MLN-8237; A dual inhibitor of aurora A and B in soft tissue sarcomas.

MLN-8237; A dual inhibitor of aurora A and B in soft tissue sarcomas. Oncotarget. 2016 Feb 12; Authors: Nair JS, Schwartz GK Abstract Aurora kinases have become an attractive target in cancer therapy due to their deregulated expression in human tumors. Liposarcoma, a type of soft tissue sarcoma in adults, account for approximately 20% of all adult soft tissue sarcomas. There are no effective chemotherapies for majority of these tumors. Efforts made to define the molecular basis of liposarcomas lead to the finding that besides the amplifications of CDK4 and MDM2, Aurora Kinase A, also was shown to be overexpressed. Based on these as well as mathematic modeling, we have carried out a successful preclinical study using CDK4 and IGF1R inhibitors in liposarcoma. MLN8237 has been shown to be a potent and selective inhibitor of Aurora A. MLN-8237, as per our results, induces a differential inhibition of Aurora A and B in a dose dependent manner. At a low nanomolar dose, cellular effects such as induction of phospho-Histone H3 (Ser10) mimicked as that of the inhibition of Aurora kinase A followed by apoptosis. However, micromolar dose of MLN-8237 induced polyploidy, a hallmark effect of Aurora B inhibition. The dose dependent selectivity of inhibition was further confirmed by using siRNA specific inhibition of Aurora A and B. This was further tested by time lapse microscopy of GFP-H2B labelled cells treated with MLN-8237. LS141 xenograft model at a dose of 30 mg/...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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ConclusionIncidence rates of STS and BS have been stable since 2001. The longer RS in STS can be attributed to advances in sarcoma patient management.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Authors: Chen M, Xu ES, Leisenring NH, Cardona DM, Luo L, Ma Y, Ventura A, Kirsch DG Abstract Myxoid liposarcoma is a malignant soft tissue sarcoma characterized by a pathognomonic t(12;16)(q13;p11) translocation that produces a fusion oncoprotein, FUS-CHOP. This cancer is remarkably sensitive to radiotherapy and exhibits a unique pattern of extrapulmonary metastasis. Here, we report the generation and characterization of a spatially and temporally restricted mouse model of sarcoma driven by FUS-CHOP. Using different Cre drivers in the adipocyte lineage, we initiated in vivo tumorigenesis by expressing FUS-CHOP in ...
Source: Sarcoma - Category: Cancer & Oncology Tags: Sarcoma Source Type: research
Conclusion.Although overall survival of patients with STS with synchronous metastases in this nationwide and “real‐life” population has improved over the years, the improvement was not statistically significant, despite new treatment options.Implications for Practice.Treatment of patients with metastatic soft tissue sarcoma (STS) has changed in the past years, with new drugs such as trabectedin (2007) and pazopanib (2012) becoming available. By using data from the nationwide Netherlands Cancer Registry, the impact of these changes in treatment policies on survival is analyzed in a “real‐life” po...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Sarcomas, European Perspectives Source Type: research
Liposarcoma(LS) is the most common soft-tissue sarcoma. The histological spectrum has a well-differentiated-liposarcoma(WDLS) and a more aggressive dedifferentiated-liposarcoma(DDLS). Advanced therapeutic strategies based on molecular mechanism are urgently needed, especially for DDLS. Previously, we reported that TIMP-1 (a member of tissue-inhibitor-of-metalloproteinase), with its receptor CD63 activates yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) to promote cancer cell proliferation.
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - Category: ENT & OMF Authors: Tags: #76 Source Type: research
CONCLUSIONS: From a genomic perspective, LMS metastases contain genetic alterations that are also found in primary tumors. WDLPS and DDLPS, however, appear to divergently evolve from a common precursor harboring 12p amplification, rather than as a transformation to a higher-grade tumor. Further efforts to identify specific drivers of these distinct evolutionary patterns may inform future translational and clinical research in STS. PMID: 31164371 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Liposarcoma (LPS) is a tumor derived from adipose tissue, and has the highest incidence among soft tissue sarcomas. Dedifferentiated liposarcoma (DDLPS) is a malignant tumor with poor prognosis. Recurrence and...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
ConclusionSTS incidence varied by histological subtype, sex, age, and primary site in an Asian population. Our results suggested regional and racial discrepancies in the incidence rates of certain STS subtypes.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Conclusions: The proposed nomogram is a reliable and robust tool for accurate prognostic prediction in patients with extremity soft tissue LMS. Introduction Soft tissue leiomyosarcoma (LMS) is an aggressive sarcoma, which originates from smooth muscle cells (1). Soft tissue LMS accounts for about 5–10% of all soft tissue sarcomas (2). It occurs in different sites, including the retroperitoneum, intraabdominal sites, and extremities (3). Extremity LMS comprised about 10–15% of extremity sarcomas, with a preference for the lower limb (4–6). Extremity LMS tends to have a better prognosis than uterine...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas. Introduction Soft-tissue sarcomas are often highly heterogeneous tumors with variable components that can include cellular tumor, fat, necrosis, and cystic change. In many soft-tissue ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThis study has clarified the epidemiology, treatment and prognosis, as well as the variables that have an impact on the survival of the Latin American patients with STS studied.ResumenObjetivoLos sarcomas de partes blandas (SFTS) conforman un grupo de neoplasias poco frecuentes y heterogéneas (menos del 1% en adultos y 15% en pediátricos), de los cuales no se cuenta con registros actualizados en población latinoamericana. El estudio tiene como objetivo describir la situación actual de los pacientes tratados en un instituto oncológico de Latinoamérica.MétodosSe obt...
Source: Cirugia Espanola - Category: Surgery Source Type: research
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