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  1. Article ; Online: Multiplex Immunofluorescence Tyramide Signal Amplification for Immune Cell Profiling of Paraffin-Embedded Tumor Tissues

    Sharia Hernandez / Frank Rojas / Caddie Laberiano / Rossana Lazcano / Ignacio Wistuba / Edwin Roger Parra

    Frontiers in Molecular Biosciences, Vol

    2021  Volume 8

    Abstract: Every day, more evidence is revealed regarding the importance of the relationship between the response to cancer immunotherapy and the cancer immune microenvironment. It is well established that a profound characterization of the immune microenvironment ... ...

    Abstract Every day, more evidence is revealed regarding the importance of the relationship between the response to cancer immunotherapy and the cancer immune microenvironment. It is well established that a profound characterization of the immune microenvironment is needed to identify prognostic and predictive immune biomarkers. To this end, we find phenotyping cells by multiplex immunofluorescence (mIF) a powerful and useful tool to identify cell types in biopsy specimens. Here, we describe the use of mIF tyramide signal amplification for labeling up to eight markers on a single slide of formalin-fixed, paraffin-embedded tumor tissue to phenotype immune cells in tumor tissues. Different panels show different markers, and the different panels can be used to characterize immune cells and relevant checkpoint proteins. The panel design depends on the research hypothesis, the cell population of interest, or the treatment under investigation. To phenotype the cells, image analysis software is used to identify individual marker expression or specific co-expression markers, which can differentiate already selected phenotypes. The individual-markers approach identifies a broad number of cell phenotypes, including rare cells, which may be helpful in a tumor microenvironment study. To accurately interpret results, it is important to recognize which receptors are expressed on different cell types and their typical location (i.e., nuclear, membrane, and/or cytoplasm). Furthermore, the amplification system of mIF may allow us to see weak marker signals, such as programmed cell death ligand 1, more easily than they are seen with single-marker immunohistochemistry (IHC) labeling. Finally, mIF technologies are promising resources for discovery of novel cancer immunotherapies and related biomarkers. In contrast with conventional IHC, which permits only the labeling of one single marker per tissue sample, mIF can detect multiple markers from a single tissue sample, and at the same time, deliver extensive information about the cell ...
    Keywords immune microenvironment ; multiplex immunofluorescence ; immune profiling ; cell phenotyping ; immunotherapy ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

    Jerfiz D. Constanzo / Ke-jing Tang / Smita Rindhe / Margherita Melegari / Hui Liu / Ximing Tang / Jaime Rodriguez-Canales / Ignacio Wistuba / Pier Paolo Scaglioni

    Neoplasia : An International Journal for Oncology Research, Vol 18, Iss 5, Pp 282-

    2016  Volume 293

    Abstract: The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell ...

    Abstract The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC) cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.
    Keywords Medicine ; R ; Internal medicine ; RC31-1245 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 570
    Publishing date 2016-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Corrigendum to “PIAS1-FAK Interaction Promotes the Survival and Progression of Non–Small Cell Lung Cancer” [Neoplasia 18 (2016) 282-293].

    Jerfiz D. Constanzo / Ke-jing Tang / Smita Rindhe / Margherita Melegari / Hui Liu / Ximing Tang / Jaime Rodriguez-Canales / Ignacio Wistuba / Pier Paolo Scaglioni

    Neoplasia: An International Journal for Oncology Research, Vol 18, Iss 7, p

    2016  Volume 457

    Keywords Medicine ; R ; Internal medicine ; RC31-1245 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Language English
    Publishing date 2016-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers

    Omar Alhalabi / Jianfeng Chen / Yuxue Zhang / Yang Lu / Qi Wang / Sumankalai Ramachandran / Rebecca Slack Tidwell / Guangchun Han / Xinmiao Yan / Jieru Meng / Ruiping Wang / Anh G. Hoang / Wei-Lien Wang / Jian Song / Lidia Lopez / Alex Andreev-Drakhlin / Arlene Siefker-Radtke / Xinqiao Zhang / William F. Benedict /
    Amishi Y. Shah / Jennifer Wang / Pavlos Msaouel / Miao Zhang / Charles C. Guo / Bogdan Czerniak / Carmen Behrens / Luisa Soto / Vassiliki Papadimitrakopoulou / Jeff Lewis / Waree Rinsurongkawong / Vadeerat Rinsurongkawong / Jack Lee / Jack Roth / Stephen Swisher / Ignacio Wistuba / John Heymach / Jing Wang / Matthew T. Campbell / Eleni Efstathiou / Mark Titus / Christopher J. Logothetis / Thai H. Ho / Jianjun Zhang / Linghua Wang / Jianjun Gao

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: The deficiency of MTAP, an enzyme of the adenine salvage pathway, occurs in some cancers. Here the authors perform a small cohort phase II clinical trial with metastatic MTAP-deficient urothelial cancer (UC) and show an increased overall response when ... ...

