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Xiaoye Yang, Xiaoqun Shi, Jianbo Ji, Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs)...
November 2018: Drug Delivery
Amy Harrison, Pamela Stavri, Lynn Ormond, Francine McEnemy, Dilan Akyol, Annum Qureshi, Hind Al-Khairulla
Cognitive remediation therapy (CRT) is a low-intensity treatment adjunct for individuals with severe and complex anorexia nervosa (AN) with difficulties in globally oriented, flexible thinking. Previously trialled in adults, this study investigated whether individual and group CRT was a feasible, acceptable, and beneficial treatment for 125 adolescent inpatients with severe and complex AN. Seventy patients (mean age = 15.22, SD = 1.44) received 10 sessions of individual CRT, and 55 patients (mean age = 14...
March 15, 2018: European Eating Disorders Review: the Journal of the Eating Disorders Association
Arkaitz Imaz, Jordi Niubó, Alieu Amara, Saye Khoo, Elena Ferrer, Juan M Tiraboschi, Laura Acerete, Benito Garcia, Antonia Vila, Daniel Podzamczer
This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C24h ), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included...
March 14, 2018: Journal of Neurovirology
Hala O El-Mesallamy, Hekmat M El Magdoub, James M Chapman, Nadia M Hamdy, Mona F Schaalan, Lamiaa N Hammad, Sondra H Berger
Thymidylate synthase (TS) is a well-validated target for the therapy of adult cancers. Propane-1,3-diphosphonic acid (PDPA) has significant inhibitory properties against human thymidylate synthase (hTS) relative to mouse TS which is not predicted to adopt an inactive conformer. The current research aims to identify novel, lead inhibitors of hTS and examine the prediction that they bind selectively to hTS enzymes existing in different conformational equilibria. Conformer-selectivity was evaluated through performing activity inhibition studies, as well as intrinsic fluorescence (IF) studies in comparison to the known orthosteric inhibitor raltitrexed (RTX)...
2018: PloS One
Shirish M Gadgeel
Anaplastic lymphoma kinase (ALK) gene rearrangements as driver genetic alterations occur in approximately 2-4% of non-small-cell lung cancer (NSCLC) patients. Alectinib, a next generation ALK inhibitor, recently demonstrated, in two separate Phase III trials, superior efficacy to crizotinib, the first ALK inhibitor to demonstrate clinical efficacy in ALK-positive NSCLC patients. Alectinib also demonstrated superior efficacy in the CNS. The data from these two Phase III studies suggest that the efficacy of starting with alectinib is superior to the overall clinical efficacy of starting with crizotinib followed by switching to alectinib at the time of disease progression...
March 14, 2018: Future Oncology
Megumi Yazaki, Takehiko Oami, Kazuya Nakanishi, Ryota Hase, Hiroyuki Watanabe
Although vancomycin administration is recommended for the treatment of infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA), it is unclear whether an alternative agent, daptomycin, can be used to treat IE with pulmonary complications. A 26-year-old female who had undergone surgical repair of a ventricular septal defect as an early teenager presented with fever, headache, and vomiting. She was admitted to our hospital and diagnosed with right-sided IE with septic pulmonary embolism caused by MRSA...
March 10, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Dongya Jia, Jun Hyoung Park, Kwang Hwa Jung, Herbert Levine, Benny Abraham Kaipparettu
Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration...
March 13, 2018: Cells
Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects...
April 2018: International Journal of Oncology
Paola Occhetta, Giuseppe Isu, Marta Lemme, Chiara Conficconi, Philipp Oertle, Christian Räz, Roberta Visone, Giulia Cerino, Marija Plodinec, Marco Rasponi, Anna Marsano
In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone...
March 13, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Michael Strupp, Ludwig Kraus, Franz Schautzer, Dan Rujescu
OBJECTIVES: Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD). METHODS: Thirteen adults aged 40-75 years (mean 58.9 years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1 year...
March 12, 2018: Journal of Neurology
Marie Duhamel, Mélanie Rose, Franck Rodet, Adriana-Nathalia Murgoci, Lea Zografidou, Anne Régnier-Vigouroux, Fabien Vanden Abeele, Firas Kobeissy, Serge Nataf, Laurent Pays, Maxence Wisztorski, Dasa Cizkova, Isabelle Fournier, Michel Salzet
High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells towards a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an anti-tumoral phenotype. Previously, we demonstrated that macrophages secreted anti-tumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Naoya Niwa, Eiji Kikuchi, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Mototsugu Oya
PURPOSE: It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57...
