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https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#1
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770822/a-size-switchable-nanoplatform-for-targeting-the-tumor-microenvironment-and-deep-tumor-penetration
#2
Xingli Cun, Man Li, Shuying Wang, Yifei Wang, Jialing Wang, Zhengze Lu, Ruixin Yang, Xian Tang, Zhirong Zhang, Qin He
The complex tumor microenvironment (TME) in solid tumors forms physiological barriers to the efficient delivery of nanomedicine, leading to limited therapeutic efficacy. Herein, to overcome these physiological barriers and improve the therapeutic effect, we constructed a novel size-adjustable nanoplatform for efficient drug delivery into solid tumors. The smart size-switchable nanoplatform (DGL/DOX@PP) was prepared by conjugating small dendrigraft poly-l-lysine (DGL) to poly(ethylene glycol)-poly(caprolactone) micelles via a matrix metalloproteinase 2 (MMP-2)-sensitive peptide...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29770167/reactive-oxygen-species-mediated-tumor-microenvironment-transformation-the-mechanism-of-radioresistant-gastric-cancer
#3
REVIEW
Huifeng Gu, Tianhe Huang, Yicheng Shen, Yin Liu, Fuling Zhou, Yanxia Jin, Haseeb Sattar, Yongchang Wei
Radioresistance is one of the primary causes responsible for therapeutic failure and recurrence of cancer. It is well documented that reactive oxygen species (ROS) contribute to the initiation and development of gastric cancer (GC), and the levels of ROS are significantly increased in patients with GC accompanied with abnormal expressions of multiple inflammatory factors. It is also well documented that ROS can activate cancer cells and inflammatory cells, stimulating the release of a variety of inflammatory cytokines, which subsequently mediates the tumor microenvironment (TME) and promotes cancer stem cell (CSC) maintenance as well as renewal and epithelial-mesenchymal transition (EMT), ultimately resulting in radioresistance and recurrence of GC...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#4
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29756123/the-quality-of-total-mesorectal-excision-specimen-a-review-of-its-macroscopic-assessment-and-prognostic-significance
#5
Shi-Bo Song, Guo-Ju Wu, Hong-Da Pan, Hua Yang, Mao-Lin Hu, Qiang Li, Qiu-Xia Yan, Gang Xiao
As a surgical procedure which could significantly lower the recurrence rate of cancers, total mesorectal excision (TME) has been the gold standard for middle and lower rectal cancer treatment. However, previous studies have shown that the procedure did not achieve the ideal theoretical local recurrence rates of rectal cancers. Some researchers pointed out it was very likely that not all so-called TME treatments completely removed the mesorectum, implying that some of these TME surgical treatments failed to meet oncological quality standards...
March 2018: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29755698/epigenetic-control-of-macrophage-polarization-implications-for-targeting-tumor-associated-macrophages
#6
REVIEW
Amber E de Groot, Kenneth J Pienta
The progression of cancer is a result of not only the growth of the malignant cells but also the behavior of other components of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are key components of the TME that influence tumor growth and disease progression. TAMs can either inhibit or support tumor growth depending on their polarization to classically-activated macrophages (M1s) or alternatively-activated macrophages (M2s), respectively. Epigenetic regulation plays a significant role in determining this polarization and manipulating the epigenetic regulation in macrophages would provide a means for selectively targeting M2s thereby eliminating tumor-supporting TAMs while sparing tumor-inhibiting M1 TAMs...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755692/defunctioning-ileostomy-reduces-leakage-rate-in-rectal-cancer-surgery-systematic-review-and-meta-analysis
#7
Magdalena Pisarska, Natalia Gajewska, Piotr Małczak, Michał Wysocki, Jan Witowski, Grzegorz Torbicz, Piotr Major, Magdalena Mizera, Marcin Dembiński, Marcin Migaczewski, Andrzej Budzyński, Michał Pędziwiatr
Objectives: The role of a defunctioning ileostomy in every anterior rectal resection with total mesorectal excision (TME) is still controversial. In this study, we aimed to review the current literature to determine the impact of ileostomy creation on postoperative outcomes in patients undergoing anterior rectal resection with TME. Methods: MEDLINE, Embase and Cochrane Library were searched for eligible studies. We analyzed data up to October 2017. Eligible studies had to compare patients with vs...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29744860/oncological-outcome-after-mri-based-selection-for-neoadjuvant-chemoradiotherapy-in-the-ocum-rectal-cancer-trial
#8
R Ruppert, T Junginger, H Ptok, J Strassburg, C A Maurer, P Brosi, J Sauer, J Baral, M Kreis, D Wollschlaeger, P Hermanek, S Merkel
BACKGROUND: It is not clear whether all patients with rectal cancer need chemoradiotherapy. A restrictive use of neoadjuvant chemoradiotherapy (nCRT) based on MRI findings for rectal cancer was investigated in this study. METHODS: This prospective multicentre observational study included patients with stage cT2-4 rectal cancer, with any cN and cM0 status. Carcinomas in the middle and lower third that were 1 mm or less from the mesorectal fascia, all cT4 tumours, and all cT3 tumours of the lower third were classified as high risk, and these patients received nCRT followed by total mesorectal excision (TME)...
