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15 results on '"Neoplasm Metastasi"'

1. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial

Author

Chiara Cremolini, Carlotta Antoniotti, Daniele Rossini, Sara Lonardi, Fotios Loupakis, Filippo Pietrantonio, Roberto Bordonaro, Tiziana Pia Latiano, Emiliano Tamburini, Daniele Santini, Alessandro Passardi, Federica Marmorino, Roberta Grande, Giuseppe Aprile, Alberto Zaniboni, Sabina Murgioni, Cristina Granetto, Angela Buonadonna, Roberto Moretto, Salvatore Corallo, Stefano Cordio, Lorenzo Antonuzzo, Gianluca Tomasello, Gianluca Masi, Monica Ronzoni, Samantha Di Donato, Chiara Carlomagno, Matteo Clavarezza, Giuliana Ritorto, Andrea Mambrini, Mario Roselli, Samanta Cupini, Serafina Mammoliti, Elisabetta Fenocchio, Enrichetta Corgna, Vittorina Zagonel, Gabriella Fontanini, Clara Ugolini, Luca Boni, Alfredo Falcone, Filippo Guglielmo Maria De Braud, Evaristo Maiello, Giovanni Luca Frassineti, Teresa Gamucci, Francesco Di Costanzo, Luca Gianni, Patrizia Racca, Giacomo Allegrini, Alberto Sobrero, Massimo Aglietta, Enrico Cortesi, Domenico Cristiano Corsi, Alberto Ballestrero, Andrea Bonetti, Francesco Di Clemente, Enzo Ruggeri, Fortunato Ciardiello, Marco Benasso, Stefano Vitello, Saverio Cinieri, Stefania Mosconi, Nicola Silvestris, Antonio Frassoldati, Samantha Cupini, Alessandro Bertolini, Giampaolo Tortora, Carmelo Bengala, Daris Ferrari, Antonia Ardizzoia, Carlo Milandri, Silvana Chiara, Gianpiero Romano, Stefania Miraglia, Laura Scaltriti, Francesca Pucci, Livio Blasi, Silvia Brugnatelli, Luisa Fioretto, Angela Stefania Ribecco, Raffaella Longarini, Michela Frisinghelli, Maria Banzi, Cremolini, C., Antoniotti, C., Rossini, D., Lonardi, S., Loupakis, F., Pietrantonio, F., Bordonaro, R., Latiano, T. P., Tamburini, E., Santini, D., Passardi, A., Marmorino, F., Grande, R., Aprile, G., Zaniboni, A., Murgioni, S., Granetto, C., Buonadonna, A., Moretto, R., Corallo, S., Cordio, S., Antonuzzo, L., Tomasello, G., Masi, G., Ronzoni, M., Di Donato, S., Carlomagno, C., Clavarezza, M., Ritorto, G., Mambrini, A., Roselli, M., Cupini, S., Mammoliti, S., Fenocchio, E., Corgna, E., Zagonel, V., Fontanini, G., Ugolini, C., Boni, L., Falcone, A., De Braud, F. G. M., Maiello, E., Frassineti, G. L., Gamucci, T., Di Costanzo, F., Gianni, L., Racca, P., Allegrini, G., Sobrero, A., Aglietta, M., Cortesi, E., Corsi, D. C., Ballestrero, A., Bonetti, A., Di Clemente, F., Ruggeri, E., Ciardiello, F., Benasso, M., Vitello, S., Cinieri, S., Mosconi, S., Silvestris, N., Frassoldati, A., Bertolini, A., Tortora, G., Bengala, C., Ferrari, D., Ardizzoia, A., Milandri, C., Chiara, S., Romano, G., Miraglia, S., Scaltriti, L., Pucci, F., Blasi, L., Brugnatelli, S., Fioretto, L., Ribecco, A. S., Longarini, R., Frisinghelli, M., and Banzi, M.

Subjects
Male, 0301 basic medicine, GONO, Organoplatinum Compounds, multicentre, Leucovorin, Colorectal Neoplasm, Gastroenterology, Settore MED/06, Antineoplastic Agents, Immunological, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, FOLFOXIRI, progression versus mFOLFOX6 plus bevacizumab, mFOLFOX6, metastatic colorectal cancer, Middle Aged, TRIBE2 trial, FOLFIRI plus bevacizumab, Neoplasm Metastasi, Bevacizumab, FOLFOXIRI plus bevacizumab, triplet FOLFOXIRI, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Female, metastatic colorectal cancer, triplet FOLFOXIRI , FOLFOXIRI plus bevacizumab, FOLFIRI plus bevacizumab, progression versus mFOLFOX6 plus bevacizumab, TRIBE2, Colorectal Neoplasms, Human, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Analogs & derivatives, open-label, NO, Young Adult, 03 medical and health sciences, Folinic acid, Internal medicine, medicine, cancer, Humans, neoplasms, Aged, Antineoplastic Combined Chemotherapy Protocol, Performance status, business.industry, Organoplatinum Compound, randomised controlled, FOLFOXIRI, bevacizumab, mFOLFOX6, FOLFIRI, metastatic colorectal cancer, TRIBE2 trial, multicentre, open-label, phase 3, randomised controlled, GONO, Irinotecan, 030104 developmental biology, phase 3, TRIBE2, Camptothecin, business
Abstract

Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.

