The impact of mitochondria on cancer treatment resistance

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.

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Decreasing the Impact of Treatment Resistance in Schizophrenia: Identifying Novel Molecular Targets/ Pathways to Increase Treatment Efficacy

10.3389/978-2-88963-962-5 ◽

2020 ◽

Keyword(s):

Treatment Efficacy ◽

Molecular Targets ◽

Treatment Resistance ◽

The Impact

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The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment

npj Breast Cancer ◽

10.1038/s41523-021-00276-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mads G. Jørgensen ◽

Navid M. Toyserkani ◽

Frederik G. Hansen ◽

Anette Bygum ◽

Jens A. Sørensen

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Cancer Treatment ◽

Breast Cancer Treatment ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

The Impact

AbstractThe impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.

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P9 A study to investigate the impact of the COVID-19 pandemic on paediatric cancer patients: an international, multicentre, observational cohort study (COVIDPaedsCancer)

BJS Open ◽

10.1093/bjsopen/zrab032.008 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

Author(s):

◽

Soham Bandyopadhyay

Keyword(s):

Cohort Study ◽

Cancer Treatment ◽

Childhood Cancer ◽

Multivariate Logistic Regression Analysis ◽

Global Health Research ◽

Cancer Outcomes ◽

Paediatric Cancer ◽

Cancer Management ◽

Anti Cancer ◽

The Impact

Abstract Introduction Childhood cancers are a leading cause of non-communicable disease deaths for paediatric patients around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases (Global Children’s NCDs) is currently undertaking the first international study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short to medium term impacts on childhood cancer outcomes. Methods and analysis This is a multicentre, international, cohort study that will use routinely collected hospital data in a de-identified and anonymised form. Patients will be recruited consecutively into the study, with a 12 -month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anti-cancer treatment for the following cancers: Acute lymphoblastic leukaemia, Burkitt’s Lymphoma, Hodgkin's lymphoma, Wilms Tumour, Sarcoma, Retinoblastoma, Gliomas, Medulloblastomas and Neuroblastomas. Patients must be newly presented or be undergoing active anti-cancer treatment from the 12th March 2020 to the 12th December 2020. The primary objective of the study is to determine 30- and 90-day all-cause mortality rates. This study will examine the factors that influenced these outcomes. Chi-squared analysis will be used to compare mortality between low and middle-income countries and high-income countries. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally, and internationally. The results will be submitted for publication in a peer reviewed journal.

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Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib

Biomolecules ◽

10.3390/biom11071049 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1049

Author(s):

Cyril Sobolewski ◽

Noémie Legrand

Keyword(s):

Cancer Treatment ◽

Metabolic Diseases ◽

Catalytic Site ◽

Antitumor Effects ◽

Anti Cancer ◽

Cox 2 ◽

Cox 2 Inhibitors ◽

The Impact ◽

Important Enzyme ◽

Specific Inhibitors

Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition of COX-2 in healthy tissues, has considerably limited their use in clinic. In addition, increasing evidence indicate that these anti-cancerous properties are not strictly dependent on the inhibition of the catalytic site. These findings have led to the development of non-active COX-2 inhibitors analogues aiming at preserving the antitumor effects of COX-2 inhibitors without their side effects. Among them, two celecoxib derivatives, 2,5-Dimethyl-Celecoxib and OSU-03012, have been developed and suggested for the treatment of viral (e.g., recently SARS-CoV-2), inflammatory, metabolic diseases and cancers. These molecules display stronger anti-tumor properties than celecoxib and thus may represent promising anti-cancer molecules. In this review, we discuss the impact of these two analogues on cancerous processes but also their potential for cancer treatment alone or in combination with existing approaches.

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Patient preference and the impact of decision-making aids on prostate cancer treatment choices and post-intervention regret

Current Oncology ◽

10.3747/co.19.1287 ◽

2012 ◽

Vol 19 (S3) ◽

Cited By ~ 21

Author(s):

J. Aning ◽

R.J. Wassersug ◽

S.L. Goldenberg

Keyword(s):

Prostate Cancer ◽

Decision Making ◽

Cancer Treatment ◽

Patient Preference ◽

Post Intervention ◽

Prostate Cancer Treatment ◽

Treatment Choices ◽

The Impact

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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 ◽

10.3390/cells10040750 ◽

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.

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