March 9, 2018: Urologic Oncology
Rosario Palacios, M Mayorga, C M González-Domenech, C Hidalgo-Tenorio, C Gálvez, L Muñoz-Medina, J de la Torre, A Lozano, M Castaño, M Omar, Jesús Santos
OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42...
January 2018: Journal of the International Association of Providers of AIDS Care
Anasheh Halabi, Kayla T B Fuselier, Ed Grabczyk
DNA repeat expansion underlies dozens of progressive neurodegenerative disorders. While the mechanisms driving repeat expansion are not fully understood, increasing evidence suggests a central role for DNA mismatch repair. The mismatch repair recognition complex MutSβ (MSH2-MSH3) that binds mismatched bases and/or insertion/deletion loops has previously been implicated in GAA•TTC, CAG•CTG and CGG•CCG repeat expansion, suggesting a shared mechanism. MutSβ has been studied in a number of models, but the contribution of subsequent steps mediated by the MutL endonuclease in this pathway is less clear...
February 26, 2018: Nucleic Acids Research
Muge Cevik, Chloe Orkin
PURPOSE OF REVIEW: In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. RECENT FINDINGS: In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes...
March 9, 2018: Current Opinion in HIV and AIDS
Ayşe Tunçer Vural, Arzu Karataş Toğral, Ayşe Tülin Güleç, Mehmet Haberal
Solid-organ transplant recipients are at higher risk of developing Kaposi sarcoma, which is a multicentric vascular neoplasm of lymphatic endothelium-derived cells. Reducing doses of immunosuppressive drugs and switching from calcineurin inhibitors to the mammalian target of rapamycin inhibitor rapamycin have been suggested as an effective first-line treatment modality in most patients. Herein, we report a 64-year-old renal transplant recipient who developed multiple cutaneous and visceral Kaposi sarcoma lesions 2 months after transplant...
March 2018: Experimental and Clinical Transplantation
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore
AIM: To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS: This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017...
February 27, 2018: World Journal of Hepatology
Tetsusuke Yoshimoto, Emi Ryu, Shiro Tomiyasu, Minoru Hojo, Hideya Kokubun, Motohiro Matoba
Pure oxycodone injection became increasingly necessary after oral oxycodone was launched in Japan in 2003. However, trials clarifying the efficacy and safety of injection are rare. Therefore, a multicenter open study on injection was designed and carried out in 2010, resulting in the launch of injection therapy in 2012. As published domestic case reports on efficacy already show widespread prescription, this study aimed to provide useful information for cancer pain relief in Japan and other countries. Our oxycodone injection study consisted of two trials, one of intravenous (S#9131) and the other of subcutaneous (S#9132) administration...
March 10, 2018: Biological & Pharmaceutical Bulletin
Francesco Franchi, Fabiana Rollini, Jose Rivas Rios, Andrea Rivas, Malhar Agarwal, Megha Kureti, Deepa Nagaraju, Mustafa Wali, Zubair Shaikh, Maryuri Briceno, Ahmed Nawaz, Jae Youn Moon, Latonya Been, Siva Suryadevara, Daniel Soffer, Martin M Zenni, Theodore A Bass, Dominick J Angiolillo
BACKGROUND : Switching between different classes of P2Y12 inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored. METHODS : This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d). After a 7-day run-in with ticagrelor (180 mg loading dose [LD] followed by 90 mg twice daily MD), patients (n=80) were randomized into 1 of 4 groups: group A, clopidogrel 600 mg LD 24 hours after the last MD of ticagrelor (C-600 mg-24h); group B, clopidogrel 600 mg LD 12 hours after the last MD of ticagrelor (C-600 mg-12h); group C, clopidogrel 75 mg/d MD 24 hours after the last MD of ticagrelor (C-75 mg-24h); and group D, ticagrelor 90 mg twice daily MD (T-90 mg twice daily)...
March 11, 2018: Circulation
Christoph Oing, Pierre Tennstedt, Ronald Simon, Jennifer Volquardsen, Kerstin Borgmann, Carsten Bokemeyer, Cordula Petersen, Ekkehard Dikomey, Kai Rothkamm, Wael Y Mansour
Here we report that BCL2 blocks DNA double strand break (DSB) repair via nonhomologous end-joining (NHEJ), through sequestration of KU80 protein outside the nucleus. We find that this effect is associated with a repair switch to the error-prone PARP1-dependent end-joining (PARP1-EJ). We present in-vitro proof-of-concept for therapeutic targeting of this switch using PARP inhibitor to specifically enhance the radiosensitivity of BCL2-overexpressing cells. Given its erroneous behavior, PARP1-EJ might allow for the accumulation of genetic alterations and tumor progression...
March 8, 2018: Cancer Letters
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