Published
2020
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2. Sleeping beauty genetic screen identifies miR-23b::BTBD7 gene interaction as crucial for colorectal cancer metastasis

Author

Milena S. Nicoloso, Andrea Vecchione, Luigi Zandonà, Gustavo Baldassarre, Erik Dassi, Ilenia Rigo, Vincenzo Canzonieri, Alex H. Mirnezami, Eleonora Grisard, Maurizio Mongiat, Eva Andreuzzi, Giulia Brisotto, Riccardo Spizzo, Eva Biscontin, Fabio Del Ben, Laura Cesaratto, Gian Luca Rampioni Vinciguerra, E. Poletto, Michela Coan, Matteo Turetta, Alice Paulitti, Grisard, E., Coan, M., Cesaratto, L., Rigo, I., Zandona, L., Paulitti, A., Andreuzzi, E., Rampioni Vinciguerra, G. L., Poletto, E., Del Ben, F., Brisotto, G., Biscontin, E., Turetta, M., Dassi, E., Mirnezami, A., Canzonieri, V., Vecchione, A., Baldassarre, G., Mongiat, M., Spizzo, R., and Nicoloso, M. S.

Subjects
0301 basic medicine, Research paper, Colorectal cancer, Colorectal Neoplasm, Cell Communication, Metastasis, DNA transposons, 0302 clinical medicine, Neoplasm Metastasis, Tumor, Adaptor Proteins, MicroRNA, General Medicine, Extracellular Matrix, 3. Good health, Neoplasm Metastasi, Gene Expression Regulation, Neoplastic, microRNA target, 030220 oncology & carcinogenesis, RNA Interference, Colorectal Neoplasms, Human, Transposable element, Epithelial-Mesenchymal Transition, Colorectal cancer metastasi, Colorectal cancer metastasis, Settore BIO/11 - Biologia Molecolare, Context (language use), Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, Gene interaction, Cell Line, Tumor, microRNA, medicine, Humans, Genetic Testing, Adaptor Proteins, Signal Transducing, Cell Proliferation, Neoplasm Staging, Neoplastic, spleeping beauty, Signal Transducing, DNA transposon, medicine.disease, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Cancer research, Human genome, Genetic screen
Abstract

Background: Metastatic colorectal cancer (CRC) remains a deadly disease. Identifying locally advanced CRC patients with high risk of developing metastasis and improving outcome of metastatic CRC patients require discovering master regulators of metastasis. In this context, the non-coding part of the human genome is still largely unexplored. Methods: To interrogate the non-coding part of the human genome and disclose regulators of CRC metastasis, we combined a transposon-based forward genetic screen with a novel in vitro assay, which forces cells to grow deprived of cell-substrate and cell-cell contacts (i.e. forced single cell suspension assay - fSCS). Findings: We proved that fSCS selects CRC cells with mesenchymal and pro-metastatic traits. Moreover, we found that the transposon insertions conferred CRC cells resistance to fSCS and thus metastatic advantage. Among the retrieved transposon insertions, we demonstrated that the one located in the 3′UTR of BTBD7 disrupts miR-23b::BTBD7 interaction and contributes to pro-metastatic traits. In addition, miR-23b and BTBD7 correlate with CRC metastasis both in preclinical experiments and in clinical samples. Interpretation: fSCS is a simple and scalable in vitro assay to investigate pro-metastatic traits and transposon-based genetic screens can interrogate the non-coding part of the human genome (e.g. miRNA::target interactions). Finally, both Btbd7 and miR-23b represent promising prognostic biomarkers and therapeutic targets in CRC. Fund: This work was supported by Marie Curie Actions (CIG n. 303877) and Friuli Venezia Giulia region (Grant Agreement n°245574), Italian Association for Cancer Research (AIRC, MFAG n°13589), Italian Ministry of Health (GR-2010-2319387 and PE-2016-02361040) and 5x1000 to CRO Aviano.

Published
2019
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3. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study

Author

Kenji Tamura, Hirofumi Mukai, Vassiliki Karantza, Hope S. Rugo, Peter Schmid, Rita Nanda, Sylvia Adams, Anne C Armstrong, Sherene Loi, Deborah Toppmeyer, David W. Cescon, H. Iwata, Minetta C. Liu, Larisa Ryvo, Antoinette R. Tan, Y. Ding, Pauline Wimberger, M. De Laurentiis, L. Jia, EP Winer, Adams, S., Loi, S., Toppmeyer, D., Cescon, D. W., De Laurentiis, M., Nanda, R., Winer, E. P., Mukai, H., Tamura, K., Armstrong, A., Liu, M. C., Iwata, H., Ryvo, L., Wimberger, P., Rugo, H. S., Tan, A. R., Jia, L., Ding, Y., Karantza, V., and Schmid, P.

