Search results for "Combination"
showing 10 items of 1379 documents
GSK3β as a novel promising target to overcome chemoresistance in pancreatic cancer
2021
Pancreatic cancer is an aggressive malignancy with increasing incidence and poor prognosis due to its late diagnosis and intrinsic chemoresistance. Most pancreatic cancer patients present with locally advanced or metastatic disease characterized by inherent resistance to chemotherapy. These features pose a series of therapeutic challenges and new targets are urgently needed. Glycogen synthase kinase 3 beta (GSK3β) is a conserved serine/threonine kinase, which regulates key cellular processes including cell proliferation, DNA repair, cell cycle progression, signaling and metabolic pathways. GSK3β is implicated in non-malignant and malignant diseases including inflammation, neurodegenerative …
T Cells Expressing Receptor Recombination/Revision Machinery Are Detected in the Tumor Microenvironment and Expanded in Genomically Over-unstable Mod…
2021
AbstractTumors undergo dynamic immunoediting as part of a process that balances immunologic sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TIL) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on T-cell receptor (TCR) specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunologic interface, tumor-infiltrating peripheral T cells could reexpress key elements of the TCR recombination machinery, namely, Rag1 and Rag2 recombinases and Tdt polymerase, as a poten…
Artesunate derived from traditional Chinese medicine induces DNA damage and repair.
2008
Abstract Artesunate is a semisynthetic derivative from artemisinin, a natural product from the Chinese herb Artemisia annua L. It exerts antimalarial activity, and, additionally, artemisinin and its derivatives are active against cancer cells. The active moiety is an endoperoxide bridge. Its cleavage leads to the formation of reactive oxygen species and carbon-centered radicals. These highly reactive molecules target several proteins in Plasmodia, which is thought to result in killing of the microorganism. DNA damage induced by artemisinins has not yet been described. Here, we show that artesunate induces apoptosis and necrosis. It also induces DNA breakage in a dose-dependent manner as sho…
Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment r…
2012
Abstract Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared wit…
Chimeric amplicons containing the c-myc gene in HL60 cells
1998
The major amplicon present in HL60 cells is chimeric in nature being composed of 70 kb of DNA sequence derived from the MYC locus linked to 80 kb of novel DNA sequence derived from a non contiguous region located telomeric to the c-myc gene at 8q24 (Feo et al., 1996). Here we show by fluorescence in situ hybridization (FISH) that these coamplified sequences, MCR (Myc Coamplified Region), are derived from a locus located 3-4 Mb telomeric to the c-myc gene in the q24.2-24.3 region of chromosome 8. Genomic cloning and Southern blot analysis indicate the arrangement of chimeric amplicons are in tandem arrays. Analysis of the DNA sequences at the juncture of the MYC locus and the MCR suggest tha…
Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: The effect of combined treatment with the topoisomerase I-inhibitor topote…
2001
Our results demonstrate that sodium phenylbutyrate, a compound with a low degree of toxicity, exerted a cytotoxic effect on human retinoblastoma Y79 cells in a time- and dose-dependent manner. Treatment of Y79 cells for 72 h with phenylbutyrate reduced cell viability by 63% at 2 mM and 90% at 4 mM. Cell death caused by phenylbutyrate exhibited the typical features of apoptosis, as shown by light and fluorescent microscopy. Western blot analysis demonstrated that exposure of Y79 cells to phenylbutyrate decreased the level of the antiapoptotic factor Bcl-2 and induced the activation of caspase-3, a key enzyme in the execution phase of apoptosis. Moreover, treatment with phenylbutyrate markedl…
Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells.
2011
Abstract Artesunate, the active agent from Artemisia annua L. used in the traditional Chinese medicine, is being applied as a first-line drug for malaria treatment, and trials are ongoing that include this drug in cancer therapy. Despite increasing interest in its therapeutic application, the mode of cell killing provoked by artesunate in human cells is unknown. Here, we show that artesunate is a powerful inducer of oxidative DNA damage, giving rise to formamidopyrimidine DNA glycosylase–sensitive sites and the formation of 8-oxoguanine and 1,N6-ethenoadenine. Oxidative DNA damage was induced in LN-229 human glioblastoma cells dose dependently and was paralleled by cell death executed by ap…
Novel recombinant GII.P16_GII.13 and GII.P16_GII.3 norovirus strains in Italy.
2014
Novel norovirus strains are continuously emerging worldwide. Molecular investigation and phylogenetic analysis identified GII.P16 recombinant noroviruses from the stools of four Italian children with gastroenteritis. The capsid gene was characterized as either GII.13 or GII.3. The GII.P16_GII.13 Italian strains were closely related to German strains involved in a large outbreak in the second half of 2012 and the Italian strains are the first recorded occurrence of GII.P16_GII.13 in Europe.
Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controv…
2016
Contains fulltext : 171468pub.pdf (Publisher’s version ) (Open Access) Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rect…
Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced ovarian failure in patients with lymphoma: 1-year follow-up of a pr…
2013
PURPOSE To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial. PATIENTS AND METHODS Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up. Results Eighty-four of 129 randomly assigned patients …