scholarly journals Metabolic Pathways and Targets in Chondrosarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ida Micaily ◽  
Megan Roche ◽  
Mohammad Y. Ibrahim ◽  
Ubaldo Martinez-Outschoorn ◽  
Atrayee Basu Mallick
Keyword(s):  
Metabolic Pathways ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Therapeutic Resistance ◽  
Isocitrate Dehydrogenase 1 ◽  
Epigenetic State ◽  
Cancer Aggressiveness ◽  
Potential Synergy ◽  
Primary Bone ◽  
The Relationship

Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and angiogenesis. Also, potential treatment strategies targeting metabolism will be discussed including potential synergy with immunotherapies.

scholarly journals Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 607
Author(s):  
Alice Indini ◽  
Francesco Grossi ◽  
Mario Mandalà ◽  
Daniela Taverna ◽  
Valentina Audrito
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Biological Behavior ◽  
Therapeutic Implications ◽  
Systemic Treatments

Malignant melanoma represents the most fatal skin cancer due to its aggressive biological behavior and high metastatic potential. Treatment strategies for advanced disease have dramatically changed over the last years due to the introduction of BRAF/MEK inhibitors and immunotherapy. However, many patients either display primary (i.e., innate) or eventually develop secondary (i.e., acquired) resistance to systemic treatments. Treatment resistance depends on multiple mechanisms driven by a set of rewiring processes, which involve cancer metabolism, epigenetic, gene expression, and interactions within the tumor microenvironment. Prognostic and predictive biomarkers are needed to guide patients’ selection and treatment decisions. Indeed, there are no recognized clinical or biological characteristics that identify which patients will benefit more from available treatments, but several biomarkers have been studied with promising preliminary results. In this review, we will summarize novel tumor metabolic pathways and tumor-host metabolic crosstalk mechanisms leading to melanoma progression and drug resistance, with an overview on their translational potential as novel therapeutic targets.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Mitochondrial Sirtuins in Reproduction

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1047
Author(s):  
Giovanna Di Emidio ◽  
Stefano Falone ◽  
Paolo Giovanni Artini ◽  
Fernanda Amicarelli ◽  
Anna Maria D’Alessandro ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabolic Pathways ◽  
Redox Balance ◽  
Antioxidant Defenses ◽  
Metabolic Abnormalities ◽  
Female Reproduction ◽  
Mitochondrial Dysfunctions ◽  
Early Embryos ◽  
The Relationship

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

scholarly journals Systematic Review of Recurrent Osteosarcoma Systemic Therapy

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1757
Author(s):  
Ioanna Gazouli ◽  
Anastasios Kyriazoglou ◽  
Ioannis Kotsantis ◽  
Maria Anastasiou ◽  
Anastasios Pantazopoulos ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Treatment Effectiveness ◽  
Treatment Strategies ◽  
Bone Cancer ◽  
Predictive Biomarkers ◽  
Mtor Inhibitors ◽  
Cytotoxic Chemotherapy ◽  
Driver Mutations ◽  
Preclinical Research ◽  
Primary Bone

Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

scholarly journals Temporal Quantitative Proteomics Analysis of Neuroblastoma Cells Treated with Bovine Milk-Derived Extracellular Vesicles Highlights the Anti-Proliferative Properties of Milk-Derived Extracellular Vesicles

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 750
Author(s):  
Pamali Fonseka ◽  
Taeyoung Kang ◽  
Sing Chee ◽  
Sai V. Chitti ◽  
Rahul Sanwlani ◽  
...  
Keyword(s):  
High Risk ◽  
Extracellular Vesicles ◽  
Quantitative Proteomics ◽  
Cell Metabolism ◽  
Bovine Milk ◽  
Neuroblastoma Cells ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Label Free ◽  
The Impact

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

scholarly journals AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Diwei Zheng ◽  
Weihai Liu ◽  
Wenlin Xie ◽  
Guanyu Huang ◽  
Qiwei Jiang ◽  
...  
Keyword(s):  
Metabolic Activity ◽  
Cancer Metabolism ◽  
Cancer Metastasis ◽  
Isocitrate Dehydrogenase 1 ◽  
Cell Growth And Migration ◽  
And Migration ◽  
The Relationship ◽  
Common Primary Malignant Bone

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

Metabolism-driven post-translational modifications of H3K9 in early bovine embryos

Reproduction ◽  
2021 ◽  
Vol 162 (3) ◽  
pp. 181-191
Author(s):  
Jessica Ispada ◽  
Aldcejam Martins da Fonseca Junior ◽  
Otávio Luiz Ramos Santos ◽  
Camila Bruna de Lima ◽  
Erika Cristina dos Santos ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Developmental Stages ◽  
De Novo ◽  
Blastocyst Stage ◽  
Developmental Model ◽  
Bovine Embryos ◽  
Acetyl Coa ◽  
Post Translational Modifications ◽  
The Relationship ◽  
Different Levels

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.

scholarly journals Self-Esteem Evaluation in Children and Adolescents Suffering from ADHD

2013 ◽  
Vol 9 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Luigi Mazzone ◽  
Valentina Postorino ◽  
Laura Reale ◽  
Manuela Guarnera ◽  
Valeria Mannino ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Treatment Strategies ◽  
Well Being ◽  
Self Esteem ◽  
Control Group ◽  
Healthy Controls ◽  
Adhd Symptoms ◽  
The Relationship ◽  
Drug Free

Background: Several recent studies investigated the relationship between self-esteem and ADHD, however, the results are still controversial. In the present study we analyze the characteristics of self-esteem in a sample of children and adolescents suffering from ADHD, with a particular focus on the relationship between ADHD symptoms severity and treatment strategies. Methods: A total of 85 patients with ADHD (44 drug-free and 41 drug-treated, 23 of which atomoxetine-treated and 18 Methylphenidate-treated) and 26 healthy controls were enrolled in the study in order to evaluate self-esteem using the Self-esteem Multidimensional Test (TMA). Results: ADHD subjects revealed lower scores on all self-esteem domains compared to controls. Both ADHD drug-free (47.1%) and ADHD drug-treated (44.1%) groups showed significantly higher rates of subjects in the pathological range as compared to normal control group (8.8%) (p <.001) with a higher percentage of subjects in the pathological range. Among ADHD drug-treated subjects, the methylphenidate group showed higher self-esteem scores as compared to the atomoxetine group. Conclusion: A lower self-esteem profile is more common in subjects suffering from ADHD than in healthy controls, suggesting the importance of an early detection of psychological well-being in these children in order to reduce the ADHD symptoms long-term impacts.

scholarly journals Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19

2021 ◽  
Vol 14 (10) ◽  
pp. 955
Author(s):  
Jen-Yu Hsu ◽  
Yan-Chiao Mao ◽  
Po-Yu Liu ◽  
Kuo-Lung Lai
Keyword(s):  
Adverse Events ◽  
Metabolic Pathways ◽  
Case Reports ◽  
Secondary Infection ◽  
Treatment Strategies ◽  
Serious Adverse Events ◽  
Small Molecule Drugs ◽  
Post Market ◽  
Inflammatory Processes ◽  
Effective Drugs

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.

Sign in / Sign up

Export Citation Format

Share Document