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https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#1
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547805/quality-and-impact-of-eviq-cancer-treatments-online-www-eviq-org-au-the-medical-oncologist-s-perspective
#2
Lydia P Y Loke, Tina Y T Chen, Craig R Lewis, Robyn L Ward, Shelley A Rushton, Jeremy D Shapiro
INTRODUCTION: eviQ Cancer Treatments Online is a free, web-based resource providing access to over 600 evidence-based treatment protocols in medical oncology, radiation oncology, hematology and cancer genetics. With over 60 000 registrants from 148 countries, eviQ is widely used by cancer clinicians globally. The aim of this study was to examine the perceived quality of eviQ by Australian medical oncologists, the impact it had on their knowledge and practice, and the effect it had on their patients...
May 25, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28536803/prospective-multicenter-phase-ii-study-of-gemcitabine-plus-cisplatin-in-patients-with-unresectable-gallbladder-cancer
#3
Yoshiki Hirooka, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Koji Nonogaki, Akira Kanamori, Takanori Hirai, Hiroki Uchida, Osamu Shirai, Hideki Ishikawa, Hidemi Goto
PURPOSE: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC). METHODS: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m(2)) and cisplatin (25 mg/m(2)) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]...
May 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28533175/dendrimer-encapsulated-and-conjugated-delivery-of-berberine-a-novel-approach-mitigating-toxicity-and-improving-in-vivo-pharmacokinetics
#4
Lokesh Gupta, Ashok Kumar Sharma, Avinash Gothwal, Mohammed Shahid Khan, Mahaveer Prasad Khinchi, Arem Qayum, Shashank Kumar Singh, Umesh Gupta
Berberine (BBR) is a nitrogenous cyclic natural alkaloid with potential anticancer activity. However it has been less explored due to its poor pharmacokinetic profile. Dendrimers (e.g. PAMAM) have promising potential to deliver anticancer drugs/bio-actives because of their well-defined architecture, monodispersity and tailor-made surface functionality. In the present study it was attempted to deliver berberine through G4 PAMAM dendrimers by conjugation (BPC) as well as encapsulation (BPE) approach. The developed encapsulated and conjugated berberine formulations were found to have size in the approximate range of 100-200nm while zeta potential was almost same as PAMAM G4 dendrimer...
May 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28529947/immune-checkpoint-blockade-for-hematologic-malignancies-a-review
#5
REVIEW
Matthew J Pianko, Yuzhou Liu, Srishti Bagchi, Alexander M Lesokhin
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28529747/amrubicin-monotherapy-may-be-an-effective-second-line-treatment-for-patients-with-large-cell-neuroendocrine-carcinoma-or-high-grade-non-small-cell-neuroendocrine-carcinoma
#6
Norimitsu Kasahara, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Akira Ono, Tetsuhiko Taira, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Keita Mori, Reiko Watanabe, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Toshiaki Takahashi
There is no standard chemotherapy for pulmonary large-cell neuroendocrine carcinoma (LCNEC) and this type of cancer is difficult to diagnose using biopsy specimens. At the Shizuoka Cancer Center, when small biopsy specimens are used, they are diagnosed as high-grade non-small-cell neuroendocrine carcinoma (HNSCNEC) and the patients are treated according to the small-cell lung cancer (SCLC) guidelines. Amrubicin is an effective second-line treatment for patients with SCLC, although it remains unclear whether amrubicin monotherapy is effective for patients with LCNEC or HNSCNEC...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28518151/disulfiram-copper-selectively-eradicates-aml-leukemia-stem-cells-in-vitro-and-in-vivo-by-simultaneous-induction-of-ros-jnk-and-inhibition-of-nf-%C3%AE%C2%BAb-and-nrf2
#7
Bing Xu, Shiyun Wang, Rongwei Li, Kai Chen, Lingli He, Manman Deng, Vinodh Kannappan, Jie Zha, Huijuan Dong, Weiguang Wang
Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28507111/real-life-assessment-of-the-safety-and-effectiveness-of-the-new-tablet-and-intravenous-formulations-of-posaconazole-in-the-prophylaxis-of-invasive-fungal-infections-analysis-of-343-courses
#8
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
BACKGROUND: Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infection (IFI) in patients with hematologic malignancy (HM). Delayed release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis in patients with HM. METHODS: A retrospective cohort of all consecutive adult inpatients with HM who received ≥3 days of posaconazole as tablet or intravenous from 12/1/2013-12/31/2015 for primary IFI prophylaxis at MD Anderson Cancer center...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28498800/locally-applied-5-fluorouracil-loaded-slow-release-patch-prevents-pancreatic-cancer-growth-in-an-orthotopic-mouse-model
#9
In Kyong Shim, Hye-Jin Yi, Hee-Gyeong Yi, Chan Mi Lee, Yu Na Lee, Yeong-Jin Choi, Seong-Yun Jeong, Eunsung Jun, Robert M Hoffman, Dong-Woo Cho, Song Cheol Kim
To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30...
