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  1. Article: Autocrine transforming growth factor-alpha is associated with modulation of a 130 kD RB protein species and 116/110 Rb as revealed by an antisense TGF alpha expression vector.

    Dobre, C / Ziober, B / Humphrey, L / Brattain, M

    International journal of oncology

    2011  Volume 8, Issue 6, Page(s) 1025–1033

    Abstract: Specific RE protein species modulated by autocrine TGF alpha are unknown. HCT116 cells transfected with TGF alpha antisense expression vector were compared with control HCT116 NEO for mitogenesis and modulation of high MW (130, 120 kD) and low MW (116, ... ...

    Abstract Specific RE protein species modulated by autocrine TGF alpha are unknown. HCT116 cells transfected with TGF alpha antisense expression vector were compared with control HCT116 NEO for mitogenesis and modulation of high MW (130, 120 kD) and low MW (116, 110, 105 kD) RE species. Nutrients alone (N) induced maximal mitogenesis in HCT116 NEO and modulated both 130 kD and 116 kD/110 kD RE species. TGF alpha antisense transfected clones required nutrients plus growth factors (GF) for maximal mitogenesis and both 130 kD/120 kD as well as 116 kD/110 kD species were modulated. Thus, autocrine TGF alpha (HCT116) was associated with 130 kD and 116/110 kD modulation while its suppression allowed modulation of a 120 kD species as well.
    Language English
    Publishing date 2011-05-03
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 1154403-x
    ISSN 1019-6439
    ISSN 1019-6439
    DOI 10.3892/ijo.8.6.1025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cerebrospinal fluid analysis in 58 ruminants showing neurological disorders

    Antônio Carlos L. Câmara / Mariana C. Gonzaga / Thaís M. Ziober / Cintia Regina R. Queiroz / Tayná C.M. Fino / Márcio B. Castro / José Renato J. Borges / Benito Soto-Blanco

    Pesquisa Veterinária Brasileira, Vol 40, Iss 5, Pp 346-

    2020  Volume 354

    Abstract: ABSTRACT: Ruminants may be affected by a wide variety of central nervous system (CNS) diseases. Cerebrospinal fluid (CSF) analysis forms the basis for ante mortem diagnostic evaluation of ruminants with clinical signs involving the CNS. Despite its ... ...

    Abstract ABSTRACT: Ruminants may be affected by a wide variety of central nervous system (CNS) diseases. Cerebrospinal fluid (CSF) analysis forms the basis for ante mortem diagnostic evaluation of ruminants with clinical signs involving the CNS. Despite its importance as a tool to aid diagnosis, data regarding CSF examinations in spontaneous cases of CNS diseases in ruminants from Brazil are limited, and most reports involve experimental studies. Therefore, this study aimed to report the results of CSF analysis in 58 ruminants showing signs of neurological disorders. CSF samples for analysis were obtained from 32 cattle, 20 sheep, and 6 goats by cerebello-medullary cistern (n=54) or lumbosacral space (n=4) puncture. These ruminants showed neurological signs related to viral (n=13), mycotic (n=3), or bacterial (n=15) infections, and toxic (n=21), traumatic (n=4), or congenital disorders (n=2). CSF analysis from ruminants with viral infections presented lymphocytic pleocytosis, even though CSF showed no changes in several cases of rabies. Neutrophilic pleocytosis, cloudiness, presence of fibrin clots, and abnormal coloration were evident in the CSF of most cases of CNS bacterial infection, such as meningoencephalitis, meningitis, abscesses, myelitis, and a case of conidiobolomycosis. On the other hand, CSF was unchanged in most cases of toxic disorders, as botulism and hepatic encephalopathy. Elevated CSF density was observed in 60% of ruminants diagnosed with polioencephalomalacia. Our findings show that evaluation of CSF is a valuable diagnostic tool when used in association with epidemiological, clinical and pathological findings for diagnosis of CNS diseases in ruminants.
    Keywords Cerebrospinal fluid ; ruminants ; neurological disorders ; central nervous system ; cytology ; liquor ; livestock ; neurology ; Veterinary medicine ; SF600-1100
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Colégio Brasileiro de Patologia Animal (CBPA)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Identification and characterization of the cell type-specific and developmentally regulated alpha7 integrin gene promoter.