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Triple Negative Breast Neoplasms, triple-negative breast neoplasm, Pembrolizumab, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Adjuvant therapy, Clinical endpoint, Humans, Medicine, Progression-free survival, Neoplasm Metastasis, Adverse effect, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Progression-Free Survival, Neoplasm Metastasi, Gene Expression Regulation, Neoplastic, Clinical trial, 030104 developmental biology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, anti-PD-1, Female, immunotherapy, pembrolizumab, Cohort Studie, business, Human
Abstract

Background Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC. Patients and methods Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival. Results All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9–31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9–34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0–2.2), and median overall survival was 18.0 months (95% CI 12.9–23.0). Conclusions Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC. Clinical trial registration ClinicalTrials.gov, NCT02447003.

Published
2019
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4. Does the Unexpected Presence of Non-organ-confined Disease at Final Pathology Undermine Cancer Control in Patients with Clinical T1N0M0 Renal Cell Carcinoma Who Underwent Partial Nephrectomy?

Author

Idir Ouzaid, Paolo Dell'Oglio, Andrea Minervini, James Lingard, Maciej Salagierski, Grant D. Stewart, Sabine Brookman-May, Maria Carmen Mir, Marco Carini, Oscar Rodriguez Faba, Bulent Akdogan, Francesco Montorsi, Marco Roscigno, Luigi F. Da Pozzo, Tobias Klatte, Emanuele Zaffuto, Christian G. Stief, Martin Marszalek, Umberto Capitanio, Capitanio, Umberto, Stewart, Grant D., Klatte, Tobia, Akdogan, Bulent, Roscigno, Marco, Marszalek, Martin, Dell'Oglio, Paolo, Zaffuto, Emanuele, Rodriguez Faba, Oscar, Salagierski, Maciej, Lingard, Jame, Carini, Marco, Ouzaid, Idir, Mir, Maria Carmen, Montorsi, Francesco, Da Pozzo, Luigi Filippo, Stief, Christian, Minervini, Andrea, Brookman-May, Sabine D., Stewart, Grant [0000-0003-3188-9140], Apollo - University of Cambridge Repository, Capitanio, U, Stewart, G, Klatte, T, Akdogan, B, Roscigno, M, Marszalek, M, Dell'Oglio, P, Zaffuto, E, Rodriguez Faba, O, Salagierski, M, Lingard, J, Carini, M, Ouzaid, I, Mir, M, Montorsi, F, Da Pozzo, L, Stief, C, Minervini, A, and Brookman-May, S

Subjects
Male, Pathology, medicine.medical_treatment, 030232 urology & nephrology, Kaplan-Meier Estimate, Disease, Nephrectomy, 0302 clinical medicine, Retrospective Studie, cancer control, Renal cell carcinoma, Partial nephrectomy, Medicine, Neoplasm Metastasis, Multivariate Analysi, Upstaging, Kidney, Cancer control, Kidney cancer, Radical nephrectomy, Renal cancer, Kidney Neoplasm, kidney cancer, Middle Aged, Kidney Neoplasms, Neoplasm Metastasi, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Disease Progression, Female, Human, radical nephrectomy, medicine.medical_specialty, partial nephrectomy, Urology, renal cancer, 03 medical and health sciences, Humans, Propensity Score, Carcinoma, Renal Cell, Proportional Hazards Models, Retrospective Studies, Aged, Neoplasm Staging, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, upstaging, Multivariate Analysis, Propensity score matching, Proportional Hazards Model, business
Abstract

Background: A non-negligible proportion of individuals diagnosed with cT1 renal cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on oncological outcomes for these patients are available to determine whether partial nephrectomy (PN) might jeopardise cancer control. Objective: To assess, within an international multi-institutional collaboration, whether PN might undermine cancer control relative to radical nephrectomy (RN) in RCC patients with unexpected pT3a disease. Design, setting, and participants: International multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC. Intervention: PN or RN. Outcome measurements and statistical analysis: We used Kaplan-Meier analyses, before and after propensity-score matching, to evaluate differences in metastatic progression (MP) and cancer-specific mortality (CSM) rates during follow-up. Univariable and multivariable Cox regression analyses were used to assess predictors of MP and CSM. Results and limitations: Overall, 309 patients with cT1abN0M0 RCC (cT1aN0M0, n = 107, 34.6%; cT1bN0M0, n = 202, 65.4%) had pT3a disease according to final pathology. Patients were treated with either PN (n = 71, 23%) or RN (n = 238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%, 13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1, 2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM was observed between the PN and RN cohorts (both p>0.3). On multivariable analysis, type of surgery (PN vs RN) was not an independent predictor of either MP (p = 0.3) or CSM (p = 0.4). Limitations include the retrospective design. Conclusions: In patients with unexpected pT3a RCC at final pathology, PN does not appear to jeopardise cancer control with regard to MP and CSM. Patient summary: Cancer control is similar between patients treated with removal of the entire kidney and those with only partial removal, even if the final histology examination demonstrates a tumour that is unexpectedly not confined within the kidney. Partial nephrectomy does not undermine cancer control when unexpected pT3a renal cancer is identified at final pathology.

