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https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#1
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636222/recent-progress-in-immunotherapy-for-urological-cancer
#2
REVIEW
Wataru Obara, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata
Cancer immunotherapy for urological tumors had made progress for several decades, but recent advances in immunotherapy, as therapeutic vaccines or immune checkpoint inhibitors, have drastically changed the present treatment strategy. Recently, nivolumab and atezolizumab have been approved by the Food and Drug Administration for treatment of urological cancers. Additional immune checkpoint inhibitors and vaccines are being tested in clinical trials. Despite advances in these therapeutic modalities, benefits are limited to a subset of patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#3
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28635560/sorafenib-in-japanese-patients-with-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-and-anaplastic-thyroid-carcinoma
#4
Yasuhiro Ito, Naoyoshi Onoda, Ken-Ichi Ito, Iwao Sugitani, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya Tsukada
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan even though vandetanib for MTC, and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We conducted an uncontrolled, open-label, multicenter, single-arm, phase 2 clinical study to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
June 21, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#5
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#6
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633594/targeting-and-delivery-of-therapeutic-enzymes
#7
Scott N Dean, Kendrick B Turner, Igor L Medintz, Scott A Walper
Biotechnology has revolutionized therapeutics for the treatment of a wide range of diseases. Recent advances in protein engineering and material science have made the targeted delivery of enzyme therapeutics using nanocarriers (NCs) a new model of treatment. Several NCs have been approved for clinical use in drug delivery. Despite their advantages, few NCs have been approved to deliver enzyme cargo in a targeted manner. This review details the current arsenal of platforms developed to deliver enzyme therapeutics as well as the advantages and challenges of using enzymes as drugs, with examples from the literature, and discusses the benefits and liabilities of a given approach...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28632134/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#8
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
June 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629920/pulmonary-hypertension-in-parenchymal-lung-diseases-any-future-for-new-therapies
#9
REVIEW
Sergio Harari, Davide Elia, Marc Humbert
Pulmonary hypertension (PH) due to chronic lung diseases is associated with a poor prognosis, regardless of the underlying respiratory condition. Updated PH guidelines recommend optimal treatment of the underlying lung disease, including long-term oxygen therapy, in patients with chronic hypoxaemia despite the lack of randomized controlled clinical trials supporting this statement. So far, randomized controlled trials on drugs approved for pulmonary arterial hypertension (PAH) have yielded discouraging results in both interstitial lung diseases (ILD) and chronic obstructive pulmonary diseases (COPD) with PH...
June 16, 2017: Chest
https://www.readbyqxmd.com/read/28629427/targeting-vegfr-3-2-signaling-pathways-with-ad0157-a-potential-strategy-against-tumor-associated-lymphangiogenesis-and-lymphatic-metastases
#10
Melissa García-Caballero, Jenny Paupert, Silvia Blacher, Maureen Van de Velde, Ana Rodríguez Quesada, Miguel Angel Medina, Agnès Noël
BACKGROUND: Lymphatic metastasis is one of the leading causes of death in patients with different types of cancer and is the main prognostic factor for the disease survival. The formation of new lymphatic vessels (lymphangiogenesis) in primary tumors facilitates tumor cell dissemination to regional lymph nodes and correlates with distant metastases. Lymphangiogenesis has thus emerged as a suitable therapeutic target to block metastases, but no anti-lymphangiogenic compounds have been approved for clinical use to date...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28629155/repositioning-fda-drugs-as-potential-cruzain-inhibitors-from-trypanosoma-cruzi-virtual-screening-in-vitro-and-in-vivo-studies
#11
Isidro Palos, Edgar E Lara-Ramirez, Julio Cesar Lopez-Cedillo, Carlos Garcia-Perez, Muhammad Kashif, Virgilio Bocanegra-Garcia, Benjamin Nogueda-Torres, Gildardo Rivera
Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies...
June 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28629126/differentiated-thyroid-cancer-treatment-state-of-the-art
#12
REVIEW
Benedikt Schmidbauer, Karin Menhart, Dirk Hellwig, Jirka Grosse
Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine...
June 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629000/formulation-and-in-vitro-efficacy-of-antifungal-mucoadhesive-polymeric-matrices-for-the-delivery-of-miconazole-nitrate
#13
G Tejada, G N Piccirilli, M Sortino, C J Salomón, M C Lamas, D Leonardi
Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28628863/simultaneous-quantification-of-endothelin-receptor-antagonists-and-phosphodiesterase-5-inhibitors-currently-used-in-pulmonary-arterial-hypertension
#14
Yeliz Enderle, Lukas Witt, Heinrike Wilkens, Ekkehard Grünig, Walter E Haefeli, Jürgen Burhenne
Combination treatment with endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5I) improved efficacy of pulmonary arterial hypertension (PAH) therapy. However, drug-drug interactions, variable exposure, non-adherence can influence plasma levels. For these reasons, drug quantification may be advantageous particularly in patients with poor treatment responses. We developed, validated, and applied an assay for the simultaneous quantification of ambrisentan, bosentan, macitentan, sildenafil, and tadalafil as well as their main (and partly active) metabolites in human plasma...
June 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28628827/evolutionary-conservation-of-influenza-a-pb2-sequences-reveals-potential-target-sites-for-small-molecule-inhibitors
#15
Hershna Patel, Andreas Kukol
The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to -10...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28628393/early-national-dissemination-of-abiraterone-and-enzalutamide-for-advanced-prostate-cancer-in-medicare-part-d
#16
Megan E V Caram, Tudor Borza, Hye-Sung Min, Jennifer J Griggs, David C Miller, Brent K Hollenbeck, Bhramar Mukherjee, Ted A Skolarus
INTRODUCTION: Abiraterone and enzalutamide were approved by the Food and Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer (mCRPC). Most men with mCRPC are > 65 years of age and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. METHODS: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data...
June 19, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28627385/advances-in-antibody-drug-conjugates-a-new-era-of-targeted-cancer-therapy
#17
REVIEW
Samaresh Sau, Hashem O Alsaab, Sushil Kumar Kashaw, Katyayani Tatiparti, Arun K Iyer
Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28625631/cd52-cd22-cd26-eg5-and-igf-1r-expression-in-thymic-malignancies
#18
J Remon, N Abedallaa, E Taranchon-Clermont, V Bluthgen, C R Lindsay, B Besse, V Thomas de Montpréville
BACKGROUND: Thymic epithelial tumours are rare cancers for which new treatment options are required. Identification of putative predictive markers is important for developing clinical trials. We studied the expression of five putative predictive biomarkers, potentially actionable by approved experimental drugs. METHODS: CD52, CD22, CD26, EG5, and IGF-1R expression were investigated by immunohistochemistry in formalin-fixed surgical samples of thymic epithelial tumour patients...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625477/challenges-and-advances-in-the-diagnosis-biology-and-treatment-of-urothelial-upper-tract-and-bladder-carcinomas
#19
REVIEW
Jeanny B Aragon-Ching
Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers...
July 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28625147/adverse-drug-reactions-related-to-drug-administration-in-hospitalized-patients
#20
Luca Gallelli, Antonio Siniscalchi, Caterina Palleria, Laura Mumoli, Orietta Staltari, Aida Squillace, Francesca Maida, Emilio Russo, Santo Gratteri, Giovambattista De Sarro
INTRODUCTION: Drug treatment may be related with the development of adverse drug reactions (ADRs). AIM: Here, we evaluated the ADRs in patients admitted to Catanzaro Hospital. METHODS: After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively...
June 15, 2017: Current Drug Safety
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