    Ziober, B L / Kramer, R H

    The Journal of biological chemistry

    1996  Volume 271, Issue 37, Page(s) 22915–22922

    Abstract: Expression of alpha7 is mainly confined to skeletal and cardiac muscle in which it appears to be the major laminin-binding integrin. When myoblasts differentiate to myotubes, alpha7 mRNA and protein expression is up-regulated. To explore the mechanisms ... ...

    Abstract Expression of alpha7 is mainly confined to skeletal and cardiac muscle in which it appears to be the major laminin-binding integrin. When myoblasts differentiate to myotubes, alpha7 mRNA and protein expression is up-regulated. To explore the mechanisms involved in the tissue-specific and developmentally regulated expression of alpha7, we isolated and characterized a genomic clone containing approximately 2.8 kilobase pairs (kb) of the 5'-flanking region of the murine alpha7 gene. The 5'-flanking region lacks both TATA and CCAAT boxes but contains five putative Sp1 binding sites located in a CpG island. Two transcription start sites, located near an initiator-like sequence, are 176 and 170 base pairs upstream of the translation start site. There are numerous binding sites for developmental and cell type-specific transcription factors, including AP-1, AP-2, GATA, and several AT-rich sites. There are also eight consensus E-boxes that bind the basic helix-loop-helix family of muscle-specific transcription factors. The approximately 2.8-kb 5'-flanking region was an active promoter in C2C12 skeletal myoblasts and exhibited increased expression upon conversion to myotubes but was inactive in HtLM2 cells, a mouse breast carcinoma epithelial cell line that does not express alpha7. Deletion analysis identified both positive and negative regulatory elements within the approximately 2.8-kb fragment. In 10T1/2 fibroblasts the approximately 2.8-kb alpha7 promoter was trans-activated by the myogenic basic helix-loop-helix proteins myogenin and MyoD but not by MRF4 and myf5. These results suggest that muscle-specific transcription factors play a role in regulating the cell-type expression of the alpha7 gene during development.
    MeSH term(s) Animals ; Antigens, CD/genetics ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors ; DNA-Binding Proteins/genetics ; Embryo Implantation ; Female ; Gene Deletion ; Gene Expression Regulation, Developmental ; Integrin alpha Chains ; Mice ; Molecular Sequence Data ; Muscles/embryology ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Restriction Mapping ; Single-Strand Specific DNA and RNA Endonucleases/metabolism ; Transcription Factors/genetics ; Transcription, Genetic
    Chemical Substances Antigens, CD ; Basic Helix-Loop-Helix Transcription Factors ; DNA-Binding Proteins ; Integrin alpha Chains ; RNA, Messenger ; Transcription Factors ; integrin alpha7 ; Single-Strand Specific DNA and RNA Endonucleases (EC 3.1.30.1)
    Language English
    Publishing date 1996-09-13
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.271.37.22915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Tumor deposition of laminin-5 and the relationship with perineural invasion.

    Anderson, T D / Feldman, M / Weber, R S / Ziober, A F / Ziober, B L

    The Laryngoscope

    2001  Volume 111, Issue 12, Page(s) 2140–2143

    Abstract: ... characterized as follows: A, few to no tumor cells positive; B, some peripheral cells positive; C ... for the PNI-positive specimens was as follows: 2% for A, 41% for B, 46% for C, and 11% for D. For tumors ... without PNI, the distribution was 28% for A, 50% for B, 22% for C, and 0% for D (P = .005). In PNI-positive ...

