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https://www.readbyqxmd.com/read/28097641/natural-products-diversity-of-marine-ascidians-tunicates-ascidiacea-and-successful-drugs-in-clinical-development
#1
REVIEW
Satheesh Kumar Palanisamy, N M Rajendran, Angela Marino
This present study reviewed the chemical diversity of marine ascidians and their pharmacological applications, challenges and recent developments in marine drug discovery reported during 1994-2014, highlighting the structural activity of compounds produced by these specimens. Till date only 5% of living ascidian species were studied from <3000 species, this study represented from family didemnidae (32%), polyclinidae (22%), styelidae and polycitoridae (11-12%) exhibiting the highest number of promising MNPs...
January 17, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#2
REVIEW
Anil Kapoor, Christopher Wu, Bobby Shayegan, Adrian P Rybak
Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28094198/late-side-effects-and-cosmetic-results-of-accelerated-partial-breast-irradiation-with-interstitial-brachytherapy-versus-whole-breast-irradiation-after-breast-conserving-surgery-for-low-risk-invasive-and-in-situ-carcinoma-of-the-female-breast-5-year-results
#3
Csaba Polgár, Oliver J Ott, Guido Hildebrandt, Daniela Kauer-Dorner, Hellen Knauerhase, Tibor Major, Jaroslaw Lyczek, José Luis Guinot, Jürgen Dunst, Cristina Gutierrez Miguelez, Pavel Slampa, Michael Allgäuer, Kristina Lössl, Bülent Polat, György Kovács, Arnt-René Fischedick, Rainer Fietkau, Alexandra Resch, Anna Kulik, Leo Arribas, Peter Niehoff, Ferran Guedea, Annika Schlamann, Richard Pötter, Christine Gall, Wolfgang Uter, Vratislav Strnad
BACKGROUND: We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. METHODS: We did this randomised, controlled, phase 3 trial at 16 centres in seven European countries...
January 13, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28094194/mabp1-as-a-novel-antibody-treatment-for-advanced-colorectal-cancer-a-randomised-double-blind-placebo-controlled-phase-3-study
#4
Tamas Hickish, Thierry Andre, Lucjan Wyrwicz, Mark Saunders, Tomasz Sarosiek, Judit Kocsis, Radim Nemecek, Wojciech Rogowski, Krzysztof Lesniewski-Kmak, Lubos Petruzelka, Ron N Apte, Prasant Mohanty, Michael Stecher, John Simard, Aimery de Gramont
BACKGROUND: MABp1, an antibody that targets interleukin 1α, has been associated with antitumour activity and relief of debilitating symptoms in patients with advanced colorectal cancer. We sought to establish the effect of MABp1 with a new primary endpoint in patients with advanced colorectal cancer. METHODS: Eligible patients for the double-blind phase of this ongoing, placebo-controlled, randomised, phase 3 trial, had metastatic or unresectable disease, Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis, and were refractory to oxaliplatin and irinotecan...
January 13, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28081304/comparison-of-an-ac-taxane-versus-ac-free-regimen-and-paclitaxel-versus-docetaxel-in-patients-with-lymph-node-positive-breast-cancer-final-results-of-the-national-surgical-adjuvant-study-of-breast-cancer-02-trial-a-randomized-comparative-phase-3-study
#5
Toru Watanabe, Masaru Kuranami, Kenichi Inoue, Norikazu Masuda, Kenjiro Aogi, Shinji Ohno, Hiroji Iwata, Hirofumi Mukai, Yukari Uemura, Yasuo Ohashi
BACKGROUND: In postoperative patients with breast cancer, the combination of an anthracycline and cyclophosphamide (AC) followed by a taxane is a standard regimen. In the current study, the authors examined whether AC could be safely omitted, and compared the effectiveness of paclitaxel versus docetaxel. METHODS: Female postoperative patients with axillary lymph node-positive breast cancer were eligible for enrollment in this phase 3, open-label, randomized controlled trial at 84 centers in Japan...
January 12, 2017: Cancer
https://www.readbyqxmd.com/read/28059952/atp-citrate-lyase-genetics-molecular-biology-and-therapeutic-target-for-dyslipidemia
#6
Amy C Burke, Murray W Huff
PURPOSE OF REVIEW: ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition. RECENT FINDINGS: ACLY is a critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis. Human genetic variants have been associated with enhanced growth and survival of several cancers, and with attenuated plasma triglyceride responses to dietary fish oil...
