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molecular oncology

Kohei Fukuoka, Yonehiro Kanemura, Tomoko Shofuda, Shintaro Fukushima, Satoshi Yamashita, Daichi Narushima, Mamoru Kato, Mai Honda-Kitahara, Hitoshi Ichikawa, Takashi Kohno, Atsushi Sasaki, Junko Hirato, Takanori Hirose, Takashi Komori, Kaishi Satomi, Akihiko Yoshida, Kai Yamasaki, Yoshiko Nakano, Ai Takada, Taishi Nakamura, Hirokazu Takami, Yuko Matsushita, Tomonari Suzuki, Hideo Nakamura, Keishi Makino, Yukihiko Sonoda, Ryuta Saito, Teiji Tominaga, Yasuhiro Matsusaka, Keiichi Kobayashi, Motoo Nagane, Takuya Furuta, Mitsutoshi Nakada, Yoshitaka Narita, Yuichi Hirose, Shigeo Ohba, Akira Wada, Katsuyoshi Shimizu, Kazuhiko Kurozumi, Isao Date, Junya Fukai, Yousuke Miyairi, Naoki Kagawa, Atsufumi Kawamura, Makiko Yoshida, Namiko Nishida, Takafumi Wataya, Masayoshi Yamaoka, Naohiro Tsuyuguchi, Takehiro Uda, Mayu Takahashi, Yoshiteru Nakano, Takuya Akai, Shuichi Izumoto, Masahiro Nonaka, Kazuhisa Yoshifuji, Yoshinori Kodama, Masayuki Mano, Tatsuya Ozawa, Vijay Ramaswamy, Michael D Taylor, Toshikazu Ushijima, Soichiro Shibui, Mami Yamasaki, Hajime Arai, Hiroaki Sakamoto, Ryo Nishikawa, Koichi Ichimura
Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group...
December 4, 2018: Acta Neuropathologica Communications
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Zacharie Segaoula, Aline Primot, Frederic Lepretre, Benoit Hedan, Emmanuel Bouchaert, Kevin Minier, Laurent Marescaux, François Serres, Sylvie Galiègue-Zouitina, Catherine André, Bruno Quesnel, Xavier Thuru, Dominique Tierny
BACKGROUND: Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging...
December 4, 2018: BMC Cancer
Kiran Rawat, Amit Shard, Manali Jadhav, Mayuri Gandhi, Prince Anand, Rituraj Purohit, Yogendra Padwad, Arun K Sinha
Gliomas are lethal and aggressive form of brain tumors with resistance to conventional radiation and cytotoxic chemotherapies; inviting continuous efforts for drug discovery and drug delivery. Interestingly, small molecule hybrids are one such pharmacophore that continues to capture interest owing to their pluripotent medicinal effects. Accordingly, we earlier reported synthesis of potent Styryl-cinnamate hybrids (analogues of Salvianolic acid F) along with its plausible mode of action (MOA). We explored iTRAQ-LC/MS-MS technique to deduce differentially expressed landscape of native & phospho-proteins in treated glioma cells...
December 1, 2018: Experimental Cell Research
Valeriia Gulaia, Vadim Kumeiko, Nikita Shved, Eduardas Cicinskas, Stanislav Rybtsov, Alexey Ruzov, Alexander Kagansky
Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma...
2018: Frontiers in Cellular Neuroscience
B Malicherova, T Burjanivova, E Minarikova, I Kasubova, T Pecova, M Bobrovska, I Homola, Z Lasabova, L Plank
Malignant melanoma is an oncological disease characterized by etiologic heterogeneity and it has increasing incidence and mortality in the Slovak Republic. While it is treated surgically in combination with chemotherapy, targeted therapy, and immunotherapy, malignant melanomas can ulcerate and are susceptible to infections. These are highly aggressive cancers with metastasis, and recent studies have shown the presence of mutations in RAC1, PPP6C and STK19 genes in melanoma patients. Mutations in these genes are driver mutations; important in oncogenesis and providing selective advantage to tumor cells...
