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Mutation Research. Genetic Toxicology... Sep 2019Drug-induced kidney injury is one of the most significant adverse events and dose limiting factor in chemotherapy as well a major cause of prospective drug attrition...
Drug-induced kidney injury is one of the most significant adverse events and dose limiting factor in chemotherapy as well a major cause of prospective drug attrition during pharmaceutical development. Moreover, kidney injury can also occur as a consequence of exposures to environmental xenobiotics such as heavy metals, fungal toxins and nanomaterials. The lack of adequate in vitro human kidney models that mimic more realistically the in vivo conditions and the absence of suitable and robust, cost-effective and predictive cell-based in vitro assays contribute to an underestimation of the kidney toxic potential of new drugs and xenobiotics. Therefore, a rapid screening system capable to detect potential nephrotoxicity at early stages of drug discovery is an urgent need. Here we provide an overview of human cell lines currently used as a surrogate in vitro kidney models in nephrotoxicity studies, including their advantages and limitations. In addition, the capacity of the single cell gel electrophoresis (SCGE)/comet assay as a potential tool in kidney toxicants screening is discussed. Despite a limited number of studies using the comet assay to evaluate the drug-induced kidney damage potential, a considerable variability in SCGE methodology (e.g. lysis, unwinding, and electrophoresis conditions) has been observed. Before the comet assay can be included in nephrotoxicity testing, a basic guideline has to be developed. To test its feasibility, additional in vitro experiments including inter-laboratory validation studies based on this guideline have to be performed.
Topics: Animals; Automation; Cell Line; Comet Assay; DNA Damage; Drug Development; Drug Evaluation, Preclinical; Forecasting; Guidelines as Topic; HEK293 Cells; Humans; Image Processing, Computer-Assisted; Kidney; Miniaturization; Nanostructures; Reproducibility of Results; Risk Assessment; Single-Cell Analysis; Th1 Cells; Toxicity Tests
PubMed: 31561894
DOI: 10.1016/j.mrgentox.2018.11.012 -
Frontiers in Pharmacology 2023Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone. PROSPERO CRD42022352127.
PubMed: 37795033
DOI: 10.3389/fphar.2023.1269863 -
International Journal of Health Policy... 2023Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic... (Review)
Review
BACKGROUND
Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic model, which was based on production and consumption, continuous growth, and resources depletion. CE allows a greener economy with sustainable development and promotes more balanced societies. The healthcare sector is a major contributor to the climate crisis, with a carbon footprint representing 4.4% of global net emissions. It is thus essential to rethink the applicability of CE in healthcare.
METHODS
We conducted a scoping review guided by the Arksey and O'Malley methodological framework and utilised PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist. A systematic search from MEDLINE complete, SCOPUS, and Web of Science databases published between 1992 and 2022.
RESULTS
Through database searching a total of 1018 records were identified and 475 duplicates were removed. From the total search, 543 articles were screened by title/abstract according to the inclusion and exclusion criteria. After screening, 38 full-text articles were selected and assessed for eligibility. Forty-seven additional records were also identified through other sources and screened for eligibility. Other sources included: 12 articles from snowballing of previous papers; 9 articles following peer-reviewers suggestions; 19 reports from relevant organisations in CE and healthcare; two webpage, and one book.
CONCLUSION
Specific areas were identified where hospitals could reduce their greenhouse gas (GHG) emissions and consequently their negative environmental impact, namely through waste management, energy, water, transportation/travel, hospital design, food optimisation, green procurement, and behaviour. Also, lack of staff awareness and knowledge of the environmental impact of healthcare, and hospitals sustainability were identified as major contributors.
Topics: Humans; Conservation of Natural Resources; Hospitals; Delivery of Health Care
PubMed: 37579377
DOI: 10.34172/ijhpm.2023.6947 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
European Journal of Cancer (Oxford,... Jun 2023The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia.
METHODS
A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database.
RESULTS
Sixteen studies-involving 837 CRC patients and 1618 controls-were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73-91%) and 70% (95% CI 63-77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied.
