RESUMEN
Percutaneous image-guided biopsies help better select patients with renal tumors smaller than 4cm. These biopsies are performed to reduce the risks of overtreatment and to discriminate between patients who need ablation therapy and those who require active surveillance. Percutaneous image-guided biopsies are effective for a definitive diagnosis with little risk of complications when cautions are observed. With the current addition of multiparametric imaging, standardized biopsy protocols may further help adapt therapeutic decisions. The aim of this review is to report the current indications and techniques of biopsy performed in case of small solid renal masses and to clarify the optimal conditions for the realization of these biopsies.
Asunto(s)
Biopsia con Aguja/métodos , Biopsia Guiada por Imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Técnicas de Ablación , Biopsia con Aguja/efectos adversos , Humanos , Consentimiento Informado , Neoplasias Renales/cirugía , Siembra Neoplásica , Pronóstico , Espera VigilanteRESUMEN
PURPOSE: Few studies have described the epidemiology of human papillomavirus (HPV) in vulvar intraepithelial neoplasia (VIN). The aim of this study was to genotype HPV on formalin fixed paraffin-embedded tissues in VIN lesions. METHODS: A 5-year retrospective study was conducted by including all patients attending the teaching hospital of Nice with a diagnosis of VIN between 1st January 2010 and 31st December 2014. For all patients, HPV genotyping was performed with the PapilloCheck® microarray kit, routinely used on cervical cytology samples, and optimized for formaldehyde fixed paraffin-embedded tissues in VIN. RESULTS: Forty patients were included in the study: 39 patients had usual VIN and one presented with differentiated VIN. Among the 39 patients with usual VIN, the prevalence of HPV was 90% (35/39). Thirty-two patients had high grade VIN (82%) and seven low grade VIN (18%). In high grade VIN, the most represented HPV types were: HPV 16 (21/32 66%), HPV 56 (3/32 9%) and HPV 33 (2/32 6%). In low grade VIN, the most represented HPV types were: HPV 16 (4/7 57%) and HPV 6 (3/7 43%). Interestingly, 5/39 (13%) of patients diagnosed with usual VIN also had co-existing lichen sclerosus. CONCLUSIONS: We have optimized a HPV genotyping technique, routinely used on cervical cytology samples, and on paraffin fixed embedded tissue showing VIN. Moreover, we have identified five patients with lichen sclerosus co-existing with usual VIN. This association has rarely been reported and proves that these two entities can coexist.
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Carcinoma in Situ/virología , Papillomavirus Humano 16/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Adhesión en Parafina , Neoplasias de la Vulva/virología , Adulto , Carcinoma in Situ/patología , ADN Viral/análisis , Femenino , Formaldehído , Genotipo , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/patología , Estudios Retrospectivos , Neoplasias de la Vulva/patologíaRESUMEN
The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC.
RESUMEN
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently identified renal malignancy. Diagnosis of this rare subtype of renal tumour can be challenging for pathologists, and as such, any additional data would be helpful to improve diagnostic reliability. As imaging features of this new and rare sub-type have not yet been clearly described, the purpose of this study was to describe the main radiologic features on computed tomography (CT) and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective review of pathology and imaging databases. Using a combination of CT/MRI features, diagnosis of MTSCC could be suggested in many cases. A combination of slow enhancement with plateau on dynamic contrast-enhanced CT/MRI, intermediate to high T2 signal intensity contrasting with low apparent diffusion coefficient values on MRI appeared evocative of this diagnosis. KEY POINTS: ⢠A slow enhancement with plateau is observed either on CT or MRI. ⢠High T2 signal components but low apparent coefficient diffusion are evocative. ⢠T2-weighted imaging features depend on the mucin components of the tumour.
Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Mucinas , Reproducibilidad de los Resultados , Estudios RetrospectivosAsunto(s)
Actinomycetaceae/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/patología , Infecciones Urinarias/microbiología , Infecciones Urinarias/patología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Infecciones Urinarias/tratamiento farmacológico , Adulto JovenRESUMEN
PURPOSE: Elastography is a novel imaging technology that shows promise in the identification of anatomic structures. The widespread use of ultrasound for screening testicular tumors in patients with cancer risk factors highlights unclassified testicular micronodules. We investigated the ability of elastography to accurately diagnose testicular nodules. MATERIAL: Patients with clinical testicular nodules were assigned to undergo elastography in a prospective study. The imaging was carried out by a single radiologist using a static elastography unit with a 9-14MHz frequency linear transducer, to identify hardness score, loss of architecture of testicular parenchyma, and surrounding effect. When orchidectomy was required, the corresponding specimens were subjected to hematoxylin and eosin staining for histologic correlation. RESULTS: We imaged 34 testicular lesions: 26/34 (76%) malignant tumors and 8/34 (24%) non-tumor lesion including 4 hematomas, 3 orchitis and 1 ischemia. Se, Sp, PPV and NPV of hardness in elastography in differentiating between malignant and benign tissue was found to be 96.2%, 37.5%, 83%, and 75%, respectively. Further, for recognizing cancer, the loss of architecture of the testicular parenchyma detecting in elastography was 92.3%, 75%, 92.3%, and 75%, respectively, and the surrounding effect was 84.6%, 87.5%, 95.6% and 63.6%, respectively. CONCLUSION: Elastography may be a promising tool at diagnosing testicular tumor when the loss of architecture and the surrounding effect were present. Further studies are needed to evaluate whether the utility of elastography is worth pursuing to identify of unclassified testicular micronodules. LEVEL OF EVIDENCE: 3.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Neoplasias Testiculares/diagnóstico por imagen , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute lymphoblastic leukemia (T-ALL)/lymphoma (T-LL) cells. We show here that a potent and LAT1 selective inhibitor (JPH203) decreased leukemic cell viability and proliferation, and induced transient autophagy followed by apoptosis. JPH203 could also alter the in vivo growth of luciferase-expressing-tPTEN-/- cells xenografted into nude mice. In contrast, JPH203 was nontoxic to normal murine thymocytes and human peripheral blood lymphocytes. JPH203 interfered with constitutive activation of mTORC1 and Akt, decreased expression of c-myc and triggered an unfolded protein response mediated by the C/EBP homologous protein (CHOP) transcription factor associated with cell death. A JPH203-resistant tPTEN-/-clone appeared CHOP induction deficient. We also demonstrate that targeting LAT1 may be an efficient broad spectrum adjuvant approach to treat deadly T-cell malignancies as the molecule synergized with rapamycin, dexamethasone, doxorubicin, velcade and l-asparaginase to alter leukemic cell viability.
