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Targeted therapies oncology

Claudia Matteucci, Emanuela Balestrieri, Ayele Argaw-Denboba, Paola Sinibaldi-Vallebona
Cancer incidence and mortality, metastasis, drug resistance and recurrence are still the critical issues of oncological diseases. In this scenario, increasing scientific evidences demonstrate that the activation of human endogenous retroviruses (HERVs) is involved in the aggressiveness of tumors such as melanoma, breast, germ cell, renal, ovarian, liver and haematological cancers. In their dynamic regulation, HERVs have also proved to be important determinants of pluripotency in human embryonic stem cells (ESC) and of the reprogramming process of induced pluripotent stem cells (iPSCs)...
October 11, 2018: Seminars in Cancer Biology
Sean M Davidson, Sapna Arjun, Maryna V Basalay, Robert M Bell, Daniel I Bromage, Hans Erik Bøtker, Richard D Carr, John Cunningham, Arjun K Ghosh, Gerd Heusch, Borja Ibanez, Petra Kleinbongard, Sandrine Lecour, Helen Maddock, Michel Ovize, Malcolm Walker, Marlene Wiart, Derek M Yellon
Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy...
October 11, 2018: Basic Research in Cardiology
Athanasios Koutsoukis, Argyrios Ntalianis, Evangelos Repasos, Efsthathios Kastritis, Meletios-Athanasios Dimopoulos, Ioannis Paraskevaidis
Cardio-oncology is a recently developed field in cardiology aimed at significantly reducing cardiovascular morbidity and mortality and improving quality of life in cancer survivors. Cancer survival rates have been constantly increasing, mainly because of the advent of new, more potent and targeted therapies. However, many of the new therapies - along with some of the older chemotherapeutic regimens such as anthracyclines - are potentially cardiotoxic, which is reflected increasingly frequently in the published literature...
August 2018: European Cardiology
Kenji Ikeda
Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during last decade. Fine powder formulation of cisplatin and new platinum agent miriplatin became standard medicines in addition to anthracyclines on transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon-occluded TACE is an effective manner of therapy for localized HCC and drug-eluting microspheres seemed to show a higher response rate in certain HCCs, definite advantages of those procedures still remained uncertain...
October 11, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Jonathan S Berek, Sean T Kehoe, Lalit Kumar, Michael Friedlander
The Gynecologic Oncology Committee of FIGO in 2014 revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system. Most of these malignancies are high-grade serous carcinomas (HGSC). Stage IC is now divided into three categories: IC1 (surgical spill); IC2 (capsule ruptured before surgery or tumor on ovarian or fallopian tube surface); and IC3 (malignant cells in the ascites or peritoneal washings). The updated staging includes a revision of Stage IIIC based on spread to the retroperitoneal lymph nodes alone without intraperitoneal dissemination...
October 2018: International Journal of Gynaecology and Obstetrics
Ganesh Narayanasamy, Dharmin Desai, Sanjay Maraboyina, Jose Penagaricano, Robert Zwicker, Ellis Lee Johnson
Introduction: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D2cm and R50% as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics...
July 2018: Journal of Medical Physics
Juliane Hübner, Marian Raschke, Isabel Rütschle, Sarah Gräßle, Tobias Hasenberg, Kerstin Schirrmann, Alexandra Lorenz, Susanne Schnurre, Roland Lauster, Ilka Maschmeyer, Thomas Steger-Hartmann, Uwe Marx
Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models. Here we established a repeated dose "safficacy" test assay for the simultaneous generation of safety and efficacy data. Therefore, a commercially available multi-organ chip platform connecting two organ culture compartments was adapted for the microfluidic co-culture of human H292 lung cancer microtissues and human full-thickness skin equivalents...
October 9, 2018: Scientific Reports
Harald Hampel, Sid E O'Bryant, José L Molinuevo, Henrik Zetterberg, Colin L Masters, Simone Lista, Steven J Kiddle, Richard Batrla, Kaj Blennow
Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes...
October 8, 2018: Nature Reviews. Neurology
Chunfeng Lian, Su Ruan, Thierry Denoeux, Hua Li, Pierre Vera
Precise delineation of target tumor is a key factor to ensure the effectiveness of radiation therapy. While hybrid positron emission tomography-computed tomography (PET-CT) has become a standard imaging tool in the practice of radiation oncology, many existing automatic/semi-automatic methods still perform tumor segmentation on mono-modal images. In this paper, a co-clustering algorithm is proposed to concurrently segment 3D tumors in PET-CT images, considering that the two complementary imaging modalities can combine functional and anatomical information to improve segmentation performance...
February 2019: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
Jakob von Frieling, Christine Fink, Jacob Hamm, Kenneth Klischies, Michael Forster, Thomas C G Bosch, Thomas Roeder, Philip Rosenstiel, Felix Sommer
The eukaryotic host is in close contact to myriads of resident and transient microbes, which influence the crucial physiological pathways. Emerging evidence points to their role of host-microbe interactions for controlling tissue homeostasis, cell fate decisions, and regenerative capacity in epithelial barrier organs including the skin, lung, and gut. In humans and mice, it has been shown that the malignant tumors of these organs harbor an altered microbiota. Mechanistic studies have shown that the altered metabolic properties and secreted factors contribute to epithelial carcinogenesis and tumor progression...
2018: Frontiers in Microbiology
Federica Morano, Francesco Sclafani
Over the last two decades the number of front-line regimens for metastatic colorectal cancer has progressively increased. Nevertheless, there is still no consensus on the optimal duration of treatment or the role of de-escalated/maintenance strategies after induction chemotherapy. In this article we provide an overview of the studies that addressed the duration of first-line systemic treatment with cytotoxic agents plus or minus targeted therapies highlighting caveats and limitations of the same. Also, we try to translate the available evidence into practical recommendations that can be used in everyday practice to inform treatment decisions...
