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Lancet Diabetes Endocrinol 2021 Jun 9. Epub 2021 Jun 9.

Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.

Background: Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers.

Methods: ARROW, a phase 1/2, open-label study done in 13 countries across 71 sites in community and hospital settings, enrolled patients 18 years or older with RET-altered locally advanced or metastatic solid tumours, including RET-mutant medullary thyroid and RET fusion-positive thyroid cancers, and an Eastern Co-operative Oncology Group performance status of 0-2 (later limited to 0-1 in a protocol amendment). Read More

Lancet Oncol 2021 Jun 9. Epub 2021 Jun 9.

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Oncogenic alterations in RET have been identified in multiple tumour types, including 1-2% of non-small-cell lung cancers (NSCLCs). We aimed to assess the safety, tolerability, and antitumour activity of pralsetinib, a highly potent, oral, selective RET inhibitor, in patients with RET fusion-positive NSCLC.

Methods: ARROW is a multi-cohort, open-label, phase 1/2 study done at 71 sites (community and academic cancer centres) in 13 countries (Belgium, China, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Spain, Taiwan, the UK, and the USA). Read More

Curr Probl Cancer 2021 Apr 15:100737. Epub 2021 Apr 15.

Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: Traditionally, peritoneal surface malignancies (PSM) were considered terminal diseases because of their advanced nature, therefore, systemic chemotherapy was given with palliative intent only. As a result, very poor survival outcomes were observed. But with the introduction of complete Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC), the scenario has changed dramatically. Read More

J Thorac Oncol 2021 Jun 8. Epub 2021 Jun 8.

Cancer Research UK Beatson Institute, Glasgow, UK.

Introduction: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan® proteomics and Fibulin-3 appeared highly accurate, but SOMAscan® has not been validated prospectively and subsequent Fibulin-3 data have been contradictory. Read More

Cancer Sci 2021 Jun 11. Epub 2021 Jun 11.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Malignant mesothelioma (MM) is one of the most aggressive tumors. We conducted bioinformatics analysis using Cancer Cell Line Encyclopedia (CCLE) datasets to identify new molecular markers in MM. Overexpression of oxytocin receptor (OXTR), which is a G-protein-coupled receptor for the hormone and neurotransmitter oxytocin, mRNA was distinctively identified in MM cell lines. Read More

Front Oncol 2021 25;11:692136. Epub 2021 May 25.

Department of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Background: Understanding common and unique mechanisms driving oncogenic processes in human tumors is indispensable to develop efficient therapies. Recent studies have proposed Twinfilin Actin Binding Protein 1 (TWF1) as a putative driver gene in lung cancer, pancreatic cancer and breast cancer, however a systematic pan-cancer analysis has not been carried out.

Methods: Here, we set out to explore the role of TWF1 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), and several bioinformatic tools. Read More

Mod Pathol 2021 Jun 10. Epub 2021 Jun 10.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Sarcomatoid mesothelioma is an aggressive malignancy that can be challenging to distinguish from benign spindle cell mesothelial proliferations based on biopsy, and this distinction is crucial to patient treatment and prognosis. A novel deep learning based classifier may be able to aid pathologists in making this critical diagnostic distinction. SpindleMesoNET was trained on cases of malignant sarcomatoid mesothelioma and benign spindle cell mesothelial proliferations. Read More

Drugs 2021 Jun 9. Epub 2021 Jun 9.

Lung Unit, Department of Medicine, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.

Immune checkpoint inhibitors (ICI) have shown important but variable efficacy in mesothelioma despite a lack of strong biological rationale. Initial trials assessed ICI monotherapy in patients with relapsed mesothelioma, with objective response rates (ORR) between 4.5 and 29%, median progression-free survival (PFS) between 2. Read More

Urologia 2021 Jun 9:3915603211022942. Epub 2021 Jun 9.

Urology Department, University of Health Sciences Tepecik Education and Research Hospital, Izmir, Turkey.

Introduction: Malignant mesothelioma (MM) of tunica vaginalis is a very rare tumor and it has a poor prognosis. It is not easy to diagnose the disease preoperatively because there is a lack of comprehensive studies and information about the disease. We would like to present our two cases with severe scrotal edema and hydrocele, which were debrided perioperatively due to scrotal necrosis, followed by radical inguinal orchiectomy and subsequently diagnosed as MM of tunica vaginalis. Read More

Nat Commun 2021 Jun 7;12(1):3569. Epub 2021 Jun 7.

The Francis Crick Institute, London, UK.

BMC Cardiovasc Disord 2021 Jun 7;21(1):282. Epub 2021 Jun 7.

Department of Cardiology, Liberec Regional Hospital, Husova 357/10, 460 63, Liberec, Czech Republic.

Left ventricular dysfunction is a common reason for patients' referral to cardiology departments for examination. Cardiac involvement is one of the possible yet rare presentations of malignant mesothelioma. We present a case of a patient in whom a routine cardiac examination and imaging revealed malignant mesothelioma. Read More

Ann Surg 2021 Jun 4. Epub 2021 Jun 4.

Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC Department of Cardiothoracic Surgery, Stanford University Medical Center.

Background: The outcomes associated with receipt of adjuvant radiation in patients following surgery for malignant pleural mesothelioma (MPM) are poorly understood.

Objective: The objective of this study was to use two registries to compare the outcomes of patients receiving adjuvant radiation or no radiation following definitive surgery for pathologic stage I-III MPM.

Methods: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (2004-2015). Read More

World J Surg Oncol 2021 Jun 5;19(1):164. Epub 2021 Jun 5.

