المؤلفون: Tuochuan Dong, Tony Sk Mok, Jay M. Lee, Masahiro Tsuboi, Cecile Blin, Ana Gómez-Rueda, Edward S. Kim, Vanessa Q. Passos, Vanessa Rodrik-Outmezguine, Pilar Garrido, Luis Gorospe, Jean-Louis Pujol, Amparo Benito, Nicolas Moreno

المصدر: Future Oncology. 17:1459-1472

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Adolescent, medicine.medical_treatment, Interleukin-1beta, Programmed Cell Death 1 Receptor, Disease, Pembrolizumab, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Humans, Medicine, Pneumonectomy, Lung cancer, Lung, Neoplasm Staging, Randomized Controlled Trials as Topic, business.industry, General Medicine, Immunotherapy, medicine.disease, Neoadjuvant Therapy, Immune checkpoint, Clinical trial, Canakinumab, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, medicine.drug

الوصف: Canakinumab is a human IgGκ monoclonal antibody, with high affinity and specificity for IL-1β. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) trial, evaluating canakinumab for cardiovascular disease, provided the first signal of the potential of IL-1β inhibition on lung cancer incidence reduction. Here, we describe the rationale and design for CANOPY-N, a randomized Phase II trial evaluating IL-1β inhibition with or without immune checkpoint inhibition as neoadjuvant treatment in patients with non-small-cell lung cancer. Patients with stage IB to IIIA non-small-cell lung cancer eligible for complete resection will receive canakinumab or pembrolizumab as monotherapy, or in combination. The primary end point is major pathological response by central review; secondary end points include overall response rate, major pathological response (local review), surgical feasibility rate and pharmacokinetics.Lay abstract A previous study showed that canakinumab reduced the risk of lung cancer in patients with heart disease. Canakinumab blocks an inflammatory protein called IL-1β that is involved in cancer. Anti-cancer drugs used before surgery (‘neo-adjuvant’) can improve the success rate of surgery and may help prevent the cancer from returning. Neo-adjuvant trials help us understand how the drugs work and how they affect cancer. CANOPY-N (NCT03968419) is an ongoing randomized, exploratory, Phase II clinical trial testing canakinumab and pembrolizumab (a different cancer immunotherapy), alone or combined, for patients with early non-small-cell lung cancer. The study will test whether treatment can kill most cancer cells in the surgery sample (‘major pathological response’). It will also investigate other effects on cancer biology, levels of molecules that measure possible clinical benefit (‘biomarkers’) and side effects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::533cf87894d6775fc54f655766423e45Test
https://doi.org/10.2217/fon-2020-1098Test

المؤلفون: Bożena Cybulska-Stopa, Barbara Ziółkowska, Łukasz Galus, Tomasz Kubiatowski, Stanisław Kieszko, Karolina Piejko, Jacek Mackiewicz, Piotr Rutkowski, Anna Drosik-Kwaśniewska, Jacek Calik, Grażyna Kamińska-Winciorek, Marcin Ziętek, Anna M. Czarnecka, Renata Pacholczak-Madej, Paweł Rogala, Katarzyna Gajewska-Wicher, Rafał Suwiński, Janusz Rolski, Agata Sałek-Zań, Natasza Kempa-Kamińska

المصدر: Immunotherapy. 13:297-307

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Multivariate analysis, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Immunology, Pembrolizumab, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, Stage (cooking), Adverse effect, Immune Checkpoint Inhibitors, Melanoma, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Immunotherapy, Middle Aged, Prognosis, medicine.disease, Progression-Free Survival, Survival Rate, Clinical trial, Nivolumab, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Poland, business

الوصف: Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC–IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75481f1f9c5cc0cca549a49f8bad084dTest
https://doi.org/10.2217/imt-2020-0217Test

المؤلفون: H Perkal, Luisa M. Villar, Ester Quintana, Clara Matute-Blanch, Manuel Comabella, Lluís Ramió-Torrentà, María Muñoz-San Martín, René Robles-Cedeño, Maria Buxó, Sandra Torras, Imma Gomez