Published
2018
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5. Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate

Author

Bruno Daniele, Teresa Bellelli, Franco Morelli, Gaetano Facchini, Gregory R. Pond, Sarah Scagliarini, Giacomo Cartenì, Guru Sonpavde, Sabino De Placido, Matteo Ferro, Giuseppe Lucarelli, Sabrina Rossetti, Piera Federico, Carlo Buonerba, Giuseppe Di Lorenzo, Di Lorenzo, G., Sonpavde, G., Pond, G., Lucarelli, G., Rossetti, S., Facchini, G., Scagliarini, S., Carteni, G., Federico, P., Daniele, B., Morelli, F., Bellelli, T., Ferro, M., De Placido, S., and Buonerba, C.

Subjects
Male, Oncology, Abiraterone Acetate, Antineoplastic Agent, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Retrospective Studie, 030212 general & internal medicine, Neoplasm Metastasis, Abiraterone, Multivariate Analysi, Medical record, Hazard ratio, Abiraterone acetate, Kallikrein, Middle Aged, Prognosis, Neoplasm Metastasi, Survival Rate, Prostatic Neoplasms, Castration-Resistant, 030220 oncology & carcinogenesis, Kallikreins, Human, medicine.medical_specialty, Statin, Prognosi, medicine.drug_class, Urology, Antineoplastic Agents, 03 medical and health sciences, Pharmacokinetics, Internal medicine, medicine, Humans, Proportional Hazards Models, Retrospective Studies, Aged, business.industry, Retrospective cohort study, Prostate-Specific Antigen, medicine.disease, Confidence interval, Surgery, chemistry, Multivariate Analysis, Proportional Hazards Model, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

Background Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37–0.72; p p 50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p Conclusions Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.

Published
2018
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6. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Carlos L. Arteaga, Mark Clemons, Soulef Hachemi, Barbara Pistilli, Javier Cortes, José Baselga, Zefei Jiang, Norikazu Masuda, Agnieszka Jagiełło-Gruszfeld, Bharani Dharan, Seock–Ah –A Im, Masato Takahashi, Patrick Urban, Peter Vuylsteke, Ling Ming Tseng, Hiroji Iwata, Mario Campone, Walter Jonat, Yoshinori Ito, Sara A. Hurvitz, Ahmad Awada, Michele De Laurentiis, Cristian Massacesi, Stephen Chia, Emmanuelle di Tomaso, Baselga, José, Im, Seock-ah, Iwata, Hiroji, Cortés, Javier, De Laurentiis, Michele, Jiang, Zefei, Arteaga, Carlos L, Jonat, Walter, Clemons, Mark, Ito, Yoshinori, Awada, Ahmad, Chia, Stephen, Jagiełło-gruszfeld, Agnieszka, Pistilli, Barbara, Tseng, Ling-ming, Hurvitz, Sara, Masuda, Norikazu, Takahashi, Masato, Vuylsteke, Peter, Hachemi, Soulef, Dharan, Bharani, Di Tomaso, Emmanuelle, Urban, Patrick, Massacesi, Cristian, and Campone, Mario

Subjects
0301 basic medicine, Morpholine, Aging, Receptor, ErbB-2, DNA Mutational Analysis, Buparlisib, Aminopyridines, Phases of clinical research, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, ErbB-2, 0302 clinical medicine, Receptors, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, Fulvestrant, Progesterone, Class I Phosphatidylinositol 3-Kinase, Cancer, education.field_of_study, Tumor, Estradiol, Alanine Transaminase, DNA, Neoplasm, Middle Aged, Neoplasm Metastasi, Postmenopause, Survival Rate, Receptors, Estrogen, Oncology, Response Evaluation Criteria in Solid Tumors, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Retreatment, Female, Drug Eruptions, Receptors, Progesterone, Breast Neoplasm, Human, Receptor, Signal Transduction, medicine.drug, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Morpholines, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Population, Response Evaluation Criteria in Solid Tumor, Breast Neoplasms, Placebo, Article, Disease-Free Survival, DNA Mutational Analysi, 03 medical and health sciences, Breast cancer, Double-Blind Method, Clinical Research, Internal medicine, Breast Cancer, Biomarkers, Tumor, medicine, Humans, Oncology & Carcinogenesis, Aspartate Aminotransferases, education, Survival rate, Aged, Gynecology, Antineoplastic Combined Chemotherapy Protocol, business.industry, Evaluation of treatments and therapeutic interventions, Aspartate Aminotransferase, DNA, Exanthema, medicine.disease, Estrogen, Aminopyridine, 030104 developmental biology, chemistry, Drug Eruption, Hyperglycemia, Neoplasm, Phosphatidylinositol 3-Kinase, business, Biomarkers
Abstract

BackgroundPhosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer. This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit.MethodsThe BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study. Postmenopausal women aged 18 years or older with histologically confirmed, hormone receptor-positive and human epidermal growth factor (HER2)-negative inoperable locally advanced or metastatic breast cancer whose disease had progressed on or after aromatase inhibitor treatment and had received up to one previous line of chemotherapy for advanced disease were included. Eligible patients were randomly assigned (1:1) using interactive voice response technology (block size of 6) on day 15 of cycle 1 to receive oral buparlisib (100 mg/day) or matching placebo, starting on day 15 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1, and on day 1 of subsequent 28-day cycles. Patients were assigned randomisation numbers with a validated interactive response technology; these numbers were linked to different treatment groups which in turn were linked to treatment numbers. PI3K status in tumour tissue was determined via central laboratory during a 14-day run-in phase. Randomisation was stratified by PI3K pathway activation status (activated vs non-activated vs and unknown) and visceral disease status (present vs absent). Patients, investigators, local radiologists, study team, and anyone involved in the study were masked to the identity of the treatment until unblinding. The primary endpoints were progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in the total population, in patients with known (activated or non-activated) PI3K pathway status, and in PI3K pathway-activated patients. Efficacy analyses were done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01610284, and is currently ongoing but not recruiting participants.FindingsBetween Sept 7, 2012, and Sept 10, 2014, 1147 patients from 267 centres in 29 countries were randomly assigned to receive buparlisib (n=576) or placebo plus fulvestrant (n=571). In the total patient population (n=1147), median progression-free survival was 6·9 months (95% CI 6·8-7·8) in the buparlisib group versus 5·0 months (4·0-5·2) in the placebo group (hazard ratio [HR] 0·78 [95% CI 0·67-0·89]; one-sided p=0·00021). In patients with known PI3K status (n=851), median progression-free survival was 6·8 months (95% CI 5·0-7·0) in the buparlisib group vs 4·5 months (3·3-5·0) in the placebo group (HR 0·80 [95% CI 0·68-0·94]; one-sided p=0·0033). In PI3K pathway-activated patients (n=372), median progression-free survival was 6·8 months (95% CI 4·9-7·1) in the buparlisib group versus 4·0 months (3·1-5·2) in the placebo group (HR 0·76 [0·60-0·97], one-sided p=0·014). The most common grade 3-4 adverse events in the buparlisib group versus the placebo group were increased alanine aminotransferase (146 [25%] of 573 patients vs six [1%] of 570), increased aspartate aminotransferase (103 [18%] vs 16 [3%]), hyperglycaemia (88 [15%] vs one [

Published
2017
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7. Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis

Author

Grazia Arpino, Fabio Puglisi, Marta Bonotto, Massimo Di Maio, Gianpiero Fasola, Lorenzo Gerratana, S. Moroso, Mauro Mansutti, Sabino De Placido, Donatella Iacono, Monica Milano, Carmine De Angelis, Marika Cinausero, Brigida Stanzione, Alessandro Marco Minisini, Piera Gargiulo, Bonotto, Marta, Gerratana, Lorenzo, Di Maio, Massimo, DE ANGELIS, Carmine, Cinausero, Marika, Moroso, Stefano, Milano, Monica, Stanzione, Brigida, Gargiulo, Piera, Iacono, Donatella, Minisini, Alessandro Marco, Mansutti, Mauro, Fasola, Gianpiero, DE PLACIDO, Sabino, Arpino, Grazia, and Puglisi, Fabio

Subjects
0301 basic medicine, Oncology, Multivariate analysis, Receptor, ErbB-2, medicine.medical_treatment, Hormone antagonist, Antineoplastic Agent, Metastatic breast neoplasms, 0302 clinical medicine, Retrospective Studie, Age Factor, Metastatic breast neoplasm, Neoplasm Metastasis, Treatment outcome, Multivariate Analysi, Chemotherapy, Decision making, Drug therapy, education.field_of_study, Age Factors, General Medicine, Middle Aged, Metastatic breast cancer, Neoplasm Metastasi, 030220 oncology & carcinogenesis, Female, Breast Neoplasm, Human, medicine.medical_specialty, Population, Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, 03 medical and health sciences, Hormone Antagonists, Pharmacotherapy, Internal medicine, medicine, Humans, Propensity Score, education, Aged, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, Surgery, Hormone Antagonist, 030104 developmental biology, Multivariate Analysis, Propensity score matching, business
Abstract

Background According to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown. Methods A consecutive series of luminal-like HER2-negative MBC patients treated from 2004 to 2014 was analyzed to test the association of disease- and patient-related factors with the choice of first-line treatment (ET vs. CT). A propensity score method was used to estimate impact of first-line strategy on outcome. Results Of 604 consecutive luminal-like MBC patients identified, 158 cases were excluded due to unknown or positive HER2-status. Among 446 HER2-negative cases, 171 (38%) received first-line CT. On multivariate analysis, the only factors significantly associated with lower CT use were old age (OR 0.25, 95%C.I. 0.13–0.49) or presence of bone metastases only (OR 0.26, 95%C.I. 0.13–0.53). In propensity score matched population, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (37.5 months and 33.4 months respectively, log-rank test, P = 0.62) or progression-free survival (13.3 months and 9.9 months respectively, log-rank test, P = 0.92). Conclusions High percentage of patients with luminal-like MBC received CT as first-line therapy in real-life. The choice was mainly driven by age and site of metastases. With the limitations of a non-randomized comparison, no differences on patients' outcome were observed depending on the first-line strategy.

Published
2017
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8. Surgery of the primary tumor in de novo metastatic breast cancer: To do or not to do?

Author

M. De Laurentiis, Giuseppe Curigliano, Grazia Arpino, Carmen Criscitiello, Michele Santangelo, Mehra Golshan, Mario Giuliano, S. De Placido, Nicola Carlomagno, Criscitiello, C., Giuliano, M., Curigliano, G., De Laurentiis, M., Arpino, G., Carlomagno, N., De Placido, S., Golshan, M., and Santangelo, M.