Department of Pathology, AIIMS, New Delhi, India.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. Read More

Br J Cancer 2021 Jun 4. Epub 2021 Jun 4.

Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a dismal prognosis. There is increasing interest in targeting chromatin regulatory pathways in difficult-to-treat cancers. In preliminary studies, we found that KDM4A (lysine-specific histone demethylase 4) was overexpressed in MPM. Read More

Mol Cancer Ther 2021 Jun 4. Epub 2021 Jun 4.

Surgery, Baylor College of Medicine

Approximately 20,000 patients per year are diagnosed with esophageal adenocarcinoma (EAC) and malignant pleural mesothelioma (MPM); fewer than 20% survive five years. Effective therapeutic strategies are limited even though patients receive a combination of chemotherapeutics. These tumors harbor thousands of mutations that contribute to tumor development. Read More

J Immunother Cancer 2021 Jun;9(6)

Department of Medical Oncology, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands.

Background: Dosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I-III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.

Methods: Advanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. Read More

Eur J Cancer 2021 Jun 1;152:60-67. Epub 2021 Jun 1.

Department of Thoracic Oncology, NKI-AvL, Amsterdam, the Netherlands.

Introduction: Recent clinical trials with immune checkpoint inhibitors (ICIs) have shown that a subgroup of patients with malignant pleural mesothelioma (MPM) could benefit from these agents. However, there are no accurate biomarkers to predict who will respond. The aim of this study was to assess the accuracy of exhaled breath analysis using electronic technology (eNose) for discriminating between responders to ICI and non-responders. Read More

Toxicol Sci 2021 Jun 4. Epub 2021 Jun 4.

Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014, Copenhagen K, Denmark.

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury and genotoxicity. To investigate pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multi-walled CNTs (MWCNT-7, NM-401 and NM-403) or single-walled CNTs (NM-411). Read More

J Thorac Oncol 2021 May 31. Epub 2021 May 31.

Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium; Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium; Department of Pulmonology, Antwerp University Hospital, Edegem, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium. Electronic address:

Background: Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Due to several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is need for diagnostic biomarkers that may contribute to early detection. Read More

J Vet Med Sci 2021 Jun 3. Epub 2021 Jun 3.

Hokkaido Research Station, National Institute of Animal Health, National Agriculture and Food Research Organization.

The histology and immunohistochemistry of pleomorphic and conventional epithelioid mesotheliomas were examined. The former was detected in two young calves aged 2 and 4 months and was characterized by pleomorphic and atypical cells with decreased expression of cytokeratin 7 (CK7). In contrast, the latter was found in a 31-month-old heifer, consisting of tumor cells uniform in size and shape with CK7 expression in nearly all cells. Read More

Pharmazie 2021 Jun;76(6):266-271

Division of Pharmaceutical Care Sciences, Center for Social Pharmacy and Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, Tokyo, Japan; Division of Pharmaceutical Care Sciences, Keio University Graduate School of Pharmaceutical Sciences, Tokyo, Japan.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. Read More

Acta Med Acad 2021 Apr;50(1):197-208

Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States.

In this review, we summarize current approaches to diagnosis of malignant pleural mesothelioma, focusing on the distinction from benign mesothelial proliferations and other malignant tumors. Current recommendations for reporting histological sub-type and tumor grade are also reviewed. Particular emphasis is placed on immunohistochemical and molecular tools that may help in establishing the diagnosis of mesothelioma with greater confidence. Read More

Cancers (Basel) 2021 May 24;13(11). Epub 2021 May 24.

Department of Oncology, University of Turin, 10043 Orbassano, Italy.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. Read More

J Clin Med 2021 May 26;10(11). Epub 2021 May 26.

Division of Thoracic Surgery, IRCCS Azienda Ospedaliera Universitaria di Bologna, 40138 Bologna, Italy.

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Read More

Cancers (Basel) 2021 May 27;13(11). Epub 2021 May 27.

Department of Medical Sciences, University of Turin, 10126 Turin, Italy.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. Read More

J Clin Med 2021 May 30;10(11). Epub 2021 May 30.

Department of Thoracic Surgery, Faculty of Medicine, University Cattolica del Sacro Cuore, 20123 Rome, Italy.

The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. Read More

Polymers (Basel) 2021 May 30;13(11). Epub 2021 May 30.

Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan.

Cisplatin (-diamminedichloroplatinum (II); CDDP) is a key chemotherapeutic agent but causes renal damage and other off-target effects. Here, we describe the pharmacological and biochemical characteristics of a novel formulation of CDDP complexed with γ-polyglutamic acid (γ-PGA) and chitosan (CS), γ-PGA/CDDP-CS, developed by complexing CDDP with γ-PGA, then adding CS (15 kDa; 10 mol%/γ-PGA). We analyzed tumor cytotoxicity in vitro, as well as blood kinetics, acute toxicity, and antitumor efficacy in vivo in BALB/cAJcl mice. Read More

J Clin Med 2021 May 25;10(11). Epub 2021 May 25.

Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy.

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. Read More

Cancers (Basel) 2021 May 18;13(10). Epub 2021 May 18.

Department of Biology, Genetic Unit, University of Pisa, via Derna 1, 56126 Pisa, Italy.

Background: Malignant pleural mesothelioma (MPM) is a fatal tumor with a poor prognosis. The recent developments of liquid biopsies could provide novel diagnostic and prognostic tools in oncology. However, there is limited information about the feasibility of this technique for MPMs. Read More

Vaccines (Basel) 2021 May 19;9(5). Epub 2021 May 19.

Department of Pulmonary Medicine, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.

Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II-III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an "immune desert" phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. Read More