Search results for "ERAS"

Blood T-cell Vβ transcriptome in melanoma patients

2004

Tumor-cells have been shown to elicit MHC-restricted and antigen-specific T-cell responses. In this article, we used a new approach to study T-cell responses in tumor-bearing patients based on a global representation of the Vβ-transcriptome, making it possible to grade CDR3-length distribution (CDR3-LD) alterations. Six patients with advanced melanoma disease, from whom blood samples were taken before and serially after tyrosinase-A peptide vaccination, were studied. The PBMC from patients displayed highly significant Vβ transcriptome alterations as compared to healthy individuals. Similar Vβ alterations could be detected both in PBMCs and at the tumor site. After vaccination, Vβ alteration…

Inactivation of O(6)-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors.

2001

The DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a decisive determinant of resistance of tumor cells to methylating and chloroethylating anti-cancer drugs. Therefore, selective inhibition of MGMT in tumors is expected to cause tumor sensitization. Several inhibitors of MGMT have been developed which function in both tumors and normal tissue. To deplete MGMT preferentially in tumors, strategies to target the inhibitor to the tumor tissue need to be developed. Here, we report on the properties of glucose-conjugated MGMT inhibitors that might be useful for tumor targeting since tumor cells frequently over-express glucose transporter. O6-Benzylguanine (O6BG), 8-aza-O6-ben…

Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)

2009

Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At mul…

Absence of mutations in the activation loop and juxtamembrane domains of VEGFR-1 and VEGFR-2 gene in chronic myelomonocytic leukemia (CMML)

2012

MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L

2011

SummaryThe histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-a…

Broad-spectrum Cross-resistance to Anticancer Drugs Mediated by Epidermal Growth Factor Receptor

2019

BACKGROUND The oncogenic role of epidermal growth factor receptor (EGFR) has been intensively studied. However, its emerging role in drug resistance has not been fully addressed. MATERIALS AND METHODS This study systematically investigated the correlation of mRNA and protein expression of EGFR, as well as gene amplification and mutations with the log-transformed half-maximal inhibitory concentration (log10IC50) values obtained from the NCI panel of 60 human tumor cell lines against 83 standard anticancer agents and the top 10 natural cytotoxic products previously screened by us. RESULTS EGFR protein expression, rather than other measurements, was most frequently associated with drug respons…

Metalloproteinase and TIMP expression by the human breast carcinoma cell line 8701-BC.

1993

It is widely accepted that collagenolytic enzymes are required to facilitate the invasion and spread of tumour cells into host tissues. Immunohistochemical, zymographic and PCR analyses have produced evidence that the recently established human mammary carcinoma cell line, 8701-BC, expresses several metalloproteinases (MMP-1, -2, -9 and -10) and their tissue inhibitors (TIMP-1 and -2). Application of these different techniques has led to several observations, both complementary and dissimilar. Whereas PCR analysis showed that mRNA was detected for each of the proteins, the immunolocalization study demonstrated that MMP-1, MMP-2, MMP-9 and TIMP-1 production was restricted to only a proportio…

Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.

2009

Abstract Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant int…

MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome

2007

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) plays a pivotal role in alkylating drug resistance. Here, we determined MGMT activity in primary and recurrent glioblastomas (GBM, WHO grade IV) of patients who received radiation therapy (RT) or RT plus chemotherapy with alkylating agents (temozolomide, chloroethylnitrosoureas). The mean MGMT activity of untreated GBM was 37 +/- 45 (range 0-205) fmol/mg proteins. In the 1st, 2nd and 3rd recurrences, MGMT activity increased from 66 +/- 50 (13-194) to 68 +/- 44 (14-143) and 182 +/- 163 (64-423) fmol/mg protein, respectively. Comparing patients who received RT only with RT plus chemotherapy, a significant increase of MGMT …

EWS/FLI-1 rearrangement in small round cell sarcomas of bone and soft tissue detected by reverse transcriptase polymerase chain reaction amplificatio…

1994

Recent cloning of the t(11;22) region has led to the detection of a number of sequences involved in the breakpoints by substituting a sequence which encodes a putative RNA binding domain for that of the DNA binding domain of the human homologue of murine FLI-1. Several tumours display consistent translocation at t(11;22) (q24;q12), a finding that suggests these fusion transcripts could be expressed and detected by reverse transcriptase polymerase chain reaction amplification. To date, only a small number of Ewing's sarcomas (Es) and peripheral neuroectodermal tumours (pPNET) of bone have been tested with this novel molecular biology approach. In this study, we confirmed the presence of the …