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Cancer therapy response monitoring

Elisa Caiola, Francesca Falcetta, Silvia Giordano, Mirko Marabese, Marina C Garassino, Massimo Broggini, Roberta Pastorelli, Laura Brunelli
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with multiple different oncogenic mutations. Approximately 25-30% of NSCLC patients present KRAS mutations, which confer poor prognosis and high risk of tumor recurrence. About half of NSCLCs with activating KRAS lesions also have deletions or inactivating mutations in the serine/threonine kinase 11 (LKB1) gene. Loss of LKB1 on a KRAS-mutant background may represent a significant source of heterogeneity contributing to poor response to therapy...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Hye-Yeong Kim, Ran Li, Thomas S C Ng, Gabriel Courties, Christopher Blake Rodell, Mark Prytyskach, Rainer H Kohler, Mikael Pittet, Matthias Nahrendorf, Ralph Weissleder, Miles A Miller
Tumor associated macrophages (TAMs) are widely implicated in cancer progression, and TAM levels can influence drug responses, particularly to immunotherapy and nanomedicines. However, it has been difficult to quantify total TAM numbers and their dynamic spatiotemporal distribution in a non-invasive and translationally relevant manner. Here, we address this need by developing a pharmacokinetically optimized, 64Cu-labeled polyglucose nanoparticle (Macrin) for quantitative positron emission tomography (PET) imaging of macrophages in tumors...
December 3, 2018: ACS Nano
Colin G Buss, Jaideep S Dudani, Reid T K Akana, Heather E Fleming, Sangeeta N Bhatia
BACKGROUND: Respiratory tract infections represent a significant public health risk, and timely and accurate detection of bacterial infections facilitates rapid therapeutic intervention. Furthermore, monitoring the progression of infections after intervention enables 'course correction' in cases where initial treatments are ineffective, avoiding unnecessary drug dosing that can contribute to antibiotic resistance. However, current diagnostic and monitoring techniques rely on non-specific or slow readouts, such as radiographic imaging and sputum cultures, which fail to specifically identify bacterial infections and take several days to identify optimal antibiotic treatments...
November 26, 2018: EBioMedicine
M Lasalvia, G Perna, L Manti, J Rasero, S Stramaglia, V Capozzi
PURPOSE: Protontherapy has been recently proposed as a radiotherapy form for breast cancer treatment in view of its potentially decreased normal-tissue toxicity compared with conventional photon-based radiotherapy. However, the risks for the healthy tissue cannot be completely eliminated. In the present study, the suitability of Raman spectroscopy to monitor the radiosensitivity of normal cells exposed to clinical proton beam was investigated. MATERIALS AND METHODS: MCF10A normal human breast cells were irradiated at two different proton doses: 0...
November 29, 2018: International Journal of Radiation Biology
Junpei Iizuka
Radium-223 is a first-in-class targeted alpha therapy indicated for treating bone metastases from metastatic castration-resistant prostate cancer (mCRPC) without visceral metastases. Imaging plays an important role in the selection of patients eligible for radium-223 therapy. In the ALSYMPCA trial protocol, bone scintigraphy was used to detect lesions, essentially osteoblastic bone metastases, whereas computed tomography (CT) was used to exclude visceral metastases, with no interim imaging until treatment completion unless clinically indicated...
November 2018: Asia-Pacific Journal of Clinical Oncology
Jose M Ayuso, Amani Gillette, Karina Lugo-Cintrón, Suehelay Acevedo-Acevedo, Ismael Gomez, Molly Morgan, Tiffany Heaster, Kari B Wisinski, Sean P Palecek, Melissa C Skala, David J Beebe
BACKGROUND: Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer. During DCIS, tumor cells remain inside the mammary duct, growing under a microenvironment characterized by hypoxia, nutrient starvation, and waste product accumulation; this harsh microenvironment promotes genomic instability and eventually cell invasion. However, there is a lack of biomarkers to predict what patients will transition to a more invasive tumor or how DCIS cells manage to survive in this harsh microenvironment...
October 25, 2018: EBioMedicine
Yeoun Jin Kim, Steve M Sweet, Jarrett D Egertson, Andrew J Sedgewick, Sunghee Woo, Wei-Li Liao, Gennifer E Merrihew, Brian C Searle, Charlie Vaske, Robert Heaton, Michael J MacCoss, Todd Hembrough
Mass spectrometry-based protein quantitation is currently used to measure therapeutically relevant protein biomarkers in CAP/CLIA setting to predict likely responses of known therapies. Selected reaction monitoring (SRM) is the method of choice due to its outstanding analytical performance. However, data-independent acquisition (DIA) is now emerging as a proteome-scale clinical assay. We evaluated the ability of DIA to profile the patient-specific proteomes of sample-limited tumor biopsies and to quantify proteins of interest in a targeted fashion using formalin-fixed, paraffin-embedded (FFPE) tumor biopsies (n=12) selected from our clinical laboratory...
