective and promising.Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vázquez, Ana María. No especifíca;Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Macías, Amparo. No especifíca
Tissue factor as a novel marker for detection of circulating cancer cells
Tissue factor (TF) is a molecular marker that is up-regulated in cancer cells and aids tumoral dissemination. Our purpose was to develop a nested RT-PCR strategy against TF for detecting blood-borne tumour cells. Our method detected TF expression in a minimum of 1.5 pg total RNA from MCF7 cells. A preliminary study in blood samples from 16 advanced breast carcinoma patients showed that 80% of patients with high TF load progressed and died, while only 18% with low TF load showed the same behaviour. Kaplan-Meier analysis confirmed worse overall survival in patients with high TF load.Fil: Otero, L. L.. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, M.. Universidad de Buenos Aires; ArgentinaFil: Cinat, G.. Universidad de Buenos Aires; ArgentinaFil: Gabri, M. R.. Universidad Nacional de Quilmes; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Cirrhosis, von Willebrand Factor (vWF) and the low incidence of metastatic malignancy in injured liver
The work by Yilmaz et al. in The Eurasian Journal of Medicine provides clinical evidence for the correlation between increased levels of von Willebrand factor (vWF) and the stage of cirrhosis. The authors observed significantly higher vWF antigen levels in cirrhotic patients compared to a control group, and also an increase with the increasing stages of cirrhosis according to the Child-Pugh score. These results indicate that vWF is produced as a reliable marker of endothelial dysfunction during hepatocellular failure in cirrhosis. Besides, in light of the results of Yilmaz et al. [1] another perspective regarding the low incidence of metastatic malignancy in cirrhotic patients and the potential role of vWF should be pointed out. The blood coagulation protein vWF is mainly secreted by endothelial cells into the subendothelial space and into the plasma, serving as an adhesive link between platelets and the vascular wall. It is known that liver sinusoidal endothelial cells are a prominent source of vWF, not only during haemostatic processes but also in tissue injury. Interestingly, many studies have implicated vWF as a key factor in resistance to metastasis. Terraube et al. demonstrated that vWF plays a protective role against metastatic spread in a vWF-deficient mouse model. It appears that vWF can induce apoptosis of metastatic cells early after their arrest in the vasculature of the target organ. In the same line, Mochizuki et al. found that aggressive cancer cells producing high levels of metalloproteinase ADAM28 are able to avoid vWF-induced apoptosis at micrometastatic sites. ADAM28 binds and degrades vWF, thus favouring the survival of metastatic cells in the target organ.Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Urokinase Exerts Antimetastatic Effects by Dissociating Clusters of Circulating Tumor Cells–Letter
Blood-borne spread is responsible for the vast majority of cancer-related deaths, and it is recognized that clusters of circulating tumor cells (CTC) are much more likely to cause metastasis than single CTCs. In the November issue of Cancer Research, Choi and colleagues utilized an elegant in vivo confocal system in the 4T1 mouse model of breast cancer metastasis to analyze the dynamics of CTC clustering in blood vessels and demonstrated that the thrombolytic agent urokinase prevented the assembly of CTC clusters (1). Urokinase is a plasminogen activator that starts fibrinolysis by converting plasminogen to active plasmin and also participates in extracellular matrix remodeling during tumor invasion (2). It is important to note that the study of Choi and colleagues (1) is in line with our previous research in the F3II mouse mammary carcinoma model, which demonstrated that although pharmacologic inhibition of urokinase blocks primary tumor invasion, it is unable to control progression of the metastatic disease (3). Moreover, we have shown that the highly potent, selective urokinase inhibitor B623, a 4-substituted benzo[b]thiophene-2-carboxamidine, induces clustering of F3II cells ex vivo in the presence of plasma and, thus, enhances metastatic lung colonization in vivo (4). Choi and colleagues have shed light on the process of CTC cluster formation, leading to new concepts for early pharmacologic interventions to prevent metastatic spread into secondary organs (1). In this regard, the perioperative period is an attractive “window of opportunity” to modulate tumor–host interactions and to reduce the risk of metastatic disease. A recent phase II dose-escalation trial in breast cancer patients explored the potential utility of perioperative administration of desmopressin, a profibrinolytic and hemostatic agent that stimulates the release from endothelial cells of urokinase and tissue-type plasminogen activator, as well as the von Willebrand factor, a multimeric plasma protein implicated in metastasis resistance (5). Interestingly, intravenous infusion of desmopressin was associated with a rapid postoperative drop in CTC counts, as measured by quantitative PCR of cytokeratin-19 transcripts (5). We consider that further evaluation of treatment strategies interfering with the formation and/or stability of CTC clusters in the blood of cancer patients is warranted.Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentin
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