RESUMEN
BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Docetaxel , Humanos , Estimación de Kaplan-Meier , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Sarcoma de Ewing/mortalidad , España , Tasa de Supervivencia , Taxoides/administración & dosificación , GemcitabinaAsunto(s)
Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Sarcoma , Estudios de Seguimiento , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Sarcoma/terapiaAsunto(s)
Neoplasias Óseas , Osteosarcoma , Sarcoma , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/epidemiología , Neoplasias Óseas/terapia , Estudios de Seguimiento , Humanos , Osteosarcoma/diagnóstico , Osteosarcoma/epidemiología , Osteosarcoma/terapia , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/terapiaAsunto(s)
Neoplasias Óseas/terapia , Oncología Médica/normas , Osteosarcoma/terapia , Participación del Paciente , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/epidemiología , Neoplasias Óseas/patología , Huesos/diagnóstico por imagen , Huesos/patología , Huesos/cirugía , Niño , Europa (Continente) , Humanos , Incidencia , Cuidados a Largo Plazo/métodos , Cuidados a Largo Plazo/normas , Imagen por Resonancia Magnética , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Estadificación de Neoplasias , Procedimientos Ortopédicos/métodos , Procedimientos Ortopédicos/normas , Osteosarcoma/diagnóstico , Osteosarcoma/epidemiología , Osteosarcoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Cintigrafía , Radioterapia Adyuvante/métodos , Radioterapia Adyuvante/normas , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Supervivencia , Resultado del TratamientoAsunto(s)
Oncología Médica/normas , Participación del Paciente , Sarcoma/terapia , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Europa (Continente) , Humanos , Incidencia , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Clasificación del Tumor , Estadificación de Neoplasias , Radioterapia Adyuvante/métodos , Radioterapia Adyuvante/normas , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/patología , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Procedimientos Quirúrgicos Operativos/métodos , Procedimientos Quirúrgicos Operativos/normas , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normas , Resultado del TratamientoAsunto(s)
Tumores del Estroma Gastrointestinal/terapia , Oncología Médica/normas , Participación del Paciente , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/normas , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Endosonografía , Europa (Continente) , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/patología , Humanos , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/normas , Incidencia , Intestinos/diagnóstico por imagen , Intestinos/patología , Intestinos/cirugía , Laparoscopía/métodos , Laparoscopía/normas , Márgenes de Escisión , Oncología Médica/métodos , Estadificación de Neoplasias , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Estómago/diagnóstico por imagen , Estómago/patología , Estómago/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Coxs regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.
Asunto(s)
Biomarcadores de Tumor/genética , Ciclina D3/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias de la Vejiga Urinaria/genética , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.
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Hematología , Neoplasias , Niño , Consenso , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/terapia , Medicina de Precisión/métodos , EspañaRESUMEN
Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region 1A (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.
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Proteínas E1A de Adenovirus/metabolismo , Genes Virales/fisiología , Proteínas de Fusión Oncogénica/genética , Oncogenes/genética , Sarcoma de Ewing/genética , Factores de Transcripción/genética , Proteínas E1A de Adenovirus/genética , Adenovirus Humanos/genética , Secuencia de Bases , Línea Celular , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 22/genética , Fibroblastos , Regulación Neoplásica de la Expresión Génica , Genes Virales/genética , Humanos , Hibridación Fluorescente in Situ , Queratinocitos , Datos de Secuencia Molecular , Peso Molecular , Mutación , Proteínas de Fusión Oncogénica/biosíntesis , Oncogenes/fisiología , Proteína Proto-Oncogénica c-fli-1 , ARN Mensajero/análisis , ARN Mensajero/genética , Proteína EWS de Unión a ARN , Sarcoma de Ewing/metabolismo , Factores de Transcripción/biosíntesis , Translocación Genética/genéticaRESUMEN
The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System.
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Consenso , Glicoproteínas de Membrana/genética , Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética , Adulto , Factores de Edad , Benzamidas/uso terapéutico , Niño , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Indazoles/uso terapéutico , Terapia Molecular Dirigida , Neoplasias/diagnóstico , Neoplasias/terapia , Proteínas de Fusión Oncogénica/análisis , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sociedades Médicas , EspañaRESUMEN
BACKGROUND: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded. METHODS: In this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes. RESULTS: In human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a reduced fitness during hypoxic induction. CONCLUSIONS: These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α over-activation.
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Neoplasias de la Mama , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Hipoxia de la Célula , Cromatina , Femenino , Humanos , HipoxiaRESUMEN
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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Hemangioendotelioma Epitelioide , Sarcoma , Adulto , Niño , Consenso , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/tratamiento farmacológico , Humanos , Oncología Médica , Defensa del Paciente , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológicoRESUMEN
The article Liquid biopsy in oncology.
RESUMEN
The proportion of cancer patients with tumours that harbour a potentially targetable genomic alteration is growing considerably. The diagnosis of these genomic alterations can lead to tailored treatment at the onset of disease or on progression and to obtaining additional predictive information on immunotherapy efficacy. However, in up to 25% of cases, the initial tissue biopsy is inadequate for precision oncology and, in many cases, tumour genomic profiling at progression is not possible due to technical limitations of obtaining new tumour tissue specimens. Efficient diagnostic alternatives are therefore required for molecular stratification, which includes liquid biopsy. This technique enables the evaluation of the tumour genomic profile dynamically and captures intra-patient genomic heterogeneity as well. To date, there are several diagnostic techniques available for use in liquid biopsy, each one of them with different precision and performance levels. The objective of this consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology is to evaluate the viability and effectiveness of the different methodological approaches in liquid biopsy in cancer patients and the potential application of this method to current clinical practice. The experts contributing to this consensus statement agree that, according to current evidence, liquid biopsy is an acceptable alternative to tumour tissue biopsy for the study of biomarkers in various clinical settings. It is therefore important to standardise pre-analytical and analytical procedures, to ensure reproducibility and generate structured and accessible clinical reports. It is essential to appoint multidisciplinary tumour molecular boards to oversee these processes and to enable the most suitable therapeutic decisions for each patient according to the genomic profile.