CONCLUSION
Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
Topics: Humans; Volatile Organic Compounds; Biomarkers, Tumor; Early Detection of Cancer; Colorectal Neoplasms; Adenoma; Colonic Neoplasms
PubMed: 37030079
DOI: 10.1016/j.ejca.2023.03.002 -
Radiography (London, England : 1995) Aug 2022Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater... (Review)
Review
INTRODUCTION
Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater level of autonomy, responsibility, and accountability in the practice of Therapeutic Radiographers/Radiation Therapists (TR/RTTs) has led to Advanced Practice (AP) roles. The published evidence of this role is scattered with confusing terminology and divergence regarding the perception of whether a specific role represents AP internationally. This study aims to establish an international baseline of evidence on AP roles in RT to identify roles and activities performed by TR/RTTs at advanced level practice and to summarise the impact.
METHODS
A systematic PRISMA review of the literature was undertaken. Thematic analysis was used to synthesise the roles and associated activities. Six RT external experts validated the list. The impact was scrutinised in terms of clinical, organisational, and professional outcomes.
RESULTS
Studies (n = 87) were included and categorised into four groups. AP roles were listed by clinical area, site-specific, and scope of practice, and advanced activities were organised into seven dimensions and 27 sub-dimensions. Three most-reported outcomes were: enhanced service capacity, higher patient satisfaction, and safety maintenance.
CONCLUSION
Evidence-based AP amongst TR/RTTs show how AP roles were conceptualised, implemented, and evaluated. Congruence studies have shown that TR/RTTs are at par with the gold-standard across the various AP roles.
IMPLICATIONS FOR PRACTICE
This is the first systematic literature review synthetisising AP roles and activities of TR/RTTs. This study also identified the main areas of AP that can be used to develop professional frameworks and education guiding policy by professional bodies, educators and other stakeholders.
Topics: Allied Health Personnel; Humans; Radiation Oncology
PubMed: 35550932
DOI: 10.1016/j.radi.2022.04.009 -
Frontiers in Pharmacology 2023Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited....
Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated. Pubmed, Embase, and Cochrane Library were searched using the keywords "radiotherapy," "immune checkpoint inhibitors," and "non-small cell lung cancer" from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel-Haenszel fixed-effects or random-effects model. The I statistic was used to determine heterogeneity, whereas funnel plots and Egger's test were used to assess publication bias. In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively]. Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.
PubMed: 36762107
DOI: 10.3389/fphar.2023.1064227 -
Clinical Oncology (Royal College of... Oct 2022Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response,...
AIMS
Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.
MATERIALS AND METHODS
A systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.
RESULTS
Of 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30-28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.
CONCLUSIONS
Reporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.
Topics: Ethnicity; Humans; Incidence; Male; Prostatic Neoplasms; Radiation Injuries
PubMed: 35431121
DOI: 10.1016/j.clon.2022.03.013 -
Environmental Science and Pollution... Sep 2020Protection of normal tissues against ionizing radiation-induced damages is a critical issue in clinical and environmental radiobiology. One of the ways of accomplishing...
Protection of normal tissues against ionizing radiation-induced damages is a critical issue in clinical and environmental radiobiology. One of the ways of accomplishing radiation protection is through the use of radioprotectors. In the search for the most effective radioprotective agent, factors such as toxicity, effect on tumors, number of tissues protected, ease of administration, long-term stability, and compatibility with other drugs need to be assessed. Thus, in the present study, we systematically review existing studies on a chemical radioprotector, Ex-RAD, with the aim of examining its efficacy of radiation protection as well as underlying mechanisms. To this end, a systematic search of the electronic databases including Pubmed, Scopus, Embase, and Google Scholar was conducted to retrieve articles investigating the radioprotective effect of Ex-RAD. From an initial search of 268 articles, and after removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 10 articles were finally included for this systematic review. Findings from the reviewed studies indicated that Ex-RAD showed potentials for effective radioprotection of the studied organs with no side effect. Furthermore, the inhibition of apoptosis through p53 signaling pathway was the main mechanism of radioprotection by Ex-RAD. However, its radioprotective effect would need to be investigated for more organs in future studies.
Topics: Radiation Protection; Radiation, Ionizing; Radiation-Protective Agents; Sulfonamides
PubMed: 32583118
DOI: 10.1007/s11356-020-09618-y -
Head & Neck Dec 2023This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue... (Review)
Review
This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD and TD = 68 Gy as the maximum ones. n = 0.06, n = 1.04, m = 0.1, and m = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.
Topics: Humans; Radiotherapy, Conformal; Probability; Head and Neck Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiobiology; Radiotherapy Dosage
PubMed: 37767820
DOI: 10.1002/hed.27469