Pre-Clinical In Vitro Models Used in Cancer Research: Results of a Worldwide Survey.
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ABSTRACT:
SUBMITTER: Martinez-Pacheco S
PROVIDER: S-EPMC8656628 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey®. Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis.
| S-EPMC9708574 | biostudies-literature
Project description:Extracellular vesicles (EVs) represent an important mode of intercellular communication. Research in this field has grown rapidly in the last few years, and there is a plethora of techniques for the isolation and characterization of EVs, many of which are poorly standardized. EVs are heterogeneous in size, origin and molecular constituents, with considerable overlap in size and phenotype between different populations of EVs. Little is known about current practices for the isolation, purification and characterization of EVs. We report here the first large, detailed survey of current worldwide practices for the isolation and characterization of EVs. Conditioned cell culture media was the most widely used material (83%). Ultracentrifugation remains the most commonly used isolation method (81%) with 59% of respondents use a combination of methods. Only 9% of respondents used only 1 characterization method, with others using 2 or more methods. Sample volume, sample type and downstream application all influenced the isolation and characterization techniques employed.
| S-EPMC5090131 | biostudies-literature
Project description:AimsWe sought to objectively assess the internal and external validity of patient-derived xenograft (PDX) models as a platform in pre-clinical research into colorectal cancer (CRC). Metastatic disease is the most common cause of death from CRC, and despite significant research, the results of current combination chemotherapy and targeted therapies have been underwhelming for most of this patient group. One of the key factors limiting the success of translational CRC research is the biologically inaccurate models in which new therapies are developed.MethodsWe used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist and SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) guidelines to search Ovid MEDLINE and Embase databases up to July 2015 to identify studies involving PDX models of CRC where the model had been validated across multiple parameters. Data was extracted including host mouse strain, engraftment rate, site of engraftment, donor tumour source and development of metastases in the model.ResultsThirteen articles satisfied the inclusion criteria. There was significant heterogeneity amongst the included studies, but overall the median engraftment rate was high (70%) and PDX models faithfully recapitulated the characteristics of their patient tumours on the microscopic, genetic and functional levels.ConclusionsPDX models of CRC have a reasonable internal validity and a high external validity. Developments in xenografting technology are broadening the applications of the PDX platform. However, the included studies could be improved by standardising reporting standards and closed following the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines.
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Project description:Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.
| S-EPMC6040159 | biostudies-literature
Project description:BACKGROUND: The primary objective was to systematically review the medical literature for instruments validated for use in epidemiological and clinical research on waterpipe smoking. METHODS: We searched the following databases: MEDLINE, EMBASE, and ISI the Web of Science. We selected studies using a two-stage duplicate and independent screening process. We included papers reporting on the development and/or validation of survey instruments to measure waterpipe tobacco consumption or related concepts. Two reviewers used a standardized and pilot tested data abstraction form to collect data from each eligible study using a duplicate and independent screening process. We also determined the percentage of observational studies assessing the health effects of waterpipe tobacco smoking and the percentage of studies of prevalence of waterpipe tobacco smoking that have used validated survey instruments. RESULTS: We identified a total of five survey instruments. One instrument was designed to measure knowledge, attitudes, and waterpipe use among pregnant women and was shown to have internal consistency and content validity. Three instruments were designed to measure waterpipe tobacco consumption, two of which were reported to have face validity. The fifth instrument was designed to measure waterpipe dependence and was rigorously developed and validated. One of the studies of prevalence and none of the studies of health effects of waterpipe smoking used validated instruments. CONCLUSIONS: A number of instruments for measuring the use of and dependence on waterpipe smoking exist. Future research should study content validity and cross cultural adaptation of these instruments.
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is a hostile solid malignancy coupled with an extremely high mortality rate. Metastatic disease is already found in most patients at the time of diagnosis, resulting in a 5-year survival rate below 5%. Improved comprehension of the mechanisms leading to metastasis is pivotal for the development of new targeted therapies. A key field to be improved are modeling strategies applied in assessing cancer progression, since traditional platforms fail in recapitulating the complexity of PDAC. Consequently, there is a compelling demand for new preclinical models that mirror tumor progression incorporating the pressure of the immune system, tumor microenvironment, as well as molecular aspects of PDAC. We suggest the incorporation of 3D organoids derived from genetically engineered mouse models or patients as promising new tools capable to transform PDAC pre-clinical modeling and access new frontiers in personalized medicine.
| S-EPMC8578999 | biostudies-literature
Project description:The National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) collect sample data and publish annual estimates of inpatient care in the United States, and both are commonly used in orthopaedic research. However, there are important differences between the databases, and because of these differences, asking these two databases the same question may result in different answers. The degree to which this is true for arthroplasty-related research has, to our knowledge, not been characterized.We tested the following null hypotheses: (1) there are no differences between the NHDS and NIS in patient characteristics, comorbidities, and adverse events in patients with hip osteoarthritis treated with THA, and (2) there are no differences between databases in factors associated with inpatient mortality, adverse events, and length of hospital stay after THA.The NHDS and NIS databases use different methods of data collection and weighting to provide data representative of all nonfederal hospital discharges in the United States. In 2006 the NHDS database contained 203,149 patients with hip arthritis treated with hip arthroplasty, and the NIS database included 193,879 patients. Multivariable analyses for factors associated with inpatient mortality, adverse events, and days of care were constructed for each database.We found that 26 of 42 of the factors in demographics, comorbidities, and adverse events after THA in the NIS and NHDS databases differed more than 10%. Age and days of care were associated with inpatient mortality with the NHDS and the NIS although the effect rates differ more than 10%. The NIS identified seven other factors not identified by the NHDS: wound complications, congestive heart failure, new mental disorder, chronic pulmonary disease, dementia, geographic region Northeast, acute postoperative anemia, and sex, that were associated with inpatient mortality even after controlling for potentially confounding variables. For inpatient adverse events, atrial fibrillation, osteoporosis, and female sex were associated with the NHDS and the NIS although the effect rates differ more than 10%. There were different directions for sources of payment, dementia, congestive heart failure, and geographic region. For longer length of stay, common factors differing more than 10% in effect rate included chronic pulmonary disease, atrial fibrillation, complication not elsewhere classified, congestive heart failure, transfusion, discharge nonroutine compared with routine, acute postoperative anemia, hypertension, wound adverse events, and diabetes mellitus, whereas discrepant factors included geographic region, payment method, dementia, sex, and iatrogenic hypotension.Studies that use large databases intended to be representative of the entire United States population can produce different results, likely related to differences in the databases, such as the number of comorbidities and procedures that can be entered in the database. In other words, analyses of large databases can have limited reliability and should be interpreted with caution.Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
| S-EPMC4182371 | biostudies-other
Project description:The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies; chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.
| S-EPMC7312079 | biostudies-literature
Project description:BackgroundUnderstanding how biological factors contribute to prostate cancer (PCa) health disparities requires mechanistic functional analysis of specific genes or pathways in pre-clinical cellular and animal models of this malignancy. The 22Rv1 human prostatic carcinoma cell line was originally derived from the parental CWR22R cell line. Although 22Rv1 has been well characterized and used in numerous mechanistic studies, no racial identifier has ever been disclosed for this cell line. In accordance with the need for racial diversity in cancer biospecimens and recent guidelines by the NIH on authentication of key biological resources, we sought to determine the ancestry of 22RV1 and authenticate previously reported racial identifications for four other PCa cell lines.MethodsWe used 29 established Ancestry Informative Marker (AIM) single nucleotide polymorphisms (SNPs) to conduct DNA ancestry analysis and assign ancestral proportions to a panel of five PCa cell lines that included 22Rv1, PC3, DU145, MDA-PCa-2b, and RC-77T/E.ResultsWe found that 22Rv1 carries mixed genetic ancestry. The main ancestry proportions for this cell line were 0.41 West African (AFR) and 0.42 European (EUR). In addition, we verified the previously reported racial identifications for PC3 (0.73 EUR), DU145 (0.63 EUR), MDA-PCa-2b (0.73 AFR), and RC-77T/E (0.74 AFR) cell lines.ConclusionsConsidering the mortality disparities associated with PCa, which disproportionately affect African American men, there remains a burden on the scientific community to diversify the availability of biospecimens, including cell lines, for mechanistic studies on potential biological mediators of these disparities. This study is beneficial by identifying another PCa cell line that carries substantial AFR ancestry. This finding may also open the door to new perspectives on previously published studies using this cell line.
| S-EPMC5687283 | biostudies-literature
Project description:ObjectiveTo inform whether the Alzheimer's Disease Neuroimaging Initiative (ADNI) should change its policy of not returning research results to ADNI participants, we surveyed investigators and research staff about disclosing ADNI biomarker information to research participants, with particular emphasis on amyloid imaging results.MethodsIn April 2012, just before Food and Drug Administration approval of the amyloid-binding radiotracer, florbetapir, all ADNI investigators and personnel were recruited to complete an anonymous online survey that contained fixed choice and free-text questions.ResultsAlthough ADNI participants often requested amyloid imaging results (the proportions of investigators who reported requests from more than half of their participants with normal cognition or mild cognitive impairment were 20% and 22%, respectively), across all diagnostic groups, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to ADNI participants. However, the majority of investigators reported that, if the Food and Drug Administration approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, but they emphasized the need for guidance on how to provide these results to participants and for research to assess the value of returning results as well as how returning results will affect study validity and participant well-being.ConclusionsA majority of ADNI investigators support returning amyloid imaging results to ADNI participants. The findings that they want guidance on how to do this and research on the impact of disclosure suggest how to develop and monitor a disclosure process.
| S-EPMC3795601 | biostudies-literature