scholarly journals Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 423
Author(s):  
Anne Gomez-Brouchet ◽  
Julia Gilhodes ◽  
Nathalie Van Acker ◽  
Regis Brion ◽  
Corinne Bouvier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Therapeutic Agent ◽  
Good Prognosis ◽  
Activity Levels ◽  
Trap Level ◽  
Response To Chemotherapy ◽  
New Perspective ◽  
Novel Therapeutic ◽  
Trap Levels

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (padj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.

Cerium oxide nanoparticles acts as a novel therapeutic agent for ulcerative colitis through anti-oxidative mechanism

Life Sciences ◽  
2021 ◽  
pp. 119500
Author(s):  
Fereshteh Asgharzadeh ◽  
Alireza Hashemzadeh ◽  
Farzad Rahmani ◽  
Atieh Yaghoubi ◽  
Seyedeh Elnaz Nazari ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cerium Oxide ◽  
Therapeutic Agent ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Novel Therapeutic

scholarly journals Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972098511
Author(s):  
Gang Li ◽  
Xu Zhang ◽  
Xiangyang Guo ◽  
Yi Li ◽  
Chong Li
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Bladder Tumor ◽  
Therapeutic Agent ◽  
Tumor Formation ◽  
The Self ◽  
Hedgehog Pathway ◽  
Self Renewal ◽  
Intravenous Anesthetic ◽  
Novel Therapeutic

Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.

Overall Survival Analysis and Characterization of an EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) Population

2018 ◽  
Vol 54 (1) ◽  
pp. 10-17
Author(s):  
Filipa Aguiar ◽  
Gabriela Fernandes ◽  
Henrique Queiroga ◽  
José Carlos Machado ◽  
Luís Cirnes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Overall Survival Analysis

scholarly journals Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

2009 ◽  
Vol 125 (4) ◽  
pp. 851-860 ◽  
Author(s):  
Sébastien Salas ◽  
Pascal Jézéquel ◽  
Loic Campion ◽  
Jean-Laurent Deville ◽  
Frédéric Chibon ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Predictive Value ◽  
Response To Chemotherapy

scholarly journals First Characterization of an Archaeal GTP-Dependent Phosphoenolpyruvate Carboxykinase from the Hyperthermophilic Archaeon Thermococcus kodakaraensis KOD1

2004 ◽  
Vol 186 (14) ◽  
pp. 4620-4627 ◽  
Author(s):  
Wakao Fukuda ◽  
Toshiaki Fukui ◽  
Haruyuki Atomi ◽  
Tadayuki Imanaka
Keyword(s):  
Binding Sites ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Cation Binding ◽  
Activity Levels ◽  
Binding Region ◽  
Hyperthermophilic Archaeon ◽  
Dependent Activity ◽  
Additional Role

ABSTRACT Phosphoenolpyruvate carboxykinase (PCK), which catalyzes the nucleotide-dependent, reversible decarboxylation of oxaloacetate to yield phosphoenolpyruvate and CO2, is one of the important enzymes in the interconversion between C3 and C4 metabolites. This study focused on the first characterization of the enzymatic properties and expression profile of an archaeal PCK from the hyperthermophilic archaeon Thermococcus kodakaraensis (Pck Tk ). Pck Tk showed 30 to 35% identities to GTP-dependent PCKs from mammals and bacteria but was located in a branch distinct from that of the classical enzymes in the phylogenetic tree, together with other archaeal homologs from Pyrococcus and Sulfolobus spp. Several catalytically important regions and residues, found in all known PCKs irrespective of their nucleotide specificities, were conserved in Pck Tk . However, the predicted GTP-binding region was unique compared to those in other GTP-dependent PCKs. The recombinant Pck Tk actually exhibited GTP-dependent activity and was suggested to possess dual cation-binding sites specific for Mn2+ and Mg2+. The enzyme preferred phosphoenolpyruvate formation from oxaloacetate, since the Km value for oxaloacetate was much lower than that for phosphoenolpyruvate. The transcription and activity levels in T. kodakaraensis were higher under gluconeogenic conditions than under glycolytic conditions. These results agreed with the role of Pck Tk in providing phosphoenolpyruvate from oxaloacetate as the first step of gluconeogenesis in this hyperthermophilic archaeon. Additionally, under gluconeogenic conditions, we observed higher expression levels of Pck Tk on pyruvate than on amino acids, implying that it plays an additional role in the recycling of excess phosphoenolpyruvate produced from pyruvate, replacing the function of the anaplerotic phosphoenolpyruvate carboxylase that is missing from this archaeon.

