Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Ultrasound Med Biol ; 50(8): 1247-1254, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38834492

RESUMO

OBJECTIVE: Needle biopsy is a common technique used to obtain cell and tissue samples for diagnostics. Currently, two biopsy methods are widely used: (i) fine-needle aspiration biopsy (FNAB) and (ii) core needle biopsy (CNB). However, these methods have limitations. Recently, we developed ultrasound-enhanced fine-needle aspiration biopsy (USeFNAB), which employs a needle that flexurally oscillates at an ultrasonic frequency of ∼32 kHz. The needle motion contributes to increased tissue collection while preserving cells and tissue constructs for pathological assessment. Previously, USeFNAB has been investigated only in ex vivo animal tissue. The present study was aimed at determining the feasibility of using USeFNAB in human epithelial and lymphoid tissue. METHODS: Needle biopsy samples were acquired using FNAB, CNB and USeFNAB on ex vivo human tonsils (N = 10). The tissue yield and quality were quantified by weight measurement and blinded pathologists' assessments. The biopsy methods were then compared. RESULTS: The results revealed sample mass increases of, on average, 2.3- and 5.4-fold with USeFNAB compared with the state-of-the-art FNAB and CNB, respectively. The quality of tissue fragments collected by USeFNAB was equivalent to that collected by the state-of-the-art methods in terms of morphology and immunohistochemical stainings made from cell blocks as judged by pathologists. CONCLUSION: Our study indicates that USeFNAB is a promising method that could improve tissue yield to ensure sufficient material for ancillary histochemical and molecular studies for diagnostic pathology, thereby potentially increasing diagnostic accuracy.


Assuntos
Tecido Linfoide , Tonsila Palatina , Humanos , Tonsila Palatina/patologia , Tonsila Palatina/diagnóstico por imagem , Tecido Linfoide/patologia , Tecido Linfoide/diagnóstico por imagem , Biópsia por Agulha Fina/métodos , Estudos de Viabilidade , Ultrassonografia de Intervenção/métodos , Biópsia Guiada por Imagem/métodos , Epitélio/patologia
2.
Appl Immunohistochem Mol Morphol ; 31(6): 399-405, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37249075

RESUMO

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Hiperplasia , Variações Dependentes do Observador , Gradação de Tumores , Proteína A7 Ligante de Cálcio S100
3.
J Acoust Soc Am ; 151(6): 3690, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35778205

RESUMO

Ultrasonic cavitation is being used in medical applications as a way to influence matter, such as tissue or drug vehicles, on a micro-scale. Oscillating or collapsing cavitation bubbles provide transient mechanical force fields, which can, e.g., fractionate soft tissue or even disintegrate solid objects, such as calculi. Our recent study demonstrates that an ultrasonically actuated medical needle can create cavitation phenomena inside water. However, the presence and behavior of cavitation and related bioeffects in diagnostic and therapeutic applications with ultrasonically actuated needles are not known. Using simulations, we demonstrate numerically and experimentally the cavitation phenomena near ultrasonically actuated needles. We define the cavitation onset within a liver tissue model with different total acoustic power levels. We directly visualize and quantitatively characterize cavitation events generated by the ultrasonic needle in thin fresh bovine liver sections enabled by high-speed imaging. On a qualitative basis, the numerical and experimental results show a close resemblance in threshold and spatial distribution of cavitation. These findings are crucial for developing new methods and technologies employing ultrasonically actuated fine needles, such as ultrasound-enhanced fine-needle biopsy, drug delivery, and histotripsy.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Acústica , Animais , Bovinos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Fígado/diagnóstico por imagem , Ultrassonografia , Água
4.
Arthritis Res Ther ; 24(1): 164, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804445

RESUMO

BACKGROUND: Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis. METHODS: We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed. RESULTS: In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease. CONCLUSION: L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.


