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https://www.readbyqxmd.com/read/29915719/past-present-and-future-of-rituximab-the-world-s-first-oncology-monoclonal-antibody-therapy
#1
REVIEW
Timothy M Pierpont, Candice B Limper, Kristy L Richards
Rituximab is a chimeric mouse/human monoclonal antibody (mAb) therapy with binding specificity to CD20. It was the first therapeutic antibody approved for oncology patients and was the top-selling oncology drug for nearly a decade with sales reaching $8.58 billion in 2016. Since its initial approval in 1997, it has improved outcomes in all B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. Despite widespread use, most mechanistic data have been gathered from in vitro studies while the roles of the various response mechanisms in humans are still largely undetermined...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29902298/prevalence-of-pdl1-amplification-and-preliminary-response-to-immune-checkpoint-blockade-in-solid-tumors
#2
Aaron M Goodman, David Piccioni, Shumei Kato, Amélie Boichard, Huan-You Wang, Garrett Frampton, Scott M Lippman, Caitlin Connelly, David Fabrizio, Vincent Miller, Jason K Sicklick, Razelle Kurzrock
Importance: Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors. Objectives: To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors...
June 14, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29899086/modulation-of-cellular-cpg-dna-methylation-by-kaposi-s-sarcoma-associated-herpesvirus
#3
Guy Journo, Carmel Tushinsky, Asia Shterngas, Nir Avital, Yonatan Eran, Marcela Viviana Karpuj, Milana Frenkel-Morgenstern, Meir Shamay
Kaposi's sarcoma associated herpesvirus (KSHV, HHV-8) is a gamma herpesvirus associated with several human malignancies. DNA methylation at CpG dinucleotides is an epigenetic mark dysregulated in many cancer types, and in KSHV infected cells. Several previous studies have analyzed in detail the CpG methylation of the KSHV episomal genomes, but little is known about the impact of KSHV on the human genome. Our knowledge of cellular CpG methylation in the context of KSHV infection is currently limited to four hyper-methylated human gene promoters...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29891112/molecular-analysis-in-liquid-biopsies-for-diagnostics-of-primary-central-nervous-system-lymphoma-review-of-literature-and-future-opportunities
#4
REVIEW
Laura S Hiemcke-Jiwa, Roos J Leguit, Tom J Snijders, N Mehdi Jiwa, Jonas J W Kuiper, Roel A de Weger, Monique C Minnema, Manon M H Huibers
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with a poor prognosis, for which accurate and timely diagnosis is of utmost importance. Unfortunately, diagnosis of PCNSL can be challenging and a brain biopsy (gold standard for diagnosis) is an invasive procedure with the risk of major complications. Thus, there is an urgent need for an alternative strategy to diagnose and monitor these lymphomas. Currently, liquid biopsies from cerebrospinal fluid (CSF) are used for cytomorphologic and flow cytometric analysis...
July 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29890998/clinicopathologic-implication-of-microrna-197-in-diffuse-large-b-cell-lymphoma
#5
Jeong Mi Yang, Ji-Young Jang, Yoon Kyung Jeon, Jin Ho Paik
BACKGROUND: Diffuse large B cell lymphoma (DLBCL) contains heterogeneous subtypes with various molecular dysregulation at the gene, protein and microRNA levels. Compared with the GCB subtype, the non-germinal center B-like (non-GCB)/activated B cell-like (ABC) subtype exhibits frequent progression despite standard immunochemotherapy. We aimed to investigate the effects of miR-197 on the progression and chemosensitivity of DLBCL with respect to the GCB and non-GCB/ABC subtypes. METHODS: To screen distinctively expressed microRNAs, microRNA expression patterns were analyzed in 10 DLBCL cases by microarray chip assays...
June 11, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29885057/genetic-instability-and-recurrent-myc-amplification-in-alk-translocated-nsclc-a-central-role-of-tp53-mutations
#6
Christina Alidousty, Till Baar, Luciano G Martelotto, Carina Heydt, Svenja Wagener, Jana Fassunke, Nicolai Duerbaum, Andreas H Scheel, Sandra Frank, Barbara Holz, Elke Binot, Anna Kron, Sabine Merkelbach-Bruse, Michaela A Ihle, Jürgen Wolf, Reinhard Buettner, Anne Maria Schultheis
The anaplastic lymphoma kinase (ALK) rearrangement defines a distinct molecular subtype of non-small cell lung cancer (NSCLC). Despite the excellent initial efficacy of ALK inhibitors in patients with ALK+ lung cancer, resistance occurs almost inevitably. To date, there is no reliable biomarker allowing the identification of patients at higher risk of relapse. Here, we analysed a subset of 53 ALK+ tumours with and without TP53 mutation and ALK+ NSCLC cell lines by NanoString nCounter technology. We found that the co-occurrence of early TP53 mutations in ALK+ NSCLC can lead to chromosomal instability: 24% of TP53-mutated patients showed amplifications of known cancer genes such as MYC (14%), CCND1 (10%), TERT (5%), BIRC2 (5%), ORAOV1 (5%) and YAP1 (5%)...