May 9, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29743887/mean-corpuscular-volume-as-a-predictive-factor-of-response-to-preoperative-chemoradiotherapy-in-locally-advanced-rectal-cancer
#9
Wen-Yi Zhang, Xing-Xing Chen, Wen-Hao Chen, Hui Zhang, Chang-Lin Zou
Background: The aim of this study was to identify if blood routine parameters and serum tumor marker are potential predictive factors for tumor response to preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer. Materials and Methods: 55 locally advanced rectal cancer patients were treated with preoperative CRT in this study. The total dose of preoperative radiotherapy was 45 Gy in 25 fractions of 1.8 in 5 weeks. All patients concurrently received 825 mg/m2 capecitabine orally twice daily on days 1 to 14 and 22 to 35...
2018: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29741811/basal-like-breast-cancer-engages-tumor-supportive-macrophages-via-secreted-factors-induced-by-extracellular-s100a4
#10
Lina Prasmickaite, Ellen M Tenstad, Solveig Pettersen, Shakila Jabeen, Eivind Valen Egeland, Silje Nord, Abhilash Pandya, Mads Haugland Haugen, Vessela N Kristensen, Anne-Lise Børresen-Dale, Olav Engebråten, Gunhild M Maelandsmo
The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer (BC), particularly in the aggressive triple-negative/basal-like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic resistance. In this study we investigated the effect of the metastasis- and inflammation-associated microenvironmental factor S100A4 on breast cancer cells (BCCs) of different subtypes, and explored their further interactions with myeloid cells...
May 9, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29739356/korean-society-of-coloproctology-kscp-trial-of-consolidation-chemotherapy-for-locally-advanced-mid-or-low-rectal-cancer-after-neoadjuvant-concurrent-chemoradiotherapy-a-multicenter-randomized-controlled-trial-konclude
#11
Chang Woo Kim, Byung Mo Kang, Ik Yong Kim, Ji Yeon Kim, Sun Jin Park, Won Cheol Park, Ki Beom Bae, Byung-Noe Bae, Seong Kyu Baek, Seung Hyuk Baik, Gyung Mo Son, Yoon Suk Lee, Suk-Hwan Lee
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) has been a standard treatment option for locally advanced rectal cancer with improved local control. However, systemic recurrence despite neoadjuvant CRT remained unchanged. The only significant prognostic factor proven to be important was pathologic complete response (pCR) after neoadjuvant CRT. Several efforts have been tried to improve survival of patients who treated with neoadjuvant CRT and to achieve more pCR including adding cytotoxic chemotherapeutic agents, chronologic modification of chemotherapy schedule or adding chemotherapy during the perioperative period...
May 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29737600/stromal-barriers-to-nanomedicine-penetration-in-the-pancreatic-tumor-microenvironment
#12
REVIEW
Hiroyoshi Y Tanaka, Mitsunobu R Kano
Pancreatic cancer is known for its dismal prognosis despite efforts to improve therapeutic outcome. Recently, cancer nanomedicine, application of nanotechnology to cancer diagnosis and treatment, has gained interest for treatment of pancreatic cancer. The enhanced permeability and retention (EPR) effect that promotes selective accumulation of nanometer-sized molecules within tumors is the theoretical rationale of treatment. However, it is clear that EPR may be insufficient in pancreatic cancer due to stromal barriers within the tumor microenvironment (TME)...
May 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29732051/dual-targeting-biomimetic-delivery-for-anti-glioma-activity-via-remodeling-the-tumor-microenvironment-and-directing-macrophage-mediated-immunotherapy
#13
Pengfei Zhao, Yonghui Wang, Xuejia Kang, Aihua Wu, Weimin Yin, Yisi Tang, Jinyu Wang, Meng Zhang, Yifei Duan, Yongzhuo Huang
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity...
March 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29725785/salvage-tme-following-tem-a-possible-indication-for-tatme
#14
F Letarte, M Raval, A Karimuddin, P T Phang, C J Brown
BACKGROUND: Salvage surgery after transanal endoscopic microsurgery (TEM) has shown mixed results. Transanal total mesorectal excision (TaTME) might be advantageous in this population. The aim of this study was to assess the short-term oncologic and operative outcomes of salvage surgery after TEM, comparing TaTME to conventional salavge TME (sTME). METHODS: Consecutive patients treated with salvage surgery after TEM were identified. Patients who underwent TaTME were compared to those who had conventional sTME...
May 4, 2018: Techniques in Coloproctology
https://www.readbyqxmd.com/read/29724655/lighting-a-fire-in-the-tumor-microenvironment-using-oncolytic-immunotherapy
#15
REVIEW
Carole Achard, Abera Surendran, Marie-Eve Wedge, Guy Ungerechts, John Bell, Carolina S Ilkow
Oncolytic virus (OV) therapy is potentially a game-changing cancer treatment that has garnered significant interest due to its versatility and multi-modal approaches towards tumor eradication. In the field of cancer immunotherapy, the immunological phenotype of the tumor microenvironment (TME) is an important determinant of disease prognosis and therapeutic success. There is accumulating data that OVs are capable of dramatically altering the TME immune landscape, leading to improved antitumor activity alone or in combination with assorted immune modulators...
April 23, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29723108/animal-models-for-studying-tumor-microenvironment-tme-and-resistance-to-lymphocytic-infiltration
#16
Ryuji Yamaguchi, Guy Perkins
In cancer immunotherapy, cytotoxic T or NK cells need to engage cancer cells to initiate the killing. However, in clinical studies and in mouse models, some solid tumors are found with no lymphocytes. It is likely that these tumors will be resistant to all sorts of immunotherapies. Thus, restoring lymphocytic infiltration will be vital to the success of immunotherapies on solid tumors. In order to understand the complex interaction between cancer cells and stromal cells, we propose to establish animal models for studying the tumor microenvironment and to develop and test therapies to restore lymphocytic infiltration of tumors Without lymphocytes infiltrating tumors, all immunotherapies on solid tumors become ineffective...
May 3, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29721365/-interleukin-10-il10-proximal-promoter-polymorphisms-beyond-clinical-response-in-classical-hodgkin-lymphoma-exploring-the-basis-for-the-genetic-control-of-the-tumor-microenvironment
#17
Gabriela Vera-Lozada, Carolina Minnicelli, Priscilla Segges, Gustavo Stefanoff, Flavia Kristcevic, Joaquin Ezpeleta, Elizabeth Tapia, Gerald Niedobitek, Mário Henrique M Barros, Rocio Hassan
Interleukin-10 (IL10) is an immune regulatory cytokine. Single nucleotide polymorphisms (SNPs) in IL10 promoter have been associated with prognosis in adult classical Hodgkin lymphoma (cHL). We analyzed IL10 SNPs -1082 and -592 in respect of therapy response, gene expression and tumor microenvironment (TME) composition in 98 pediatric patients with cHL. As confirmatory results, we found that -1082AA/AG; -592CC genotypes and ATA haplotype were associated with unfavourable prognosis: Progression-free survival (PFS) was shorter in -1082AA+AG (72...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29720380/car-t-cells-surface-engineered-with-drug-encapsulated-nanoparticles-can-ameliorate-intratumoral-t-cell-hypofunction
#18
Natnaree Siriwon, Yu Jeong Kim, Elizabeth Louise Siegler, Xianhui Chen, Jennifer A Rohrs, Yarong Liu, Pin Wang
One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment, which inactivates the function of tumor infiltrating lymphocytes (TILs) through the production of immunosuppressive molecules such as adenosine. Adenosine inhibits the function of CD4+ and CD8+ T cells by binding to and activating the A2a adenosine receptor (A2aR) expressed on their surface. This suppression pathway can be blocked using the A2aR-specific small molecule antagonist SCH-58261 (SCH), but its applications have been limited owing to difficulties delivering this drug to immune cells within the tumor microenvironment (TME)...
May 2, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29720116/vista-expression-associated-with-cd8-confers-a-favorable-immune-microenvironment-and-better-overall-survival-in-hepatocellular-carcinoma
#19
Ming Zhang, Hua-Jin Pang, Wei Zhao, Yu-Fa Li, Li-Xu Yan, Zhong-Yi Dong, Xiao-Feng He
BACKGROUND: Hepatocellular carcinoma (HCC) often arises in the setting of chronic inflammation with multiple inhibitory immune signals. V-domain Ig suppressor of T cell activation (VISTA) is identified as a novel negative checkpoint regulator. This study sought to determine the expression and prognostic value of VISTA in HCC and classify tumor microenvironments (TMEs) based on VISTA and CD8+ tumor-infiltrating lymphocytes (TILs). METHODS: The expression of VISTA and CD8 proteins was assessed in 183 HCC tissue microarrays (TMAs) by immunohistochemistry (IHC)...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29719257/csf1r-macrophages-sustain-pancreatic-tumor-growth-through-t-cell-suppression-and-maintenance-of-key-gene-programs-that-define-the-squamous-subtype
#20
Juliana B Candido, Jennifer P Morton, Peter Bailey, Andrew D Campbell, Saadia A Karim, Thomas Jamieson, Laura Lapienyte, Aarthi Gopinathan, William Clark, Ewan J McGhee, Jun Wang, Monica Escorcio-Correia, Raphael Zollinger, Rozita Roshani, Lisa Drew, Loveena Rishi, Rebecca Arkell, T R Jeffry Evans, Colin Nixon, Duncan I Jodrell, Robert W Wilkinson, Andrew V Biankin, Simon T Barry, Frances R Balkwill, Owen J Sansom
Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model...
May 1, 2018: Cell Reports
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