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https://www.readbyqxmd.com/read/29351242/-vessels-in-the-storm-searching-for-prognostic-and-predictive-angiogenic-factors-in-colorectal-cancer
#1
REVIEW
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Ficorella Corrado
High expectations are placed upon anti-angiogenic compounds for metastatic colorectal cancer (mCRC), the first malignancy for which such type of treatment has been approved. Indeed, clinical trials have confirmed that targeting the formation of new vessels can improve in many cases clinical outcomes of mCRC patients. However, current anti-angiogenic drugs are far from obtaining the desirable or expected curative results. Many are the factors probably involved in such disappointing results, but particular attention is currently focused on the validation of biomarkers able to improve the direction of treatment protocols...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#2
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29351105/stem-cell-modeling-of-lipid-genetics
#3
Kiran Musunuru
PURPOSE OF REVIEW: To summarize recent advances with respect to the use of human pluripotent stem cells to study the genetics of blood lipid traits. RECENT FINDINGS: Human pluripotent stem cell models have been used to elucidate the mechanisms by which genes contribute to dyslipidemia, to discover new lipid-related DNA variants and genes, and to perform drug screens. SUMMARY: In addition to enabling a better understanding of the genetic basis of lipid metabolism, human pluripotent stem cells are identifying potential therapeutic targets as well as potential therapies...
January 17, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29350549/abiraterone-acetate-and-its-use-in-the-treatment-of-metastatic-prostate-cancer-a-review
#4
Orazio Caffo, Antonello Veccia, Stefania Kinspergher, Francesca Maines
Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development...
January 19, 2018: Future Oncology
https://www.readbyqxmd.com/read/29350495/the-current-landscape-of-3d-in-vitro-tumor-models-what-cancer-hallmarks-are-accessible-for-drug-discovery
#5
REVIEW
Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Alison P McGuigan
Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted...
January 19, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29350487/pediatric-patients-with-cutaneous-melanoma-a-european-study
#6
Ines B Brecht, Angela De Paoli, Gianni Bisogno, Daniel Orbach, Dominik T Schneider, Ulrike Leiter, Sonja Offenmueller, Giovanni Cecchetto, Jan Godzinski, Ewa Bien, Teresa Stachowicz-Stencel, Tal Ben-Ami, Stefano Chiaravalli, Andrea Maurichi, Gian Luca De Salvo, Silvia Sorbara, Christine Bodemer, Claus Garbe, Yves Reguerre, Andrea Ferrari
INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. METHODS: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350175/update-on-the-nephrotoxicity-of%C3%A2-novel%C3%A2-anticancer-agents%C3%A2
#7
Eliezer Zachary Nussbaum, Mark A Perazella
Anticancer drug-induced kidney disease is a problem commonly encountered by nephrologists. The number of medications employed by oncologists causing acute and chronic kidney injury as well as electrolyte and acid-base disturbances has increased significantly over the past several decades. While conventional chemotherapeutic drugs induce a number of kidney lesions, emergence of very effective and well-tolerated targeted therapies and novel immunotherapies has increased the occurrence of drug-induced acute and chronic kidney injury in cancer patients...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29349597/drug-repurposing-screening-identifies-bortezomib-and-panobinostat-as-drugs-targeting-cancer-associated-fibroblasts-cafs-by-synergistic-induction-of-apoptosis
#8
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#9
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348812/design-and-synthesis-of-isoquinolidinobenzodiazepine-dimers-a-novel-class-of-antibody-drug-conjugate-payload
#10
Sean W Smith, Vasu Jammalamadaka, Dmitry Borkin, Jianyu Zhu, Sylvia J Degrado, Jennifer Lu, Jianqing Huang, Ying-Ping Jiang, Nareshkumar Jain, Jagath R Junutula
Antibody-drug conjugates (ADCs) represent an important class of emerging cancer therapeutics. Recent ADC development efforts highlighted the use of pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers. We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class of PBD dimer family of DNA damaging payloads. We have successfully synthesized all three IQB stereoisomers, experimentally showed that the purified (S,S)-D211 isomer is functionally more active than (R,R)-D221 and (S,R)-D231 isomers by >50,000-fold and ∼200-fold, respectively...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#11
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348306/novel-targeted-therapeutics-for-men2
#12
REVIEW
Sara Redaelli, Ivan Plaza-Menacho, Luca Mologni
The rearranged during transfection (RET) proto-oncogene was recognized as the multiple endocrine neoplasia type 2 (MEN2) causing gene in 1993. Since then, much effort has been put into a clear understanding of its oncogenic signaling, its biochemical function and ways to block its aberrant activation in MEN2 and related cancers. Several small molecules have been designed, developed or redirected as RET inhibitors for the treatment of MEN2 and sporadic MTC. However, current drugs are mostly active against several other kinases, as they were not originally developed for RET...
