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Renata Ottes Vasconcelos, Simona Serini, Ana Paula de Souza Votto, Gilma Santos Trindade, Caterina Fanali, Alessandro Sgambato, Gabriella Calviello
The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy...
December 13, 2018: Melanoma Research
Y Z Liang, X L Nong
The head and neck cancer is one of the most common malignant tumors in the world. There are more than 600 000 new cases in the world every year. Cisplatin is often used in the treatment of head and neck cancer at present. However, because of its side effects and drug resistance, cisplatin often failed in the treatment of head and neck cancer. Artemisinin and its derivatives as first-line antimalarial drugs have the advantages of high efficiency, low toxicity and so on. Further study found that artemisinin and its derivatives had cytotoxic effects against head and neck cancer through inducing cell cycle arrest, inducing tumor cell apoptosis and inhibiting cell invasion and migration, oxidative damage, blocking the cell signal transduction and inhibiting angiogenesis...
October 5, 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
V L Andronova
Modern chemotherapy of cytomegalovirus (CMV) infections has a very limited arsenal of first-line drugs. These are preparations of ganciclovir (GCV) belonging to the class of modified nucleosides and its metabolic precursor ganciclovir valine ester. After three-step phosphorylation, GCV, as a structural analogue of the natural nucleotide, competes with it for binding to DNA polymerase and, due to its structural features, inhibits its activity. However, with prolonged use of GCV, mainly under conditions of immunosuppression, the virus develops drug resistance associated in most cases with changes in pUL97 catalyzing the first stage of GCV phosphorylation, as well as in the catalytic subunit of DNA polymerase...
2018: Voprosy Virusologii
Hanne Huygelier, Céline R Gillebert
Spatial neglect is characterized by a spatial bias in response to stimuli. The disorder is often assessed with a cancellation task, where several measures can be used to quantify the spatial bias of cancellation responses (e.g., the difference between cancellations on the left and right side, the average location of cancelled targets, and the total number of omissions). Typically, measures of cancellation performance are validated by studying the correlation with measures derived from other tasks to assess neglect (e...
December 14, 2018: Journal of Neuropsychology
Mario Salvi, Danila Covelli
Steroid therapy in GO is first line treatment but has limitations, as it is potentially harmful at high doses and often refused by patients. A steroid sparing therapy is a reasonable option as long as it is rapidly effective and devoid of long term adverse reactions. Combined immunosuppressive therapy must be studied in randomized clinical trials designed to test efficacy and the potentially increased risk of side effects. This article is protected by copyright. All rights reserved.
December 14, 2018: Clinical Endocrinology
Chiang-Wen Lee, Miao-Ching Chi, Tsung-Ming Chang, Ju-Fang Liu
Osteosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. However, because of side effects and drug resistance in chemotherapy and the insufficiency of an effective adjuvant therapy for osteosarcoma, it is necessary to research novel treatments. This study was the first to investigate the anticancer effects of the flavonoid derivative artocarpin in osteosarcoma. Artocarpin induced cell apoptosis in three human osteosarcoma cell lines-U2OS, MG63, and HOS...
December 13, 2018: Journal of Cellular Physiology
Jordan T Jones, Nasreen Talib, Daniel Lovell, Mara L Becker
BACKGROUND: Arthropathy of Down syndrome (DA) is largely under-recognized, with an average 2-year delay in diagnosis. Most patients present with polyarthritis, and treatment has historically been challenging. OBJECTIVES: Our objective was to investigate the clinical features and treatment of DA in the largest cohort reported to date. METHODS: In a retrospective chart review at two tertiary care hospitals, International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes for Down syndrome (DS) and juvenile idiopathic arthritis (JIA), between 1 January 1995 and 31 December 2015, were identified and charts reviewed...
