Cristina Colarossi

Sapienza University of Rome, Roma, Latium, Italy

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Publications (49)111.65 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: Mesenchymal stem cells (MSCs) play a crucial role in regulating normal skeletal homeostasis and, in case of injury, in bone healing and reestablishment of skeletal integrity. Recent scientific literature is focused on the development of bone regeneration models where MSCs are combined with biomimetic three-dimensional scaffolds able to direct MSC osteogenesis. In this work the osteogenic potential of human MSCs isolated from adipose tissue (hADSCs) has been evaluated in vitro in combination with collagen/Mg doped hydroxyapatite scaffolds. Results demonstrate the high osteogenic potential of hADSCs when cultured in specific differentiation induction medium, as revealed by the Alizarin Red S staining and gene expression profile analysis. In combination with collagen/hydroxyapatite scaffold, hADSCs differentiate into mature osteoblasts even in the absence of specific inducing factors; nevertheless, the supplement of the factors markedly accelerates the osteogenic process, as confirmed by the expression of specific markers of pre-osteoblast and mature osteoblast stages, such as osterix, osteopontin (also known as bone sialoprotein I), osteocalcin and specific markers of extracellular matrix maturation and mineralization stages, such as ALPL and osteonectin. Hence, the present work demonstrates that the scaffold per se is able to induce hADSCs differentiation, while the addition of osteo-inductive factors produces a significant acceleration of the osteogenic process. This observation makes the use of our model potentially interesting in the field of regenerative medicine for the treatment of bone defects.
    Full-text · Article · Mar 2016 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.
    Full-text · Article · Aug 2015 · Stem cell International
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    [Show abstract] [Hide abstract] ABSTRACT: The Low-Affinity Nerve Growth Factor Receptor (LNGFR), also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271 + and CD271 − mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271 + and CD271 − mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. − mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271 + mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271 + mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.
    Full-text · Article · Jul 2015 · International Journal of Molecular Sciences
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    Iannolo G · Sciuto MR · Buccheri S · Colarossi C · De Maria R · Memeo L · Conaldi PG
    [Show abstract] [Hide abstract] ABSTRACT: The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the basis, undergoing to a differentiation process that involves various developmental signals and regulatory pathways. During the last ten years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvment in in vitro differentiation. We demonstrated that Numb in high proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC). where we observed a direct correlation between the expression of Numb and Ki67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer.
    Full-text · Article · May 2015 · Cell Transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the basis, undergoing to a differentiation process that involves various developmental signals and regulatory pathways. During the last ten years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvment in in vitro differentiation. We demonstrated that Numb in high proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC). where we observed a direct correlation between the expression of Numb and Ki67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer.
    Full-text · Article · May 2015 · Cell Transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: Purpose: New treatment options for gastric cancer are in great demand. Histone deacetylases (HDACs) are exciting therapeutic targets, but only the class I HDACs 1, 2, and 3 have been studied in gastric cancer. We have investigated class IIa HDAC expression and inhibition in gastric cancer cells. Experimental design: We measured the level of 27 (phospho)proteins related to class IIa HDAC expression and function in ten laser-capture microdissection gastric tumor samples compared to patient-matched adjacent normal mucosa. Following, we evaluated class IIa HDAC inhibition by MC1568 in SNU-16 gastric cancer cells alone and in combination with cisplatin or docetaxel. Results: We demonstrate for the first time an increase of HDAC4 in gastric tumor cells. HDAC4 inhibition had a synergistic effect with docetaxel treatment, shifting the cellular response from a cytostatic to a cytotoxic phenotype. This effect was associated with increased levels of cleaved caspases 3 and 9 and increased acetylated histone H3 Lys9/Lys14. Conclusions and clinical relevance: These data support in vivo studies investigating the potential clinical use of HDAC4 inhibitors in combination with docetaxel for the treatment of gastric cancer, lowering treatment doses of docetaxel to reduce the burden of adverse side effects on patients.