Subjects
Oncology, medicine.medical_specialty, Primary metastatic breast cancer, Survival, medicine.medical_treatment, Breast Neoplasms, Disease, law.invention, Breast cancer, Randomized controlled trial, law, Internal medicine, medicine, Humans, Neoplasm Metastasis, Chemotherapy, business.industry, Cancer, General Medicine, medicine.disease, Metastatic breast cancer, Primary tumor, Surgery, Neoplasm Metastasi, Survival Rate, Radiation therapy, Treatment Outcome, Female, business, Breast Neoplasm, Human
Abstract

Approximately five percent of all breast cancer patients in developed countries present with distant metastases at initial diagnosis. Due to its incurability, metastatic breast cancer is generally treated with systemic therapies to achieve disease control and reduce tumor-related symptoms. Primary treatments for metastatic breast cancer are chemotherapy, endocrine- and biologic therapy, whereas surgery with or without radiotherapy is usually performed to treat impending wound issues. Since 2002, several retrospective non-randomized clinical studies have shown that extirpation of the primary tumor correlates with a significantly improved survival in patients with primary metastatic breast cancer. Others have argued that this survival benefit associated with surgery may be due to selection biases. Therefore, in the absence of published results from randomized controlled trials carried out in India and Turkey and completion of a trial in the United States, there is no clear conclusion on whether surgical excision of the primary breast cancer translates into a survival benefit for patients with de novo metastatic disease. Furthermore, timing and type of surgical procedure, as well as selection of patients who could benefit the most from this approach, represent additional points of uncertainty. Despite the epidemiological burden of this condition, there are no guidelines on how to manage breast cancer patients presenting with de novo metastatic breast cancer; and decisions are often left to provider and patient preferences. Here, we present a critical overview of the literature focusing on the rationale and potential role of primary tumour excision in patients with de novo metastatic breast cancer.

Published
2015
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9. Metastasis-directed Therapy of Regional and Distant Recurrences After Curative Treatment of Prostate Cancer: A Systematic Review of the Literature

Author

Gianluca Giannarini, Piet Ost, Alberto Briganti, Alberto Bossi, Karel Decaestecker, R. Jeffrey Karnes, Mack Roach, Gert De Meerleer, Ost, P, Bossi, A, Decaestecker, K, De Meerleer, G, Giannarini, G, Karnes, Rj, Roach, M, and Briganti, Alberto

Subjects
Neoplasm recurrence, Male, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Urology, medicine.medical_treatment, Salvage therapy, Context (language use), Radiosurgery, Metastasis, Androgen deprivation therapy, Prostate cancer, Recurrence, medicine, Humans, Androgen Antagonist, Neoplasm Metastasis, Salvage Therapy, business.industry, Prostatic Neoplasms, Androgen Antagonists, medicine.disease, Surgery, Neoplasm Metastasi, Radiation therapy, Lymph node excision, Treatment Outcome, Systematic review, Chemotherapy, Adjuvant, Positron-Emission Tomography, Prostatic Neoplasm, Lymph Node Excision, Radiology, Neoplasm Recurrence, Local, business, Human, Radical retropubic prostatectomy
Abstract

Context The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. Objective To perform a systematic review of MDT for oligometastatic PCa recurrence. Evidence acquisition This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Evidence synthesis Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven studies were considered of acceptable quality. Oligometastatic PCa recurrence was diagnosed with positron emission tomography with coregistered computed tomography in most of the patients (98%). Nodal, bone, and visceral metastases were treated in 78%, 21%, and 1%, respectively. Patients were treated with either RT (66%) or lymph node dissection (LND) (34%). Adjuvant androgen deprivation was given in 61% of patients ( n =275). In the case of nodal metastases, prophylactic nodal irradiation was administered in 49% of patients ( n =172). Overall, 51% of patients were progression free 1–3 yr after salvage MDT, with most of them receiving adjuvant treatment. For RT, grade 2 toxicity was observed in 8.5% of patients, with one case of grade 3 toxicity. In the case of LND, 11% and 12% of grade 2 and grade 3 complications, respectively, were reported. Conclusions MDT is a promising approach for oligometastatic PCa recurrence, but the low level of evidence generated by small case series does not allow extrapolation to a standard of care. Patient summary We performed a systematic review to assess complications and outcomes of treating oligometastatic prostate cancer recurrence with surgery or radiotherapy. We concluded that although this approach is promising, it requires validation in randomised controlled trials.

