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https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#1
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#2
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#3
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107576/non-invasive-anaesthetic-methods-for-dermatological-laser-procedures-a-systematic-review
#4
REVIEW
K Greveling, E P Prens, L Liu, M B A van Doorn
Pain is a common side-effect of dermatological laser procedures. Non-invasive anaesthetic drugs and anaesthetic procedures can be used to provide pain relief and increase patient satisfaction and treatment efficacy. However, it remains unclear which method provides the best pain relief. The objective of this systematic review was therefore to assess the efficacy and safety of non-invasive anaesthetic methods during dermatological laser procedures. A systematic literature search was conducted. Randomized and non-randomized controlled clinical trials (RCTs and CCTs) were included...
January 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28107451/effect-of-nocturnal-hemodialysis-versus-conventional-hemodialysis-on-end-stage-renal-disease-a-meta-analysis-and-systematic-review
#5
Fangjie Liu, Yiting Sun, Tianhua Xu, Li Sun, Linlin Liu, Wei Sun, Xin Feng, Jianfei Ma, Lining Wang, Li Yao
OBJECTIVES: The purpose of this study is to assess the efficacy and safety of nocturnal hemodialysis on end-stage renal disease (ESRD) patients. METHODS: We searched Medline, EmBase, and the Cochrance Central Register of Controlled Trials for studies up to January 2016. Analysis was done to compare variant outcomes of different hemodialysis schedules, including mortality, cardiovascular-associated variables, uremia-associated variables, quality of life (QOL), side-effects, and drug usage...
2017: PloS One
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#6
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106485/management-strategies-for-atrial-fibrillation
#7
Peysh A Patel, Noman Ali, Andrew Hogarth, Muzahir H Tayebjee
Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone...
January 2017: Journal of the Royal Society of Medicine
https://www.readbyqxmd.com/read/28106372/folate-engineered-microvesicles-for-enhanced-target-and-synergistic-therapy-towards-breast-cancer
#8
Lian Zhu, Di Dong, Zi-Li Yu, Yi-Fang Zhao, Dai-Wen Pang, Zhi-Ling Zhang
As an ideal nanovector candidate, microvesicles (MVs) have been gradually utilized for packaging kinds of functional molecules for effective tumor diagnosis and therapy; however, the deficiency of their tumor targeting influenced their therapy efficacy. Through a facile phospholipid substitution strategy, MVs based drug delivery system (DDS) was apparently endowed with high tumor targeting towards breast cancer thanks to the modified folate onto the membrane of MVs, simultaneously possessed of synergistic anti-tumor effect, and in vivo tumor imaging attributed to the SA-QDs labeling...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28105857/feasibility-of-obtaining-in-situ-nanocapsules-through-modified-self-microemulsifying-drug-delivery-systems-a-new-manufacturing-approach-for-oral-route-administration
#9
Viridiana Gisela Llera-Rojas, L Alicia Del Real, Néstor Mendoza-Muñoz, Luz María Melgoza-Contreras, David Quintanar-Guerrero
Nanocapsules (NCs) are submicron-sized core shell systems which present important advantages such as improvement of drug efficacy and bioavailability, prevention of drug degradation, and provision of controlled-release delivery. The available methods for NC production require expensive recovery and purification steps which compromised the morphology of nanocapsules. Industrial applications of NCs have been avoided due to the aforementioned issues. In this study, we developed a new method based on a modified self automicroemulsifying drug delivery system (SMEDDS) for in situ NCs production within the gastrointestinal tract...
January 20, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28105850/next-generation-tau-models-in-alzheimer-s%C3%A2-disease-research-virus-based-gene-delivery-systems
#10
V Cubinková, B Valachová, V Brezovaková, R Szabó, I Zimová, Z Kostecká, S Jadhav
Alzheimer's disease (AD) the most common form of dementia is characterized by cognitive decline and progressive loss of neurons in the central nervous system. Despite huge scientific progress, there are only few animal models that recapitulate at least majority of the AD pathology and related symptomatology. Therefore, alternative methods to develop animal models for neurodegenerative diseases are constantly explored. Recently, recombinant adeno-associated viruses (AAVs) are widely used viral vectors in development of novel models for neurodegenerative diseases...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#11
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28105389/chemophototherapy-an-emerging-treatment-option-for-solid-tumors
#12
REVIEW
Dandan Luo, Kevin A Carter, Dyego Miranda, Jonathan F Lovell
Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non-ionizing radiation to well-defined target tissue volumes. Light-based therapies including photodynamic therapy (PDT) and laser-induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically...
