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https://www.readbyqxmd.com/read/30006588/extracellular-atp-and-p2-purinergic-signalling-in-the-tumour-microenvironment
#1
REVIEW
Francesco Di Virgilio, Alba Clara Sarti, Simonetta Falzoni, Elena De Marchi, Elena Adinolfi
Modulation of the biochemical composition of the tumour microenvironment is a new frontier of cancer therapy. Several immunosuppressive mechanisms operate in the milieu of most tumours, a condition that makes antitumour immunity ineffective. One of the most potent immunosuppressive factors is adenosine, which is generated in the tumour microenvironment owing to degradation of extracellular ATP. Accruing evidence over the past few years shows that ATP is one of the major biochemical constituents of the tumour microenvironment, where it acts at P2 purinergic receptors expressed on both tumour and host cells...
July 13, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/30006168/synthesis-in-vitro-antiproliferative-activity-and-kinase-inhibitory-effects-of-pyrazole-containing-diarylureas-and-diarylamides
#2
Mohammed I El-Gamal, Byung-Jun Park, Chang-Hyun Oh
Twenty pyrazole-containing diarylureas and diarylamides were designed and synthesized. They were tested for in vitro antiproliferative activity over a 58-cancer cell line panel at the NCI, USA. The diarylurea derivatives 1b-e and 1g exerted the strongest antiproliferative activity. Among them, compound 1e possessing 3,5-bis(trifluoromethyl)phenyl terminal ring and 3`-methoxy-5`-chlorophenyl ring attached to the central pyrazole ring was the most potent. Its IC50 values were in sub-micromolar range against most of the tested cell lines...
July 6, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30006140/calcium-signaling-defects-underlying-salivary-gland-dysfunction
#3
REVIEW
Indu Ambudkar
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Saliva secretion is regulated by stimulation of specific signaling mechanisms within the acinar cells of the gland. Neurotransmitter-stimulated increase in cytosolic [Ca2+ ] ([Ca2+ ]i ) in acinar cells is the primary trigger for salivary fluid secretion from salivary glands, the loss of which is a critical factor underlying dry mouth conditions in patients...
July 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/30005587/zoledronic-acid-induced-orbital-inflammation-in-a-patient-with-multiple-myeloma
#4
Marisela Tan, Evan Kalin-Hajdu, Rupa Narayan, Sandy W Wong, Thomas G Martin
Multiple myeloma is a cancer of malignant plasma cells which stimulates osteoclasts and is associated with increased bone turnover and osteolysis. Bisphosphonates including zolendronic acid are used to prevent skeletal complications in patients with multiple myeloma. Orbital inflammation is a rare but serious complication following use of bisphosphonates. The diagnosis is made by excluding other possible causes in patients with myeloma and rapid initiation of therapy is required. Corticosteroids are the mainstay of therapy but the ideal treatment course has not been delineated...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/30005226/cxcr5-cd8-t-cells-displayed-higher-activation-potential-despite-high-pd-1-expression-in-tumor-involved-lymph-nodes-from-patients-with-thyroid-cancer
#5
Yu Zhou, Linqi Guo, Huawei Sun, Jianbo Xu, Tu Ba
Thyroid cancer is one of the malignancies with better clinical outcomes. However, a minority of patients develops an aggressive anaplastic thyroid carcinoma. Development of innovative and multimodal therapeutic strategies is urgently needed. Here, we investigated the role of CXCR5+ CD8 T cells in the peripheral blood, tumor-involved lymph nodes (TILN), and tumor mass of thyroid cancer patients. In peripheral blood mononuclear cells, CXCR5+ cells represented 1.4% ± 0.84% (mean ± s.d.) of total CD8 T cells, while in TILN and in tumor, the frequencies of CXCR5+ CD8 T cells were significantly higher at 27...
July 9, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30004146/%C3%AE-catenin-regulates-irf3-mediated-innate-immune-signalling-in-colorectal-cancer
#6
Chengming Ding, Jun He, Jun Zhao, Junhua Li, Jie Chen, Wenyan Liao, Yi Zeng, Jing Zhong, Chaoying Wei, Liming Zhang, Mei Zhou, Zeming Jia, Yaoting Zhang, Hui Li, Yuzheng Zhou, Xiaolong Xiao, Dong Han, Chong Li, Zhu Zhu, Zanxian Xia, Jian Peng
OBJECTIVE: β-catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage-associated molecular patterns (DAMPs) and primes the anti-tumour adaptive responses. While the function of β-catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β-catenin in inhibiting RIG-I-like receptor (RLR)-mediated IFN-β signalling in colorectal cancer...
July 13, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/30003393/the-clinical-relevance-of-serum-vascular-endothelial-growth-factor-vegf-in-correlation-to-circulating-tumor-cells-and-other-serum-biomarkers-in-patients-with-metastatic-breast-cancer
#7
Malgorzata Banys-Paluchowski, Isabell Witzel, Sabine Riethdorf, Klaus Pantel, Brigitte Rack, Wolfgang Janni, Peter A Fasching, Bahriye Aktas, Sabine Kasimir-Bauer, Andreas Hartkopf, Erich-Franz Solomayer, Tanja Fehm, Volkmar Müller
PURPOSE: VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancer patients and to explore the relationship between sVEGF and other blood-based biomarkers. METHODS: Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study...
July 12, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30003075/p2rx7-purinoceptor-as-a-therapeutic-target-the-second-coming
#8
REVIEW
Chris N J Young, Dariusz C Górecki
The P2RX7 receptor is a unique member of a family of extracellular ATP (eATP)-gated ion channels expressed in immune cells, where its activation triggers the inflammatory cascade. Therefore, P2RX7 has been long investigated as a target in the treatment of infectious and inflammatory diseases. Subsequently, P2RX7 signaling has been documented in other physiological and pathological processes including pain, CNS and psychiatric disorders and cancer. As a result, a range of P2RX7 antagonists have been developed and trialed...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/30002659/vectorized-delivery-of-alpha-galactosylceramide-and-tumor-antigen-on-filamentous-bacteriophage-fd-induces-protective-immunity-by-enhancing-tumor-specific-t-cell-response
#9
Rossella Sartorius, Luciana D'Apice, Pasquale Barba, Deborah Cipria, Laura Grauso, Adele Cutignano, Piergiuseppe De Berardinis
We have exploited the properties of filamentous bacteriophage fd to deliver immunologically active lipids together with antigenic peptides. Filamentous bacteriophages resemble for size, capability to be permeable to blood vessels, and high density antigen expression, a nature-made nanoparticle. In addition, their major coat protein pVIII, which is arranged to form a tubular shield surrounding the phage genome, has a high content of hydrophobic residues promoting lipid association. We conjugated bacteriophages to alpha-GalactosylCeramide (α-GalCer), a lipid antigen-stimulating invariant natural killer T (iNKT) cells and capable of inducing their anti-tumoral activities...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30002604/vasodilator-stimulated-phosphoprotein-vasp-a-novel-target-of-mir-4455-promotes-gastric-cancer-cell-proliferation-migration-and-invasion-through-activating-the-pi3k-akt-signaling-pathway
#10
Haiqun Chen, Gang Dai, Yiting Cai, Qinhao Gong, Wei Wu, Min Gao, Zhewei Fei
Background: MicroRNAs (miRNAs) are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC). Expression profiling of miRNAs in paired gastric cancer and adjacent normal gastric tissues has demonstrated that miR-4455 is down-regulated in gastric cancer tissues, but its functional role in the carcinogenesis of GC had not previously been investigated. Aims: The purpose of this study was to investigate the functional and biological mechanisms of miR-4455 in the progression of GC, in vitro...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/30001871/immunological-mechanisms-responsible-for-radiation-induced-abscopal-effect
#11
REVIEW
María E Rodríguez-Ruiz, Claire Vanpouille-Box, Ignacio Melero, Silvia Chiara Formenti, Sandra Demaria
Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy...
July 9, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29999574/exosome-mediated-regulation-of-tumor-immunology
#12
Naohiro Seo, Kazunari Akiyoshi, Hiroshi Shiku
Exosomes are the representative extracellular vesicles (EVs) derived from multivesicular endosomes (MVEs), and have been described as new players in communication of neighborhood and/or distant cells by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and nucleotides including micro (mi) RNAs. Exosomes from immune cells and tumor cells act in part as a regulator in tumor immunology. CD8+ T cells that exhibit potent cytotoxic activity against tumor cells reside as an inactive naïve form in T cell zone of the secondary lymphoid organs...
July 12, 2018: Cancer Science
https://www.readbyqxmd.com/read/29998736/photoactivated-specific-mrna-detection-in-single-living-cells-by-coupling-signal-on-fluorescence-and-signal-off-electrochemical-signals
#13
Fujian Huang, Meihua Lin, Ruilin Duan, Xiaoding Lou, Fan Xia, Itamar Willner
The spatiotemporal detection of a target mRNA in a single living cell is a major challenge in nanoscience and nanomedicine. We introduce a versatile method to detect mRNA at a single living cell level that uses photocleavable hairpin probes as functional units for the optical (fluorescent) and electrochemical (voltammetric) detection of MnSOD mRNA in single MCF-7 cancer cells. The fluorescent probe is composed of an ortho-nitrophenylphosphate ester functionalized hairpin that includes the FAM fluorophore in a caged configuration quenched by Dabcyl...
July 12, 2018: Nano Letters
https://www.readbyqxmd.com/read/29998457/effects-of-genistein-on-insulin-pathway-related-genes-in-mouse-differentiated-myoblast-c2c12-cell-line-evidences-for-two-independent-modes-of-action
#14
Sławomir Lewicki, Aneta Lewicka, Bolesław Kalicki, Agnieszka Sobolewska-Ruta, Bogdan Debski, Robert Zdanowski, Tomasz Syryło, Malgorzata Kloc, Jacek Zbigniew Kubiak
INTRODUCTION: Genistein (plant isoflavone) is a well-known anti-cancer drug with estrogenic-like properties. Genistein also regulates sugar and lipid metabolism; thus, it has anti-diabetic properties. The aim of the study was to evaluate in vitro effects of genistein on glucose transport, fatty acids oxidation, activation of PKB, and expression of genes related to insulin pathway in differentiated myoblast C2C12 mouse cell line. MATERIAL AND METHODS: Differentiated myoblast C2C12 mouse cell line was used to assess the effects of different genistein concentrations on glucose transport and fatty acids oxidation measured by radioactivity technique, activation of PKB, and expression of selected genes related to insulin signaling pathway (IR-α, IR-β, IRS-1, PKB, GLUT-4, PP2A, SH-PTP2) at the mRNA and protein levels...
July 12, 2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29998417/micelle-like-nanoparticles-as-sirna-and-mirna-carriers-for-cancer-therapy
#15
Daniel F Costa, Vladimir P Torchilin
Gene therapy has emerged as an alternative in the treatment of cancer, particularly in cases of resistance to chemo and radiotherapy. Different approaches to deliver genetic material to tumor tissues have been proposed, including the use of small non-coding RNAs due to their multiple mechanisms of action. However, such promise has shown limits in in vivo application related to RNA's biological instability and stimulation of immunity, urging the development of systems able to overcome those barriers. In this review, we discuss the use of RNA interference in cancer therapy with special attention to the role of siRNA and miRNA and to the challenges of their delivery in vivo...
July 12, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29998219/novel-tumour-antigens-and-the-development-of-optimal-vaccine-design
#16
REVIEW
Victoria A Brentville, Suha Atabani, Katherine Cook, Lindy G Durrant
The interplay between tumours and the immune system has long been known to involve complex interactions between tumour cells, immune cells and the tumour microenvironment. The progress of checkpoint inhibitors in the clinic in the last decade has highlighted again the role of the immune system in the fight against cancer. Numerous efforts have been undertaken to develop ways of stimulating the cellular immune response to eradicate tumours. These interventions include the identification of appropriate tumour antigens as targets for therapy...
