1,721,851 research outputs found
Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in myeloma
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Serological proteome analysis (SERPA) as a tool for the identification of tumor antigens capable of eliciting immune responses in chronic lymphocytic leukemia (CLL)
No full textThe mutation of N-ras oncogene does not involve myeloid and erythroid lineages in a case of multiple myeloma
No full textEffective anti-tumor immunomodulatory properties of zoledronic acid in Balb/c mice transgenic for the her-2/Neu oncogene
No full textSelinexor in Combination with Chemotherapy or Idelalisib Elicits a Synergistic Cytotoxic Effect in Primary CLL Cells
No full textAbstract 2072: Selinexor in combination with chemotherapy or idelalisib elicits a synergistic cytotoxic effect in primary CLL cells
No full textProceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GADespite the therapeutic efficacy of new targeted drugs in chronic lymphocytic leukemia (CLL), treatment of high-risk patients remains an unmet clinical need. Tumor suppressor proteins (TSPs) and growth regulatory proteins (e.g. p53, p21, FoxO3a - the effector of Akt signal transduction, and IκB - the endogenous inhibitor of NF-κB) bind the nuclear export protein XPO1 and are carried through the nuclear pore complex into the cell cytoplasm. XPO1 overexpression plays a pathogenic role in CLL by mislocalizing TSPs and other cargoes in the cytoplasm. Selinexor is an oral inhibitor of XPO1, which is active as single agent in different hematologic malignancies. The purpose of this study was to evaluate the in vitro cytotoxic effects of selinexor, used in combination with chemotherapy drugs or with the PI3K inhibitor, idelalisib, against primary CLL cells. Specifically, this study aimed at identifying combination regimens that might overcome single agent resistance. Purified CLL cells from 29 patients were exposed to selinexor (Sel) in combination with fludarabine (F-ara-A), bendamustine (Ben) or idelalisib (Ide). Drug concentrations and exposure times were selected based on data obtained in an initial cohort of 5 patients. In selected experiments, the M2-10B4 murine stromal cell (SC) line was used in co-culture with CLL primary cells. Cell viability was analysed by Annexin-V/propidium Iodide immunostaining and flow cytometry. Combination index (CI) was determined using Calcusyn software. NF-kB and Akt activity was tested through an ELISA assay. After 72-hour culture, a significant decrease in CLL cell viability was observed when samples were treated with drug combinations (i.e. Sel 0.1 { extmu}M + F-ara-A 1 { extmu}M/F-ara-A 10 { extmu}M/Ben 30 { extmu}M/Ben 50 { extmu}M/Ide 0.1 { extmu}M/Ide 1 { extmu}M/ Ide 10 { extmu}M; Sel 1 { extmu}M + F-ara-A 1 { extmu}M/Ben 30 { extmu}M/Ben 50 { extmu}M) compared to the single compounds. The majority of combinations exerted synergistic cytotoxic effects. Interestingly, the addition of selinexor was effective in restoring the fludarabine sensitivity of CLL cells showing in vitro resistance to fludarabine. Sel was also capable to overcome the SC-mediated drug resistance, as shown by the significantly increased and synergistic cytotoxicity exerted by drug combinations, compared to single agents, toward leukemic cells co-cultured with SC. From the molecular standpoint, preliminary data showed that Sel significantly potentiated the inhibitory effect exerted by single-agent idelalisib on NF-kB and Akt activity. Our data demonstrate that the combination of Sel with chemotherapy or idelalisib has synergistic cytotoxic effects, also counteracting intrinsic or SC-mediated drug resistance. In vivo experiments in the Eμ-TCL-1 mouse model are currently ongoing to further corroborate the efficacy of selected drug combinations.Citation Format: Maria Todaro, Valentina Griggio, Chiara Salvetti, Chiara Riganti, Yosef Landesman, Mario Boccadoro, Candida Vitale, Marta Coscia. Selinexor in combination with chemotherapy or idelalisib elicits a synergistic cytotoxic effect in primary CLL cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2072
Selinexor in Combination with Chemotherapy or Idelalisib Elicits a Synergistic Cytotoxic Effect in Primary CLL Cells, Also Overcoming Intrinsic and Stromal Cells-Mediated Fludarabine Resistance
No full textRegulatory T Cells (Tregs) Are Highly Preserved in Multiple Myeloma Patients and Can Dominate Effector Functions
No full text- …