February 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29346118/mycobacterium-avium-complex-pulmonary-disease-new-epidemiology-and-management-concepts
#13
Leah Lande, Jason George, Theodore Plush
PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related pulmonary disease has been increasing because of environmental factors, changes in organism virulence, and evolving host susceptibility. Treatment is often complicated by adverse effects, development of drug resistance, and refractory disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization of water, soil, or dusts are the likely sources of MAC-related pulmonary disease in susceptible individuals...
January 15, 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29345579/genistein-as-a-potential-anticancer-agent-against-head-and-neck-squamous-cell-carcinoma
#14
Fatima Ardito, Giovanni Di Gioia, Mario Roberto Pellegrino, Lorenzo Lo Muzio
The use of nutraceuticals as protection drugs against chronic diseases gained a vast success. Many studies found that nutraceuticals may reduce the tumorigenic actions of carcinogens, inhibiting the adhesion and proliferation of tumor cells. Genistein is a natural isoflavone preventing osteoporosis, menopause problems and heart diseases. It is also known in China and Japan for its anticancer properties. The available treatment protocols for Head and neck squamous cell cancer (HNSCC) have led to poor results and new therapies are necessary...
January 16, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29345456/pre-occupation-of-empty-carriers-decreases-endo-lysosome-escape-and-reduces-the-protein-delivery-efficiency-of-mesoporous-silica-nanoparticles
#15
Wenqing Li, Liping Sun, Yiqiu Xia, Si-Jie Hao, Gong Cheng, Zhigang Wang, Yuan Wan, Chuandong Zhu, Hongzhang He, Si-Yang Zheng
Endo/lysosome escape is a major challenge in nanoparticles-based protein delivery for cancer therapy. To enhance endo/lysosomal escape and increase the efficacy of proteins delivery, current strategies mainly focuses on destroying endo/lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes, cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize that pre-treatment with empty nanocarriers might make endo/lysosomes occupied and affect the endo/lysosomal escape of subsequent protein delivery by nanocarriers...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29344438/new-therapeutic-approaches-in-obesity-and-metabolic-syndrome-associated-with-polycystic-ovary-syndrome
#16
REVIEW
Fatima Saleem, Syed W Rizvi
Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices. PCOS is commonly associated with a high prevalence of insulin resistance and obesity; this association carries an increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Guidelines recommend lifestyle modification, metformin, hormonal contraceptives (HCs), and bariatric surgery as the main treatment options in obese patients with PCOS. Studies are being conducted to test the efficacy of existing treatment options as well as to discover new therapies...
November 13, 2017: Curēus
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#17
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344328/management-of-functional-dyspepsia-state-of-the-art-and-emerging-therapies
#18
REVIEW
Hiroshi Yamawaki, Seiji Futagami, Mako Wakabayashi, Noriko Sakasegawa, Shuhei Agawa, Kazutoshi Higuchi, Yasuhiro Kodaka, Katsuhiko Iwakiri
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344327/secukinumab-a-review-of-the-anti-il-17a-biologic-for-the-treatment-of-psoriasis
#19
REVIEW
Jillian Frieder, Dario Kivelevitch, Alan Menter
Psoriasis is a systemic inflammatory disease associated with numerous comorbidities and a profound impact on patients' quality of life. While its complex immune pathogenesis is still not fully delineated, current evidence supports a fundamental role of the T-helper-17 (TH-17) pathway and its related interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been developed to block this key cytokine and its downstream effects. Secukinumab is a fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to be approved by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29343949/clinical-observations-on-the-use-of-new-anti-vegf-drug-conbercept-in-age-related-macular-degeneration-therapy-a-meta-analysis
#20
Chunmei Cui, Hong Lu
Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug approved for the treatment of age-related macular degeneration (AMD). Although this novel drug has been widely used in clinic, unlike other anti-VEGF drugs, validation and consensus on its method of clinical application and clinical safety have not yet been achieved. Methods: Relevant literature was searched on PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data...
2018: Clinical Interventions in Aging
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