Assuntos
Anquilose , Sacroileíte , Espondilartrite , Espondilite Anquilosante , Feminino , Antígeno HLA-B27/genética , Humanos , Inflamação/patologia , Lipocalina-2 , Imageamento por Ressonância Magnética , Masculino , Metaloproteinase 9 da Matriz , Articulação Sacroilíaca/patologia , Sacroileíte/patologia , Espondilartrite/diagnóstico por imagem , Espondilartrite/patologia
5.
Sci Rep ; 11(1): 8234, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859220

RESUMO

Despite the ubiquitous use over the past 150 years, the functions of the current medical needle are facilitated only by mechanical shear and cutting by the needle tip, i.e. the lancet. In this study, we demonstrate how nonlinear ultrasonics (NLU) extends the functionality of the medical needle far beyond its present capability. The NLU actions were found to be localized to the proximity of the needle tip, the SonoLancet, but the effects extend to several millimeters from the physical needle boundary. The observed nonlinear phenomena, transient cavitation, fluid streams, translation of micro- and nanoparticles and atomization, were quantitatively characterized. In the fine-needle biopsy application, the SonoLancet contributed to obtaining tissue cores with an increase in tissue yield by 3-6× in different tissue types compared to conventional needle biopsy technique using the same 21G needle. In conclusion, the SonoLancet could be of interest to several other medical applications, including drug or gene delivery, cell modulation, and minimally invasive surgical procedures.


Assuntos
Agulhas , Ultrassonografia de Intervenção , Animais , Biópsia por Agulha Fina/instrumentação , Biópsia por Agulha Fina/métodos , Bovinos , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes/instrumentação , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Imagens de Fantasmas , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodos , Ultrassom/instrumentação , Ultrassom/métodos , Ultrassonografia de Intervenção/instrumentação , Ultrassonografia de Intervenção/métodos
6.
Expert Rev Mol Diagn ; 21(3): 289-298, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33682567

RESUMO

INTRODUCTION: Oral epithelial dysplasia is considered a potential histologic precursor of subsequent squamous cell cancer. As standard clinical practice, pathologists grade dysplasia to assess risk for progression to malignancy. Except for the most advanced grade, severe dysplasia, dysplasia grading has failed to correlate well with the risk to develop invasive cancer. The questions of what process dysplasia grading best represents and what clinical utility dysplasia grading may have are explored. AREAS COVERED: This narrative review is based on PubMed search with emphasis on papers since 2010. Epithelial dysplasia as a precursor lesion of cancer and dysplasia grading as a risk assessment tool for progression to cancer are discussed. The close clinical association of dysplasia with known carcinogens, alcohol, and tobacco products is presented. EXPERT OPINION: Oral epithelial dysplasia is often, associated with prolonged exposure to tobacco and alcohol products. With reduction of carcinogen exposure, dysplasia is known to regress in some cases. It is proposed that histologic dysplasia grade together with macroscopic images of dysplastic clinical lesions be used as an educational tool to incentivize patients to reduce their known carcinogen exposure. This strategy has the potential to reduce lesion progression thereby reducing the disease burden of oral cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Transformação Celular Neoplásica , Humanos , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/etiologia , Leucoplasia Oral/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/etiologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/etiologia
7.
J Pers Med ; 10(4)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066312

RESUMO

The heterogeneity of colon cancers and their reactions presents both a challenge and promise for personalized medicine. The challenge is to develop effective biologically personalized therapeutics guided by predictive and prognostic biomarkers. Presently, there are several classes of candidate biomarkers, including genomic probes, inhibitory RNAs, assays for immunity dysfunction and, not to be forgotten, specific histopathologic and histochemical features. To develop effective therapeutics, candidate biomarkers must be qualified and validated in comparable independent cohorts, no small undertaking. This process and subsequent deployment in clinical practice involves not only the strong association of the biomarker with the treatment but also careful attention to the prosaic aspects of representative tumor site selection, obtaining a fully adequate sample which is preserved and prepared to optimize high quality analysis. In the future, the clinical utility of biomarker analytical results will benefit from associated clinical and basic science data with the assistance of artificial intelligence techniques. By application of an individualized, selected suite of biomarkers, comprehensively interpreted, individualized, more effective and less toxic therapy for colon cancer will be enabled, thereby fulfilling the promise of personalized medicine.

8.
Arthritis Res Ther ; 22(1): 51, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188494

RESUMO

BACKGROUND: Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis. METHODS: Baseline colonic pathology was conducted in the ank/ank mouse model. Serum lipocalin 2 was analyzed by ELISA, in ank/ank mutants versus C3FeB6-A/Aw-jwt/wt, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the ank/ank mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was examined by real-time PCR. Intraperitoneal injection was done with the PPARγ agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day. RESULTS: This study showed that the ank/ank mice with fully fused spines had concurrent colonic inflammation. By first using the ank/ank mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the ank/ank mouse model involving PPARγ. Colonic expression of PPARγ was negatively associated with the degree of gut inflammation. The PPARγ agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPARγ in the aberrant expression of lipocalin 2. CONCLUSIONS: In summary, lipocalin 2 modulated by PPARγ could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.