المصدر: Epigenomics. 12:2065-2076

مصطلحات موضوعية: Adult, Male, Oncology, Circulating mirnas, Cancer Research, medicine.medical_specialty, Population, Biology, Cerebrospinal fluid, Neurofilament Proteins, Internal medicine, microRNA, Genetics, medicine, Humans, Prognostic biomarker, Chitinase-3-Like Protein 1, Circulating MicroRNA, education, education.field_of_study, Multiple sclerosis, Syndrome, Middle Aged, Prognosis, medicine.disease, Female, Biomarkers, Demyelinating Diseases

الوصف: Aim: Some clinical and biological characteristics have been described as prognostic factors for clinical conversion into clinically definite multiple sclerosis in radiologically isolated syndrome (RIS) population. The aim of this study was to assess signatures of circulating miRNAs in those patients according to their conversion status after 5 years of follow-up. Patients & methods: OpenArray plates assessing 216 miRNA candidates were run in 15 RIS patients, and their relative abundances were analyzed. Results: A specific profile of deregulated circulating miRNAs (miR-144-3p, miR-448 and miR-653-3p in cerebrospinal fluid and miR-142-3p, miR-338-3p, miR-363-3p, miR-374b-5p, miR-424-5p, miR-483-3p in plasma) differentiated individuals who remained as RIS after 5 years of follow-up. Conclusion: Circulating miRNAs might be used as prognostic biomarkers for RIS patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::129b1a911cbaf764131e98eac5d1b609Test
https://doi.org/10.2217/epi-2020-0172Test

المؤلفون: Adrian Muenscher, Philippe Schafhausen, Henrike Barbara Zech, Nikolaus Moeckelmann, Mascha Binder, Arne Boettcher, Christian Stephan Betz, Chia-Jung Busch, Eik Vettorazzi, Carsten Bokemeyer

المصدر: Future Oncology. 16:3035-3043

مصطلحات موضوعية: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Mitomycin, Programmed Cell Death 1 Receptor, Ipilimumab, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Adjuvant therapy, Clinical endpoint, Humans, Medicine, CTLA-4 Antigen, Prospective Studies, 030223 otorhinolaryngology, Immune Checkpoint Inhibitors, Neoplasm Staging, Squamous Cell Carcinoma of Head and Neck, business.industry, Head and neck cancer, Chemoradiotherapy, Adjuvant, General Medicine, Middle Aged, medicine.disease, Head and neck squamous-cell carcinoma, Neoadjuvant Therapy, Clinical trial, stomatognathic diseases, Nivolumab, Chemotherapy, Adjuvant, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, Fluorouracil, Cisplatin, Neoplasm Recurrence, Local, business, medicine.drug

الوصف: Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting. Clinical Trial Registration: NCT03700905 ( ClinicalTrials.gov )

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41f2b4123f6aefe3592460ca34f1940eTest
https://doi.org/10.2217/fon-2020-0595Test

المؤلفون: Jun-Li Qin, Yi Gong, Wei Zou, Guang-Yu Lian, Junhui Wan, Qing-Ming Wang

المصدر: Future Oncology. 15:1729-1744

مصطلحات موضوعية: Adult, DNA (Cytosine-5-)-Methyltransferase 1, 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Bisulfite sequencing, Uterine Cervical Neoplasms, Apoptosis, Decitabine, Metastasis, 03 medical and health sciences, Suppressor of Cytokine Signaling 1 Protein, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Genes, Reporter, Cell Line, Tumor, medicine, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Aged, Cell Proliferation, Neoplasm Staging, Suppressor of cytokine signaling 1, business.industry, NF-kappa B, General Medicine, Methylation, DNA Methylation, Middle Aged, medicine.disease, Gene Expression Regulation, Neoplastic, Blot, MicroRNAs, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, RNA Interference, Signal transduction, business

الوصف: Aims: To investigate roles of miR-29a-DNMT1-SOCS1 axis in cervical cancer invasion and migration. Materials & methods: The methylation level of SOCS1 was determined by methylation specific PCR. The cell apoptosis, proliferation, migration and invasion were examined by Annexin-V/PI staining, MTT and colony formation assays, plus scratch and transwell assays respectively. The expressions of epithelial–mesenchymal transition and NF-κB related proteins were determined by western blotting. Results: MiR-29a was downregulated, accompanied with DNMT1 upregulation and SOCS1 downregulation in cervical cancer tissues. MiR-29a suppressed DNMT1, inhibited SOCS1 promoter methylation and upregulated its expression. Moreover, miR-29a promoted cell apoptosis, suppressed proliferation, inhibited migration and invasion via inactivation of NF-κB signaling pathway in cervical cancer cells. Conclusion: MiR-29a-DNMT1-SOCS1 axis plays an important role on invasion and metastasis in cervical cancer via NF-κB signaling pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c3d916c914883f25744a63732cd7fdbTest
https://doi.org/10.2217/fon-2018-0497Test