June 9, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29881714/mechanisms-and-therapy-for-cancer-metastasis-to-the-brain
#7
REVIEW
Federica Franchino, Roberta Rudà, Riccardo Soffietti
Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60-70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29872358/clean-colorectum-at-diagnostic-colonoscopy-subsequent-detection-of-extracolonic-malignancies-by-plasma-protein-biomarkers
#8
Michael Wilhelmsen, Ib J Christensen, Lars N Jørgensen, Mogens R Madsen, Jesper Vilandt, Thore Hillig, Michael Klærke, Knud T Nielsen, Søren Laurberg, Susan Gawel, Xiaoping Yang, Gerard Davis, Anne Meike Heijboer, Frans Martens, Hans J Nielsen
Introduction: Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases. Methods: EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers...
2018: Biomarkers in Cancer
https://www.readbyqxmd.com/read/29858404/microrna-17-and-the-prognosis-of-human-carcinomas-a-systematic-review-and-meta-analysis
#9
Chengzhi Huang, Mengya Yu, Xueqing Yao
OBJECTIVE: Although the role of microRNA-17 (miR-17) has been identified as a tumour biomarker in various studies, its prognostic value in cancers remains unclear. Therefore, we performed a systematic review and meta-analysis to analyse and summarise the relationship between the miR-17 status and clinical outcome in a variety of human cancers. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science and Embase from the first year of records to 15 May 2017...
May 31, 2018: BMJ Open
https://www.readbyqxmd.com/read/29844839/evaluation-of-latent-membrane-protein-1-and-microrna-155-for-the-prognostic-prediction-of-diffuse-large-b-cell-lymphoma
#10
Xue Wu, Fei Wang, Yuan Li, Xiyong Wang, Ping Liu, Haijun Zhang, Zheng Ge, Xiaoping Zhang, Chong Gao, Baoan Chen
Diffuse large B cell lymphoma (DLBCL) has previously been demonstrated to contribute to the mortality of lymphoma with various aggressive features. The prognostic role of the biomarkers latent membrane protein (LMP) 1 and microRNA-(miR)-155 in DLBCL remain controversial. The present study primarily aimed to assess the effect of LMP1 and miR-155 on the survival of DLBCL patients, and additionally evaluate the clinical features to observe their influence on outcomes, compared with previous studies. Formalin-fixed and paraffin-embedded samples were collected from our center between May 2010 and December 2011...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29844818/b-cell-lymphoma-2-is-associated-with-advanced-tumor-grade-and-clinical-stage-and-reduced-overall-survival-in-young-chinese-patients-with-colorectal-carcinoma
#11
Jiasheng Wang, Gan He, Qiang Yang, Lian Bai, Bin Jian, Qugang Li, Zhongfu Li
The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29807272/over-expression-of-circulating-mir-155-predicts-prognosis-in-diffuse-large-b-cell-lymphoma
#12
Mohammad Ahmadvand, Mahsa Eskandari, Hossein Pashaiefar, Marjan Yaghmaie, Saba Manoochehrabadi, Golnaz Khakpour, Fatemeh Sheikhsaran, Mostafa Montazer Zohour
INTRODUCTION: The expression patterns of microRNAs in plasma are involved in potential biomarkers for several diseases. The goal of this study was to explore the expression level of miR-155 in diffuse large B-cell lymphoma (DLBCL) and its clinical significance. MATERIALS AND METHODS: We used qRT-PCR to assess the peripheral blood plasma of 40 DLBCL patients for the expression of miRNA-155. The median of miR-155 expression divided the DLBCL patients into miR-155 low-expression (miR-155low ) and miR-155 high-expression (miR-155high ) groups...