January 5, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28058215/more-than-skin-deep-potential-nicotinamide-treatment-applications-in-chronic-kidney-transplant-recipients
#7
REVIEW
Andrew G Bostom, Basma Merhi, Joanna Walker, Leslie Robinson-Bostom
Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history. The unique aggressiveness of SCCs in KTRs increases patient morbidity, due to the high rate of new lesions requiring treatment, frequently surgical excision...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28038862/survival-after-associating-liver-partition-and-portal-vein-ligation-for-staged-hepatectomy-alpps-for-advanced-colorectal-liver-metastases-a-case-matched-comparison-with-palliative-systemic-therapy
#8
Pim B Olthof, Joost Huiskens, Dennis A Wicherts, Pablo E Huespe, Victoria Ardiles, Ricardo Robles-Campos, René Adam, Michael Linecker, Pierre-Alain Clavien, Miriam Koopman, Cornelis Verhoef, Cornelis J A Punt, Thomas M van Gulik, Eduardo de Santibanes
BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows the resection of colorectal liver metastases with curative intent which would otherwise be unresectable and only eligible for palliative systemic therapy. This study aimed to compare outcomes of ALPPS in patients with otherwise unresectable colorectal liver metastases with matched historic controls treated with palliative systemic treatment. METHODS: All patients with colorectal liver metastases from the international ALPPS registry were identified and analyzed...
December 27, 2016: Surgery
https://www.readbyqxmd.com/read/28028828/thyroid-abnormalities-following-the-use-of-ctla-4-and-pd-1-inhibitors-in-the-treatment-of-melanoma
#9
D L Morganstein, Z Lai, L Spain, S Diem, D Levine, C Mace, M Gore, J Larkin
CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies, but are associated with a high rate of immune side effects, including endocrinopathy. OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course. DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either Ipilimumab, Nivolumab, Pembrolizumab or the combination of Ipilimumab and Nivolumab were identified...
December 27, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/28011050/could-the-addition-of-cetuximab-to-conventional-radiation-therapy-improve-organ-preservation-in-those-patients-with-locally-advanced-larynx-cancer-who-respond-to-induction-chemotherapy-an-organ-preservation-spanish-head-and-neck-cancer-cooperative-group-phase
#10
Ricard Mesía, Jose A Garcia-Saenz, Alicia Lozano, Miguel Pastor, Juan J Grau, Javier Martínez-Trufero, Julio Lambeaz, Joaquina Martínez-Galán, Jose R Mel, Belen González, Silvia Vázquez, Manel Mañós, Miren Taberna, Beatriz Cirauqui, Elvira Del Barco, Esther Casado, Jordi Rubió-Casadevall, Angles Rodríguez-Jaráiz, Juan J Cruz
PURPOSE: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors. METHODS AND MATERIALS: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%...
November 17, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28008145/msh2-brca1-expression-as-a-dna-repair-signature-predicting-survival-in-early-stage-lung-cancer-patients-from-the-ifct-0002-phase-3-trial
#11
Guénaëlle Levallet, Fatéméh Dubois, Pierre Fouret, Martine Antoine, Solenn Brosseau, Emmanuel Bergot, Michèle Beau-Faller, Valérie Gounant, Elisabeth Brambilla, Didier Debieuvre, Olivier Molinier, Françoise Galateau-Sallé, Julien Mazieres, Elisabeth Quoix, Jean-Louis Pujol, Denis Moro-Sibilot, Alexandra Langlais, Franck Morin, Virginie Westeel, Gérard Zalcman
INTRODUCTION: DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. METHODS: We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002)...
December 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/28007457/padeliporfin-vascular-targeted-photodynamic-therapy-versus-active-surveillance-in-men-with-low-risk-prostate-cancer-clin1001-pcm301-an-open-label-phase-3-randomised-controlled-trial
#12
Abdel-Rahmène Azzouzi, Sébastien Vincendeau, Eric Barret, Antony Cicco, François Kleinclauss, Henk G van der Poel, Christian G Stief, Jens Rassweiler, Georg Salomon, Eduardo Solsona, Antonio Alcaraz, Teuvo T Tammela, Derek J Rosario, Francisco Gomez-Veiga, Göran Ahlgren, Fawzi Benzaghou, Bertrand Gaillac, Billy Amzal, Frans M J Debruyne, Gaëlle Fromont, Christian Gratzke, Mark Emberton
BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance...
December 19, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/28006059/the-kras-variant-and-cetuximab-response-in-head-and-neck-squamous-cell-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#13
Joanne B Weidhaas, Jonathan Harris, Dörthe Schaue, Allen M Chen, Robert Chin, Rita Axelrod, Adel K El-Naggar, Anurag K Singh, Thomas J Galloway, David Raben, Dian Wang, Chance Matthiesen, Vilija N Avizonis, Rafael R Manon, Omar Yumen, Phuc Felix Nguyen-Tan, Andy Trotti, Heath Skinner, Qiang Zhang, Robert L Ferris, David Sidransky, Christine H Chung
Importance: There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment. Objectives: To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based transforming growth factor β1 (TGF-β1)...