Assuntos
Anquilose/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Lipocalina-2/metabolismo , Espondilite Anquilosante/metabolismo , Animais , Anquilose/sangue , Anquilose/genética , Feminino , Humanos , Inflamação/sangue , Inflamação/genética , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Lipocalina-2/sangue , Lipocalina-2/genética , Masculino , Camundongos Knockout , PPAR gama/agonistas , PPAR gama/genética , PPAR gama/metabolismo , Rosiglitazona/farmacologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/genética , Regulação para Cima/efeitos dos fármacos
9.
BMC Vet Res ; 15(1): 453, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842875

RESUMO

BACKGROUND: Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms. RESULTS: An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival. CONCLUSIONS: Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma não Hodgkin/veterinária , RNA Neoplásico/análise , Animais , Ciclofosfamida/uso terapêutico , Cães , Doxorrubicina/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Prednisona/uso terapêutico , Intervalo Livre de Progressão , Vincristina/uso terapêutico
10.
Arch Pathol Lab Med ; 143(11): 1399-1415, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31100015

RESUMO

CONTEXT.­: Needle biopsy of diseased tissue is an essential diagnostic tool that is becoming even more important as precision medicine develops. However, the capability of this modality to efficiently provide samples adequate for diagnostic and prognostic analysis remains quite limited relative to current diagnostic needs. For physicians and patients, inadequate biopsy frequently leads to diagnostic delay, procedure duplication, or insufficient information about tumor biology leading to delay in treatment; for health systems, this results in substantial incremental costs and inefficient use of scarce specialized diagnostic resources. OBJECTIVE.­: To review current needle biopsy technology, devices, and practice with a perspective to identify current limitations and opportunities for improvement in the context of advancing precision medicine. DATA SOURCES.­: PubMed searches of fine-needle aspiration and core needle biopsy devices and similar technologies were made generally, by tissue site, and by adequacy as well as by health economics of these technologies. CONCLUSIONS.­: Needle biopsy adequacy can be improved by recognizing the importance of this diagnostic tool by promoting common criteria for needle biopsy adequacy; by optimizing needle biopsy procedural technique, technologies, clinical practice, professional education, and quality assurance; and by bundling biopsy procedure costs with downstream diagnostic modalities to provide better accountability and incentives to improve the diagnostic process.


Assuntos
Biópsia por Agulha Fina/normas , Medicina de Precisão , Biópsia por Agulha Fina/economia , Biópsia por Agulha Fina/instrumentação , Diagnóstico Tardio , Humanos
11.
J Orthop Res ; 37(4): 855-866, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30737811

RESUMO

One of the earliest changes in osteoarthritis (OA) is a surface discontinuity of the articular cartilage (AC), and these surface changes become gradually more complex with OA progression. We recently developed a contrast enhanced micro-computed tomography (µCT) method for visualizing AC surface in detail. The present study aims to introduce a µCT analysis technique to parameterize these complex AC surface features and to demonstrate the feasibility of using these parameters to quantify degenerated AC surface. Osteochondral plugs (n = 35) extracted from 19 patients undergoing joint surgery were stained with phosphotungstic acid and imaged using µCT. The surface micro-topography of AC was analyzed with developed method. Standard root mean square roughness (Rq ) was calculated as a reference, and the Area Under Curve (AUC) for receiver operating characteristic analysis was used to compare the acquired quantitative parameters with semi-quantitative visual grading of µCT image stacks. The parameters quantifying the complex micro-topography of AC surface exhibited good sensitivity and specificity in identifying surface continuity (AUC: 0.93, [0.80 0.99]), fissures (AUC: 0.94, [0.83 0.99]) and fibrillation (AUC: 0.98, [0.88 1.0]). Standard Rq was significantly smaller compared with the complex roughness (CRq ) already with mild surface changes with all surface reference parameters - continuity, fibrillation, and fissure sum. Furthermore, only CRq showed a significant difference when comparing the intact surface with lowest fissure sum score. These results indicate that the presented method for evaluating complex AC surfaces exhibit potential to identify early OA changes in superficial AC and is dynamic throughout OA progression. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. Society. 9999:1-12, 2019.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Ácido Fosfotúngstico , Microtomografia por Raio-X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem
14.
Oral Oncol ; 72: 1-6, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28797444