    Abstract Objectives/hypothesis: Perineural invasion (PNI) is increasingly being recognized as an important indicator of aggressiveness in head and neck squamous cell carcinoma. The mechanisms of PNI are poorly understood. Laminin-5, an important basement membrane constituent, has been shown to be essential in head and neck squamous cell carcinoma invasion and motility. We hypothesized that tumors exhibiting increased expression of laminin-5 are more likely to be neurotropic.
    Study design: Analysis of archived surgical specimens with and without PNI for presence and intensity of laminin-5 tumor staining.
    Methods: Immunohistochemistry of archived head and neck squamous cell carcinoma specimens with known PNI was performed with anti-laminin-5 antibodies and appropriate positive and negative control specimens. The staining patterns were characterized as follows: A, few to no tumor cells positive; B, some peripheral cells positive; C, all peripheral cells positive; and D, almost all tumor cells positive. Statistical analysis was by chi2 analysis.
    Results: Forty-six PNI-positive and 18 PNI-negative specimens were analyzed. The staining distribution for the PNI-positive specimens was as follows: 2% for A, 41% for B, 46% for C, and 11% for D. For tumors without PNI, the distribution was 28% for A, 50% for B, 22% for C, and 0% for D (P = .005). In PNI-positive tumors, no significant difference in staining was seen between areas with and without PNI.
    Conclusions: We found a significant correlation between laminin-5 staining and the presence of PNI in head and neck squamous cell carcinoma. Expression of laminin-5 by tumors is, possibly, an important step in the process of PNI. These preliminary findings support the concept that deposition of basement membrane constituents are required in the multistep process of nerve invasion.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Laminin/metabolism ; Male ; Middle Aged ; Neoplasm Invasiveness ; Otorhinolaryngologic Neoplasms/pathology ; Peripheral Nerves/pathology ; Prognosis
    Chemical Substances Laminin
    Language English
    Publishing date 2001-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80180-x
    ISSN 1531-4995 ; 0023-852X
    ISSN (online) 1531-4995
    ISSN 0023-852X
    DOI 10.1097/00005537-200112000-00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Adhesive mechanisms regulating invasion and metastasis in oral cancer.

    Ziober, B L / Silverman, S S / Kramer, R H

    Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists

    2001  Volume 12, Issue 6, Page(s) 499–510

    Abstract: It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ... ...

    Abstract It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated by cadherins. The process of squamous cell carcinoma invasion and dissemination requires active cell migration through the extracellular matrix with the simultaneous remodeling of intercellular adhesions. Integrins are clearly important in the invasive process, whereas intercellular adhesion receptors restrain invasion and promote a more differentiated phenotype.
    MeSH term(s) Animals ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Adhesion/physiology ; Cell Adhesion Molecules/metabolism ; Cell Movement/physiology ; Extracellular Matrix Proteins/metabolism ; Humans ; Integrins/metabolism ; Lymphatic Metastasis ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Neoplasm Invasiveness/pathology ; Signal Transduction
    Chemical Substances Cell Adhesion Molecules ; Extracellular Matrix Proteins ; Integrins
    Language English
    Publishing date 2001-12-31
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1130962-3
    ISSN 1045-4411
    ISSN 1045-4411
    DOI 10.1177/10454411010120060401
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The laminin-binding activity of the alpha 7 integrin receptor is defined by developmentally regulated splicing in the extracellular domain.

    Ziober, B L / Chen, Y / Kramer, R H

    Molecular biology of the cell

    1997  Volume 8, Issue 9, Page(s) 1723–1734

    Abstract: The expression pattern of the laminin-binding alpha 7 beta 1 integrin is developmentally regulated in skeletal, cardiac, and smooth muscle. The X1/X2 alternative splicing in the extracellular domain of alpha 7 is found in the variable region between ... ...

    Abstract The expression pattern of the laminin-binding alpha 7 beta 1 integrin is developmentally regulated in skeletal, cardiac, and smooth muscle. The X1/X2 alternative splicing in the extracellular domain of alpha 7 is found in the variable region between conserved alpha-chain homology repeat domains III and IV, a site implicated in ligand binding. To assess differences in X1/X2 isoform activity, we generated MCF-7 cell lines transfected with alpha 7-X1/X2 cDNAs. Transfectants expressing the alpha 7-X2 variant adhered rapidly to laminin 1, whereas those expressing alpha 7-X1 failed to attach. That alpha 7-X1 exists in an inactive state was established in assays using an activating beta 1 antibody that induced X1-dependent cell adhesion and spreading. Furthermore, the activation of alpha 7-X1 was cell type specific, and when expressed in HT1080 cells, the integrin was converted into a fully functional receptor capable of promoting adhesion. Thus, the expression of the alpha 7-X1/X2 integrin is a novel mechanism that regulates receptor affinity states in a cell-specific context and may modulate integrin-dependent events during muscle development and repair.
    MeSH term(s) Alternative Splicing ; Breast Neoplasms ; Carcinoma ; Cell Adhesion/drug effects ; Cell Culture Techniques ; Gene Expression Regulation, Developmental ; Humans ; Integrins/immunology ; Integrins/metabolism ; Isomerism ; Laminin/metabolism ; Ligands ; Manganese/pharmacology ; Protein Binding ; Receptors, Laminin/metabolism ; Tumor Cells, Cultured
    Chemical Substances Integrins ; Laminin ; Ligands ; Receptors, Laminin ; Manganese (42Z2K6ZL8P) ; integrin alpha7beta1 (KYD8S41U3X)
    Language English
    Publishing date 1997-09
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.8.9.1723
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Laminin-binding integrins in tumor progression and metastasis.