    Full-text · Article · Dec 2014 · PROTEOMICS - CLINICAL APPLICATIONS
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    [Show abstract] [Hide abstract] ABSTRACT: Background Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Mutations in the KRAS and BRAF genes have been confirmed as negative predictors of the response to EGFR-targeted therapies.In this study we evaluated KRAS and BRAF status in 159 colorectal cancer samples obtained from the University of Tirana.Methods We evaluated KRAS mutations in codons 12, 13, 61, 146 and in codon 600 of BRAF by direct sequencing.. 90 patients were male (57%) and 69 female (43%); the patients¿ ages ranged from 17 to 85 (median 61.7). 24 patient were stage I, 36 stage II, 84 stage III and 15 stage IV.ResultsOut of the 159 cases, 28 (17,6%) showed KRAS mutation (13 G12D, 4 G12C, 4 G12V, 3 G12A, 2 G13 D, 1 G12S and 1 A146T), and 10 (6,3%) showed BRAF mutation (all V600E). No significant correlations between KRAS and BRAF mutations and various clinicopathological parameters was found.This is the first report of KRAS and BRAF status in Albanian patients with colorectal carcinoma (CRC) and though the relatively small sample size might not provide enough statistics power.Conclusions The results of KRAS and BRAF mutation analysis could be used in the selection of patients for anti-EGFR therapy.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_187.
    Full-text · Article · Sep 2014 · Diagnostic Pathology
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    [Show abstract] [Hide abstract] ABSTRACT: Non-small cell lung cancer (NSCLC) is a major public health problem, accounting from more cancer-related deaths than any other cancer. Both immunotherapy, based on the expression of tumor-specific antigens, and targeted therapy, based on the presence of oncogenic mutations, are under development in NSCLC. In this study, we analyzed the expression of MAGE-A, of the CTA group, in tumors from a cohort of resected NSCLC with respect to their clinicopathological characteristics and to the mutational status of the EGFR and KRAS genes. We found MAGE-A expression, by immunohistochemistry, in 43% of the tumors. MAGE-A expression was significantly more frequent in squamous than in adenous tumors, did not correlate with disease stage, but was significantly correlated with high tumor grade and poorer survival. EGFR and KRAS mutations were present in adenous, but not in squamous tumors. Whereas the presence of EGFR mutations did not appear to impact survival, that of KRAS mutations was associated with early stage disease and better survival. MAGE-A expression was absent from KRAS mutated adenous tumors, but was not significantly different in tumors bearing or not EGFR mutations. Altogether, the reported results provide guidance for the design of combination therapies in patients with NSCLC.
    Full-text · Article · May 2014 · Cancer Immunology Research
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    [Show abstract] [Hide abstract] ABSTRACT: CD200 is a relatively ubiquitously expressed molecule that plays a role in cancer immune evasion through interaction with its receptors. High expression levels of CD200 have been described in different human malignancies. For example, CD200 has been shown to be targeted after RAS/RAF/MEK/ERK activation in melanoma. Here we present the analysis of CD200 expression in human Multiple Myeloma (MM) samples. We found that CD200-positive cells express ERK and p-ERK. Moreover, UO126, a MEK inhibitor, reduces CD200 expression. Furthermore, we observe that CD200-positive cells show reduced immunogenicity compared to normal lymphocytes and that such immunogenicity increases when UO126 is used. We therefore hypothesize that CD200 expression in MM could suppress antitumor response and that anti-CD200 treatment might be therapeutically beneficial in CD200-expressing tumors.
    Full-text · Article · Sep 2013 · Leukemia research
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    [Show abstract] [Hide abstract] ABSTRACT: Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2973228795724608 Melanocytic nevi are the most common tumors of the conjunctiva, accounting for 28% of all neoplastic lesions. These tumors, despite their benign behavior, share some atypical histological features with nevi found in other anatomic sites like the genital and acral regions, globally designated as nevi with site-related atypia. Moreover, in children and adolescents, rapidly growing conjunctival nevi show sometimes worrisome histological patterns in association with a prominent inflammatory infiltrate that may lead to diagnostic problems. In this paper we describe a juvenile compound nevus characterized by marked melanocytic atypia and severe inflammation, which can be considered a rare case of juvenile conjunctival atypical nevus. The final diagnosis relied on morphological and immunohistochemical characterization of the large epithelioid melanocytic cells, and on the results of FISH analysis.