January 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28105230/dendritic-cell-activated-cytokine-induced-killer-cell-mediated-immunotherapy-is-safe-and-effective-for-cancer-patients-65-years-old
#13
Yanfeng Liu, Haibo Liu, Hausheng Liu, Pengcheng He, Jing Li, Xin Liu, Limei Chen, Mengchang Wang, Jiejing Xi, Huaiyu Wang, Haitao Zhang, Ying Zhu, Wei Zhu, Jing Ning, Caili Guo, Chunhong Sun, Mei Zhang
Individuals >65 years old account for a large proportion of cancer patients, and usually have poor prognoses due to relative weaker physiological function and lower drug tolerance. To characterize the efficacy and safety of dendritic cell (DC)-activated cytokine-induced killer cell (CIK)-mediated treatment, and develop an adoptive immunotherapy for cancer patients >65 years old, a retrospective study was performed in 58 cancer sufferers who received 1-4 cycles of DC-activated CIK (DC-CIK) treatment and evaluated the response (tumor remission rate) and toxicity (side effects to the treatment)...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105226/expression-of-epidermal-growth-factor-like-domain-7-may-be-a-predictive-marker-of-the-effect-of-neoadjuvant-chemotherapy-for-locally-advanced-uterine-cervical-cancer
#14
Makoto Yamauchi, Takeshi Fukuda, Takuma Wada, Masaru Kawanishi, Kenji Imai, Reiko Tasaka, Tomoyo Yasui, Toshiyuki Sumi
Neoadjuvant chemotherapy (NAC) followed by hysterectomy may be effective for the treatment of locally advanced uterine cervical cancer and improve patient prognosis. It is important to identify markers that are able to predict whether NAC may be successful. Epidermal growth factor-like domain 7 (EGFL7) regulates vascular sprouting in blood vessel formation. In numerous types of human cancer, EGFL7 is upregulated and inhibits endothelial cell adhesion molecules, decreasing vascular tightness and, thus, increasing vascular permeability...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105171/collagen-gel-droplet-embedded-culture-drug-sensitivity-testing-in-squamous-cell-carcinoma-cell-lines-derived-from-human-oral-cancers-optimal-contact-concentrations-of-cisplatin-and-fluorouracil
#15
Kaname Sakuma, Akira Tanaka, Izumi Mataga
The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of extremely small samples, and it is suited to primary cultures of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues available for testing are limited. However, since the optimal contact concentrations of anticancer drugs have yet to be established in OSCC, CD-DST for detecting drug sensitivities of OSCC is currently performed by applying the optimal contact concentrations for stomach cancer...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105163/selection-of-antitumor-displayed-peptides-for-the-specific-delivery-of-the-anticancer-drug-lactaptin
#16
Anna Andreevna Nemudraya, Elena Vladimirovna Kuligina, Alexandr Alexeevich Ilyichev, Alexandr Sergeevich Fomin, Grigory Alexandrovich Stepanov, Anna Valentinovna Savelyeva, Olga Alexandrovna Koval, Vladimir Alexandrovich Richter
It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cells in vitro and suppress the growth of HA-1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105152/evaluation-by-quantitative-image-analysis-of-anticancer-drug-activity-on-multicellular-spheroids-grown-in-3d-matrices
#17
Aurélie Gomes, Adrien Russo, Guillaume Vidal, Elise Demange, Pauline Pannetier, Zied Souguir, Jean-Michel Lagarde, Bernard Ducommun, Valérie Lobjois
Pharmacological evaluation of anticancer drugs using 3D in vitro models provides invaluable information for predicting in vivo activity. Artificial matrices are currently available that scale up and increase the power of such 3D models. The aim of the present study was to propose an efficient and robust imaging and analysis pipeline to assess with quantitative parameters the efficacy of a particular cytotoxic drug. HCT116 colorectal adenocarcinoma tumor cell multispheres were grown in a 3D physiological hyaluronic acid matrix...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104743/active-brown-fat-during-18fdg-pet-ct-imaging-defines-a-patient-group-with-characteristic-traits-and-an-increased-probability-of-brown-fat-redetection
#18
Carlos Gerngroß, Johanna Schretter, Martin Klingenspor, Markus Schwaiger, Tobias Fromme
Brown adipose tissue (BAT) provides a means of non-shivering thermogenesis. In humans, active BAT can be visualized by (18)F-fluoro-desoxyglucose (FDG) uptake as detected by positron emission tomography (PET) combined with computer tomography (CT). The retrospective analysis of clinical scans is a valuable source to identify anthropometric parameters that influence BAT mass and activity and thus the potential efficacy of envisioned drugs targeting this tissue to treat metabolic disease. We analyzed 2854 FDG-PET/CT scans from 1644 patients and identified 98 scans from 81 patients with active BAT...
January 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28104736/pharmacological-treatment-and-risk-of-psychiatric-hospital-admission-in-bipolar-disorder
#19
Erik Joas, Alina Karanti, Jie Song, Guy M Goodwin, Paul Lichtenstein, Mikael Landén
BACKGROUND: Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice. AIMS: To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder. METHOD: We used national registers to identify 35 022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009...
January 19, 2017: British Journal of Psychiatry: the Journal of Mental Science
https://www.readbyqxmd.com/read/28104700/inhibition-of-4ebp-phosphorylation-mediates-the-cytotoxic-effect-of-mtor-kinase-inhibitors-in-aggressive-b-cell-lymphomas
#20
Chengfeng Bi, Xuan Zhang, Ting Lu, Xiaoyan Zhang, Xianhuo Wang, Bin Meng, Huilai Zhang, Ping Wang, Julie M Vose, Wing C Chan, Timothy W McKeithan, Kai Fu
Mechanistic target of rapamycin complex 1 (mTORC1) is a central integrator of nutrient and growth factor inputs that controls cell growth in eukaryotes. The second generation of mTOR kinase inhibitors (TORKi), directly targeting the mTOR catalytic site, are more effective than rapamycin and its analogs in cancer treatment, particularly in inducing apoptosis. However, the mechanism underlying the cytotoxic effect of TORKi remains elusive. Herein, we demonstrated that TORKi-induced apoptosis is predominantly dependent on loss of mTORC1-mediated 4EBP activation...
January 19, 2017: Haematologica
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