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Tam + chemo

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...
October 18, 2016: 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...
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...
February 8, 2016: 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
Constantine S Tam, Stephan Stilgenbauer
Patients with chronic lymphocytic leukemia (CLL) carrying deletion of 17p (17p-) or mutations of TP53 have a uniquely poor prognosis related to increased propensities to progress to symptomatic disease, poor responses to chemo(immuno)therapy and high rates of Richter transformation. Both traditional fludarabine, cyclophosphamide and rituximab (FCR)-based chemoimmunotherapy and alemtuzumab-based regimens are inadequate in controlling 17p- CLL durably, and allogeneic stem cell transplant holds the only prospect for long-term survival...
March 2015: Leukemia & Lymphoma
Christian Marinaccio, Giuseppe Ingravallo, Francesco Gaudio, Tommasina Perrone, Beatrice Nico, Eugenio Maoirano, Giorgina Specchia, Domenico Ribatti
Diffuse Large B-cell Lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma characterized by clinical and biological heterogeneity attributable both to the tumor cells and the complex tumor-microenvironment surrounding them. Tumor-associated macrophages (TAMs) and mast cells are two major components of the tumor inflammatory infiltrate with a definite role in enhancing tumor angiogenesis. In this study, we have investigated CD68 and tryptase expression and their relationship with microvascular density (MVD) in chemo-resistant and chemosensitive patients affected by DLBCL...
November 2014: Leukemia Research
Bamaprasad Dutta, Ren Yan, Sai Kiang Lim, James P Tam, Siu Kwan Sze
In contrast to the intensely studied genetic and epigenetic changes that induce host cell transformation to initiate tumor development, those that promote the malignant progression of cancer remain poorly defined. As emerging evidence suggests that the hypoxic tumor microenvironment could re-model the chromatin-associated proteome (chromatome) to induce epigenetic changes and alter gene expression in cancer cells, we hypothesized that hypoxia-driven evolution of the chromatome promotes malignant changes and the development of therapy resistance in tumor cells...
December 2014: Molecular & Cellular Proteomics: MCP
Kabir Ahmed, Gary Timmerman, Robert Meyer, Tara Miller, Miroslaw Mazurczak, Kimberlee Tams, Muslim Atiq
Verrucous carcinoma of the esophagus is a rare variant of squamous cell carcinoma associated with human papillomavirus. We report the case of a 58-year-old female who presented with ongoing symptoms of dysphagia. On previous endoscopies she had been noted to have a large polyp-like mass involving the esophagus, with negative biopsies for malignancy. Repeat endoscopy with concurrent endoscopic ultrasound showed a large semi-pedunculated polyp in the distal esophagus and a hypoechoic, irregular mass involving the gastroesophageal junction with esophageal thickening...
September 2013: Case Reports in Gastroenterology
Francesco Pantano, Pierpaolo Berti, Francesco Maria Guida, Giuseppe Perrone, Bruno Vincenzi, Michelina Maria Carla Amato, Daniela Righi, Emanuela Dell'aquila, Francesco Graziano, Vincenzo Catalano, Marco Caricato, Sergio Rizzo, Andrea Onetti Muda, Antonio Russo, Giuseppe Tonini, Daniele Santini
Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count...
November 2013: Journal of Cellular and Molecular Medicine
Chengqun Chen, Lin Hou, Huijuan Zhang, Ling Zhu, Hongling Zhang, Chaofeng Zhang, Jinjin Shi, Lei Wang, Xin Jia, Zhenzhong Zhang
An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug tamoxifen (TAM). This TAM-loaded NGR modified SWCNTs (TAM/NGR-SWCNTs) not only retained both optical properties of SWCNTs and cytotoxicity of TAM, but also could accumulate in tumors and enter into 4T1 cells, which facilitated combination chemotherapy with photothermal therapy in one targeting system. Enhanced cellular uptake, antitumor effect and cell apoptosis of TAM/NGR-SWCNTs on 4T1 cells were observed in vitro, compared with the TAM solution, TAM/SWCNTs and photothermal therapy alone...
November 2013: Journal of Drug Targeting
Raffaella Giannice, Marco Erreni, Paola Allavena, Mauro Buscaglia, Roberto Tozzi
Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion. TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment...
November 2013: Cytokine
Alexander J Neuwelt, Tam Nguyen, Y Jeffrey Wu, Andrew M Donson, Rajeev Vibhakar, Sujatha Venkatamaran, Vladimir Amani, Edward A Neuwelt, Louis B Rapkin, Nicholas K Foreman
BACKGROUND: Atypical teratoid rhabdoid tumors (AT-RT) are pediatric tumors of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) with high dose acetaminophen (AAP), may improve therapeutic efficacy in AT-RT in vitro. PROCEDURE: BT16 (cisplatin-resistant) and BT12 (cisplatin-sensitive) AT-RT cell lines were treated with combinations of AAP, cisplatin, and the anti-oxidant N-acetylcysteine (NAC)...
January 2014: Pediatric Blood & Cancer
Kevin M Foote, Kevin Blades, Anna Cronin, Shaun Fillery, Sylvie S Guichard, Lorraine Hassall, Ian Hickson, Xavier Jacq, Philip J Jewsbury, Thomas M McGuire, J Willem M Nissink, Rajesh Odedra, Ken Page, Paula Perkins, Abid Suleman, Kin Tam, Pia Thommes, Rebecca Broadhurst, Christine Wood
ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways. We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition. Optimization from a high quality screening hit within tight SAR space led to compound 6 (AZ20) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM...
March 14, 2013: Journal of Medicinal Chemistry
Ellen J Schlette, Joan Admirand, William Wierda, Lynne Abruzzo, Katherine I Lin, Susan O'Brien, Susan Lerner, Michael J Keating, Constantine Tam
Although chromosome 17p abnormalities and TP53 mutations have been reported as poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not been defined in patients with CLL treated with chemoimmunotherapy, particularly in the context of other novel markers such as ZAP-70 expression and IgVH mutation status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR)...
October 2009: Leukemia & Lymphoma
Mika Iizuka, Norihiko Sengoku, Takashi Nakakuma, Naoko Yoshimura, Keiko Hayashi, Takumo Enomoto, Masaru Kuranami, Masahiko Watanabe
We here describe a case of advanced breast cancer (Stage IV) in which an oral S-1+TAM therapy following a primary systemic chemo-radiotherapy has been effective in maintaining the patient's QOL. A 40-year-old woman visited our hospital because of her left breast tumor. On physical examination, the tumor had invaded to the skin adjacent to the nipple forming a skin ulcer and marked deformity of the entire breast. Also noted were swollen lymph nodes in the left armpit. Subsequently, radiographic imaging tests revealed that the tumor had metastasized to the liver and lungs, as well as the skull...
November 2008: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Chi Keung Lau, Zhen Fan Yang, Shuk Pik Lam, Chi Tat Lam, Patricia Ngai, Ka Ho Tam, Ronnie Tung-Ping Poon, Sheung Tat Fan
The present study investigated the effect of YC-1, a novel anti-cancer agent, on the chemo-sensitivity of hepatocellular carcinoma (HCC). YC-1 was administered with chemo-cytotoxic drug, cisplatin, both in vitro and in vivo. YC-1 alone downregulated the expression of phosphorylated form of signal transducers and activators of transcription 3 (P-Stat3[705]), a key mediator in chemo-resistance. When combined with cisplatin, YC-1 further promoted tumor cell apoptosis, decreased the expression of P-Stat3(705), Bcl-xL, CyclinD1 and survivin, and induced the cleavage of caspase 9 and PARP...
December 2007: Cancer Biology & Therapy
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