April 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28493308/north-central-cancer-treatment-group-n0543-alliance-a-phase-2-trial-of-pharmacogenetic-based-dosing-of-irinotecan-oxaliplatin-and-capecitabine-as-first-line-therapy-for-patients-with-advanced-small-bowel-adenocarcinoma
#10
Robert R McWilliams, Nathan R Foster, Michelle R Mahoney, Thomas C Smyrk, Joseph A Murray, Matthew M Ames, L Elise Horvath, Daniel J Schneider, Timothy J Hobday, Aminah Jatoi, Jeffrey P Meyers, Matthew P Goetz
BACKGROUND: Oxaliplatin in combination with either 5-fluorouracil or capecitabine is commonly used as first-line therapy for patients with small bowel adenocarcinoma. The addition of irinotecan improves survival in other gastrointestinal tumors but at the cost of hematologic toxicity. The authors performed a phase 2 cooperative group study (North Central Cancer Treatment Group N0543, Alliance) using genotype-dosed capecitabine, irinotecan, and oxaliplatin (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would improve outcomes; and 2) whether UGT1A1 genotype-based dosing could optimize tolerability...
May 10, 2017: Cancer
https://www.readbyqxmd.com/read/28489985/preclinical-evaluation-of-the-imipridone-family-analogues-of-clinical-stage-anti-cancer-small-molecule-onc201-reveals-potent-anti-cancer-effects-of-onc212
#11
Jessica Wagner, Christina Leah Kline, Marie D Ralff, Avital Lev, Amriti Lulla, Lanlan Zhou, Gary L Olson, Bhaskara Rao Nallaganchu, Cyril H Benes, Joshua E Allen, Varun V Prabhu, Martin Stogniew, Wolfgang Oster, Wafik S El-Deiry
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives...
May 10, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28488730/octreotide-associated-neutropenia
#12
Stacy S Tse, Troy Kish
Drug-induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analogue that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudo-obstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug...
May 10, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28486692/early-results-of-a-randomized-two-by-two-factorial-phase-ii-trial-comparing-neoadjuvant-chemotherapy-with-two-and-four-courses-of-cisplatin-s-1-and-docetaxel-cisplatin-s-1-as-neoadjuvant-chemotherapy-for-locally-advanced-gastric-cancer
#13
T Aoyama, K Nishikawa, K Fujitani, K Tanabe, S Ito, T Matsui, A Miki, H Nemoto, K Sakamaki, T Fukunaga, Y Kimura, N Hirabayashi, T Yoshikawa
Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received 2 or 4 courses of cisplatin (60 mg/m 2 at day 8)/S-1 (80 mg/m 2 for 21 days with 1 week rest) or docetaxel (40 mg/m 2 at day 1)/cisplatin (60 mg/m 2 at day 1)/S-1 (80 mg/m 2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy...
May 9, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28482702/an-introduction-to-biosimilar-cancer-therapeutics-definitions-rationale-for-development-and-regulatory-requirements
#14
Christian Buske, Michinori Ogura, Hyuk-Chan Kwon, Sang Wook Yoon
Monoclonal antibodies and other biologic drugs play important roles in the treatment of various hematological malignancies and solid tumors. However, such drugs are intrinsically more expensive to develop than small molecules and their clinical benefits are often accompanied by challenges relating to affordability and access. Patent expiry for 'originator' biologics is providing opportunities for a new generation of biosimilar drugs, potentially capable of relieving pressure on healthcare budgets. This article discusses key characteristics of biosimilars, distinguishes them from generics and noncomparable biologics and outlines the robust regulatory requirements that must be followed to establish biosimilarity with a reference product...