RESUMO

OBJECTIVES: Straticyte™ was previously shown to be a more effective prognostic assessment than the current standard of care, histopathological dysplasia grading, to assess progression risk of oral epithelial dysplasia to invasive cancer [Hwang JT, Gu YR, Shen M, Ralhan R, Walfish PG, Pritzker KP, et al. Individualized five-year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:374-81]. In this follow-up study, our aim is to confirm the prognostic value of Straticyte using an independent cohort of oral biopsy cases previously assessed as epithelial dysplasia of various grades. MATERIALS AND METHODS: Using Visiopharm image analysis system, we analyzed an independent retrospective cohort of 51 oral biopsy samples with known outcomes and a follow-up history of up to 12years, to verify Straticyte, an individualized 5-year risk assessment for progression of oral potentially malignant lesions to invasive squamous cell carcinoma. RESULTS: Straticyte classified the lesions more accurately than histopathological oral epithelial dysplasia grading for risk for progression to cancer over five years. The sensitivity of low-risk vs. non-low-risk Straticyte groups was 100% compared to 68% for mild vs. non-mild dysplasia. The sensitivity of high-risk vs. non-high-risk Straticyte was 71% compared to 3% for severe vs. non-severe dysplasia. Furthermore, the Negative Predictive Value (NPV) for Straticyte was 100% for low-risk vs. non-low-risk, whereas the NPV for mild vs. non-mild dysplasia was 38%. CONCLUSION: In this cohort, Straticyte ascertains as a more useful assessment for risk of cancer progression in oral potentially malignant lesions than oral epithelial dysplasia grade.

15.
Artigo em Inglês | MEDLINE | ID: mdl-28110942

RESUMO

OBJECTIVE: The standard of care for premalignant lesion risk assessment is dysplasia grading by histopathology. With significant overlap between dysplasia grades and high inter- and intraobserver variations, histopathology dysplasia grading alone is not a useful prognostic tool. Our aim is to investigate whether a method for quantitatively assessing S100A7, a prognostic biomarker, using image analysis can better predict clinical outcome in cases with oral dysplasia. STUDY DESIGN: Using the Visiopharm image analysis system, we analyzed a cohort of 150 oral biopsy samples to build and test Straticyte, a model for individualized assessment of the 5-year risk of progression of oral precancerous lesions to invasive squamous cell carcinomas. RESULTS: Straticyte classified lesions more accurately than histopathological dysplasia grading for risk to progression to cancer over the following 5 years. The sensitivity of low-risk versus intermediate- and high-risk Straticyte groups was 95% compared to 75% for mild versus moderate and severe dysplasia. Furthermore, the negative predictive value for low-risk versus intermediate- and high-risk Straticyte groups was 78% compared to 59% for mild versus moderate and severe dysplasia. CONCLUSION: By quantitatively assessing S100A7, Straticyte better defines the risk for developing oral squamous cell carcinoma than histopathological dysplasia grading alone.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Medição de Risco
16.
Am J Primatol ; 78(1): 152-66, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25771746

RESUMO

While osteopenia (OPE) and osteoporosis (OPO) have been studied in various species of aging nonhuman primates and extensively in ovariectomized rhesus and cynomolgus macaques, there is virtually no information on the effects of castration on the skeleton of male nonhuman primates. Most information on castrated male primates comes from a few studies on the skeletons of eunuchs. This report used a subset of the Caribbean Primate Research Center's (CPRC) Cayo Santiago (CS) rhesus macaque skeletal collection to qualitatively and quantitatively compare the bone mineral density (BMD) of castrated and age-matched intact males and, thereby, determine the long-term effects of castration (orchidectomy) on bone. Lumbar vertebrae, femora, and crania were evaluated using dual-energy X-ray absorptiometry (DEXA or DXA) and digital radiography augmented, when fresh tissues were available, with autoradiography and histology. Results confirmed physical examinations of long bones that castration causes changes in the skeleton of male rhesus macaques similar to those found in eunuchs, including OPE and OPO of the vertebrae and femora, thinning of the skull, and vertebral fractures and kyphosis of the spine more severe than that caused by normal aging alone. Also like eunuchs, some castrated CS male rhesus monkeys had a longer life span than intact males or females. Based on these results and the effects of castration on other tissues and organs of eunuchs, on behavior, hormone profiles and possibly on cognition and visual perception of human and nonhuman primates, and other mammals, castrated male rhesus macaques should be used with caution for laboratory studies and should be considered a separate category from intact males. Despite these caveats, the castrated male rhesus macaque should make an excellent animal model in which to test hormone replacement therapies for boys and men orchidectomized for testicular and prostate cancer.