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Neoplasias de la Mama/tratamiento farmacológico , Animales , Apoptosis , Western Blotting , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Adhesión Celular , Ciclo Celular , Movimiento Celular , Proliferación Celular , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: To evaluate the toxicity of therapeutic sequences High Intensity Focused Ultrasound (HIFU)-salvage radiotherapy (HIFU-RT) or radiotherapy-salvage HIFU (RT-HIFU) in case of locally recurrent prostate cancer. MATERIALS AND METHODS: Nineteen patients had a local recurrence of prostate cancer. Among them, 10 patients were treated by HIFU-RT and 9 patients by RT- HIFU (4 by external beam radiotherapy [EBR] and 5 by brachytherapy [BRACHY]). Urinary side effects were assessed using CTCAE v4. RESULTS: At the time of the initial management, the median age was 66.5 years (53-72), the median PSA was 10.8ng/mL (3.4-50) and the median initial Gleason score was 6.3 (5-8). Median follow-up after salvage treatment was 46.3 months (2-108). Thirty percent of the patients in the HIFU-RT group and 33.3 % of the patients in the RT-HIFU group, all belonging to the sub-group BRACHY-HIFU, had urinary complication greater than or equal to grade 2. Among all the patients, only 1 had grade 1 gastrointestinal toxicity. CONCLUSION: BRACHY-HIFU sequence seems to be purveyor of many significant urinary side effects. A larger database is needed to confirm this conclusion.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Recurrencia Local de Neoplasia/terapia , Neoplasias de la Próstata/terapia , Terapia Recuperativa/métodos , Anciano , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radioterapia Adyuvante , Estudios Retrospectivos , Resultado del Tratamiento , UltrasonografíaRESUMEN
The IgG4-related systemic disease is a recently described entity of fibro-inflammatory systemic damage. Although initially described in some forms of pancreatitis, the disease can affect all organs. The common histological features include a lymphoplasmacytic infiltration (especially to IgG4), fibrosis and phlebitis. Elevated serum level of IgG4 is also often present. This rare but certainly underdiagnosed disease must be kept in mind of all clinician faced to a non-specific inflammatory lesion. We report a case of ocular inflammation and lung tumors in a patient of 84 years for which the diagnosis was made through immunolabelling with IgG4 in lesions biopsied.
Asunto(s)
Inmunoglobulina G/sangre , Enfermedades Pulmonares/inmunología , Seudotumor Orbitario/inmunología , Anciano de 80 o más Años , Femenino , Glucocorticoides/uso terapéutico , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Seudotumor Orbitario/tratamiento farmacológicoRESUMEN
The development and maintenance of most tissues and organs require the presence of multipotent and unipotent stem cells that have the ability of self-renewal as well as of generating committed, further differentiated cell types. The transcription factor Sox2 is essential for embryonic development and maintains pluripotency and self-renewal in embryonic stem cells. It is expressed in immature osteoblasts/osteoprogenitors in vitro and in vivo and is induced by fibroblast growth factor signaling, which stimulates osteoblast proliferation and inhibits differentiation. Sox2 overexpression can by itself inhibit osteoblast differentiation. To elucidate its function in the osteoblastic lineage, we generated mice with an osteoblast-specific, Cre-mediated knockout of Sox2. These mice are small and osteopenic, and mosaic for Sox2 inactivation. However, culturing calvarial osteoblasts from the mutant mice for 2-3 passages failed to yield any Sox2-null cells. Inactivation of the Sox2 gene by Cre-mediated excision in cultured osteoblasts showed that Sox2-null cells could not survive repeated passage in culture, could not form colonies, and arrested their growth with a senescent phenotype. In addition, expression of Sox2-specific shRNAs in independent osteoblastic cell lines suppressed their proliferative ability. Osteoblasts capable of forming 'osteospheres' are greatly enriched in Sox2 expression. These data identify a novel function for Sox2 in the maintenance of self-renewal in the osteoblastic lineage.