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Biopsia Líquida/normas , Oncología Médica/normas , Neoplasias/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Consenso , Genómica , Humanos , Biopsia Líquida/métodos , Oncología Médica/organización & administración , Neoplasias/genética , Medicina de Precisión , Reproducibilidad de los Resultados , EspañaRESUMEN
BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and many have been identified in heterologous model systems. METHODS: We have developed a stable RNA interference model knocking down EWS-FLI1 in the Ewing sarcoma cell line TC71. Gene expression analyses were performed to study the effect of RNA interference on the genetic signature of EWS-FLI1 and to identify genes that could contribute to tumourigenesis. RESULTS: EWS-FLI1 inhibition induced apoptosis, reduced cell migratory and tumourigenic capacities, and caused reduction in tumour growth. IGF-1 was downregulated and the IGF-1/IGF-1R signalling pathway was impaired. PBK/TOPK (T-LAK cell-originated protein kinase) expression was decreased because of EWS-FLI1 inhibition. We showed that TOPK is a new target gene of EWS-FLI1. TOPK inhibition prompted a decrease in the proliferation rate and a dramatic change in the cell's ability to grow in coalescence. CONCLUSION: This is the first report of TOPK activity in Ewing sarcoma and suggests a significant role of this MAPKK-like protein kinase in the Ewing sarcoma biology.
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Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/biosíntesis , Receptor IGF Tipo 1/metabolismo , Sarcoma de Ewing/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Regulación hacia Abajo , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/antagonistas & inhibidores , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Factor I del Crecimiento Similar a la Insulina/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteína Proto-Oncogénica c-fli-1 , Interferencia de ARN , Proteína EWS de Unión a ARN , Receptor IGF Tipo 1/antagonistas & inhibidores , Receptor IGF Tipo 1/biosíntesis , Receptor IGF Tipo 1/genética , Sarcoma de Ewing/enzimología , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Radiofrequency heating of the intervertebral disc has been proposed for the treatment of chronic low back pain using two methods: a flexible needle inserted into the annulus fibrosus achieving a full 360 degrees penetration, or a rigid needle inserted into the nucleus pulposus. The first technique is effective on pain, but the clinical benefit of the second is uncertain. PURPOSE: To evaluate a technique for radiofrequency heating of the lumbar intervertebral disc by a needle placed into the nucleus pulposus. MATERIAL AND METHODS: The method was tested in 17 patients according to the criteria used in previous intradiscal radiofrequency studies. Before and after treatment, disability was assessed by the Oswestry disability score. A pain reduction of at least 50% was considered a success. RESULTS: Fifteen patients were responders at 1 month (88%), nine at 3 months (53%), and 12 at 6 months (70.6%). No complications were observed. CONCLUSION: A new method of providing discal radiofrequency treatment for lower back pain had a substantial clinical benefit in 71% of the observed patients. A prospective study comparing this new method with placebo should be conducted to confirm these initial results.
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Ablación por Catéter/métodos , Disco Intervertebral/cirugía , Dolor de la Región Lumbar/cirugía , Cloruro de Sodio/administración & dosificación , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dimensión del Dolor/métodos , Dimensión del Dolor/estadística & datos numéricos , Estudios Retrospectivos , Conductividad TérmicaRESUMEN
Animals inheriting the slick hair gene have a short, sleek, and sometimes glossy coat. The objective of the present study was to determine whether slick-haired Holstein cows regulate body temperature more effectively than wild-type Holstein cows when exposed to an acute increase in heat stress. Lactating slick cows (n = 10) and wild-type cows (n = 10) were placed for 10 h in an indoor environment with a solid roof, fans, and evaporative cooling or in an outdoor environment with shade cloth and no fans or evaporative cooling. Cows were exposed to both environments in a single reversal design. Vaginal temperature, respiration rate, surface temperature, and sweating rate were measured at 1200, 1500, 1800, and 2100 h (replicate 1) or 1200 and 1500 h (replicate 2), and blood samples were collected for plasma cortisol concentration. Cows in the outdoor environment had higher vaginal and surface temperatures, respiration rates, and sweating rates than cows in the indoor environment. In both environments, slick-haired cows had lower vaginal temperatures (indoor: 39.0 vs. 39.4 degrees C; outdoor 39.6 vs. 40.2 degrees C; SEM = 0.07) and respiration rate (indoor: 67 vs. 79 breaths/ min; outdoor 97 vs. 107 breaths/min; SEM = 5.5) than wild-type cows and greater sweating rates in unclipped areas of skin (indoor: 57 vs. 43 g x h(-1)/m(2); outdoor 82 vs. 61 g x h(-1)/m(2); SEM = 8). Clipping the hair at the site of sweating measurement eliminated the difference between slick-haired and wild-type cows. Results indicate that slick-haired Holstein cows can regulate body temperature more effectively than wild-type cows during heat stress. One reason slick-haired animals are better able to regulate body temperature is increased sweating rate.