Published
2015
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10. Tumor associated macrophages and neutrophils in cancer

Author

Maria Rosaria Galdiero, Cecilia Garlanda, Eduardo Bonavita, Sébastien Jaillon, Alberto Mantovani, Isabella Barajon, Galdiero, MARIA ROSARIA, Bonavita, Eduardo, Barajon, Isabella, Garlanda, Cecilia, Mantovani, Alberto, and Jaillon, Sébastien

Subjects
Neutrophils, Macrophage, MDSC, Tumor initiation, HNSCC, Metastasis, Cell Movement, Neoplasms, Tumor Microenvironment, Immunology and Allergy, tumor associate neutrophil, Neoplasm Metastasis, HCC, Cancer, MMP, vascular endothelial growth factor, Effector, Neutrophil, Cell Differentiation, hepatocellular carcinoma, Hematology, head and neck squamous cellular cancer, VEGF, CRC, matrix metalloprotease, Neoplasm Metastasi, myeloid derived suppressor cell, Cytokines, medicine.symptom, Human, extracellular matrix, Immunology, colorectal cancer, Inflammation, Biology, Immune system, medicine, Humans, tumor entrained neutrophil, Cytokine, Tumor microenvironment, ECM, Macrophages, Macrophage Activation, medicine.disease, tumor associated macrophage, TEN, TAM, Cancer research, Myeloid-derived Suppressor Cell, Neoplasm, TAN
Abstract

The tumor microenvironment is a complex framework, in which myeloid cells play important roles in sculpting cancer development from tumor initiation to metastasis. Immune cells are key participants of the tumor microenvironment where they can promote or inhibit cancer formation and development. Plasticity is a widely accepted hallmark of myeloid cells and in particular of the monocyte-macrophage lineage. It includes the ability to display a wide spectrum of activation states in response to distinct signals and classical M1 or alternative M2 macrophages represent a paradigm of this feature. Neutrophils have long been viewed as terminally differentiated effector cells, playing a major role during the acute phase of inflammation and resistance against microbes. Recent evidence questioned this limited point of view, indicating that neutrophils can interact with distinct cell populations and produce a wide number of cytokines and effector molecules. Therefore, macrophages and neutrophils are both integrated in the regulation of the innate and adaptive immune responses in various inflammatory situations, including cancer.

Published
2013
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11. Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients

Author

Giuseppe Curigliano, Luca Mazzarella, Sara Caputo, Donata Galbiati, Nicole Rotmensz, Davide Disalvatore, Pier Giuseppe Pelicci, Vincenzo Bagnardi, Mazzarella, L, Disalvatore, D, Bagnardi, V, Rotmensz, N, Galbiati, D, Caputo, S, Curigliano, G, and Pelicci, P

Subjects
Adult, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Breast Neoplasms, Body Mass Index, Breast cancer, Trastuzumab, HER2, Internal medicine, Prevalence, medicine, Humans, Cumulative incidence, Obesity, Neoplasm Metastasis, skin and connective tissue diseases, Survival analysis, Aged, Aged, 80 and over, Breast neoplasm, business.industry, Incidence, Incidence (epidemiology), Hazard ratio, Middle Aged, medicine.disease, Survival Analysis, Neoplasm Metastasi, Receptors, Estrogen, Female, Survival Analysi, business, Body mass index, Human, medicine.drug
Abstract

Background: Obesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. Patients and methods: We assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER-) HER2+ cases. Results: In ER-/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI > 30) versus normal/underweight (BMI < 25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. Conclusions: Obesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER-/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer. © 2013 Elsevier Ltd. All rights reserved.

Published
2013
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12. Epithelial–mesenchymal transition and breast cancer: Role, molecular mechanisms and clinical impact

Author

Giovanna Damia, Chiara Foroni, Massimo Broggini, Daniele Generali, Foroni, Chiara, Broggini, Massimo, Generali, Daniele, and Damia, Giovanna

Subjects
Oncology, Radiology, Nuclear Medicine and Imaging, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Drug Resistance, Antineoplastic Agents, Breast Neoplasms, Biology, Cell Transformation, Neoplastic Cells, Metastasis, Antineoplastic Agent, Breast cancer, Cancer stem cell, Nuclear Medicine and Imaging, Internal medicine, Circulating, medicine, Humans, Radiology, Nuclear Medicine and imaging, Molecular Targeted Therapy, Epithelial–mesenchymal transition, Neoplasm Metastasis, Epidermal-mesenchymal transition, Biomarkers, Cell Transformation, Neoplastic, Drug Resistance, Neoplasm, Female, Neoplastic Cells, Circulating, Signal Transduction, Neoplastic, Mesenchymal stem cell, Biomarker, General Medicine, medicine.disease, Neoplasm Metastasi, Cancer cell, Cancer research, Neoplasm, Radiology, Breast carcinoma, Breast Neoplasm, Human, Mesenchymal phenotype
Abstract

Epithelial–mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In this process, cells acquire molecular alterations that facilitate dysfunctional cell–cell adhesive interactions and junctions. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Such transformation has implications in progression of breast carcinoma to metastasis, and increasing evidences support most tumors contain a subpopulation of cells with stem-like and mesenchymal features that is resistant to chemotherapy. This review focuses on the physiological and pathological role of EMT process, its molecular related network, its putative role in the metastatic process and its implications in response/resistance to the current and/or new approaching drugs in the clinical management of breast cancer.