المؤلفون: Sebastian Haferkamp, Florian Scholz, Hartmut Richter, Victoria Banks, Peter Mohr, Katarina Öhrling, Karly S. Louie

المصدر: Future Oncology. 16:317-328

مصطلحات موضوعية: Adult, Male, Cancer Research, medicine.medical_specialty, Volume Administered, Databases, Factual, Patient characteristics, Herpesvirus 1, Human, Kaplan-Meier Estimate, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Prescription database, Germany, Internal medicine, medicine, Humans, Summary of Product Characteristics, Medical prescription, Melanoma, Aged, Retrospective Studies, Aged, 80 and over, Oncolytic Virotherapy, Biological Products, business.industry, Retrospective cohort study, General Medicine, Guideline, Middle Aged, Prognosis, Combined Modality Therapy, Oncolytic Viruses, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Talimogene laherparepvec, business, Follow-Up Studies

الوصف: Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3–26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c95bbaa7aa6794049cfd27431febefc9Test
https://doi.org/10.2217/fon-2019-0838Test

المؤلفون: Piotr Rutkowski, Sama Ahsan, Jean-Jacques Grob, Matteo S. Carlino, James R. Anderson, Merrick I. Ross, John M. Kirkwood, Jeffrey E. Gershenwald, Caroline Robert, Jason J. Luke, Nageatte Ibrahim, Charles H. Yoon, Peter Mohr, Georgina V. Long, Alexander M.M. Eggermont, Axel Hauschild, Paolo A. Ascierto, Andrew Poklepovic, Richard A. Scolyer

المصدر: Future Oncology. 16:4429-4438

مصطلحات موضوعية: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Skin Neoplasms, Adolescent, medicine.medical_treatment, Dermatologic Surgical Procedures, Programmed Cell Death 1 Receptor, Pembrolizumab, Antibodies, Monoclonal, Humanized, Placebo, Disease-Free Survival, Placebos, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Internal medicine, medicine, Adjuvant therapy, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Young adult, Child, Melanoma, Neoplasm Staging, Randomized Controlled Trials as Topic, Cross-Over Studies, business.industry, General Medicine, medicine.disease, Crossover study, Clinical trial, Clinical Trials, Phase III as Topic, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Adjuvant

الوصف: Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT03553836

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6a00dd1a28f82ed3c8216b416ba2d53Test
https://doi.org/10.2217/fon-2019-0666Test

المؤلفون: Maria Teresa Fierro, Virginia Caliendo, Simone Ribero, Simona Osella-Abate, Martina Sanlorenzo, Ottavia Malavenda, Pietro Quaglino, Paolo Fava, Chiara Astrua, Elena Marra

المصدر: Future Oncology. 15:133-139

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, MAP Kinase Kinase 1, combination therapy, 0302 clinical medicine, Piperidines, Antineoplastic Combined Chemotherapy Protocols, Oximes, MEK inhibitors, Complete response, Aged, 80 and over, Trametinib, Melanoma, Imidazoles, BRAF inhibitors, General Medicine, Middle Aged, Treatment Outcome, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Metastatic melanoma, Combination therapy, Pyridones, melanoma, Pyrimidinones, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Protein Kinase Inhibitors, Aged, Retrospective Studies, business.industry, Dabrafenib, medicine.disease, 030104 developmental biology, Survival benefit, Vemurafenib, Mutation, Azetidines, business