    Full-text · Article · Apr 2013 · Diagnostic Pathology
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    [Show abstract] [Hide abstract] ABSTRACT: Neuroendocrine carcinoma of the urinary bladder is a rare entity, accounting less then 1% of urinary bladder malignancies. The vast majority of the neuroendocrine carcinoma of the urinary bladder is represented by small cell neuroendocrine carcinoma while just few cases of large cell neuroendocrine carcinoma (LCNEC) have been reported. In this cases report we describe a rare case of primary bladder LCNEC. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2474700528951562.
    Full-text · Article · Feb 2013 · Diagnostic Pathology
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    Dataset: Figure S1
    [Show abstract] [Hide abstract] ABSTRACT: A) Tumorigenicity of stem and differentated LMS cells. Percentage of tumor positive mice after injection of low numbers of stem-like or differentiated LMS cells. 5 mice were injected with 104 cells and tumor formation evaluated after 4 months. B) In vivo differentiation of LMS stem-like cells. Flow cytometry analysis for CD105 and CD146 expression in parental tumor, sarcospheres (S), adherent culture (A) or differentiated LMS cells obtained from freshly dissociated xenografts generated by sarcosphere or adherent culture cell injection. The percentage of positive cells is represented by the different histograms corresponding to the cell populations or tumor types as indicated. (TIF)
    Preview · Dataset · Oct 2012
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Tumor cells with stem-like phenotype and properties, known as cancer stem cells (CSC), have been identified in most solid tumors and are presumed to be responsible for driving tumor initiation, chemoresistance, relapse, or metastasis. A subpopulation of cells with increased stem-like potential has also been identified within sarcomas. These cells are endowed with increased tumorigenic potential, chemoresistance, expression of embryonic markers, and side population(SP) phenotype. Leiomyosarcomas (LMS) are soft tissue sarcomas presumably arising from undifferentiated cells of mesenchymal origin, the Mesenchymal Stem Cells (MSC). Frequent recurrence of LMS and chemoresistance of relapsed patients may likely result from the failure to target CSC. Therefore, therapeutic cues coming from the cancer stem cell (CSC) field may drastically improve patient outcome. Methodology/principal findings: We expanded LMS stem-like cells from patient samples in vitro and examined the possibility to counteract LMS malignancy through a stem-like cell effective approach. LMS stem-like cells were in vitro expanded both as "tumor spheres" and as "monolayers" in Mesenchymal Stem Cell (MSC) conditions. LMS stem-like cells displayed MSC phenotype, higher SP fraction, and increased drug-extrusion, extended proliferation potential, self-renewal, and multiple differentiation ability. They were chemoresistant, highly tumorigenic, and faithfully reproduced the patient tumor in mice. Such cells displayed activation of EGFR/AKT/MAPK pathways, suggesting a possibility in overcoming their chemoresistance through EGFR blockade. IRESSA plus Vincristine treatment determined pathway inactivation, impairment of SP phenotype, high cytotoxicity in vitro and strong antitumor activity in stem-like cell-generated patient-like xenografts, targeting both stem-like and differentiated cells. Conclusions/significance: EGFR blockade combined with vincristine determines stem-like cell effective antitumor activity in vitro and in vivo against LMS, thus providing a potential therapy for LMS patients.
