Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa

The causative molecular pathways underlying the pathogenesis of colorectal cancer (CRC) need to be better characterized. The purpose of our study was to better understand the genetic mechanism of oncogenesis for human colorectal cancer and to identify new potential tumor markers of use in clinical practice. We used cDNA microarrays to compare gene expression profiles of colorectal biopsies from 25 CRC patients and 13 normal mucosa from adjacent non-cancerous tissues. Findings were validated by real-time PCR; in addition, western blotting and immunochemistry analysis were carried out as further confirmation of differential expression at a protein level. Comparing cancerous tissues with normal colonic mucosa we identified 584 known genes differentially expressed to a significant degree (p<0.001). Many of the transcripts that were more abundant in tumors than in non-neoplastic tissues appear to reflect important events for colon carcinogenesis. For example, a significant number of these genes serve as apoptotic inhibitors (e.g. BFAR, BIRC1, BIRC6). Furthermore, we observed the simultaneous up-regulation of HLA-E and the down-regulation of beta2-microglobulin; these genes strongly support a potential tumor escape strategy from immune surveillance in colon cancer tissues. Our study provides new gene candidates in the pathogenesis of human CRC disease. From our results we hypothesize that CRC cells escape immune surveillance through a specific gene expression alteration; moreover, over-expression of several survival genes seems to confer a more anti-apoptotic phenotype. These genes are involved in pathways not previously implicated in CRC pathogenesis and they may provide new targets for therapy.Fil: Bianchini, Michele. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; ArgentinaFil: Levy, Estrella Mariel. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Zucchini, Cinzia. Università di Bologna; ItaliaFil: Pinski, Victor. Universidad de Buenos Aires; ArgentinaFil: Macagno, Carlo. Universidad de Buenos Aires; ArgentinaFil: De Sanctis, Paola. Università di Bologna; ItaliaFil: Valvassori, Luisa. Università di Bologna; ItaliaFil: Carinci, Paolo. Università di Bologna; ItaliaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentin

Micro-imaging VIS-IR spectroscopy of Martian meteorites in support of the future MaMIss spectrometer measurements

In the view of the future ExoMars 2020 mission, an activity of VIS-IR spectral investigations on terrestrial and extraterrestrial Mars Analogues is ongoing, in support of the Ma Miss in situ measurements. Ma_Miss is an imaging spectrometer that works in the range 0.4-2.2 μm with 20nm spectral sampling and that will observe the lateral wall of the borehole generated by ExoMars Rover's drill (Coradini et al., 2001). In this abstract, we describe some results about the spectral properties and characterization of mineral grains of the slabs of two Martian meteorites by means of the SPIM imaging spectrometer. SPIM works in the 0.22-5.05 μm spectral range, with a spatial resolution of 38x38 μm on the sample and represents the spare of the spectrometer on Dawn spacecraft (De Angelis et al., 2015). The meteorites investigated are North West Africa 8657 (NWA8657) and Dar Al Gani 489 (DAG489), basaltic shergottites. The average spectrum of the NWA8657 slab, in comparison with spectral measurements on other martian meteorites (Mcfadden & Cline, 2005) shows low reflectance values and 1 and 2 μm spectral absorptions indicating the strong presence of Ca-pyroxenes. The successive pixel by pixel analyses for the pyroxenes spectral speciation showed a great variability of clinopyroxenes in NWA8657. In fact, the 2 μm absorption at longer wavelength in some pixel does not always correspond to the 1 μm feature at longer wavelength. The average spectrum of DAG 489 is marked by a signature typical of low-Ca pyroxenes. Pixel by pixel analyses of DAG489 shows a more homogeneous composition of the pyroxenes characterized by the two major features centered at 0.98-0.99 and 1.98-2 μm. Further spectral absorptions related to sulfates, phosphates and carbonates were detected that are being validated by SEM-BSD to constrain the formation hystories of these two shergottites

Phytosociology and taxonomic notes on some endemic-rich associations of the Naples Gulf

The Gulf of Naples is an important centre of endemism, well known from the floristic point of view, but much less from the phytosociological one. In this paper we investigated the non-forest vegetation focusing on communities rich in endemics. We described two communities as new: Eryngio amethystini-Santolinetum neapolitanae for the garrigues on limestone, Globulario neapolitanae-Loniceretum stabianae for the vegetation on dolomitic rocks, both from the Lattari mountains, and we extend the area of Crithmo maritimi-Limonietum cumani for the vegetation on volcanic rocks and rarely on limestones along the coast, which was known for a few localities. The syntaxonomical position and the phytogeographical context of these communities are discussed. A few taxonomic notes are added on rare or interesting species retrieved in the course of the enquiry

Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient's risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (&gt; 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines

Spectral characterization of volcanic rocks in the VIS-NIR for martian exploration