November 27, 2018: Journal of Proteome Research
Ramanathan Vaidyanathan, Ren Hao Soon, Pan Zhang, Kuan Jiang, Chwee Teck Lim
Technological advancements in research on circulating biomarkers from patient derived blood have enabled a less invasive means of diagnosing non-hematologic cancers. Considered a more practical way of real-time patient monitoring than traditional tumor biopsy, liquid biopsy markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) and exosomes certainly have the potential to change the dynamics of cancer management and treatment. Liquid biopsy essentially presents a snapshot of the disease from the primary and/or distant tumor locations and can be utilized for repeated sampling of tumor markers to adjust therapy according to the patient's response to treatment, also known as personalized or precision treatment...
November 27, 2018: Lab on a Chip
Jeanne M Quinn, Molly M Greenwade, Marguerite L Palisoul, Gregory Opara, Katina Massad, Lei Guo, Peinan Zhao, Hollie Beck-Noia, Ian S Hagemann, Andrea R Hagemann, Carolyn K McCourt, Premal H Thaker, Matthew A Powell, David G Mutch, Katherine C Fuh
Ovarian cancer (OvCa), one of the deadliest malignancies in female cancer patients, is characterized by recurrence and poor response to cytotoxic chemotherapies. Fewer than 30% of patients with resistant disease will respond to additional chemotherapy treatments. This study aims to determine whether and how inhibition of the receptor tyrosine kinase AXL can restore sensitivity to front-line platinum and taxane therapy in OvCa. AXL staining was quantified in a patient tissue microarray and correlated with chemoresponse of patients...
November 26, 2018: Molecular Cancer Therapeutics
Chiara Molinari, Giorgia Marisi, Alessandro Passardi, Laura Matteucci, Giulia De Maio, Paola Ulivi
High inter-patient variability and high spatial heterogeneity are features of colorectal cancer (CRC). This may influence the molecular characterization of tumor tissue, now mandatory for patients with metastatic CRC who are candidates for treatment with an anti-EGFR mAb, as false-negative results can occur, leading to non optimal therapy. Moreover, temporal molecular heterogeneity during treatment is known to influence the response to therapy and prognosis. We present a literature overview of advances made in characterizing molecular heterogeneity in CRC, underlining that the analysis of liquid biopsy could represent an efficient non-invasive tool to overcome the problem...
November 23, 2018: International Journal of Molecular Sciences
Miguel Alcaide, Matthew Cheung, Kevin Bushell, Sarah E Arthur, Hui-Li Wong, Joanna Karasinska, Daniel Renouf, David F Schaeffer, Suzan McNamara, Mathilde Couetoux du Tertre, Gerald Batist, Hagen F Kennecke, Aly Karsan, Ryan D Morin
Recurrent activating point mutations in KRAS are critical drivers in pancreatic cancer and have been attributed to resistance to anti-epidermal growth factor receptor therapy in colorectal cancer. Although KRAS genotyping provides limited clinical utility in the diagnosis and management of pancreatic cancer patients at present, inferences about the fractional abundance of KRAS mutations may inform on tumor purity in traditionally challenging clinical specimens and their potential use in precision medicine. KRAS genetic testing has indeed become an essential tool to guide treatment decisions in colorectal cancer, but there is an unmet need for methods standardization...
November 22, 2018: Journal of Molecular Diagnostics: JMD
Su Hu, Liang Pan, Junjie Shangguan, Matteo Figini, Aydin Eresen, Chong Sun, Bin Wang, Quanhong Ma, Chunhong Hu, Vahid Yaghmai, Yuri Velichko, Jia Yang, Zhuoli Zhang
The LSL-KrasG12D/+ ;LSL-Trp53R172H/+ ;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival...
November 20, 2018: Journal of Immunological Methods
Andrew M Heitzer, Jason M Ashford, Brian T Harel, Adrian Schembri, Michelle A Swain, Joanna Wallace, Kirsten K Ness, Fang Wang, Hui Zhang, Thomas E Merchant, Giles W Robinson, Amar Gajjar, Heather M Conklin
PURPOSE: Advantages to computerized cognitive assessment include increased precision of response time measurement and greater availability of alternate forms. Cogstate is a computerized cognitive battery developed to monitor attention, memory, and processing speed. Although the literature suggests the domains assessed by Cogstate are areas of deficit in children undergoing treatment for medulloblastoma, the validity of Cogstate in this population has not been previously investigated. METHODS: Children participating in an ongoing prospective trial of risk-adapted therapy for newly diagnosed medulloblastoma (n = 73; mean age at baseline = 12...
