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https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#1
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352490/oral-lichenoid-reaction-showing-multiple-ulcers-associated-with-anti-programmed-death-cell-receptor-1-treatment-a-report-of-two-cases-and-published-work-review
#2
Koya Obara, Mamiko Masuzawa, Yasuyuki Amoh
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29352431/analysis-and-comparison-of-the-8th-edition-american-joint-committee-on-cancer-ajcc-nodal-staging-system-in-cutaneous-and-oral-squamous-cell-cancer-of-the-head-and-neck
#3
Nikolaus Moeckelmann, Ardalan Ebrahimi, Richard Dirven, Jessica Liu, Tsu-Hui Hubert Low, Ruta Gupta, Bruce Ashford, Sydney Ch'ng, Carsten E Palme, Jonathan R Clark
BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016)...
January 19, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29351761/selective-serotonin-reuptake-inhibitor-use-and-breast-cancer-survival-a-population-based-cohort-study
#4
John Busby, Ken Mills, Shu-Dong Zhang, Fabio Giuseppe Liberante, Chris R Cardwell
BACKGROUND: Nearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Therefore, we used UK population-based data to more robustly investigate the association between SSRI use and cancer-specific mortality...
January 19, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29351058/development-and-characterization-of-an-in-vitro-model-for-radiation-induced-fibrosis
#5
Dhruv Kumar, Sreeya Yalamanchali, Jacob New, Sean Parsel, Natalie New, Andrew Holcomb, Sumedha Gunewardena, Ossama Tawfik, Chris Lominska, Bruce F Kimler, Shrikant Anant, Kiran Kakarala, Terance Tsue, Yelizaveta Shnayder, Kevin Sykes, Subhash Padhye, Sufi Mary Thomas
Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β)...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29351056/remediation-of-radiation-induced-cognitive-dysfunction-through-oral-administration-of-the-neuroprotective-compound-nsi-189
#6
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#7
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350471/variability-assessment-of-90-salivary-proteins-in-intra-day-and-inter-day-samples-from-healthy-donors-by-multiple-reaction-monitoring-mass-spectrometry
#8
Yung-Chin Hsiao, Lichieh Julie Chu, Yi-Ting Chen, Lang-Ming Chi, Kun-Yi Chien, Wei-Fan Chiang, Ya-Ting Chang, Szu-Fan Chen, Wei-Shun Wang, Yao-Ning Chuang, Shih-Yu Lin, Chih-Yen Chien, Kai-Ping Chang, Yu-Sun Chang, Jau-Song Yu
PURPOSE: Saliva is an attractive sample source for the biomarker-based testing of several diseases, especially oral cancer. Here, we sought to apply multiplexed LC-MRM-MS to precisely quantify 90 disease-related proteins and assess their intra- and inter-individual variability in saliva samples from healthy donors. EXPERIMENTAL DESIGN: We developed two multiplexed LC-MRM-MS assays for 122 surrogate peptides representing a set of disease-related proteins. Saliva samples were collected from 10 healthy volunteers at three different time points (Day 1 morning and afternoon, and Day 2 morning)...
January 19, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29350463/brim-p-a-phase-i-open-label-multicenter-dose-escalation-study-of-vemurafenib-in-pediatric-patients-with-surgically-incurable-braf-mutation-positive-melanoma
#9
Julia C Chisholm, Jozef Suvada, Ira J Dunkel, Michela Casanova, Weijiang Zhang, Natasha Ritchie, YounJeong Choi, Jane Park, Meghna Das Thakur, Stephen Simko, Nga Wan Rachel Tam, Andrea Ferrari
BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12-17 years with this tumor type (NCT01519323). PROCEDURE: Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29349773/progestin-only-and-combined-oral-contraceptives-and-receptor-defined-premenopausal-breast-cancer-risk-the-norwegian-women-and-cancer-study
#10
Marit Busund, Nora S Bugge, Tonje Braaten, Marit Waaseth, Charlotta Rylander, Eiliv Lund
Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of this study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort - The Norwegian Women and Cancer study (NOWAC)...
January 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29349624/combined-effects-of-aspirin-and-vitamin-d3-on-two-oscc-cell-lines-a-preliminary-study
#11
Ting-Ting Xiao, Xian Li, Jia-Li Feng, Yong Li
OBJECTIVES: We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells. RESULTS: Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis...