    Ziober, B L / Lin, C S / Kramer, R H

    Seminars in cancer biology

    1996  Volume 7, Issue 3, Page(s) 119–128

    Abstract: Interactions between tumor cells and extracellular matrix occur at several points during the metastatic cascade. Epithelial tumors, which represent nearly 90% of human neoplasia, must invade their underlying basement membrane to enter the interstitial ... ...

    Abstract Interactions between tumor cells and extracellular matrix occur at several points during the metastatic cascade. Epithelial tumors, which represent nearly 90% of human neoplasia, must invade their underlying basement membrane to enter the interstitial stroma. For distant metastasis, malignant cells must penetrate basement membranes to gain access to blood vessels and organ parenchyma. Integrin receptors that bind to multiple laminin isoforms appear to mediate tumor cell adhesion to basement membranes before and during invasion. It is notable that changes in several laminin-binding integrins occur during tumor progression. These changes may include increased or decreased expression, or changes in distribution from a polarized to a dispersed pattern. Integrins not only mediate cell adhesion and motility but also transduce important downstream signaling events that regulate cell growth, survival, and gene expression. During tumor progression, the development of variant cells with changes in integrin expression and the associated signaling pathways could result in cells with a highly invasive and metastatic phenotype.
    MeSH term(s) Disease Progression ; Extracellular Matrix/chemistry ; Humans ; Integrins/chemistry ; Integrins/physiology ; Laminin/biosynthesis ; Neoplasm Metastasis/physiopathology
    Chemical Substances Integrins ; Laminin
    Language English
    Publishing date 1996-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1006/scbi.1996.0017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Alpha7 integrin mediates cell adhesion and migration on specific laminin isoforms.

    Yao, C C / Ziober, B L / Squillace, R M / Kramer, R H

    The Journal of biological chemistry

    1996  Volume 271, Issue 41, Page(s) 25598–25603

    Abstract: ... cardiac muscles and by certain melanocytic cells. We have assessed the potential role of the alpha7A/B integrin ...

    Abstract The laminin-binding alpha7beta1 integrin receptor is expressed at high levels by skeletal and cardiac muscles and by certain melanocytic cells. We have assessed the potential role of the alpha7A/B integrin isoforms in mediating cell adhesion and motility and determined the laminin isoform specificity of this integrin. When MCF-7 breast carcinoma cells, normally nonadherent to laminin 1, were stably transfected with cDNA for mouse alpha7, they adhered with high efficiency and migrated on laminin 1 substrates. Function-perturbing monoclonal antibodies generated to mouse alpha7 subunit blocked both adhesion and migration of alpha7 transfectants on laminin 1 substrates. Additional studies with MCF-7 transfectants revealed that alpha7beta1 binds well to laminin 1 and to a mixture of laminin 2 and 4 but not to laminin 5. Importantly, alpha7beta1 was capable of promoting motility on both laminin 1 and laminin 2/4 substrates. However, MCF-7 cells transfected with cDNA for either alpha7A or alpha7B showed no significant differences in cell adhesion or motility on laminin 1 substrates. Although the role for the alternatively spliced cytoplasmic variants of alpha7 remains unknown, the results establish that alpha7beta1 mediates cell adhesive activities on a restricted number of laminin isoforms.
    MeSH term(s) Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/pharmacology ; Antigens, CD/biosynthesis ; Antigens, CD/chemistry ; Antigens, CD/physiology ; Base Sequence ; Breast Neoplasms ; Cell Adhesion ; Cell Line ; Cell Movement ; DNA Primers ; Female ; Humans ; Integrin alpha Chains ; Integrins/physiology ; Kinetics ; Laminin ; Mice ; Molecular Sequence Data ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Transfection
    Chemical Substances Antibodies, Monoclonal ; Antigens, CD ; DNA Primers ; Integrin alpha Chains ; Integrins ; Laminin ; Recombinant Proteins ; integrin alpha7 ; integrin alpha7beta1 (KYD8S41U3X)
    Language English
    Publishing date 1996-10-11
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.271.41.25598
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: The beta1 cytoplasmic domain regulates the laminin-binding specificity of the alpha7X1 integrin.