    Full-text · Article · Oct 2012 · PLoS ONE
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    Dataset: Table S1
    [Show abstract] [Hide abstract] ABSTRACT: Genetic pattern of LMS stem-like cells. The specific primers used for amplification of the listed genes are reported. PCR products were analyzed and compared with the corresponding Genebank sequences of each gene for the presence of tumor-associated alterations. The status of DNA is indicated as wt when similarity among PCR product and genebank sequence was 100%. (XLS)
    Preview · Dataset · Oct 2012
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    Dataset: Figure S2
    [Show abstract] [Hide abstract] ABSTRACT: A) Immunohistochemistry for the indicated antigens performed on patient tumor (left), tumor generated by subcutaneous injection of LMS spheres (middle) or adherent undifferentiated cells (right). B) Tumor growth rate of undifferentiated LMS cells (adherent cultures) injected subcutaneously in NOD-SCID mice with or without Matrigel as indicated. The values represent mean +/− SD of three independent experiments. Student’ s T test was used to determine p-value. ***p<0,001. C) Hematoxylin and eosin (H&E) or immunohistochemistry for the indicated antigens performed on secondary tumors or tumors generated by differentiated LMS cells, as indicated. (TIF)
    Preview · Dataset · Oct 2012
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    Dataset: Figure S4
    [Show abstract] [Hide abstract] ABSTRACT: EGF/EGFR pathway is generally activated in leiomyosarcomas. A) p-EGFR and EGF immunohistochemistry in 3 out of 10 representative patient-derived LMS specimens. B) Table showing the EGF and pEGFR expression in 10 LMS patient-derived specimens and in 5 non tumoral tissue specimen (Myometrium). Values 1 to 4 indicating the percentage of positive cells with 0 = negative, 1<10%; 2 = 10–25%; 3 = 25–50%, 4<50% and letters A to C indicating the intensity of expression (A = weak,; B = moderate; C = high intensity). (TIF)
    Preview · Dataset · Oct 2012
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    Dataset: Figure S5
    [Show abstract] [Hide abstract] ABSTRACT: A) Cytofluorimetric cell sorting of side population (SP) cells (right panel). B) Tumor growth rate of xenografts generated by subcutaneous injection of sorted SP cells and unsorted undifferentiated LMS cells (adherent cultures). The values represent mean +/− SD of three independent experiments. Student’ s T test was used to determine p-value. **p<0,01. (TIF)
    Preview · Dataset · Oct 2012
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    Dataset: Figure S3
    [Show abstract] [Hide abstract] ABSTRACT: A) Effect of IRESSA on LMS stem-like cell proliferation. LMS stem like cells were plated and left untreated or exposed to IRESSA for the indicated time points. Cell growth is indicated as percentage of treated cell versus control cell numbers ateach time. B) Morphologycal appearance of LMS stem-like cells untreated (control) or treated 3 days as indicated. C) Cell cycle distribution of the same cells as in B after 2 days drug esposure. (TIF)
    Preview · Dataset · Oct 2012
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    Full-text · Article · Aug 2012 · British Journal of Haematology
  • [Show abstract] [Hide abstract] ABSTRACT: Diagnostic and prognostic implications of endocrine differentiation were evaluated in 103 common gastric adenocarcinomas and undifferentiated carcinomas. Maturely differentiated exocrine and endocrine phenotypes were evaluated by using gastric exocrine and endocrine markers along with intestinal exocrine and endocrine markers. Immunohistochemical analysis revealed that 66 tumors (64%) were positive for generic endocrine markers such as chromogranin A and/or synaptophysin. The 14 patients with more than 20% tumor cells positive for at least 1 endocrine marker experienced a poorer prognosis than patients with no (n = 37) or 1% to 20% (n = 52) positivity. The 16 carcinomas expressing the maturely differentiated exocrine gastric phenotype significantly correlated with poorer outcome compared with carcinomas with mature exocrine intestinal (n = 22) or mixed/gastrointestinal (n = 64) phenotypes. Among tumors expressing chromogranin A and/or synaptophysin, the maturely differentiated endocrine gastric phenotype (n = 26) was a negative prognostic factor compared with mature endocrine intestinal (n = 21) and mixed/gastrointestinal (n = 5) phenotypes. Endocrine differentiation and maturely exocrine/endocrine gastric phenotypes are associated with an unfavorable prognosis and may identify subsets of patients for tailored therapy.
    No preview · Article · May 2012 · American Journal of Clinical Pathology