November 2018: Critical Reviews in Oncology/hematology
Katy L Simonsen, Paula M Fracasso, Steven H Bernstein, Megan Wind-Rotolo, Manish Gupta, Adriana Comprelli, Timothy P Reilly, Jim Cassidy
BACKGROUND: The unprecedented success of immuno-oncology (I-O) agents targeting the cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/programmed death-ligand 1 pathways has stimulated the rapid development of other I-O agents against novel immune targets. Bristol-Myers Squibb has designed a novel phase II platform trial, the Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) Program, to efficiently identify promising combinations for patients with specific malignancies...
October 3, 2018: European Journal of Cancer
Peter S Potrebko, Andrew Keller, Sean All, Samir Sejpal, Julie Pepe, Kunal Saigal, Shravan Kandula, William F Sensakovic, Ravi Shridhar, Jan Poleszczuk, Matthew Biagioli
The purpose of this work was to compare dose distributions between two radiosurgery modalities, single-isocenter volumetric modulated arc therapy (VMAT), and GammaKnife Perfexion (GK), in the treatment of a large number (≥7) of brain metastases. Twelve patients with 103 brain metastases were analyzed. The median number of targets per patient was 8 (range: 7-14). GK plans were compared to noncoplanar VMAT plans using both 6-MV flattening filter-free (FFF) and 10-MV FFF modes. Parameters analyzed included radiation therapy oncology group conformity index (CI), 12, 6, and 3 Gy isodose volumes (V12 Gy, V6 Gy, V3 Gy), mean and maximum hippocampal dose, and maximum skin dose...
October 4, 2018: Journal of Applied Clinical Medical Physics
Miljana Tanić, Ana Krivokuća, Milena Čavić, Jasmina Mladenović, Vesna Plesinac Karapandžić, Stephan Beck, Siniša Radulović, Snezana Susnjar, Radmila Janković
BACKGROUND: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity...
October 1, 2018: Radiation Oncology
Christina R Bellinger, Deepankar Sharma, Travis Dotson, Jimmy Ruiz, Graham Parks, Edward F Haponik
OBJECTIVES: Targeted therapies for non-small-cell lung cancers (NSCLCs) are based on the presence of driver mutations such as epidermal growth factor receptor (EGFR) and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation. Endobronchial ultrasound-guided-transbronchial needle aspiration (EBUS-TBNA) is a first-line modality for diagnosing and staging NSCLC. A quality improvement protocol maximizing tissue acquisition for molecular analysis has not been previously described...
October 2018: Southern Medical Journal
C Grávalos, O Sanmartín, A Gúrpide, A España, M Majem, H J Suh Oh, I Aragón, S Segura, C Beato, R Botella
Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1...
October 3, 2018: Clinical & Translational Oncology
Enrique A Castellón
One of the most relevant problems in clinical oncology is to know the response of each patient to the different treatments available, to be able to choose the best therapy, or combination of them, at the opportune moment once the cancer is diagnosed. Twenty years ago, trastuzumab was approved as therapy for breast cancer, an antibody directed specifically against the Her2 receptor that only a group of patients expressed in their tumors. This monoclonal humanized antibody is considered the first targeted therapy...
October 3, 2018: Oral Diseases
D Pfirrmann, P Simon, M Mehdorn, M Hänsig, S Stehr, L Selig, A Weimann, M Knödler, F Lordick, A Mehnert, I Gockel
BACKGROUND: Postoperative complications after complex visceral oncological surgery can lead to substantial impairment of patients. In addition, preoperative physical performance and the severity of postoperative complications determine the long-term recovery process of physical function. Therefore, preconditioning in the preoperative period should be an important part of the preoperative/neoadjuvant treatment. OBJECTIVE: The aim of this article is a critical appraisal of current concepts of prehabilitation as well as their development potential and applicability in visceral surgery...
October 2, 2018: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
Mukul Bhattarai, Tamer Hudali, Robert Robinson, Mohammad Al-Akchar, Carrie Vogler, Youssef Chami
Researchers are extensively searching for modifiable risk factors including high-risk medications such as anticoagulation to avoid rehospitalisation. The influence of oral anticoagulant therapy on hospital readmission is not known. We investigated the impact of warfarin and direct oral anticoagulants (DOACs) on all cause 30-day hospital readmission retrospectively in an academic centre. We study the eligible cohort of 1781 discharges over 2-year period. Data on age, gender, diagnoses, 30-day hospital readmission, discharge medications and variables in the HOSPITAL score (Haemoglobin level at discharge, Oncology at discharge, Sodium level at discharge, Procedure during hospitalisation, Index admission, number of hospital Admissions, Length of stay) and LACE index (Length of stay, Acute/emergent admission, Charlson comorbidity index score, Emergency department visits in previous 6 months), which have higher predictability for readmission were extracted and matched for analysis...
October 2, 2018: BMJ evidence-based medicine
David Hui, Breffni L Hannon, Camilla Zimmermann, Eduardo Bruera
Over the past decade, a large body of evidence has accumulated supporting the integration of palliative care into oncology practice for patients with advanced cancer. The question is no longer whether palliative care should be offered, but what is the optimal model of delivery, when is the ideal time to refer, who is in greatest need of a referral, and how much palliative care should oncologists themselves be providing. These questions are particularly relevant given the scarcity of palliative care resources internationally...
September 2018: CA: a Cancer Journal for Clinicians
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