December 13, 2018: Paediatric Drugs
Tomonari Suetsugu, Nobuhisa Matsuhashi, Takao Takahashi, Toshiyuki Tanahashi, Satoshi Matsui, Hisashi Imai, Yoshihiro Tanaka, Kazuya Yamaguchi, Kazuhiro Yoshida
Pathological complete response is achievable with mFOLFOX6 plus cetuximab therapy for unresectable colorectal cancer with multiple paraaortic lymph node metastases (mCRC) despite right-sided colonic origin. A 62-year-old woman with synchronous paraaortic lymph node metastases of transverse colon cancer was treated with mFOLFOX6 plus cetuximab as first-line therapy. The tumor size was markedly decreased following 6 courses of chemotherapy, and all lymph node metastases had disappeared. The patient then underwent conventional right hemicolectomy with D3 lymph node dissection plus sampling excision of the paraaortic lymph nodes...
December 2018: Molecular and Clinical Oncology
Frank Erhard Uschner, Florian Schueller, Ivelina Nikolova, Sabine Klein, Robert Schierwagen, Fernando Magdaleno, Stefanie Gröschl, Sven Loosen, Thomas Ritz, Christoph Roderburg, Michael Vucur, Glen Kristiansen, Twan Lammers, Tom Luedde, Jonel Trebicka
Background and Aims: Angiogenesis is critically involved in the development of liver fibrosis, portal hypertension (PHT) and hepatocellular carcinoma (HCC). Regorafenib is a novel second-line therapy for HCC, but might also be beneficial in fibrosis and PHT even in absence of HCC. This study investigated the effects of regorafenib in experimental models without HCC. Methods: Fibrosis ( in vivo and in vitro ), inflammation, liver damage (aminotransferases), angiogenesis (matrigel implantation) and in vivo systemic and portal hemodynamics were assessed in different mouse and rat models (bile duct ligation, CCl4 , partial portal vein ligation) after acute and chronic treatment with regorafenib...
November 16, 2018: Oncotarget
Jeremy D Kratz, Nataliya V Uboha, Sam J Lubner, Daniel L Mulkerin, Linda Clipson, Yanyao Yi, Menggang Yu, Kristina A Matkowskyj, Noelle K LoConte, Dustin A Deming
Background: Molecular profiles guide the clinical management of metastatic colorectal cancer (mCRC), particularly related to the use of anti-epidermal growth factor receptor (EGFR) antibodies. Tumor sidedness has also been implicated in resistance to these therapies, but has largely been studied in the first-line setting. We examined the role of tumor sidedness and disease bulk in predicting clinical outcomes to anti-EGFR therapy in the treatment-refractory setting. Methods: We identified a retrospective cohort of 62 patients with KRAS wild-type mCRC who received anti-EGFR therapy in the late-line setting...
December 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Leonardo Gomes da Fonseca, Guilherme Nader Marta, Maria Ignez Freitas Melro Braghiroli, Aline Lopes Chagas, Flair Jose Carrilho, Paulo Marcelo Hoff, Jorge Sabbaga
BACKGROUND: Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib...
December 13, 2018: BMC Cancer
Zonghong Han, Zhongming He, Caoye Wang, Qi Wang
RATIONALE: Most patients with hepatocellular carcinoma (HCC) have lost the chance of radical treatment at the time of their visit, and the prognosis of metastatic HCC is even worse. Sorafenib is currently regarded as a first-line systemic therapy in patients with advanced and metastatic HCC. Apatinib is a new inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase, which has been reported to be effective in some solid tumors. We herein report a case of apatinib in the treatment of the patient with metastatic HCC who was resistant to sorafenib...
December 2018: Medicine (Baltimore)
(no author information available yet)
OBJECTIVEAblative procedures are still useful in the treatment of intractable pain despite the proliferation of neuromodulation techniques. In the paper the authors present the results of Gamma Knife thalamotomy (GKT) in various pain syndromes.METHODSBetween 1996 and 2016, unilateral GKT was performed in 30 patients suffering from various severe pain syndromes in whom conservative treatment had failed. There were 20 women and 10 men in the study population, with a median age of 80 years (range 53-89 years)...
December 1, 2018: Journal of Neurosurgery
Ashwani Kumar, Vineet Mehta, Utkarsh Raj, Pritish Kumar Varadwaj, Malairaman Udayabanu, Ragothaman M Yennamalli, Tiratha Raj Singh
BACKGROUND: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is to identify new and safer 'disease-modifying drugs'. METHODS: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism...
