0000000000062037
AUTHOR
Nicoletta Staropoli
Additional file 5: of Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Figure S4. A Western blot showing expression levels of anti-apoptotic proteins BCL-2 and MCL-1 in U266 and MM1S treated with different doses of trabectedin. B Representative dot plot of apoptosis induction and ROS production in U266 and MM1S cells after trabectedin-treatment respect to control, in presence or absence of ascorbic acid. C Western blot reporting protein expression of cell-cycle and DNA-damage regulators (p21, p-Chk2, RAD51 and gH2AX) in OPM2 cell line, after trabectedin treatment. D Representative immunohistochemistry showing gamma-h2ax foci (in brown) in the nuclei of U266 cells growth in matrigel-based spheroids, after 2.5 nM trabectedin treatment. E Surface expression of MI…
A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?
It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005–2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655–0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%…
Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine
// Pierpaolo Correale 1 , Cirino Botta 2 , Nicoletta Staropoli 3 , Valerio Nardone 4 , Pierpaolo Pastina 4 , Cristina Ulivieri 5 , Claudia Gandolfo 6 , Tatiana Cosima Baldari 5 , Stefano Lazzi 7 , Domenico Ciliberto 3 , Rocco Giannicola 1 , Antonella Fioravanti 8 , Antonio Giordano 9 , Silvia Zappavigna 10 , Michele Caraglia 9, 10 , Pierfrancesco Tassone 2, 3, 10 , Luigi Pirtoli 4 , Maria Grazia Cusi 6 and Pierosandro Tagliaferri 3 1 Unit of Medical Oncology, Grand Metropolitan Hospital Bianchi Melacrino Morelli, Reggio-Calabria, Italy 2 Medical Oncology Unit, AUO Mater Domini, Magna Graecia University, Catanzaro, Italy 3 Department of Experimental and Clinical Medicine, Magna Graecia Unive…
Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients.
Bevacizumab is a humanized anti-VeGF monoclonal antibody able to produce clinical beneit in advanced non-squamous non-small cell lung cancer (nsCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identiied and validated for baseline patient selection. preclinical indings suggest an important role for myeloid-derived inlammatory cells, such as neutrophils and monocytes, in the development of VeGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inlammatory index, the neutrophil-toly…
The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis
Abstract Introduction Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods Clinical trials were selected by searching “Pubmed” database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free surv…
Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10–0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who …
Early blood rise in auto-antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic-non-small cell lung cancer patients treated with PD-1 immune-check point blockade by nivolumab
Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity- associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (…
Targeting a Specific Glycosylated Epitope of CD43 with a New Humanized Monoclonal Antibody for the Treatment of Pediatric and Adult T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Abstract Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for about 20% of pediatric and adult ALL cases. Despite the use of intensive chemotherapy protocols, 25% of children and 50% of adult patients fail to respond or relapse. The 3-years prognosis for these patients is poor and novel treatment options are needed. The targeting of tumor-associated antigens by monoclonal antibodies (mAb) is among the most investigated immune-therapeutic strategies. Accordingly, we developed a new humanized mAb (hUMG1), directed against a heavy glycosylated epitope of CD43 which presents a high reactivity against T-ALL cells. Here we investigated the pre-clinical therapeutic activity and t…
Additional file 3: of Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Figure S2. A Dot plots reporting pro-apoptotic activity of trabectedin after 24 h treatment in primary myeloma cells from three different patients. On the right, histogram reporting the % of viable cells. B Western blot images of a panel of 12 MM cell lines representing proteins belonging to NER pathway, which not exhibited a pattern associated with response to trabectedin. C Expression of the genes belonging to the NER pathway obtained by interrogating 2 different publicly available datasets (GSE68379 and GSE6205) including several MM cell lines used in our in vitro experiments. Cell lines segregate, in an unsupervised hierarchical clustering, accordingly to their response to trabectedin. …
Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included…
Additional file 4: of Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Figure S3. A GSEA results according to clueGO grouped by functions dependent on upregulated or downregulated genes. B Genes belonging to NER pathway resulted to be upregulated following trabectedin treatment in U266. Below, western blot to confirm DDB2 upregulation in 2 different cell lines. (PDF 974 kb)
Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice
Epithelial ovarian cancer (EOC) is the sixth most common malignancy in women. Ovarian tumors consist of several clinical and pathological entities that share an anatomic site. The gold standard treatment, both in front-line and in adjuvant setting, is represented by carboplatin/paclitaxel combination. Conversely, the second-line treatment is not well defined. The response to platinum is the major prognostic factor for survival. In this review we discuss the current views on platinum-refractory/resistant patient treatment only, which includes patients progressing or relapsing within 6 months from the last platinum-based course. Concerning this subgroup, the activity of several conventional d…
Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer
Abstract Aim A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer. Methods By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to …
A retrospective analysis of pegylated liposomal doxorubicin in ovarian cancer: do we still need it?
Abstract Background Ovarian cancer (OC) is the sixth most common cancer in women. Currently, carboplatin/paclitaxel ± bevacizumab is the cornerstone of front-line treatment. Conversely, the therapeutic options for recurrent or progressive disease are not well defined. For platinum-sensitive patients the best therapeutic approach is still a re-challenge with a platinum-based regimen. Pegylated liposomal doxorubicin (PLD), is considered one of the most active therapeutic options for recurrent or progressive OC. In this retrospective mono-institutional analysis, we evaluated the impact of PLD on the outcome of OC patients. Patients and methods We performed the retrospective study on a cohort o…
GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up
Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled …
Pegylated liposomal doxorubicin in the management of ovarian cancer
Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no consensus for management of recurrent/progressive disease, in which pegylated liposomal doxorubicin (PLD) ± carboplatin is widely used. We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment. Data were extracted from randomized trials comparing PLD-based treatment to any other regimens in the January 2000-January 2013 time-frame. Study end-points were overall survival (OS), progression free survival (PFS), response rate (RR), CA125…
The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis
Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled…
Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation
// Nicoletta Staropoli 1, * , Domenico Ciliberto 1, * , Silvia Chiellino 1 , Francesca Caglioti 1 , Teresa Del Giudice 1 , Simona Gualtieri 1 , Angela Salvino 1 , Alessandra Strangio 1 , Cirino Botta 1 , Sandro Pignata 2 , Pierfrancesco Tassone 1, * , Pierosandro Tagliaferri 1, * 1 Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy 2 Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Naples, Italy * These authors have contributed equally to this work Correspondence to: Pierosandro Tagliaferri, email: tagliaferri@unicz.it Keywords: ovarian cancer, targeted therapy, systemic chemotherapy, systemat…
Additional file 2: of Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Figure S1. A Meta-analysis of 4 different GEP datasets of MM comparing the expression levels of genes belonging to different DNA-repair pathways (BER, MMR, HR, c-NHEJ, a-NHEJ, FA) in PCs from MM patients with PCs from healthy donors. B For each panel: on the left, forest plot showing the results of the multivariate COX regression analysis performed on all genes included in the specific DNA repair system. On the right, Kaplan-Meyer curve report results of prognostic system in which patients were divided into “low” and “high” risk group, according to the expression of genes identified by previous multivariate analysis. (PDF 605 kb)
Additional file 1: of Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Table S1. List of genes included in DNA repair systems. (XLSX 11 kb)
Additional file 1: of Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
Figure S1. Correlation of platinum sensitivity status with survival. Kaplan Meier curves of EOC patients grouped according to platinum sensitive (PS) or resistant (PR) disease. Patients with a platinum sensitive ovarian cancer presents a significant longer survival thus confirming the reliability of the sample. (JPG 182 kb)