الوصف: Aim: A survival benefit was demonstrated by dabrafenib + trametinib for metastatic BRAF-mutated melanoma patients. Best response is a strong prognostic marker for survival. Patients & methods: The specific features associated with complete response (CR) were evaluated. Results: A total of 15/66 patients achieved CR. Median size of lesions was 3 cm (range: 0.5–10). Using that value as cut-off, the CR rate was 39.3% in patients with smaller lesions and 10.5% in patients with bigger size (p = 0.006). The clinical features associated with CR were the number of metastatic sites and the largest diameter of the biggest metastatic site. Conclusion: The number of the metastases and the diameter of the largest metastatic site are associated with a higher CR rate.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5fa36af49f03985cb916fae76f51f9fTest
https://doi.org/10.2217/fon-2018-0386Test

المؤلفون: Maria Pia Foschini, Giuseppe Lamberti, S. Minichillo, Enrico Di Oto, Alexandro Paccapelo, Daniela Bartolini, Andrea Lanese, Antonella Mura, Alicia Tosoni, E. Zunarelli, Stefano Pizzolitto, Enrico Franceschi, Alba A. Brandes, Daniela Danieli, Giovanni Lanza, Dario de Biase, Annalisa Pession, Michela Visani, Enrico Maria Silini, Giovanni Tallini, Stefania Bartolini

المساهمون: Franceschi E, Mura A, De Biase D, Tallini G, Pession A, Foschini MP, Danieli D, Pizzolitto S, Zunarelli E, Lanza G, Bartolini D, Silini EM, Visani M, Di Oto E, Tosoni A, Minichillo S, Lamberti G, Lanese A, Paccapelo A, Bartolini S, Brandes AA

المصدر: Future Oncology. 14:1559-1567

مصطلحات موضوعية: Male, Oncology, Cancer Research, Multivariate analysis, medicine.medical_treatment, Neurosurgical Procedures, IDH 1/2, surgery, Cohort Studies, 0302 clinical medicine, Risk Factors, Medicine, MGMT methylation, DNA Modification Methylases, Univariate analysis, low-grade glioma, treatment, Brain Neoplasms, Glioma, General Medicine, Middle Aged, Prognosis, Isocitrate Dehydrogenase, Idh mutation, Chromosomes, Human, Pair 1, NGS, 030220 oncology & carcinogenesis, 1p19q co-deletion, IDH 1/2IDH mutation, low-grade gliomas, MGMT methylation, NGS, surgery, treatment, Female, Chromosome Deletion, Mgmt methylation, Risk assessment, Clinical risk factor, Adult, medicine.medical_specialty, Adolescent, low-grade gliomas, IDH 1/2IDH mutation, 1p19q co-deletion, Extent of resection, NO, 03 medical and health sciences, Internal medicine, Humans, Aged, business.industry, Tumor Suppressor Proteins, IDH mutation, Radiation therapy, DNA Repair Enzymes, Multivariate Analysis, Mutation, business, 030217 neurology & neurosurgery

الوصف: Aim: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. Methods: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. Results: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p

وصف الملف: STAMPA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38c94c152974785bac440ab86d6ca414Test
https://doi.org/10.2217/fon-2017-0634Test

المؤلفون: Pablo Martinez, Josep María Del Campo

المصدر: Immunotherapy. 9:467-470

مصطلحات موضوعية: Adult, Oncology, medicine.medical_specialty, medicine.medical_treatment, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, Immunology, Uterine Cervical Neoplasms, Antineoplastic Agents, Cervix Uteri, Pembrolizumab, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cervical carcinoma, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Cervix, Peritoneal Neoplasms, Neoplasm Staging, Chemotherapy, business.industry, Remission Induction, Treatment options, Cancer, medicine.disease, Tumor Burden, Squamous carcinoma, medicine.anatomical_structure, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Immunotherapy, Neoplasm Recurrence, Local, business

الوصف: No definitive cure is known for recurrent, persistent or metastatic cervical carcinoma. Chemotherapy remains the standard of care, although available options are scarce and do not provide satisfactory results. Immune checkpoint inhibitors have shown a strong and prolonged response in several types of cancer, although only in a subset of patients. Defining the profile of the patients likely to benefit from such treatment is a subject of active research. Here, we present a case of a heavily pretreated patient with recurrent advanced squamous cell carcinoma of the cervix who had exhausted all available treatment options and showed a striking response to the immune checkpoint inhibitor pembrolizumab.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f28707cdd297a6e7276ec734648ac0cfTest
https://doi.org/10.2217/imt-2016-0119Test