Papers by Antonio Giovanni Solimando
Hematological Oncology, Jul 11, 2022
The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM)... more The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors and/or immunomodulatory drugs +/− the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis of 27 phase 2/3 randomized trials including a total of 12,935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric used to build a ranking chart. With a mean SUCRA of 83.8 and 80.08 respectively, VMP + Daratumumab (DrVMP) and Rd + Daratumumab (DrRd) reached the top of the chart. However, SUCRA is designed to work for single outcomes. To overcome this limitation, we undertook a dimensionality reduction approach through a principal component analysis, that unbiasedly grouped the 23 regimens into three different subgroups. On the bases of This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Cells, Mar 25, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
PDF file, 113K, Effect of SU11274 treatment on PCs of newly diagnosed MM patients.
This was performed by SYBR Green and the StepOne system (Applied Biosystems, Foster City, CA, USA... more This was performed by SYBR Green and the StepOne system (Applied Biosystems, Foster City, CA, USA) (1). The PCR was conducted using HGF (5'-TCCACGGAAGAGGAGATGAGA-3'/5'-GGCCATATACCAGCTGGGAAA-3'), cMET (5'-GCTAAAATGCTGGCACCCTAA-3'/5'-ATATCCGGGACACCAGTTCAGA-3'), and control glyceraldehyde 3 phosphate dehydrogenase (GAPDH; 5′-GAAGGTGAAGGTCGGAGT-3′/5′-CATGGGTGGAATCATATTGGAA-3′) primers (Invitrogen, Paisley, UK). The mRNA was quantified using GAPDH as the reference gene and the 2-∆∆CT formula (2). Immunoprecipitation and Western blot Total proteins from the MM patients' plasma cells (PCs, 5×10 5 /patient) and the MM cell lines (2×10 6 /sample) were incubated with anti-cMET antibody, and antigen-antibody complexes immunoprecipitated by Protein G/agarose. Protein aliquots (50 μg) were immunoblotted with anti-cMET and anti-phospho(p)-cMET (p-cMET, Tyr1349) antibodies (both from Cell Signaling Technology, Danvers, MA, USA) (3). Immunoreactive bands were detected with enhanced chemiluminescence (LiteAblot ® , Euroclone, Milan, Italy) and the Gel-Logic1500 system (Eastman Kodak Co., Rochester, NY, USA), and quantified as optical density (OD) units by the Kodak imaging software. Florescence-activated cell sorting (FACS) Patients' bone marrow mononuclear cells (BMMCs, 1×10 6 cells/tube) and the MM cell lines (5×10 5 cells/tube) were incubated with fluorescein isothiocyanate (FITC)-conjugated mouse anti-cMET, rabbit anti-p-cMET (Y1234/1235), and isotype matched control antibodies (R&D Systems, Inc.,
Supplementary Figure S1. No effects on MMECs apoptosis and proliferation by the cMET inhibition.
FACS analysis of cMET/phospho(p)-cMET expression in MM.1R vs. MM.1S cells. (A) The cell rate as c... more FACS analysis of cMET/phospho(p)-cMET expression in MM.1R vs. MM.1S cells. (A) The cell rate as co-expression or mono-expression is given. Note the higher expression of p-cMET in MM.1R cells. (B) p-cMET expression upon a 6-h treatment with SU11274 at 1 µM: only MM.1R cells reduced the expression substantially. A representative experiment out of five is shown. Supplementary Figure S2 Effect of SU11274 treatment on cMET/phospho(p)-cMET expression in R5 vs. RPMI8226 cells; and plasma cells (PCs) from relapsed/resistant vs. newly diagnosed MM patients. (A)
PDF file, 97K, SU11274 impacts marginally on in vivo growth of RPMI8226 plasmocytomas. It reverts... more PDF file, 97K, SU11274 impacts marginally on in vivo growth of RPMI8226 plasmocytomas. It reverts bortezomib-resistance in R5 plasmocytomas.
Supplementary Table 2. Proteins identified in MMECs upon treatment with SU11274 or SU11274 plus b... more Supplementary Table 2. Proteins identified in MMECs upon treatment with SU11274 or SU11274 plus bortezomib or plus lenalidomide (MALDI-TOF/TOF mass spectrometry).
PDF file, 93K, FACS analysis of cMET/phospho(p)-cMET expression in MM.1R vs. MM.1S cells.
Supplementary Figure S4. mRNA expression of the angiogenesis-related cytokines (identified by an ... more Supplementary Figure S4. mRNA expression of the angiogenesis-related cytokines (identified by an angiogenesis Western blot array) and of the proteins (identified by mass spectrometry) in SU11274-treated MMECs.
Supplementary Figure S2. SU11274 dose finding.
Purpose: The aim of the study was to verify the hypothesis that the cMet oncogene is implicated i... more Purpose: The aim of the study was to verify the hypothesis that the cMet oncogene is implicated in chemio- and novel drug resistance in multiple myeloma.Experimental Design: We have evaluated the expression levels of cMET/phospho-cMET (p-cMET) and the activity of the novel selective p-cMET inhibitor (SU11274) in multiple myeloma cells, either sensitive (RPMI-8226 and MM.1S) or resistant (R5 and MM.1R) to anti–multiple myeloma drugs, in primary plasma cells and in multiple myeloma xenograft models.Results: We found that resistant R5 and MM.1R cells presented with higher cMET phosphorylation, thus leading to constitutive activation of cMET-dependent signaling pathways. R5 cells exhibited a higher susceptibility to the SU11274 inhibitory effects on viability, proliferation, chemotaxis, adhesion, and to its apoptogenic effects. SU11274 was able to revert drug resistance in R5 cells. R5 but not RPMI-8226 cells displayed cMET-dependent activation of mitogen-activated protein kinase pathwa...
PDF file, 77K, An anti-cMET neutralizing antibody leads to modulation of phospho(p)-proteins in M... more PDF file, 77K, An anti-cMET neutralizing antibody leads to modulation of phospho(p)-proteins in MM cell lines.
Methods in Molecular Biology
Medicina-lithuania, Oct 17, 2019
Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of ... more Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standard care for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results in an alternative first-line treatment for the Chinese clinical oncology guidelines. Moreover, nivolumab and pembrolizumab, two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approved for subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessment of new ICIs-based combinatory approaches.
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Papers by Antonio Giovanni Solimando