397 research outputs found

    Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

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    Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an ‘oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested ‘PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type

    Factors associated with uremic pruritus

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    Cell block sensitivity for immunohistochemical detection of cytokeratin 5, oestrogen and progesterone receptors in canine primary mammary carcinoma

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    Mammary carcinomas are relatively common ailments among female canines aged around 10 years old, presentingan important morbidity with an average survival of five years. The cytoinclusion technique is frequently employed in human medicine as the investigative method of choice as it quickly provides resources for the determination of the correct therapeutic response, however, the effectiveness of the technique in canines remains understudied in veterinary medicine. This study aims at evaluating the degree of correlation with immunohistochemical marking for cytokeratin 5 (CK5), oestrogen and progesterone receptors (ER and PR) between the cytoinclusion and the histopathology technique in mammary carcinomas. Twenty-five samples of mammary carcinoma, both for the cytoinclusion and histopathological techniques were submitted for histological processing; microscope slides were created for hematoxylin-eosin (HE) staining and the immunohistochemical technique (IHC) was assessed for the ER, PR and CK5 receptors. Through the HE staining, we reached a concordance rate of 100% between the cytoinclusion and the histopathological analysis in the diagnosis of carcinomas. The immunohistochemical assay presented sensitivity of 85.71%, 95.45% and 100% and Cohen’s kappa of 0.78, 0.84 and 0.95 for ER, PR and CK5, respectively, as well as 100% specificity and P<0.01 for all three markers. Therefore, cytoinclusion represents an accessible, fast and low-cost method, offering high sensitivity for the cytomorphological and immunohistochemical diagnosis of mammary carcinoma in female canines

    Ginzburg-Landau vortex dynamics with pinning and strong applied currents

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    We study a mixed heat and Schr\"odinger Ginzburg-Landau evolution equation on a bounded two-dimensional domain with an electric current applied on the boundary and a pinning potential term. This is meant to model a superconductor subjected to an applied electric current and electromagnetic field and containing impurities. Such a current is expected to set the vortices in motion, while the pinning term drives them toward minima of the pinning potential and "pins" them there. We derive the limiting dynamics of a finite number of vortices in the limit of a large Ginzburg-Landau parameter, or \ep \to 0, when the intensity of the electric current and applied magnetic field on the boundary scale like \lep. We show that the limiting velocity of the vortices is the sum of a Lorentz force, due to the current, and a pinning force. We state an analogous result for a model Ginzburg-Landau equation without magnetic field but with forcing terms. Our proof provides a unified approach to various proofs of dynamics of Ginzburg-Landau vortices.Comment: 48 pages; v2: minor errors and typos correcte

    Tc-99m-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model

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    Background: Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model. Findings: Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation. 99mTc-NTP 15-5 imaging was performed at regular intervals with the target-to-background ratio (TBR) determined. Tumor volume was monitored using a calliper, and histology was performed at the end of the study. From day 11 to day 48, mean TBR values ranged from 1.7 ± 0.6 to 2.3 ± 0.6 in ZOL-treated rats and from 2.1 ± 1.0 to 4.9 ± 0.9 in controls. Tumor growth inhibition was evidenced using a calliper from day 24 and associated to a decrease in PG content in treated tumor tissues (confirmed by histology). Conclusions: This work demonstrated two proofs of concept: (1) biphosphonate therapy could be a promising therapeutic approach for chondrosarcoma; (2) 99mTc-NTP 15-5 is expected to offer a novel imaging modality for the in vivo evaluation of the extracellular matrix features of chondrosarcoma, which could be useful for the follow-up and quantitative assessment of proteoglycan ‘downregulation’ associated to the response to therapeutic attempts

    Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

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    Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.<br /
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