scholarly journals Evaluating the potential of IL-27 as a novel therapeutic agent in HIV-1 infection

2013 ◽  
Vol 24 (6) ◽  
pp. 571-577 ◽  
Author(s):  
Sanjay Swaminathan ◽  
Lue Dai ◽  
H. Clifford Lane ◽  
Tomozumi Imamichi
Keyword(s):  
Therapeutic Agent ◽  
Hiv 1 ◽  
Novel Therapeutic

Combination of quantitative features from H&E biopsies and CT scans predicts response to chemotherapy and overall survival in small cell lung cancer (SCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8572-8572
Author(s):  
Cristian Barrera ◽  
Mohammadhadi Khorrami ◽  
Prantesh Jain ◽  
Pingfu Fu ◽  
Kate Butler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Model ◽  
Risk Score ◽  
Risk Group ◽  
Image Features ◽  
Small Cell ◽  
Ct Scans ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Response To Chemotherapy

8572 Background: Small Cell Lung Cancer (SCLC) is an aggressive malignancy with a rapid growth, and Chemotherapy remains mainstay of treatment. Identifying therapeutic targets in SCLC presents a challenge, partially due to a lack of accurate and consistently predictive biomarkers. In this study we sought to evaluate the utility of a combination of computer-extracted radiographic and pathology features from pretreatment baseline CT and H&E biopsy images to predict sensitivity to platinum-based chemotherapy and overall survival (OS) in SCLC. Methods: Seventy-eight patients with extensive and limited-stage SCLC who received platinum-doublet chemotherapy were selected. Objective response to chemotherapy (RECIST criteria) and overall survival (OS) as clinical endpoints were available for 51 and 78 patients respectively. The patients were divided randomly into two sets (Training (Sd), Validation (Sv)) with a constraint (equal number of responders and nonresponders in Sd)—Sd comprised twenty-one patients with SCLC. Sv included thirty patients. CT scans and digitized Hematoxylin Eosin-stained (H&E) biopsy images were acquired for each patient. A set of CT derived (46%) and tissue derived (53%) image features were captured. These included shape and textural patterns of the tumoral and peritumoral regions from CT scans and of tumor regions on H&E images. A random forest feature selection and linear regression model were used to identify the most predictive CT and H&E derived image features associated with chemotherapy response from Sd. A Cox proportional hazard regression model was used with these features to compute a risk score for each patients in Sd. Patients in Sv were stratified into high and low-risk groups based on the median risk score. Kaplan-Meier survival analysis was used to assess the prognostic ability of the risk score on Sv. Results: The risk score comprised nine CT (intra and peri-tumoral texture) and six H&E derived (cancer cell texture and shape) features. A linear regression model in conjunction with these 15 features was significantly associated with chemo-sensitivity in Sv (AUC = 0.76, PRC = 0.81). A multivariable model with these 15 features was significantly associated with OS in Sv (HR = 2.5, 95% CI: 1.3-4.9, P = 0.0043). Kaplan-Meier survival analysis revealed a significantly reduced OS in the high-risk group compared to the low-risk group. Conclusions: A combined CT and H&E tissue derived image signature model predicted response to chemotherapy and improved OS in SCLC patients. Image features from baseline CT scans and H&E tissue slide images may help in better risk stratification of SCLC patients. Additional independent validation of these quantitative image-based biomarkers is warranted.

scholarly journals Should hydrogen therapy be included in a musculoskeletal medicine routine?

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2659 ◽  
Author(s):  
Sergej M. Ostojic
Keyword(s):  
Health Professionals ◽  
Molecular Hydrogen ◽  
Therapeutic Agent ◽  
Metabolic Diseases ◽  
Neuromuscular Disorders ◽  
Surrogate Markers ◽  
Musculoskeletal Medicine ◽  
Inflammatory Agent ◽  
Medicinal Properties ◽  
Novel Therapeutic

Molecular hydrogen (H2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer, H2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of H2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.

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