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Osteoblastos/citología , Factores de Transcripción SOXB1/metabolismo , Factor de Transcripción Activador 2/metabolismo , Animales , Diferenciación Celular , Línea Celular , Linaje de la Célula , Desarrollo Embrionario , Ratones , Ratones Noqueados , Interferencia de ARN , Factores de Transcripción SOXB1/genética , Transducción de SeñalAsunto(s)
Ascomicetos/patogenicidad , Micosis/microbiología , Senos Paranasales/microbiología , Sinusitis/microbiología , Ascomicetos/clasificación , Ascomicetos/aislamiento & purificación , Enfermedad Crónica , Humanos , Inmunocompetencia , Masculino , Persona de Mediana Edad , Micosis/patología , Micosis/cirugía , Senos Paranasales/patología , Senos Paranasales/cirugía , Sinusitis/patología , Sinusitis/cirugíaRESUMEN
Fibroblast growth factor (FGF)-4 gene expression in the inner cell mass of the blastocyst and in EC cells requires the combined activity of two transcriptional regulators, Sox2 and Oct-3, which bind to adjacent sites on the FGF-4 enhancer DNA and synergistically activate transcription. Sox2 and Oct-3 bind cooperatively to the enhancer DNA through their DNA-binding, high mobility group and POU domains, respectively. These two domains, however, are not sufficient to activate transcription. We have analyzed a number of Sox2 and Oct-3 deletion mutants to identify the domains within each protein that contribute to the activity of the Sox2 x Oct-3 complex. Within Oct-3, we have identified two activation domains, the N-terminal AD1 and the C-terminal AD2, that play a role in the activity of the Sox2 x Oct-3 complex. AD1 also displays transcriptional activation functions in the absence of Sox2 while AD2 function was only detected within the Sox2 x Oct-3 complex. In Sox2, we have identified three activation domains within its C terminus: R1, R2, and R3. R1 and R2 can potentiate weak activation by Sox2 in the absence of Oct-3 but their deletion has no effect on the Sox2 x Oct-3 complex. In contrast, R3 function is only observed when Sox2 is complexed with Oct-3. In addition, analysis of Oct-1/Oct-3 chimeras indicates that the Oct-3 homeodomain also plays a critical role in the formation of a functional Sox2 x Oct-3 complex. Our results are consistent with a model in which the synergistic action of Sox2 and Oct-3 results from two major processes. Cooperative binding of the factors to the enhancer DNA, mediated by their binding domains, stably tethers each factor to DNA and increases the activity of intrinsic activation domains within each protein. Protein-protein and protein-DNA interactions then may lead to reciprocal conformational changes that expose latent activation domains within each protein. These findings define a mechanism that may also be utilized by other Sox x POU protein complexes in gene activation.
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Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , Elementos de Facilitación Genéticos , Factores de Crecimiento de Fibroblastos/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Secuencia de Bases , Sitios de Unión , Cartilla de ADN , Factor 4 de Crecimiento de Fibroblastos , Regulación de la Expresión Génica , Proteínas HMGB , Células HeLa , Humanos , Factor 3 de Transcripción de Unión a Octámeros , Factores de Transcripción SOXB1RESUMEN
Several genetic forms of human dwarfism have been linked to activating mutations in FGF receptor 3, indicating that FGF signaling has a critical role in chondrocyte maturation and skeletal development. However, the mechanisms through which FGFs affect chondrocyte proliferation and differentiation remain poorly understood. We show here that activation of FGF signaling inhibits chondrocyte proliferation both in a rat chondrosarcoma (RCS) cell line and in primary murine chondrocytes. FGF treatment of RCS cells induces phosphorylation of STAT-1, its translocation to the nucleus, and an increase in the expression of the cell-cycle inhibitor p21WAF1/CIP1. We have used primary chondrocytes from STAT-1 knock-out mice to provide genetic evidence that STAT-1 function is required for the FGF mediated growth inhibition. Furthermore, FGF treatment of metatarsal rudiments from wild-type and STAT-1(-/-) murine embryos produces a drastic impairment of chondrocyte proliferation and bone development in wild-type, but not in STAT-1(-/-) rudiments. We propose that STAT-1 mediated down regulation of chondrocyte proliferation by FGF signaling is an homeostatic mechanism which ensures harmonious bone development and morphogenesis.