December 12, 2018: Current Alzheimer Research
Katarína Holubová, Goetz Hensel, Petr Vojta, Petr Tarkowski, Véronique Bergougnoux, Petr Galuszka
Barley is one of the most important cereals, which is used for breweries, animal and human feeds. Genetic manipulation of plant hormone cytokinins may influence several physiological processes, besides others stress tolerance, root formation and crop yield. In planta , endogenous cytokinin status is finely regulated by the enzyme cytokinin dehydrogenase (EC; CKX), that irreversible degrades the side chain of adenine-derived isoprenoid cytokinins. Increasing grain yield by mean of manipulation of endogenous cytokinin content was assayed by the silencing of the HvCKX1 gene...
2018: Frontiers in Plant Science
Carlo C Campa, Rangel L Silva, Jean P Margaria, Tracey Pirali, Matheus S Mattos, Lucas R Kraemer, Diego C Reis, Giorgio Grosa, Francesca Copperi, Eduardo M Dalmarco, Roberto C P Lima-Júnior, Silvio Aprile, Valentina Sala, Federica Dal Bello, Douglas Silva Prado, Jose Carlos Alves-Filho, Claudio Medana, Geovanni D Cassali, Gian Cesare Tron, Mauro M Teixeira, Elisa Ciraolo, Remo C Russo, Emilio Hirsch
PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action...
December 12, 2018: Nature Communications
Sita Nirupama Nishtala, Avish Arora, Jorge Reyes, Myles H Akabas
Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophic. They import purines via an equilibrative nucleoside transporter (ENT). In P. falciparum , the most virulent species, the equilibrative nucleoside transporter 1 (PfENT1) represents the primary purine uptake pathway. This transporter is a potential target for the development of antimalarial drugs. In the absence of a high-resolution structure for either PfENT1 or a homologous ENT, we used the substituted cysteine accessibility method (SCAM) to investigate the membrane-spanning domain structure of PfENT1 to identify potential inhibitor-binding sites...
December 12, 2018: Journal of Biological Chemistry
Esben Andreas Carlsen, Nicola Fazio, Dan Granberg, Simona Grozinsky-Glasberg, Hojjat Ahmadzadehfar, Chiara Maria Grana, Wouter T Zandee, Jaroslaw Cwikla, Martin A Walter, Peter Sandor Oturai, Anja Rinke, Andrew Weaver, Andrea Frilling, Sara Gritti, Anne Kirstine Arveschoug, Amichay Meirovitz, Ulrich Knigge, Halfdan Sorbye
Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1-2 (G1-G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity...
February 1, 2019: Endocrine-related Cancer
Wenwen Luo, Deyi Zhang, Shumin Ma, Chenyao Wang, Qian Zhang, Huafei Wang, Kunyan He, Zhixue Liu
Background: Cancer stem cells (CSCs) are responsible for tumor relapse after chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC). The aim of this study is to explore the profile and role of microRNA (miRNA) in CSC of NSCLC. Materials and Methods: We studied the expression of stem cell marker in side population cells and serum-free cultured spheres of NSCLC. We identified that CD133+ CD34- cells are NSCLC stem cell. We isolated CD133+ CD34- cells and CD133- CD34+ cells with MicroBead Kit...
December 2018: Journal of Cancer Research and Therapeutics
Matthias Müller, Yimin Wang, Michael R Squillante, Kathryn D Held, R Rox Anderson, Martin Purschke
BACKGROUND AND PURPOSE: Radiation therapy is the gold standard treatment for inoperable malignant tumors. However, due to the heterogeneity of the tumor, some regions are more radio resistant and can lead to metastasis and tumor recurrence. In this study, we propose combining traditional X-ray treatment with UVC-emitting LuPO4 :Pr3+ nanoparticles (NPs) to increase the tumor control as well as to reduce tumor recurrence and metastasis. These NPs convert ionizing radiation into UVC-photons (UVC range: 200-280 nm) locally at the tumor site...
December 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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