May 2017: Future Oncology
https://www.readbyqxmd.com/read/28477160/current-status-of-biosimilars-in-oncology
#15
REVIEW
Luis H Camacho
Four medicinal cancer biological blockbusters will end their patent lifespan by 2020. It is estimated that the total market for cancer biologicals will reach approximately US$68 billion at that time. Approximately 20 biosimilars have entered the European market since the launch of the original approval guidelines in 2005, and four biosimilars have been approved in the USA since 2015. Data from European countries with the highest market entrance of biosimilars suggest that the incorporation of biosimilars into healthcare systems worldwide may result in a 30-45% cost savings...
June 2017: Drugs
https://www.readbyqxmd.com/read/28471248/natural-killer-cells-as-a-promising-tool-to-tackle-cancer-a-review-of-sources-methodologies-and-potentials
#16
Senthilkumar Preethy, Vidyasagar Devaprasad Dedeepiya, Rajappa Senthilkumar, Mathaiyan Rajmohan, Ramalingam Karthick, Hiroshi Terunuma, Samuel J K Abraham
Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies...
May 4, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28471199/-zinc-modified-nanotransporter-for-target-drug-therapy-of-breast-cancer
#17
S Skaličková, M Gargulák, M Löffelmann, B Ruttkay-Nedecký, M Kepinská, T Parák, R Kizek
BACKGROUND: In the centre of nanomedical interest stands the nanotechnological modification of anthracycline antibiotics, which are often used in antitumor treatment of hematological malignancies and solid tumors. Chitosan nanoparticles are gaining more attention in the field of targeted transport of drugs because of their stability, low toxicity and simple preparation. The main objective of the project, was the design of chitosan nanotransporter of anthracycline antibiotics with zinc modified surface, for a specific interaction with metallothionein...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28466376/phase-i-study-of-nedaplatin-a-platinum-based-antineoplastic-drug-combined-with-nab-paclitaxel-in-patients-with-advanced-squamous-non-small-cell-lung-cancer
#18
Satoshi Igawa, Sakiko Otani, Yoshiro Nakahara, Shinichiro Ryuge, Yasuhiro Hiyoshi, Tomoya Fukui, Hisashi Mitsufuji, Masaru Kubota, Masato Katagiri, Yuichi Sato, Jiichiro Sasaki, Noriyuki Masuda
Background This study was designed to determine the recommended dose of a combination of nedaplatin (NED) and nab-paclitaxel (nab-PTX) in chemotherapy-naive patients with advanced squamous non-small-cell lung cancer (NSCLC). Methods Patients received escalating doses of NED on day 1 and nab-PTX on days 1, 8, and 15 every 4 weeks by an intravenous infusion for up to six cycles. Results A dose of 100 mg/m(2) NED and 100 mg/m(2) nab-PTX was determined to be the recommended dose for patients with advanced squamous NSCLC...
May 2, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28459941/german-adjuvant-intergroup-node-positive-study-gain-a-phase-iii-trial-comparing-two-dose-dense-regimens-iddepc-vs-ddec-pwx-in-high-risk-early-breast-cancer-patients
#19
V Moebus, G von Minckwitz, C Jackisch, H-J Lück, A Schneeweiss, H Tesch, D Elling, N Harbeck, B Conrad, T Fehm, J Huober, V Müller, I Bauerfeind, A du Bois, S Loibl, V Nekljudova, M Untch, C Thomssen
Background: Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The GAIN trial aimed at optimizing intense dose-dense (idd) strategies by evaluating drug combinations and the addition of capecitabine. Patients and Methods: Women (aged 18 and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150mg/m 2 , paclitaxel (P) 225mg/m 2 and cyclophosphamide (C) 2500mg/m 2 (reduced to 2000mg/m 2 after recruitment of 1200 patients) q2w intravenously (i...
April 28, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28441374/fever-in-patients-with-cancer
#20
Yanina Pasikhova, Steven Ludlow, Aliyah Baluch
BACKGROUND: The definition of fever is flexible and depends on the clinical context. Fever is frequently observed in patients with cancer. METHODS: Infectious and noninfectious causes of fever in patients with various oncological and hematological malignancies and the usefulness of biomarkers are discussed. RESULTS: To treat patients in a timely manner and to minimize morbidity and mortality, it is paramount that health care professionals determine the cause of fever...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
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