Assuntos
Densidade Óssea , Fêmur/fisiologia , Vértebras Lombares/fisiologia , Macaca mulatta/fisiologia , Orquiectomia/veterinária , Crânio/fisiologia , Absorciometria de Fóton/veterinária , Animais , Autorradiografia/veterinária , Masculino , Porto Rico , Intensificação de Imagem Radiográfica
17.
Breast Cancer Res Treat ; 153(1): 135-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26208483

RESUMO

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , RNA Neoplásico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Resultado do Tratamento
18.
Expert Rev Mol Diagn ; 15(8): 971-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26134385

RESUMO

While both prognostic and predictive cancer biomarkers predict clinical outcome, the term 'predictive biomarker' is reserved for the association of a specific therapy with a specific clinical outcome. The advent of genomic signatures and next generation sequencing as candidate predictive biomarkers has led to lengthy and expensive processes for biomarker qualification. The urgency to bring novel predictive cancer biomarkers to practice faster and cheaper requires strategies to lower the bar to biomarker implementation. Three strategies are suggested: identify biomarkers closely coupled to biologic mechanism associated with the clinical endpoint and scalable from cells to humans; identify biomarkers that can be reliably detected and quantified; and assess biomarkers by capacity to reduce toxicity as well as to increase therapy efficacy. Biomarker selection directly and closely related to production of end points by biologic mechanism demonstrated by a ladder of evidence should require less burden of proof clinically than biomarkers that are merely associative.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias/metabolismo , Humanos , Prognóstico
19.
Endocr Relat Cancer ; 21(3): 459-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24812057

RESUMO

Androgen hormones and the androgen receptor (AR) pathway are the main targets of anti-hormonal therapies for prostate cancer. However, resistance inevitably develops to treatments aimed at the AR pathway resulting in androgen-independent or hormone-refractory prostate cancer (HRPC). Therefore, there is a significant unmet need for new, non-androgen anti-hormonal strategies for the management of prostate cancer. We demonstrate that a relaxin hormone receptor antagonist, AT-001, an analog of human H2 relaxin, represents a first-in-class anti-hormonal candidate treatment designed to significantly curtail the growth of androgen-independent human prostate tumor xenografts. Chemically synthesized AT-001, administered subcutaneously, suppressed PC3 xenograft growth by up to 60%. AT-001 also synergized with docetaxel, standard first-line chemotherapy for HRPC, to suppress tumor growth by more than 98% in PC3 xenografts via a mechanism involving the downregulation of hypoxia-inducible factor 1 alpha and the hypoxia-induced response. Our data support developing AT-001 for clinical use as an anti-relaxin hormonal therapy for advanced prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de Peptídeos/antagonistas & inibidores , Taxoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ligação Competitiva , Western Blotting , Proliferação de Células/efeitos dos fármacos , Docetaxel , Sinergismo Farmacológico , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Orthop Clin North Am ; 43(2): 155-71, v, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22480466

RESUMO

In this article, development of articular cartilage and endochondral ossification is reviewed, from the perspective of both morphologic aspects of histogenesis and molecular biology, particularly with respect to key signaling molecules and extracellular matrix components most active in cartilage development. The current understanding of the roles of transforming growth factor ß and associated signaling molecules, bone morphogenic proteins, and molecules of the Wnt-ß catenin system in chondrogenesis are described. Articular cartilage development is a highly conserved complex biological process that is dynamic and robust in nature, which proceeds well without incident or failure in all joints of most young growing individuals.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Cartilagem Articular/metabolismo , Condrogênese/genética , Fator de Crescimento Transformador beta/metabolismo , Adulto , Fatores Etários , Biópsia por Agulha , Proteínas Morfogenéticas Ósseas/genética , Cartilagem Articular/patologia , Criança , Pré-Escolar , Condrócitos/metabolismo , Condrogênese/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Biologia Molecular , Transdução de Sinais , Fator de Crescimento Transformador beta/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA