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Tam + chemo

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
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
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
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
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...
May 8, 2017: European Radiology
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 chemo-immunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinico-pathological features of PD and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pre-treated patients on three early phase clinical trials...
May 4, 2017: Blood
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
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
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
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
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
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
Yoshihiro Komohara, Motohiro Takeya
Many non-tumour host cells such as inflammatory cells, fibroblasts, and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo-resistance of the tumour cells. Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively. TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti-tumour phenotype under specific conditions...
February 2017: Journal of Pathology
Junko Tsuboki, Yukio Fujiwara, Hasita Horlad, Daisuke Shiraishi, Toshihiro Nohara, Shingo Tayama, Takeshi Motohara, Yoichi Saito, Tsuyoshi Ikeda, Kiyomi Takaishi, Hironori Tashiro, Yukihiro Yonemoto, Hidetaka Katabuchi, Motohiro Takeya, Yoshihiro Komohara
It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies...
July 12, 2016: Scientific Reports
Jing Li, Kun He, Ping Liu, Lisa X Xu
Chemotherapeutic efficacy is also regulated by the tumor microenvironment. IL-6 produced by TAMs and downstream IL-6/STAT3 signaling pathway is central regulator in chemotherapeutic response. The M2-like phenotype of TAMs is characterized by elevated iron uptake. Whether iron participates in chemo-resistance need to be elucidated. In the present study, we found that IL-6 participated in breast cancer chemoresistance. Local IL-6 paracrine loop acted as exogenous IL-6 rich niche for chemo-sensitive breast cancer cells, leading to de novo acquired drug resistance...
June 24, 2016: Biochemical and Biophysical Research Communications
Adriana Baritchii, Anca Jurj, Olga Soritau, Ciprian Tomuleasa, Layos Raduly, Oana Zanoaga, Dana Cernea, Cornelia Braicu, Ioana Neagoe, Ioan Stefan Florian
PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Despite maximal cytoreductive surgery followed by chemoradiotherapy the prognosis is still poor. Although surgery and radiotherapy may have reached maximal effectiveness, chemotherapy has the potential to improve survival. The aim of this study was to evaluate in vitro the antitumor efficacy of tamoxifen (TAM), raloxifen (RAL), pyrimethamine (PYR) and alphanizomenon flos-aquae (AFA) in combination with temozolomide (TMZ) plus ionizing radiation against cultured glioblastoma stem-like cells and primary glioblastoma cells , as possible way to increase the treatment options in patients with therapy-refractory GBM...
January 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Lutian Yao, Mengyi Wang, Zheyu Niu, Qiaofei Liu, Xiang Gao, Li Zhou, Quan Liao, Yupei Zhao
Pancreatic cancer is characterized as inflammatory malignancy with a dismal prognosis. There is abundant intratumoral infiltration of macrophages, and most of these tumor associated macrophages (TAM) are induced to be M2 phenotype. The M2 polarized TAM has been demonstrated to promote progression and induce chemo-resistance of pancreatic cancer. Interleukin (IL)-27 is a novel member of IL-12 cytokine family and its roles in regulation of phenotypes and functions of TAM remain largely unknown. In this study, we demonstrated IL-27 significantly inhibited the M2 macrophages polarization and dampened the proliferation, migration and metastasis of pancreatic cancer cells and as well enhanced the efficacy of gemcitabine...
January 2017: Cytokine
Gianpiero Cera, Tobias Haven, Lutz Ackermann
Triazole assistance set the stage for a unified strategy for the iron-catalyzed C-H allylation of arenes, heteroarenes, and alkenes with ample scope. The versatile catalyst also proved competent for site-selective methylation, benzylation, and alkylation with challenging primary and secondary halides. Triazole-assisted C-H activation proceeded chemo-, site-, and diastereo-selectively, and the modular TAM directing group was readily removed in a traceless fashion under exceedingly mild reaction conditions.
January 22, 2016: Angewandte Chemie
Bivas Biswas, Mehar Chand Sharma, Asit Ranjan Mridha, Sameer Bakhshi
BACKGROUND: Cysteine protease Cathepsin L is involved in bone remodeling and expressed in activated macrophages. It is highly expressed in metastatic tumor tissue, especially with bone metastases. AIMS: We evaluated immunohistochemical expression of Cathepsin L in tumor cells and tumor-associated macrophages (TAMs) in chemo-naive Ewing sarcoma. SETTINGS AND DESIGN: Retrospective evaluation of archived specimens of Ewing sarcoma. MATERIALS AND METHODS: Immunohistochemical staining was performed on archived blocks of chemo-naive patients with Ewing sarcoma treated with uniform chemotherapy at our institute between January 2009 and November 2011...
April 2015: Indian Journal of Pathology & Microbiology
Jayashree C Jagtap, D Parveen, Reecha D Shah, Aarti Desai, Dipali Bhosale, Ashish Chugh, Deepak Ranade, Swapnil Karnik, Bhushan Khedkar, Aaishwarya Mathur, Kumar Natesh, Goparaju Chandrika, Padma Shastry
Glioblastoma multiforme (GBM) is the most malignant form of brain tumor and is associated with resistance to conventional therapy and poor patient survival. Prostate apoptosis response (Par)-4, a tumor suppressor, is expressed as both an intracellular and secretory/extracellular protein. Though secretory Par-4 induces apoptosis in cancer cells, its potential in drug-resistant tumors remains to be fully explored. Multicellular spheroids (MCS) of cancer cells often acquire multi-drug resistance and serve as ideal experimental models...
2015: FEBS Open Bio
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