    Abstract The deficiency of MTAP, an enzyme of the adenine salvage pathway, occurs in some cancers. Here the authors perform a small cohort phase II clinical trial with metastatic MTAP-deficient urothelial cancer (UC) and show an increased overall response when comparing to MTAP-proficient UC patients.
    Keywords Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Author Correction

    Jingying Nong / Yuhua Gong / Yanfang Guan / Xin Yi / Yuting Yi / Lianpeng Chang / Ling Yang / Jialin Lv / Zhirong Guo / Hongyan Jia / Yuxing Chu / Tao Liu / Ming Chen / Lauren Byers / Emily Roarty / Vincent K. Lam / Vassiliki A. Papadimitrakopoulou / Ignacio Wistuba / John V. Heymach /
    Bonnie Glisson / Zhongxing Liao / J. Jack Lee / P. Andrew Futreal / Shucai Zhang / Xuefeng Xia / Jianjun Zhang / Jinghui Wang

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer

    2019  Volume 1

    Abstract: The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article. ...

    Abstract The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Jingying Nong / Yuhua Gong / Yanfang Guan / Xin Yi / Yuting Yi / Lianpeng Chang / Ling Yang / Jialin Lv / Zhirong Guo / Hongyan Jia / Yuxing Chu / Tao Liu / Ming Chen / Lauren Byers / Emily Roarty / Vincent K. Lam / Vassiliki A. Papadimitrakopoulou / Ignacio Wistuba / John V. Heymach /
    Bonnie Glisson / Zhongxing Liao / J. Jack Lee / P. Andrew Futreal / Shucai Zhang / Xuefeng Xia / Jianjun Zhang / Jinghui Wang

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer

    2019  Volume 1

    Abstract: The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article. ...

    Abstract The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer

    Ming Chen / Runzhe Chen / Ying Jin / Jun Li / Xin Hu / Jiexin Zhang / Junya Fujimoto / Shawna M. Hubert / Carl M. Gay / Bo Zhu / Yanhua Tian / Nicholas McGranahan / Won-Chul Lee / Julie George / Xiao Hu / Yamei Chen / Meijuan Wu / Carmen Behrens / Chi-Wan Chow /
    Hoa H. N. Pham / Junya Fukuoka / Jia Wu / Edwin Roger Parra / Latasha D. Little / Curtis Gumbs / Xingzhi Song / Chang-Jiun Wu / Lixia Diao / Qi Wang / Robert Cardnell / Jianhua Zhang / Jing Wang / Xiuning Le / Don L. Gibbons / John V. Heymach / J. Jack Lee / William N. William / Chao Cheng / Bonnie Glisson / Ignacio Wistuba / P. Andrew Futreal / Roman K. Thomas / Alexandre Reuben / Lauren A. Byers / Jianjun Zhang

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold ... ...

    Abstract Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold and heterogeneous T cell repertoire.
    Keywords Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer

    Jingying Nong / Yuhua Gong / Yanfang Guan / Xin Yi / Yuting Yi / Lianpeng Chang / Ling Yang / Jialin Lv / Zhirong Guo / Hongyan Jia / Yuxing Chu / Tao Liu / Ming Chen / Lauren Byers / Emily Roarty / Vincent K. Lam / Vassiliki A. Papadimitrakopoulou / Ignacio Wistuba / John V. Heymach /
    Bonnie Glisson / Zhongxing Liao / J. Jack Lee / P. Andrew Futreal / Shucai Zhang / Xuefeng Xia / Jianjun Zhang / Jinghui Wang

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 8

    Abstract: Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during ...

    Abstract Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during therapy.
    Keywords Science ; Q
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer

    Jingying Nong / Yuhua Gong / Yanfang Guan / Xin Yi / Yuting Yi / Lianpeng Chang / Ling Yang / Jialin Lv / Zhirong Guo / Hongyan Jia / Yuxing Chu / Tao Liu / Ming Chen / Lauren Byers / Emily Roarty / Vincent K. Lam / Vassiliki A. Papadimitrakopoulou / Ignacio Wistuba / John V. Heymach /
    Bonnie Glisson / Zhongxing Liao / J. Jack Lee / P. Andrew Futreal / Shucai Zhang / Xuefeng Xia / Jianjun Zhang / Jinghui Wang

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 8

    Abstract: Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during ...

    Abstract Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during therapy.
    Keywords Science ; Q
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Rol patogénico del gen supresor de tumores PTEN en cáncer ovárico asociado a endometriosis Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis

    Adriana Castiblanco G / Yumay Pires N / Ignacio Wistuba O / Erick Riquelme S / Leonardo Andrade M / Alejandro Corvalán R

    Revista Médica de Chile, Vol 134, Iss 3, Pp 271-

    2006  Volume 278

    Abstract: Background: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian ... ...

    Abstract Background: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. Aim: To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). Material and methods: Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. Results: Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p <0.005). There was a histological correlation between EA and a higher cellular proliferation index. PTEN was negative in 5 of 15 EN, 9 of 15 EA and 30 of 37 CE/CC. There was a correlation between LOH and loss of PTEN protein in EN, EA and ET (60%). Conclusions: Negative expression on PTEN in EN; EA; ET and CE/CC is a manifestation of the inactivation of this gene. The mechanisms that cause this inactivation, must be elucidated
    Keywords Endometrial neoplasms ; Endometriosis ; Ovarian neoplasms ; PTEN protein ; human ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 616
    Language Spanish
    Publishing date 2006-03-01T00:00:00Z
    Publisher Sociedad Médica de Santiago
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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