January 18, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#12
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348572/areca-nut-extracts-mobilize-calcium-and-release-pro-inflammatory-cytokines-from-various-immune-cells
#13
Malika Faouzi, Ram P Neupane, Jian Yang, Philip Williams, Reinhold Penner
Betel nut consumption has significant implications for the public health globally, as the wide-spread habit of Areca chewing throughout Asia and the Pacific is associated with a high prevalence of oral carcinoma and other diseases. Despite a clear causal association of betel nut chewing and oral mucosal diseases, the biological mechanisms that link Areca nut-contained molecules, inflammation and cancer remain underexplored. In this study we show that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various immune cell lines...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348495/preclinical-evaluation-of-antitumor-activity-of-the-proteasome-inhibitor-mln2238-ixazomib-in-hepatocellular-carcinoma-cells
#14
Giuseppa Augello, Martina Modica, Antonina Azzolina, Roberto Puleio, Giovanni Cassata, Maria Rita Emma, Caterina Di Sano, Antonella Cusimano, Giuseppe Montalto, Melchiorre Cervello
Hepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348123/rash-associated-with-rivaroxaban-use
#15
Kelly M Rudd, Narmadha Panneerselvam, Anush Patel
PURPOSE: A case of a patient who developed a hypersensitivity reaction to rivaroxaban in the form of a diffuse, exanthematous rash is reported. SUMMARY: After starting rivaroxaban for treatment of cancer-associated deep vein thrombosis (DVT) with pulmonary embolism (PE), a 69-year-old Caucasian woman arrived at an oncology clinic with a diffuse, exanthematous (morbilliform) rash on her neck and torso, spreading to her upper and lower extremities. She reported that the symptoms started to develop about 48 hours after transitioning from subcutaneous enoxaparin to oral rivaroxaban...
January 18, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#16
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346580/smoking-sex-and-non-small-cell-lung-cancer-steroid-hormone-receptors-in-tumor-tissue-s0424
#17
Ting-Yuan David Cheng, Amy K Darke, Mary W Redman, Gary R Zirpoli, Warren Davis, Rochelle Payne Ondracek, Wiam Bshara, Angela R Omilian, Robert Kratzke, Mary E Reid, Julian R Molina, Jill M Kolesar, Yuhchyau Chen, Robert M MacRae, James Moon, Philip Mack, David R Gandara, Karen Kelly, Regina M Santella, Kathy S Albain, Christine B Ambrosone
Background: To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods: Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)...
January 13, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29346528/a-novel-stromal-lncrna-signature-reprograms-fibroblasts-to-promote-the-growth-of-oral-squamous-cell-carcinoma-via-lncrna-caf-interleukin-33
#18
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, Xiaofeng Huang, Qingang Hu, Hui Wang, Yuxian Song, Yanhong Ni, Yayi Hou
Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune cells in the tumor microenvironment (TME). CAFs interact with cancer cells to promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate cell growth, apoptosis, and metastasis of cancer cells, but their role in stromal cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29346467/modification-of-the-associations-between-duration-of-oral-contraceptive-use-and-ovarian-endometrial-breast-and-colorectal-cancers
#19
Kara A Michels, Ruth M Pfeiffer, Louise A Brinton, Britton Trabert
Importance: Although oral contraceptive (OC) use is common, the influence of OC use on carcinogenesis is not fully understood. A recent Agency for Healthcare Research and Quality report identified a need to understand the consistency of OC use and cancer associations across subpopulations, including smokers and obese women. Objective: To determine whether associations between duration of OC use and risk of specific cancers were modified by lifestyle characteristics...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346386/histological-subtypes-of-mouse-mammary-tumors-reveal-conserved-relationships-to-human-cancers
#20
Daniel P Hollern, Matthew R Swiatnicki, Eran R Andrechek
Human breast cancer has been characterized by extensive transcriptional heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse models of breast cancer also have heterogeneous transcriptomes and we noted that specific histological subtypes were associated with particular subsets. We hypothesized that unique sets of genes define each tumor histological type across mouse models of breast cancer. Using mouse models that contained both gene expression data and expert pathologist classification of tumor histology on a sample by sample basis, we predicted and validated gene expression signatures for Papillary, EMT, Microacinar and other histological subtypes...
January 2018: PLoS Genetics
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