    Yeh, Ming-Guang / Ziober, Barry L / Liu, Baomei / Lipkina, Galina / Vizirianakis, Ioannis S / Kramer, Randall H

    Molecular biology of the cell

    2003  Volume 14, Issue 9, Page(s) 3507–3518

    Abstract: During muscle development, the laminin-specific alpha7 integrin is alternatively spliced in the putative ligand-binding domain to yield either the alpha7X1 or the alpha7X2 variant. The relative level of alpha7X1 and alpha7X2 is developmentally regulated. ...

    Abstract During muscle development, the laminin-specific alpha7 integrin is alternatively spliced in the putative ligand-binding domain to yield either the alpha7X1 or the alpha7X2 variant. The relative level of alpha7X1 and alpha7X2 is developmentally regulated. Similarly, the partner beta1 integrin cytoplasmic domain is converted from the beta1A to the beta1D splice variant. To determine whether beta1D modulates the activity of the alpha7 receptor, cells were transfected with alpha7X1 and beta1D cDNA. alpha7X1 coupled with beta1A failed to adhere to laminin-1, whereas cotransfectants expressing alpha7X1 and beta1D showed strong adhesion. Interestingly, alpha7X1 complexed with beta1A and beta1D displayed the same level of poor adhesion to laminin-2/4 or strong adhesion to laminin-10/11. These findings indicate that alpha7 function is regulated not only by X1/X2 in its extracellular domain but also by beta1 cytoplasmic splice variants. It is likely that expression of beta1D alters alpha7X1 binding to laminin isoforms by a process related to ligand affinity modulation. Functional regulation of alpha7beta1 by developmentally regulated splicing events may be important during myogenic differentiation and repair because the integrin mediates adhesion, motility, and cell survival.
    MeSH term(s) Alternative Splicing/genetics ; Animals ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Carrier Proteins/metabolism ; Cell Adhesion/physiology ; Cloning, Molecular ; Flow Cytometry ; Humans ; Integrin alpha Chains/genetics ; Integrin alpha Chains/metabolism ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Laminin/physiology ; Mice ; Protein Isoforms/genetics ; Protein Subunits/metabolism ; Tumor Cells, Cultured
    Chemical Substances Antigens, CD ; Carrier Proteins ; Integrin alpha Chains ; Integrin beta1 ; Laminin ; Protein Isoforms ; Protein Subunits ; integrin alpha7
    Language English
    Publishing date 2003-09
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E02-12-0824
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers.

    Mota, Alba / Colás, Eva / García-Sanz, Pablo / Campoy, Irene / Rojo-Sebastián, Alejandro / Gatius, Sonia / García, Ángel / Chiva, Luis / Alonso, Sonsoles / Gil-Moreno, Antonio / González-Tallada, Xavier / Díaz-Feijoo, Berta / Vidal, August / Ziober-Malinowska, Patrycja / Bobiński, Marcin / López-López, Rafael / Abal, Miguel / Reventós, Jaume / Matias-Guiu, Xavier /
    Moreno-Bueno, Gema

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

    2016  Volume 30, Issue 1, Page(s) 134–145

    Abstract: Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is ... ...

    Abstract Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.
    MeSH term(s) Aged ; Aged, 80 and over ; Carcinoma, Endometrioid/diagnosis ; Carcinoma, Endometrioid/genetics ; Carcinoma, Endometrioid/pathology ; Carcinosarcoma/diagnosis ; Carcinosarcoma/genetics ; Carcinosarcoma/pathology ; Endometrial Neoplasms/diagnosis ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Female ; Humans ; Middle Aged ; Mutation ; Uterus/pathology
    Language English
    Publishing date 2016-09-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645073-8
    ISSN 1530-0285 ; 0893-3952
    ISSN (online) 1530-0285
    ISSN 0893-3952
    DOI 10.1038/modpathol.2016.143
    Database MEDical Literature Analysis and Retrieval System OnLINE

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