May 21, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29805631/identification-of-circulating-tumor-cells-with-eml4-alk-translocation-using-fluorescence-in-situ-hybridization-in-advanced-alk-positive-patients-with-lung-cancer
#13
Young Hun Kim, Eunjoo Hwang, Hye Seon Lee, Ji-Hyun Uh, Myoung Shin Kim, Byung Hee Jeon
Analysis of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) is considered to be a useful tool when considering predictive biomarker detection for evaluating eligibility for targeted therapy. It is not always possible to perform a tumor biopsy in patients. Isolation and culturing of circulating tumor cells (CTCs) may be an alternative to tumor biopsies for the diagnosis of ALK rearrangement. Blood was collected from 22 patients with NSCLC harboring ALK rearrangement and was divided into two groups: One for immunofluorescence staining and the other for culture...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29805607/upregulation-of-let-7f-5p-promotes-chemotherapeutic-resistance-in-colorectal-cancer-by-directly-repressing-several-pro-apoptotic-proteins
#14
Yateng Tie, Chong Chen, Yanli Yang, Zhen Qian, Hang Yuan, Huan Wang, Haili Tang, Yao Peng, Xilin Du, Bin Liu
Colorectal cancer (CRC) is one of the most frequently occurring primary malignant tumors worldwide. Chemotherapeutic resistance is a major clinical problem in the treatment of CRC. Therefore, it is of great importance to investigate novel biomarkers that may predict chemoresistance and facilitate the development of individualized treatment for patients with CRC. The present study reported that let-7f-5p expression was elevated in chemotherapy-resistant CRC tissues compared with chemotherapy-sensitive tissues...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29805590/suppression-of-tumor-cell-proliferation-and-migration-by-human-umbilical-cord-mesenchymal-stem-cells-a-possible-role-for-apoptosis-and-wnt-signaling
#15
Yin Yuan, Chang Zhou, Xuan Chen, Changli Tao, Huiqing Cheng, Xin Lu
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent potential therapeutic tools for solid tumors. However, there are numerous inconsistent results regarding the effects of hUCMSCs on tumors, and the mechanisms underlying this remain poorly understood. The present study further examined this controversial issue by analyzing the molecular mechanisms of the inhibitory effects of hUCMSCs on the proliferation and migration of the human lung cancer A549 cell line and the human hepatocellular carcinoma (HCC) BEL7402 cell line in vitro ...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29803640/loss-of-5-hydroxymethylcytosine-is-an-epigenetic-biomarker-in-cutaneous-t-cell-lymphoma
#16
Lei Qiu, Fengjie Liu, Shengguo Yi, Xueying Li, Xiaoqing Liu, Cheng Xiao, Christine Guo Lian, Ping Tu, Yang Wang
DNA hydroxymethylation at the 5 position of cytosine (5-hmC) is a product of the ten-eleven translocation (TET) family of DNA hydroxylases. Accumulating evidence shows that loss of 5-hmC is critical for various biological and pathological processes. However, its level in cutaneous T cell lymphoma remains largely unknown. Here we report that the loss of 5-hmC is an epigenetic hallmark of cutaneous T cell lymphoma (CTCL), with diagnostic and prognostic implications. Immunohistochemistry staining on 90 mycosis fungoides (MF) cases demonstrated a significant decrease of 5-hmC staining in CD4+ T cells in patch and tumor stages, especially in MF-LCT, compared to benign inflammatory dermatoses...
May 24, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29794791/oncogenomic-analysis-identifies-novel-biomarkers-for-tumor-stage-mycosis-fungoides
#17
Zhengbang Dong, Xiaomei Zhu, Yang Li, Lu Gan, Hao Chen, Wei Zhang, Jianfang Sun
Patients with mycosis fungoides (MF) developing tumors or extracutaneous lesions usually have a poor prognosis with no cure has so far been available. To identify potential novel biomarkers for MF at the tumor stage, a genomic mapping of 41 cutaneous lymphoma biopsies was used to explore for significant genes.The gene expression profiling datasets of MF were obtained from Gene Expression Omnibus database (GEO). Gene modules were simulated using Weighted Gene Co-expression Network Analysis (WGCNA) and the top soft-connected genes (hub genes) were filtrated with a threshold (0...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29789628/targetable-vulnerabilities-in-t-and-nk-cell-lymphomas-identified-through-preclinical-models
#18
Samuel Y Ng, Noriaki Yoshida, Amanda L Christie, Mahmoud Ghandi, Neekesh V Dharia, Joshua Dempster, Mark Murakami, Kay Shigemori, Sara N Morrow, Alexandria Van Scoyk, Nicolas A Cordero, Kristen E Stevenson, Maneka Puligandla, Brian Haas, Christopher Lo, Robin Meyers, Galen Gao, Andrew Cherniack, Abner Louissaint, Valentina Nardi, Aaron R Thorner, Henry Long, Xintao Qiu, Elizabeth A Morgan, David M Dorfman, Danilo Fiore, Julie Jang, Alan L Epstein, Ahmet Dogan, Yanming Zhang, Steven M Horwitz, Eric D Jacobsen, Solimar Santiago, Jian-Guo Ren, Vincent Guerlavais, D Allen Annis, Manuel Aivado, Mansoor N Saleh, Amitkumar Mehta, Aviad Tsherniak, David Root, Francisca Vazquez, William C Hahn, Giorgio Inghirami, Jon C Aster, David M Weinstock, Raphael Koch
T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs)...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29780646/incorporating-cystatin-c-to-predict-methotrexate-elimination-in-patients-with-cns-lymphoma-and-suspicious-renal-function
#19
Jason N Barreto, Allison L McClanahan, Andrew D Rule, Carrie A Thompson, Erin Frazee
High-dose methotrexate (MTX; ≥1 g/m2 ) is a renally eliminated and nephrotoxic first-line therapy for central nervous system (CNS) lymphoma. Creatinine-based estimation of renal function is the recommended approach to dosing MTX in these cases, but nonrenal determinants of creatinine production and elimination in cancer patients such as malnutrition and cachexia lead to overestimation of glomerular filtration rate (GFR) by this method and a heightened risk for drug toxicity. Serum cystatin C is one of the first readily available, relatively inexpensive, endogenous biomarkers to emerge as a practical adjunct to creatinine for estimation of renal function for drug dosing...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#20
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
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