August 9, 2018: Neoplasma
Alexandre Roux, Myriam Edjlali, Sayuri Porelli, Arnault Tauziede-Espariat, Marc Zanello, Edouard Dezamis, Gilles Zah-Bi, Marc Sanson, Stéphanie Puget, Laurent Capelle, Pascale Varlet, Catherine Oppenheim, Johan Pallud
OBJECTIVE: To determine the prevalence of developmental venous anomaly in adult patients with diffuse glioma. METHODS: We performed a retrospective cohort study (2010-2016) of consecutive adult patients harboring a supratentorial diffuse glioma in 2 centers: Sainte-Anne Hospital (experimental and control sets) and Pitié-Salpêtrière Hospital (external validation set). We included 219 patients with diffuse glioma (experimental set), 252 patients with brain metastasis (control set), and 200 patients with diffuse glioma (validation set)...
November 30, 2018: Neurology
Hanaa Amrani Hassani Joutei, Nabila Marchoudi, Wafaa Mahfoud, Ilham Sadaoui, Taoufiq Fechtali, Hakima Benomar
BACKGROUND AND STUDY AIMS: Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of PI3KCA and BRAF mutations in Moroccan HER2 overexpressed patients, in order to introduce targeted therapy in the arsenal of therapeutic modalities for management in Morocco. PATIENTS AND METHODS: 98 gastric adenocarcinoma tissue samples were collected. Further histological and immunohistochemical examinations were carried out at the Laboratory of Anatomy Pathology in Pasteur Institute-Morocco, in order to select HER2 positive cases...
November 28, 2018: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
Chun-Yan Sang, Wen-Wen Qin, Xiu-Juan Zhang, Yu Xu, You-Zhen Ma, Xing-Rong Wang, Ling Hui, Shi-Wu Chen
The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking...
November 7, 2018: Bioorganic & Medicinal Chemistry
Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Naval Daver, Courtney D DiNardo, Marina Konopleva, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, Joseph D Khoury, Jeffrey Jorgensen, Nitin Jain, Joie Alvarez, Susan O'Brien, Hagop Kantarjian
BACKGROUND: The combination of chemotherapy and ponatinib in Philadelphia chromosome-positive acute lymphoblastic leukaemia has the potential to be a new standard of care for the disease; however, long-term efficacy and safety data are needed. Our aim was to evaluate the long-term efficacy and safety of this regimen in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia in this ongoing phase 2 trial. METHODS: In our single-centre, phase 2, single-arm trial in the USA, adult patients with previously untreated Philadelphia chromosome-positive acute lymphoblastic leukaemia were sequentially enrolled...
December 2018: Lancet Haematology
Jordan R Hansford
Modern paediatric oncology practice has rapidly evolved from a fatal condition at diagnosis in the 1940s to modern survival rates of over 80%. With the advent of the 'omics' era and modern diagnostics platforms, we can now determine many of the molecular driving mechanisms of malignancy. Current molecular diagnostics trials PRISM and AIM/MNP, open in Australia, allow accurate diagnosis and determination of the molecular drivers of many cancers leading to new targeted opportunities for treatment. Unfortunately, clinical trial support, development and drug access for children has lagged behind...
November 30, 2018: Journal of Paediatrics and Child Health
Lin Tu, Peter Hohenberger, Heike Allgayer, Hui Cao
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. With the considerable research and application of molecular-targeted therapy for GISTs in the last two decades, GISTs have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those by the European Society of Medical Oncology (ESMO), the clinical situations in China are different from those in European countries. There are distinct differences between the clinical practice, diagnostic methods, surgical approach, and availability of new targeted agents in China and those in Europe...
October 2018: Visceral Medicine
Kalpalata Tripathy, Aparajita Mishra, Ajit K Singh, Pragnya L Panda, Arup Mahapatra, Anusaya Lenka
Context: Efficacy of immunocytochemistry (ICC) in determining molecular biomarkers like estrogen receptor (ER), progesterone receptors (PRs), and human epidermal growth factor receptor-2 (HER2). Aims: To evaluate biomarkers using ICC in breast cancer as per American Society of Clinical Oncology/College of American Pathology (ASCO/CAP) guidelines. Settings and Design: The study was conducted over a period of 2 years from September 2012 to August 2014 and is the first such study in eastern India...