November 22, 2018: Journal of Neuro-oncology
Soheil Zorofchian, Fatima Iqbal, Mayank Rao, Phyu P Aung, Yoshua Esquenazi, Leomar Y Ballester
Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome...
November 22, 2018: Journal of Clinical Pathology
Dong-Yang Zhang, Yue Zheng, Hang Zhang, Gang-Gang Yang, Cai-Ping Tan, Liang He, Liang-Nian Ji, Zong-Wan Mao
Nano-drug delivery systems with multi-modality imaging capacities are worth pursuing because they integrate diagnostic and therapeutic functions. Herein, we report the design, synthesis and evaluation of modified iridium sulfide (IrSx) nanoparticles (NPs) for cancer therapy in vitro and in vivo. This nanosystem was prepared by modifying IrSx with polyethylene glycol (PEG) conjugated to the targeting ligand folate (FA) for multimodal imaging-guided combined chemo-photothermal therapy. Upon PEG modification, the small IrSx NPs (about 4 nm) self-assembled into much larger (about 120 nm) IrSx-PEG-FA NPs, which exhibited high photostability, ideal photothermal effect, high drug loading and pH-/photothermal-responsive drug release properties...
November 22, 2018: Nanoscale
Tugba Yildiz, Renpeng Gu, Stefan Zauscher, Tania Betancourt
Introduction: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer...
2018: International Journal of Nanomedicine
Kai Huang, Winfried Brenner, Vikas Prasad
Radioligand therapy (RLT) is considered a safe treatment for patients with metastasized neuroendocrine tumors (NET) and prostate cancer (PC), and the occurrence of tumor lysis syndrome (TLS) with 177 Lutetium (177 Lu)-labeled peptides has not been reported so far. We retrospectively screened our patients' database for TLS after RLT in NET and PC. Methods: The database was searched for patients receiving RLT with 177 Lu-DOTATATE, -DOTATOC or -PSMA and showing laboratory or clinical abnormalities typical for TLS within 7 days after start of treatment...
November 21, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Riziero Esposito Abate, Raffaella Pasquale, Francesca Fenizia, Anna Maria Rachiglio, Cristin Roma, Francesca Bergantino, Laura Forgione, Matilde Lambiase, Alessandra Sacco, Maria Carmela Piccirillo, Alessandro Morabito, Nicola Normanno
Circulating cell-free DNA (cfDNA) testing has emerged as an alternative to tumor tissue analyses for the management of metastatic non-small-cell lung cancer (NSCLC) patients. Analysis of cfDNA is a minimally invasive procedure that might better reflect tumor heterogeneity and allows repeated testing over the time. Areas Covered: This review article covers the different applications of cfDNA testing in NSCLC: early diagnosis of the disease; detection of minimal residual disease in early lung cancer; identification of predictive and prognostic markers in advanced NSCLC patients; monitoring the response to therapy; assessment of tumor mutation burden...
November 21, 2018: Expert Review of Anticancer Therapy
Sandra Heskamp, Peter J Wierstra, Janneke Dm Molkenboer-Kuenen, Gerwin W Sandker, Soley Thordardottir, Jeannette Cany, Daniel Olive, Johan Bussink, Otto C Boerman, Harry Dolstra, Erik H J G Aarntzen, Willemijn Hobo
Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of cancer patients. PD-L1 expression in tumors seems to be a prerequisite for treatment response. However, it is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment. Imaging of PD-L1 could aid in patient selection. Previously, we showed the feasibility to image PD-L1+ tumors in immunodeficient mice. However, PD-L1 is also expressed on immune cell subsets...
November 20, 2018: Cancer Immunology Research
Guohua Qi, Haijuan Li, Ying Zhang, Chuanping Li, Shuping Xu, Minmin Wang, Yongdong Jin
Cytochrome c (Cyt c) release and cellular pH change are two important mediators of apoptosis. Effective methods to regu-late and/or monitor such two events are therefore highly desired for apoptosis research and cancer cell therapy. Herein, we exploited electrostimulation to regulate cellular Cyt c release and apoptosis process, and by designing and preparing a smart and efficient plasmonic nanorobot (with surface-modified Cyt c-specific aptamer and 4-mercaptobenzoic acid) that capa-ble of Cyt c capture and self-sensing, real-time SERS monitoring of dynamic Cyt c release and simultaneous cell acidifica-tion in apoptosis during electrostimulation was achieved...
November 20, 2018: Analytical Chemistry
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