Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazine-induced rat colon carcinogenesis: correlation with nuclear β-catenin.

BACKGROUND: Colon cancer stem cells may drive carcinogenesis and account for chemotherapeutic failure. Although many markers for these cells have been proposed, there is no complete agreement regarding them, nor has their presence in the early phases of carcinogenesis been characterized in depth. METHODS: The expression of the putative markers LGR-5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), MSI-1 (Musashi-1) and DCAMKL-1 (doublecortin and calcium/calmodulin-dependent protein kinase-like-1) was studied in normal colon mucosa (NM), in the precancerous lesions Mucin Depleted Foci (MDF) and in macroscopic tumours (adenomas) of 1,2-dimethylhydrazine-treated rats. Co-localization between these markers and nuclear β-catenin (NBC), an attributed feature of cancer stem cells, was also determined. Moreover, since PGE(2) could increase NBC, we tested whether short-term treatment with celecoxib, a COX-2 inhibitor (2 weeks, 250 ppm in the diet) could reduce the expression of these markers. RESULTS: LGR-5 expression in NM was low (Labelling Index (LI): 0.22±0.03 (means±SE)) with positive cells located mainly at the base of the crypts. Compared to NM, LGR-5 was overexpressed in MDF and tumours (LI: 4.7±2.0 and 2.9±1.0 in MDF and tumours, respectively, P<0.01 compared to NM). DCAMKL-1 positive cells, distributed along the length of normal crypts, were reduced in MDF and tumours. Nuclear expression of MSI-1, located mainly at the base of normal crypts, was not observed in MDF or tumours. In both MDF and tumours, few cells co-expressed LGR-5 and NBC (LI: 1.0±0.3 and 0.4±0.2 in MDF and tumours, respectively). Notwithstanding the lower expression of DCAMKL-1 in tumours, the percentage of cells co-expressing DCAMKL-1 and NBC was higher than in NM (LI: 0.5±0.1 and 0.04±0.02 in tumours and NM, respectively). MSI-1 and NBC co-localization was not observed. Celecoxib did not reduce cells co-expressing LGR-5 and NBC. CONCLUSIONS: Based on its prevalent localization at the base of normal crypts, as expected for stem cells, and on the overexpression in precancerous lesions and tumours, we support LGR-5, but not MSI-1 or DCAMKL-1, as putative neoplastic stem cell marker. In both MDF and tumours, we identified LGR-5-positive cells co-expressing NBC which could be a subpopulation with the highest stem cell features

Alterações clínicas e laboratoriais da Erliquiose Monocítica canina crônica e reagudizada: um relato de caso: Clinical and laboratory changes in chronic and regudized canine Monocytic Ehrliquiosis: a case report

A erliquiose monocítica canina é uma das hemoparasitoses mais comuns na rotina clínica de atendimento aos cães. Este fato, somado à possibilidade de desenvolvimento crônico da doença assintomática ou com sintomas inespecíficos, justifica a inclusão de exames para o diagnóstico da doença em painéis preventivos. O caso ilustrado neste artigo corrobora para estes achados de doença assintomática, sem alterações hematológicas e diagnosticada por exames de rotina dado o histórico antigo de ixodidiose. O desafio no tratamento desta doença reside no fato de que, mesmo por tempo prolongado, pode haver reminiscência do agente infeccioso em tecido esplênico e medula óssea, o que foi observado no caso descrito, dada a reagudização da doença após imunossupressão do paciente. Os motivos para a ineficácia terapêutica são diversos podendo-se aventar a possibilidade de resistência aos tratamentos propostos em literatura e atentando para a necessidade de mais estudos para a definição de propostas terapêuticas mais eficazes

Immediate breast reconstruction with a saline implant and AlloDerm, following removal of a Phyllodes tumor