October 2018: Journal of Cytology
Fatima Valdes-Mora, Kristina Handler, Andrew M K Law, Robert Salomon, Samantha R Oakes, Christopher J Ormandy, David Gallego-Ortega
Cancer is a heterogeneous and complex disease. Tumors are formed by cancer cells and a myriad of non-cancerous cell types that together with the extracellular matrix form the tumor microenvironment. These cancer-associated cells and components contribute to shape the progression of cancer and are deeply involved in patient outcome. The immune system is an essential part of the tumor microenvironment, and induction of cancer immunotolerance is a necessary step involved in tumor formation and growth. Immune mechanisms are intimately associated with cancer progression, invasion, and metastasis; as well as to tumor dormancy and modulation of sensitivity to drug therapy...
2018: Frontiers in Immunology
Luca Falzone, Salvatore Salomone, Massimo Libra
The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the first modern therapeutic approach in medical oncology...
2018: Frontiers in Pharmacology
Ellen K Ritchie
For patients with chronic myeloid leukemia in chronic phase with sustained deep molecular responses on long-term tyrosine kinase inhibitor (TKI) therapy, treatment-free remission (TFR) feasibility has been established. TFR is now a treatment goal for patients meeting specific criteria; NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) for CML have developed criteria for attempting TFR outside clinical trials, and TFR was added to the US Food and Drug Administration-approved nilotinib label...
November 27, 2018: Leukemia & Lymphoma
Tomer Cooks, Sofia Dp Theodorou, Eleni Paparouna, Sophia V Rizou, Vassilios Myrianthopoulos, Vassilis G Gorgoulis, Ioannis S Pateras
In the era of precision medicine immunohistochemistry (IHC) and immunocytochemistry (ICC) share some of the highlights in personalized treatment. Survival data obtained from clinical trials shape the cut-offs and IHC scoring that serve as recommendations for patient selection both for targeted and conventional therapies. Assessment of Estrogen and Progesterone Receptors along with HER2 status has been among the first approved immunostaining assays revolutionizing breast cancer treatment. Similarly, ALK positivity predicts the efficacy of ALK inhibitors in patients with non-small cell lung cancer (NSCLC)...
November 27, 2018: Histology and Histopathology
Elisabeth G E de Vries, Laura Kist de Ruijter, Marjolijn N Lub-de Hooge, Rudi A Dierckx, Sjoerd G Elias, Sjoukje F Oosting
Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug-target engagement and responses to treatment...
November 27, 2018: Nature Reviews. Clinical Oncology
Zeina Al-Mansour, Linda Pang, Venu Bathini
With the worldwide trend of aging populations, the number of older adults who develop and survive cancer is likely to increase. In the last decade, oncology drug development has shifted away from conventional chemotherapeutics towards agents that can 'target' a driver mutation of a specific cancer or 'unleash' the patient's native immune system to attack the cancer-so-called molecularly targeted therapies and immunotherapeutics. The basic algorithms of cancer treatment in elderly patients are essentially the same as in younger patients; however, one needs to pay exceptional attention to the effects of co-morbidities, interaction with other drugs, and the organ function reserve of an older individual before determining his/her 'eligibility' for a specific cancer treatment modality...
November 27, 2018: Drugs & Aging
H Reis, T Szarvas
Urachal cancer is a rare but aggressive disease. In addition to the non-glandular tumors, non-cystic urachal adenocarcinomas are nowadays distinguished from the primary cystic variant. (Immunohistochemical) markers are only of minor differential diagnostic value and, therefore, the diagnosis is primarily established in a multidisciplinary approach. The non-cystic variant accounts for the majority of cases (83%), is more common in men (63%), shows a median age at diagnosis of 51 years and has a 5-year survival rate of about 50%...
November 23, 2018: Der Pathologe
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