Published
2012
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13. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

Author

Tathiane M. Malta, Artem Sokolov, Andrew J. Gentles, Tomasz Burzykowski, Laila Poisson, John N. Weinstein, Bożena Kamińska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwińska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, Alex Krasnitz, Andrew K. Godwin, Alexander J. Lazar, Joshua M. Stuart, Katherine A. Hoadley, Peter W. Laird, Houtan Noushmehr, Maciej Wiznerowicz, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. 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Subjects
0301 basic medicine, Carcinogenesis, pan-cancer, Cancer Genome Atlas Research Network, medicine.disease_cause, Biochemistry, epigenomic, Epigenesis, Genetic, genomic, Machine Learning, GENE-EXPRESSION SIGNATURE, TUMOR, Neoplasms, Databases, Genetic, Tumor Microenvironment, LS4_6, Stemness, Neoplasm Metastasis, 610 Medicine & health, Induced pluripotent stem cell, 11 Medical and Health Sciences, Carcinogenesi, Epigenomics, Cancer stem cells, Stem Cells, PROLIFERATION, MicroRNA, Sciences bio-médicales et agricoles, CANCER, stemne, Neoplasm Metastasi, CONNECTIVITY MAP, ALGORITMOS, Stem cell, Life Sciences & Biomedicine, Human, Biochemistry & Molecular Biology, cancer stem cell, The Cancer Genome Atlas, Biology, Article, General Biochemistry, Genetics and Molecular Biology, NO, ANNEXIN 1, 03 medical and health sciences, Stem Cell, Cancer stem cell, medicine, Humans, Epigenetics, EMBRYONIC STEM, Tumor microenvironment, Science & Technology, Biochemistry, Genetics and Molecular Biology(all), dedifferentiation, Cell Biology, 06 Biological Sciences, Cell Dedifferentiation, DNA Methylation, Immune checkpoint, SELF-RENEWAL, MicroRNAs, 030104 developmental biology, CELLS, Cancer research, Neoplasm, OVEREXPRESSION, The Cancer Genome Atla, Transcriptome, cancer stem cells, machine learning, stemness, Genetics and Molecular Biology(all), Developmental Biology
Abstract

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation. Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveal novel biological and clinical insight, as well as potential drug targets for anti-cancer therapies., 0, info:eu-repo/semantics/published

Published
2018
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14. Activity of Gefitinib in a Non–Small-Cell Lung Cancer Patient with Both Activating and Resistance EGFR Mutations

Author

Renato Franco, Raffaele Costanzo, Raffaella Pasquale, Gaetano Rocco, Anna Maria Rachiglio, Agnese Montanino, Claudia Sandomenico, Alessandro Morabito, Elisabetta De Lutio, Nicola Normanno, Morabito, Alessandro, Costanzo, Raffaele, Rachiglio, Anna Maria, Pasquale, Raffaella, Sandomenico, Claudia, Franco, Renato, Montanino, Agnese, De Lutio, Elisabetta, Rocco, Gaetano, and Normanno, Nicola

Subjects
Male, Pulmonary and Respiratory Medicine, Lung Neoplasms, Prognosi, Protein Kinase Inhibitor, Gefitinib, Text mining, Carcinoma, Non-Small-Cell Lung, Humans, Medicine, Neoplasm Metastasis, Lung cancer, Protein Kinase Inhibitors, Aged, business.industry, Quinazoline, Prognosis, medicine.disease, ErbB Receptors, Lung Neoplasm, Neoplasm Metastasi, Oncology, Drug Resistance, Neoplasm, Egfr mutation, Mutation, Quinazolines, Cancer research, Carcinoma, Large Cell, Receptor, Epidermal Growth Factor, Non small cell, business, Human, medicine.drug
Published
2013
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15. Effects of isomeric aryldimethyltriazenes on lewis lung carcinoma growth and metastases in mice

Author

Lucia Lassiani, Tullio Giraldi, R. Dogani, Gianni Sava, Sava, Gianni, Giraldi, Tullio, Lassiani, Lucia, and Dogani, R.

Subjects
Aryltriazene, Lung Neoplasms, Animals, Drug Evaluation, Preclinical, Lethal Dose 50, Mice, Neoplasm Metastasis, Structure-Activity Relationship, Triazenes, Stereochemistry, Carboxylic acid, Potassium, Drug Evaluation, Preclinical, Salt (chemistry), chemistry.chemical_element, Metastasi, Toxicology, Metastasis, medicine, chemistry.chemical_classification, Animal, Lewis lung carcinoma, General Medicine, medicine.disease, Antineoplastic, Primary tumor, Lung Neoplasm, Neoplasm Metastasi, Aryltriazenes, Tumour, chemistry, Tumor progression, Toxicity
Abstract

Summary The effects of the ortho and para isomers of aryldimethyltriazeno carboxylic and benzensulfonic acids and amides have been examined in mice bearing subcutaneous Lewis lung carcinoma. The toxicity of these compounds varies widely and does not correlate with the effects on tumor progression. The growth of subcutaneous primary tumor is unaffected or only marginally inhibited by all the tested compounds, while a marked depression in the formation of spontaneous lung metastasis is observed, with the exception of the sodium salt of the ortho benzensulfonic acid. The compounds showing the greatest activity on metastasis are the hydrosoluble salts of the ortho and para carboxylic acid and the para sulfonamido derivative, indicating that, in addition to the activity reported for the potassium salt of the para carboxylic acid, also its ortho isomer and the para sulfonamido derivative possess selective and pronounced antimetastatic effects. No correlation can be found between the reported effects on tumor progression and physicochemical parameters of the triazenes tested.

Published
1983
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