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https://www.readbyqxmd.com/read/29477032/3d-3-culture-a-tool-to-unveil-macrophage-plasticity-in-the-tumour-microenvironment
#1
Sofia P Rebelo, Catarina Pinto, Tatiana R Martins, Nathalie Harrer, Marta F Estrada, Pablo Loza-Alvarez, José Cabeçadas, Paula M Alves, Emilio J Gualda, Wolfgang Sommergruber, Catarina Brito
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents...
May 2018: Biomaterials
https://www.readbyqxmd.com/read/29458614/microstructure-and-chemo-physical-characterizations-of-functional-graphene-oxide-iron-oxide-silver-ternary-nanocomposite-synthesized-by-one-pot-hydrothermal-method
#2
Pham Thi Lan Huong, Tran Van Son, Vu Ngoc Phan, Le Thi Tam, Anh-Tuan Le
In this work, a functional graphene oxide-iron oxide-silver (GO-Fe3O4-Ag) ternary nanocomposite was synthesized by using one-pot hydrothermal treatments of mixture solutions of silver nitrate (AgNO3), ferrous chloride tetrahydrate (FeCl2 4H2O), polyvinylpyrrolidone (PVP), graphene oxide (GO), and ammonium hydroxide solution (NH4OH). The systematic effects of synthesis conditions on the microstructure and formation of binary and ternary composite systems were studied. Importantly, high-crystalline GO-Fe3O4-Ag ternary nanomaterials with average sizes of Fe3O4 particles ~16 nm and of Ag particles ~20 nm were obtained at optimized conditions (125 °C, 2...
August 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29381962/effects-of-treatment-with-chemotherapy-and-or-tamoxifen-on-the-biomarkers-of-cardiac-injury-and-oxidative-stress-in-women-with-breast-cancer
#3
Fabricio Bragança Silva, Walckiria Garcia Romero, Ana Ligia Rodrigues de Abreu Carvalho, Gleyce Ariadne Alves Souza, Erick Roberto Gonçalves Claudio, Glaucia Rodrigues Abreu
There has been an increase in deaths from cardiovascular diseases following breast cancer therapy. Evidence has shown that this outcome is, in part, associated with cardiotoxicity induced by the chemotherapeutic drugs and the increase in oxidative stress. The aim of this study was to evaluate the effects of chemotherapy and hormone therapy with tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer.Thirty women were followed-up for 1 year and were divided into 3 groups according to the treatment protocol: women treated only with tamoxifen and clinical follow up for 12 months (Tam, n = 10); women treated only with chemotherapy for 6 months with clinical follow up for an additional 6-month period (Chemo, n = 10); and women who received chemotherapy for 6 months followed by a 6-month period only with tamoxifen therapy and clinical follow up (Chemo + Tam, n = 10)...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29362121/treatment-outcomes-of-nasopharyngeal-carcinoma-in-modern-era-after-intensity-modulated-radiotherapy-imrt-in-hong-kong-a-report-of-3328-patients-hknpcsg-1301-study
#4
K H Au, Roger K C Ngan, Alice W Y Ng, Darren M C Poon, W T Ng, K T Yuen, Victor H F Lee, Stewart Y Tung, Anthony T C Chan, Henry C K Sze, Ashley C K Cheng, Anne W M Lee, Dora L W Kwong, Anthony H P Tam
PURPOSE: To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010. MATERIAL AND METHODS: Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed...
February 2018: Oral Oncology
https://www.readbyqxmd.com/read/29320562/m1-like-macrophages-change-tumor-blood-vessels-and-microenvironment-in-murine-melanoma
#5
Magdalena Jarosz-Biej, Natalia Kamińska, Sybilla Matuszczak, Tomasz Cichoń, Jolanta Pamuła-Piłat, Justyna Czapla, Ryszard Smolarczyk, Daria Skwarzyńska, Klaudia Kulik, Stanisław Szala
Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression...