April 2018: Therapeutic advances in vaccines and immunotherapy
https://www.readbyqxmd.com/read/29998217/bispecific-antibodies-in-cancer-immunotherapy
#17
REVIEW
Eva Dahlén, Niina Veitonmäki, Per Norlén
Following the clinical success of immune checkpoint antibodies targeting CTLA-4, PD-1 or PD-L1 in cancer treatment, bispecific antibodies are now emerging as a growing class of immunotherapies with potential to further improve clinical efficacy and safety. We describe three classes of immunotherapeutic bispecific antibodies: (a) cytotoxic effector cell redirectors; (b) tumor-targeted immunomodulators; and (c) dual immunomodulators. Cytotoxic effector cell redirectors are dominated by T-cell redirecting compounds, bispecific compounds engaging a tumor-associated antigen and the T-cell receptor/CD3 complex, thereby redirecting T-cell cytotoxicity to malignant cells...
February 2018: Therapeutic advances in vaccines and immunotherapy
https://www.readbyqxmd.com/read/29998193/epitope-mapping-of-anti-mouse-podoplanin-monoclonal-antibody-pmab-1
#18
Shinji Yamada, Shunsuke Itai, Mika K Kaneko, Satoru Konnai, Yukinari Kato
Mouse podoplanin (mPDPN) is a type I transmembrane sialoglycoprotein, which is expressed on lymphatic endothelial cells, podocytes of the kidney, and type I alveolar cells of the lung. mPDPN is known as a platelet aggregation-inducing factor and possesses four platelet aggregation-stimulating (PLAG) domains: PLAG1, PLAG2, and PLAG3 in the N-terminus and PLAG4 in the middle of the mPDPN protein. mPDPN overexpression in cancers has been reportedly associated with hematogenous metastasis through interaction with the C-type lectin-like receptor 2 of platelets...
September 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29998149/the-value-of-technetium-99m-labeled-alpha-melanocyte-stimulating-hormone-99m-tc-%C3%AE-msh-in-diagnosis-of-primary-and-metastatic-lesions-of-malignant-melanoma
#19
Saeed Farzanefar, Rahman Etemadi, Mohammad Shirkhoda, Habibollah Mahmoodzadeh, Mostafa Erfani, Babak Fallahi, Mehrshad Abbasi, Narjess Ayati, Arman Hassanzadeh-Rad, Mohammad Eftekhari, Davood Beiki
Objectives: Malignant melanoma is the most lethal type of skin cancers with unfavorable prognosis. Alpha-MSH peptide analogues have a high affinity for melanocortine-1 (MC1) receptors on melanocytes over expressing in malignant melanoma cells. Pre-clinical studies have shown promising results for radiolabeled MSH imaging in this malignancy. The purpose of this study is to assess the diagnostic value of 99m Tc-α-MSH imaging in malignant melanoma. Methods: Twenty-one patients (13 men) with pathologically confirmed malignant melanoma with or without metastatic distribution were included in this study...
2018: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/29997938/effect-of-lung-protective-ventilation-on-coronary-heart-disease-patients-undergoing-lung-cancer-resection
#20
Wenjun Liu, Qian Huang, Duomao Lin, Liyun Zhao, Jun Ma
Background: Mechanical ventilation, especially large tidal volume (Vt) one-lung ventilation (OLV), can cause ventilator-induced lung injury (VILI) that can stimulate cytokines. Meanwhile, cytokines are considered very important factor influencing coronary heart disease (CHD) patient prognosis. So minimization of pulmonary inflammatory responses by reduction of cytokine levels for CHD undergoing lung resection during OLV should be a priority. Because previous studies have demonstrated that lung-protective ventilation (LPV) reduced lung inflammation, this ventilation approach was studied for CHD patients undergoing lung resection here to evaluate the effects of LPV on pulmonary inflammatory responses...
May 2018: Journal of Thoracic Disease
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