Igneous effusive rocks cover much of the surface of Mars [1,2,3]. Initially only two types of lithologies were thought to constitute the Martian crust, i.e. a basaltic one and a more andesitic one [1,2], while more evolved lithologies were ruled out.Nevertheless a more complex situation is appearing in the last years. Recently several observations have highlighted the presence of evolved, acidic rocks. High-silica dacite units were identified in Syrtis Major caldera by thermal IR data [4]. Outcrops in Noachis Terra were interpreted as constituted of felsic (i.e. feldspar-rich) rocks essentially by the observation of a 1.3-µm spectral feature in CRISM data, attributed to Fe2+ in feldspars [5]. However different interpretations exist, invoking plagioclase-enriched basalts [6] rather than felsic products.The increasing of high-resolution and in-situ rover-based observations datasets and the changing of the initial paradigm justify a new systematic spectral study of igneous effusive rocks. In this work we focus on the spectral characterization of volcanic effusive rocks in the 0.35-2.5-µm range. We are carrying out measurements and spectral analyses on a wide ensemble of effusive samples, from mafic to sialic, with variable alkali contents, following the classification in the Total-Alkali-Silica diagram, and discussing the influence on spectral characteristics of different mineral assemblages and/or texture ([7], [8]). [1] Bandfield J.L., et al., Science, 287, 1626, 2000; [2] Christensen P.R., et al., J. Geophys. Res., 105, N.E4, 9609-9621, 2000; [3] Ehlmann B.L. & Edwards C.S., Annu. Rev. Earth Planet. Sci., 42, 291-315, 2014; [4] Christensen P.R., et al., Nature, 436, 504-509, 2005; [5] Wray J.J., et al., 44th LPSC, abs. n.3065, 2013; [6] Rogers A.D. & Nekvasil H., Geophys. Res. Lett., 42, 2619-2626, 2015; [7] Carli C. and Sgavetti M.,Icarus, 211, 1034-1048, 2011; [7] Carli C. et al., SGL, doi 10.1144/SP401.19, 2015. <P /

Performance of Circulating Placental Growth Factor as A Screening Marker for Diagnosis of Ovarian Endometriosis: A Pilot Study

The aim of this study is to compare the circulating placental growth factor (PlGF) concentration in women with and without endometrioma to verify the performance of this marker to diagnose the disease

Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer

Background: Complex tumor and immune microenvironment render pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint inhibitors (ICIs). Therefore, a strategy to convert the immune hostile into an immunopermissive tumor is required. Recent studies showed that intratumoral injection of Toll-like receptor 9 agonist IMO-2125 primes the adaptive immune response. Phase I and II trials with intratumoral IMO-2125 demonstrated its safety and antitumoral activity. Methods: We generated an array of preclinical models by orthotopically engrafting PDAC-derived cell lines in syngeneic mice and categorized them as high, low and no immunogenic potential, based on the ability of tumor to evoke T lymphocyte or NK cell response. To test the antitumor efficacy of IMO-2125 on locally treated and distant sites, we engrafted cancer cells on both flanks of syngeneic mice and treated them with intratumoral IMO-2125 or vehicle, alone or in combination with anti-PD1 ICI. Tumor tissues and systemic immunity were analyzed by transcriptomic, cytofluorimetric and immunohistochemistry analysis. Results: We demonstrated that intratumoral IMO-2125 as single agent triggers immune system response to kill local and distant tumors in a selected high immunogenic subtype affecting tumor growth and mice survival. Remarkably, intratumoral IMO-2125 in combination with systemic anti-PD1 causes a potent antitumor effect on primary injected and distant sites also in pancreatic cancer models with low immunogenic potential, preceded by a transition toward an immunopermissive microenvironment, with increase in tumor-infiltrating dendritic and T cells in tumor and lymph nodes. Conclusion: We demonstrated a potent antitumor activity of IMO-2125 and anti-PD1 combination in immunotherapy-resistant PDAC models through the modulation of immune microenvironment, providing the rationale to translate this strategy into a clinical setting

Efficacy of residual site radiation therapy (ISRT) in patients with primary mediastinal lymphoma with Deauville Score 4 following R-CHT: results of a retrospective mono institutional study

Background: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). Methods: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. Results: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26–64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Conclusion: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival

Padrões hematológicos em Cebus apella, anestesiados com quetamina

Blood samples were collected from 124 captive Capuchin monkeys (Cebus apella) at Fundação Parque Zoológico de São Paulo, anesthetized with ketamine (10 mg/kg, IM). Hematological parameters (RBC, WBC, differential count, hematocrit, hemoglobin, MCV, MCH and MCHC) were determined, and influence of sex and age on hematologic values was studied.Amostras de sangue foram colhidas de 124 macacos-prego (Cebus apella) da Fundação Parque Zoológico de São Paulo, anestesiados com quetamina (10 mg/kg, IM), com a finalidade de determinar os seguintes parâmetros hematológicos: contagens globais de hemácias e leucócitos, contagem diferencial de leucócitos, hematócrito, hemoglobina e índices hematimétricos (VCM, HCM e CHCM), expressos em média e desvio padrão. Estudou-se a influência do sexo e da idade sobre os referidos parâmetros