2018: PloS One
https://www.readbyqxmd.com/read/29250930/management-of-high-risk-chronic-lymphocytic-leukaemia-cll-patients-in-australia
#6
REVIEW
Bryone J Kuss, Constantine S Tam
BACKGROUND: Chronic lymphocytic leukaemia (CLL) frequently responds to chemoimmunotherapy combining cytotoxic chemotherapy and monoclonal antibodies. However, CLL is associated with significant genetic heterogeneity, and some high-risk forms are known to be chemo-resistant and associated with early relapse. AIMS: To review the current treatment paradigm of patients with high-risk disease, in particular those with del(17p) and TP53 variants. RESULTS: A 'watch and wait' approach is recommended for all patients who are asymptomatic...
December 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/29059867/spatial-targeting-of-tumor-associated-macrophage-and-tumor-cells-with-a-designer-nanocarrier-for-cancer-chemo-immunotherapy
#7
Jun Wang
Chemo-immunotherapy which combines chemotherapeutics with immune-modulating agents represents an appealing approach to improving cancer therapy [1, 2]. To maximize its efficacy, differential and precise targeting of the multiple therapeutics into corresponding cells is desirable. Here we develop an immunostimulatory nanocarrier that simultaneously loads platinum (Pt)-based chemotherapeutic prodrug and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of tumor-associated macrophages (TAMs) [3], to spatially target tumor cells and TAMs for cancer chemo-immunotherapy...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28881682/inhibition-of-fak-kinase-activity-preferentially-targets-cancer-stem-cells
#8
Vihren N Kolev, Winnie F Tam, Quentin G Wright, Sean P McDermott, Christian M Vidal, Irina M Shapiro, Qunli Xu, Max S Wicha, Jonathan A Pachter, David T Weaver
Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured ex vivo...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28769933/reprogramming-of-tumor-associated-macrophages-with-anticancer-therapies-radiotherapy-versus-chemo-and-immunotherapies
#9
REVIEW
Géraldine Genard, Stéphane Lucas, Carine Michiels
Tumor-associated macrophages (TAMs) play a central role in tumor progression, metastasis, and recurrence after treatment. Macrophage plasticity and diversity allow their classification along a M1-M2 polarization axis. Tumor-associated macrophages usually display a M2-like phenotype, associated with pro-tumoral features whereas M1 macrophages exert antitumor functions. Targeting the reprogramming of TAMs toward M1-like macrophages would thus be an efficient way to promote tumor regression. This can be achieved through therapies including chemotherapy, immunotherapy, and radiotherapy (RT)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28654915/inhibition-of-fak-kinase-activity-preferentially-targets-cancer-stem-cells
#10
Vihren N Kolev, Winnie F Tam, Quentin G Wright, Sean P McDermott, Christian M Vidal, Irina M Shapiro, Qunli Xu, Max S Wicha, Jonathan A Pachter, David T Weaver
Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured ex vivo...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28582845/elevated-lactate-dehydrogenase-ldh-can-be-a-marker-of-immune-suppression-in-cancer-interplay-between-hematologic-and-solid-neoplastic-clones-and-their-microenvironments
#11
Jennifer Ding, Judith E Karp, Ashkan Emadi
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment...
July 4, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28488871/spatial-targeting-of-tumor-associated-macrophages-and-tumor-cells-with-a-ph-sensitive-cluster-nanocarrier-for-cancer-chemoimmunotherapy
#12
Song Shen, Hong-Jun Li, Kai-Ge Chen, Yu-Cai Wang, Xian-Zhu Yang, Zhe-Xiong Lian, Jin-Zhi Du, Jun Wang
Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as (BLZ-945)SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. (BLZ-945)SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs...