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Desarrollo Óseo , Condrocitos/citología , Proteínas de Unión al ADN/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Transactivadores/metabolismo , Células 3T3 , Animales , Desarrollo Óseo/efectos de los fármacos , Huesos/metabolismo , División Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/metabolismo , Proteínas de Unión al ADN/genética , Factor 1 de Crecimiento de Fibroblastos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Huesos Metatarsianos/efectos de los fármacos , Huesos Metatarsianos/crecimiento & desarrollo , Ratones , Ratones Noqueados , Técnicas de Cultivo de Órganos , Fosforilación , Ratas , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Factor de Transcripción STAT1 , Factor de Transcripción STAT3 , Transactivadores/genética , Células Tumorales CultivadasAsunto(s)
Factores de Crecimiento de Fibroblastos/genética , Regulación de la Expresión Génica/fisiología , Ratones/embriología , Ratones/genética , Proteínas Proto-Oncogénicas/genética , Animales , Secuencia de Bases , Desarrollo Embrionario y Fetal/fisiología , Factor 4 de Crecimiento de Fibroblastos , Datos de Secuencia MolecularRESUMEN
Octamer binding and Sox factors are thought to play important roles in development by potentiating the transcriptional activation of specific gene subsets. The proteins within these factor families are related by the presence of highly conserved DNA binding domains, the octamer binding protein POU domain or the Sox factors HMG domain. We have previously shown that fibroblast growth factor 4 (FGF-4) gene expression in embryonal carcinoma cells requires a synergistic interaction between Oct-3 and Sox2 on the FGF-4 enhancer. Sox2 and Oct-3 bind to adjacent sites within this enhancer to form a ternary protein-DNA complex (Oct-3*) whose assembly correlates with enhancer activity. We now demonstrate that increasing the distance between the octamer and Sox binding sites by base pair insertion results in a loss of enhancer function. Significantly, those enhancer "spacing mutants" which failed to activate transcription were also compromised in their ability to form the Oct* complexes even though they could still bind both Sox2 and the octamer binding proteins, suggesting that a direct interaction between Sox2 and Oct-3 is necessary for enhancer function. Consistent with this hypothesis, Oct-3 and Sox2 can participate in a direct protein-protein interaction in vitro in the absence of DNA, and both this interaction and assembly of the ternary Oct* complexes require only the octamer protein POU and Sox2 HMG domains. Assembly of the ternary complex by these two protein domains occurs in a cooperative manner on FGF-4 enhancer DNA, and the loss of this cooperative interaction contributes to the defect in Oct-3* formation observed for the enhancer spacing mutants. These observations indicate that Oct-3* assembly results from protein-protein interactions between the domains of Sox2 and Oct-3 that mediate their binding to DNA, but it also requires a specific arrangement of the binding sites within the FGF-4 enhancer DNA. Thus, these results define one parameter that is fundamental to synergistic activation by Sox2 and Oct-3 and further emphasize the critical role of enhancer DNA sequences in the proper assembly of functional activation complexes.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Elementos de Facilitación Genéticos , Factores de Crecimiento de Fibroblastos/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , Factor 4 de Crecimiento de Fibroblastos , Regulación de la Expresión Génica , Proteínas HMGB , Ratones , Factor 3 de Transcripción de Unión a Octámeros , Unión Proteica , Factores de Transcripción SOXB1 , TransfecciónRESUMEN
The non-conservative substitution of the tyrosine residue at position 121 of human interleukin-1 beta (IL-1 beta) generates protein mutants showing strong reduction of the capacity to induce (a) prostaglandin E2 (PGE2) release from fibroblasts and smooth muscle cells, (b) murine T-cells proliferation and (c) activation of interleukin-6 (IL-6) gene expression. It is generally accepted that these functions are mediated by the type-I interleukin-1 receptor (IL-1RI). However, the mutant proteins maintain the binding affinity to the types-I and II IL-1 receptors, which is the same as the control IL-1 beta, suggesting that this amino acid substitution does not alter the structure of the molecule, except locally. Thus we have identified a new functional site of IL-1 beta different from the known receptor binding region, responsible for fundamental IL-1 beta functions. Moreover, we show that the same mutants maintain at least two hypothalamic functions, that is, the in vitro short-term PGE2 release from rat hypothalamus and the induction of fever in rabbits. This result suggests that there is yet another site of the molecule responsible for the hypothalamic functions, implying that multiple active sites on the IL-1 beta molecule, possibly binding to more than one receptor chain, trigger different signals.