<p>Abstract</p> <p>Background</p> <p>Phyllodes tumors are uncommon tumors of the breast that exhibit aggressive growth. While surgical management of the tumor has been reported, a single surgical approach with immediate breast reconstruction using AlloDerm has not been reported.</p> <p>Case presentation</p> <p>A 22-year-old woman presented with a 4 cm mass in the left breast upon initial examination. Although the initial needle biopsy report indicated a fibroadenoma, the final pathologic report revealed a 6.5 cm × 6.4 cm × 6.4 cm benign phyllodes tumor <it>ex vivo</it>. Treatment was a simple nipple-sparing mastectomy coupled with immediate breast reconstruction. After the mastectomy, a subpectoral pocket was created for a saline implant and AlloDerm was stitched to the pectoralis and serratus muscle in the lower-pole of the breast.</p> <p>Conclusions</p> <p>Saline implant with AlloDerm can be used for immediate breast reconstruction post-mastectomy for treatment of a phyllodes tumor.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Arabinoxylan oligosaccharides (AXOS) reduce preneoplastic lesions in the colon of rats treated with 1,2-dimethylhydrazine (DMH)

Background Prebiotics are non-digestible compounds that beneficially affect the host by stimulating the growth and/or activity of one or a limited number of resident colonic bacteria in the gut. Reported beneficial effects of prebiotics include reduced gut infections, better absorption of minerals, and notably, antitumorigenic effects. Arabinoxylan (AX)-oligosaccharides (AXOS) have been suggested to exert prebiotic effects in the gut, but their effect on colon carcinogenesis has not been studied so far. Aim of the study To test the effect of AXOS in a rat colon carcinogenesis model. Methods We determined the occurrence of two types of preneoplastic lesions [aberrant crypt foci (ACF) and mucin depleted foci (MDF)] in the colon of rats treated with the colon carcinogen 1,2-dimethylhydrazine (DMH) and fed either a control diet or a diet containing AXOS (4.8% w/w) (15 rats in each group). Results Thirteen weeks after DMH treatment, MDF counts were significantly lower in the entire colon of AXOS fed rats (MDF/colon were 7.5 ± 0.6 and 5.5 ± 0.6, in Control and AXOS groups, respectively, means ± SE, P < 0.05). Although the number of ACF in the entire colon was not significantly different between Control and AXOS fed rats, AXOS fed rats had significantly fewer ACF in the distal part of the colon than Control group rats (ACF/distal colon were 135.5 ± 15 and 84.4 ± 11, in Control and AXOS groups, respectively, means ± SE, P < 0.05). Conclusions The present study shows that dietary intake of AXOS by rats reduces the occurrence of two types of preneoplastic lesions, thus suggesting a chemopreventive effect on colon carcinogenesis that should be confirmed in a long-term carcinogenesis experiment.status: publishe

Identification of mucin depleted foci in the human colon.

Aberrant crypt foci (ACF) originally described in rodents treated with colon-specific carcinogens have been identified also in humans at high risk of colon cancer (CRC) and are extensively used as cancer biomarkers. However, studies documenting the heterogeneity of ACF have questioned their precancerous nature. Recently, we described dysplastic foci depleted of mucins (MDF) in the colon of rats treated with colon-specific carcinogens. Like colon tumors, MDFs show activation of Wnt signaling driven by mutations in the \u3b2-catenin gene and Apc, a key gene in colorectal carcinogenesis. Because MDFs have been identified thus far only in rodents, we wanted to search for similar lesions in humans. Familial adenomatous polyposis (FAP) subjects, carrying germ-line mutations in the APC gene, are at high risk of CRC. Therefore, we first searched for MDF-like lesions in unsectioned colon samples from FAP patients and then in patients with sporadic CRC. MDFs were present in the colon of FAP patients (average of 0.0577 lesions/cm2) and at a much lower density in CRC patients (average of 0.0006 lesions/cm2). ACFs were also observed in all patients. Histologic preparations of all the MDFs identified in FAP and CRC consisted of microadenomas at variable grades of dysplasia. The occurrence of MDF-like lesions in high-risk patients provides evidence that these lesions have a counterpart in human pathology and, as observed in rodents, may represent the very early stages of CRC