Alex Almasan - Academia.edu (original) (raw)

Papers by Alex Almasan

Cancer Research, 2004

Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a tumor necr... more Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a tumor necrosis factor superfamily member that induces apoptosis through the death receptors DR4 and/or DR5 in various cancer cell types but not in most normal cells. Several lung cancer cell lines express DR4 and DR5 and undergo apoptosis in vitro in response to Apo2L/TRAIL. We investigated the efficacy of recombinant soluble human Apo2L/TRAIL and its interaction with chemotherapy in xenograft models based on human NCI-H460 non-small cell lung carcinoma cells. In vitro, Taxol enhanced caspase activation and apoptosis induction by Apo2L/TRAIL. In vivo, Apo2L/TRAIL or Taxol plus carboplatin chemotherapy partially delayed progression of established subcutaneous tumor xenografts, whereas combined treatment caused tumor regression and a substantially longer growth delay. Apo2L/TRAIL, chemotherapy, or the combination of both inhibited growth of preformed orthotopic lung parenchymal tumors versus control...

Cancer Research, 2010

Cell death and survival signaling plays an important role in the response to irradiation (IR) and... more Cell death and survival signaling plays an important role in the response to irradiation (IR) and antitumor chemotherapy. IR and other apoptotic insults, such as the Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL), are used as prostate cancer therapeutics, however cellular resistance may hinder their effectiveness. PC3 cells were more sensitive to Apo2L/TRAIL-mediated cell death compared to LNCaP-derived C4-2 prostate cancer cells. The cell death observed showed both apoptotic as well as nonapoptotic features, raising the possibility that apart from classical apoptosis, autophagy might also contribute to cytotoxicity. Following Apo2L/TRAIL treatment of PC3 cells, microtubule associated protein 1 light chain LC3 (ATG8), a classical marker for autophagy, was recruited into autophagosomes following its cleavage (LC3 I) and lipid modification (LC3 II). In contrast, LC3 failed to associate with the autophagosomes in C4-2 cells. IR also resulted in increa...

drives chemotherapeutic resistance in B-cell lymphoid malignancies

Cancer Biology & Therapy, 2009

Methods in Molecular Biology, 2012

Application of Apoptosis to Cancer Treatment, 2005

... Suparna Mazumder1, Dragos Plesca1,2, and Alexandru Almasan1,2,3 1Department of Cancer Biology... more ... Suparna Mazumder1, Dragos Plesca1,2, and Alexandru Almasan1,2,3 1Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195; 2Department of Biological Sciences, Kent State University, Kent, 2 44242; 3Department ...

Radiation Research, 1998

Radiation-induced gene expression was examined in cells of a radioresistant human glioblastoma ce... more Radiation-induced gene expression was examined in cells of a radioresistant human glioblastoma cell line, T98G, using RNA fingerprinting by arbitrary primer polymerase chain reaction. Three of the differentially induced transcripts were cloned and identified as the mitochondrially encoded cytochrome c oxidase (MTCO) subunits 1 and 2, and NADH dehydrogenase subunit 4. The levels of all three mRNAs were increased 1 h after irradiation, with elevated expression persisting for at least 24 h. Similar to radiation, other oxidants lead to induction of MTCO1, an effect which could be prevented by the antioxidant pyrrolidine dithiocarbamate. These results indicate that the increase in mitochondrial gene expression is mediated by oxidative stress. Mitochondria could be a target of signaling by ionizing radiation and oxidants since it is known to be at the site of cellular oxidative stress. The proteins encoded by MTCO1 and other mitochondrial mRNAs characterized are part of the mitochondrial respiratory chain which produces adenosine triphosphate through the process of oxidative phosphorylation. Adenosine triphosphate levels and the mitochondrial membrane potential were found to be increased significantly after irradiation, while mitochondrial mass and mitochondrial DNA levels were unaffected. These data demonstrate the specificity of changes in mitochondrial activity and gene expression after irradiation.

Molecular Cancer Therapeutics, 2007

Leukemia & Lymphoma, 2003

Cytokine & Growth Factor Reviews, 2003

Cell Death and Differentiation, 2003

Cancer research, 2003

Because apoptosis is deregulated in most cancers, apoptosis-modulating approaches offer an attrac... more Because apoptosis is deregulated in most cancers, apoptosis-modulating approaches offer an attractive opportunity for clinical therapy of many tumors, including that of the prostate. LNCaP-derived C4-2 human prostate cancer cells are quite resistant to treatment with Apo2 ligand (Apo2L) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), when using a nontagged, Zn-bound recombinant trimeric version that is devoid of any exogeneous sequences and therefore least likely to be immunogenic in human patients and that has been optimized for maximum efficacy and minimum toxicity. When combined with the topoisomerase I inhibitor CPT-11 (irinotecan), Apo2L/TRAIL exhibits enhanced apoptotic activity in C4-2 cells cultured in vitro as well as xenografted as tumors in vivo. Apoptosis both in vitro and in vivo was characterized by two major molecular events. First, apoptosis induction was accompanied by changes in expression levels of the Bcl-2 family genes and their products. How...