June 14, 2017: Nano Letters
https://www.readbyqxmd.com/read/28484824/prognostic-value-of-incidental-hypervascular-micronodules-detected-on-cone-beam-computed-tomography-angiography-of-patients-with-liver-metastasis
#13
Bruno C Odisio, Veronica L Cox, Silvana C Faria, Suguru Yamashita, Xiao Shi, Joe Ensor, Aaron K Jones, Armeen Mahvash, Sanjay Gupta, Alda L Tam, Jean-Nicolas Vauthey, Ravi Murthy
PURPOSE: To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver metastasis undergoing transarterial (chemo)embolization (TACE/TAE). MATERIAL AND METHODS: This was a HIPAA-compliant institutional review board-approved single-institution retrospective review of 95 non-cirrhotic patients (52 men; mean age, 60 years) who underwent CBCTA prior to (chemo)embolic delivery...
November 2017: European Radiology
https://www.readbyqxmd.com/read/28473407/clinicopathological-features-and-outcomes-of-progression-of-cll-on-the-bcl2-inhibitor-venetoclax
#14
Mary Ann Anderson, Constantine Tam, Thomas E Lew, Surender Juneja, Manu Juneja, David Westerman, Meaghan Wall, Stephen Lade, Alexandra Gorelik, David C S Huang, John F Seymour, Andrew W Roberts
The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials...
June 22, 2017: Blood
https://www.readbyqxmd.com/read/28427401/ki-67-protein-expression-and-tumor-associated-inflammatory-cells-macrophages-and-mast-cells-in-canine-colorectal-carcinoma
#15
M Woldemeskel, I Hawkins, L Whittington
BACKGROUND: Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC were compared with those in adenomas (n = 13) and control (n = 9). RESULTS: Ki-67 index in CRC (17...
April 20, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28285690/the-cell-cell-interaction-between-tumor-associated-macrophages-and-small-cell-lung-cancer-cells-is-involved-in-tumor-progression-via-stat3-activation
#16
Toyohisa Iriki, Koji Ohnishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Cheng Pan, Koei Ikeda, Takeshi Mori, Makoto Suzuki, Hidenori Ichiyasu, Hirotsugu Kohrogi, Motohiro Takeya, Yoshihiro Komohara
OBJECTIVES: Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. It is well known that various stromal cells, including macrophages, play a role in tumor progression in several types of malignant tumors; however, the significance of tumor-associated macrophages (TAMs) in SCLC has not been fully elucidated. Signal transducer and activator of transcription 3 (STAT3) is a molecule well-known to be related to tumor progression. In the present study, we investigated the relationship of TAMs and SCLC cells to test the hypothesis that TAMs induce tumor progression in SCLC via STAT3 activation...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#17
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh N Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28177547/iron-catalyzed-c-h-alkynylation-through-triazole-assistance-expedient-access-to-bioactive-heterocycles
#18
Gianpiero Cera, Tobias Haven, Lutz Ackermann
Triazole assistance enabled the first iron-catalyzed C-H alkynylation of arenes, heteroarenes, and alkenes. The modular TAM directing group set the stage for a sequential C-H alkynylation/annulation strategy with ample scope, enabling the iron-catalyzed assembly of isoquinolones, pyridones, pyrrolones, and isoindolinones with high levels of chemo-, site-, and regioselectivity.
March 13, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27935336/rrx-001-a-systemically-non-toxic-m2-to-m1-macrophage-stimulating-and-prosensitizing-agent-in-phase-ii-clinical-trials
#19
REVIEW
Bryan Oronsky, Ramasamy Paulmurugan, Kira Foygel, Jan Scicinski, Susan J Knox, Donna Peehl, Hongjuan Zhao, Shoucheng Ning, Pedro Cabrales, Thomas A Summers, Tony R Reid, William L Fitch, Michelle M Kim, Jane B Trepel, Min-Jung Lee, Santosh Kesari, Nacer D Abrouk, Regina M Day, Arnold Oronsky, Carolyn M Ray, Corey A Carterg
According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27916840/ligand-activation-of-tam-family-receptors-implications-for-tumor-biology-and-therapeutic-response
#20
REVIEW
Viralkumar Davra, Stanley G Kimani, David Calianese, Raymond B Birge
The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology...
November 29, 2016: Cancers
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