December 22, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/28001301/tumor-response-to-neoadjuvant-chemotherapy-predicts-long-term-survival-outcomes-in-patients-with-locoregionally-advanced-nasopharyngeal-carcinoma-a-secondary-analysis-of-a-randomized-phase-3-clinical-trial
#14
Hao Peng, Lei Chen, Wen-Fei Li, Rui Guo, Yan-Ping Mao, Yuan Zhang, Ying Guo, Ying Sun, Jun Ma
BACKGROUND: Tumor response to neoadjuvant chemotherapy using the regimen of cisplatin and 5-fluorouracil could define high-risk patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, the regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) appears to be more effective than the regimen of cisplatin and 5-fluorouracil. Therefore, one needs to redefine the high-risk subpopulation of patients receiving neoadjuvant chemotherapy with TPF. METHODS: A total of 231 patients from a randomized phase 3 trial with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC (except T3-T4N0 disease) who were receiving treatment with the TPF regimen were enrolled...
December 21, 2016: Cancer
https://www.readbyqxmd.com/read/27986369/updated-european-association-of-urology-guidelines-regarding-adjuvant-therapy-for-renal-cell-carcinoma
#15
Axel Bex, Laurence Albiges, Börje Ljungberg, Karim Bensalah, Saeed Dabestani, Rachel H Giles, Fabian Hofmann, Milan Hora, Markus A Kuczyk, Thomas B Lam, Lorenzo Marconi, Axel S Merseburger, Michael Staehler, Alessandro Volpe, Thomas Powles
: The European Association of Urology Renal Cell Carcinoma (RCC) guidelines panel updated their recommendation on adjuvant therapy in unfavourable, clinically nonmetastatic RCC following the recently reported results of a second randomised controlled phase 3 trial comparing 1-yr sunitinib to placebo for high-risk RCC after nephrectomy (S-TRAC). On the basis of conflicting results from the two available studies, the panel rated the quality of the evidence, the harm-to-benefit ratio, patient preferences, and costs...
December 13, 2016: European Urology
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#16
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27979383/atezolizumab-versus-docetaxel-in-patients-with-previously-treated-non-small-cell-lung-cancer-oak-a-phase-3-open-label-multicentre-randomised-controlled-trial
#17
Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara
BACKGROUND: Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer. METHODS: We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1...
December 12, 2016: Lancet
https://www.readbyqxmd.com/read/27978787/synthesis-and-antiproliferative-activity-of-new-pyrazolo-3-4-c-pyridines
#18
Efthymios-Spyridon Gavriil, Nikolaos Lougiakis, Nicole Pouli, Panagiotis Marakos, Alexios-Leandros Skaltsounis, Sangkil Nam, Richard Jove, David Horne, Katerina Gioti, Harris Pratsinis, Dimitris Kletsas, Roxane Tenta
BACKGROUND: Several pyrazolopyridines possess promising pharmacological activities, mainly attributed to their antagonistic nature towards the natural purines in many biological processes. Cytotoxicity and anticancer potential of this class of compounds is mainly related to induction of apoptotic cell death and inhibition of protein kinases. OBJECTIVES: This prompted us to design, synthesize and study the antiproliferative activity of a number of new 3,7-disubstituted pyrazolo[3,4-c] pyridines...
December 13, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/27968861/effects-of-induction-taxotere-platinum-and-fluorouracil-tpf-chemotherapy-in-patients-with-stage-iii-and-iva-b-nasopharyngeal-cancer-treated-with-concurrent-chemoradiation-therapy-final-results-of-two-parallel-phase-2-clinical-trials
#19
Lin Kong, Youwang Zhang, Chaosu Hu, Ye Guo, Jiade J Lu
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced nasopharyngeal cancer. The effect of induction chemotherapy plus CCRT in patients with this stage of disease is unclear. We therefore examined the long-term outcomes of the addition of induction chemotherapy (consisting of docetaxel, cisplatin, and fluorouracil [TPF]) to CCRT in patients with stage III and IVA/B nasopharyngeal cancer. METHODS: Between January, 2007, and July, 2011, we synchronously undertook two parallel phase 2 single-arm trials to evaluate the efficacy and toxicity of TPF-based induction chemotherapy...
October 2016: Lancet
https://www.readbyqxmd.com/read/27966237/assessment-of-pharmacokinetic-interaction-between-rilotumumab-and-epirubicin-cisplatin-and-capecitabine-ecx-in-a-phase-3-study-in-gastric-cancer
#20
Yilong Zhang, Mita Kuchimanchi, Min Zhu, Sameer Doshi, Tien Hoang, Sreeneeranj Kasichayanula
AIMS: Rilotumumab is a fully human monoclonal antibody investigated for the treatment of MET-positive gastric cancer. The aim of this study was to evaluate the potential pharmacokinetic (PK)-based drug-drug interaction (DDI) between rilotumumab and epirubicin (E), cisplatin(C) and capecitabine (X). METHODS: This was a Phase 3 double-blind, placebo-controlled study, in which rilotumumab, epirubicin and cisplatin were administered intravenously at 15 mg kg(-1) , 50 mg m(-2) , and 60 mg m(-2) Q3W, respectively, while capecitabine was given orally at 625 mg m(-2) twice daily...
November 7, 2016: British Journal of Clinical Pharmacology
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