Large-scale human tissue analysis identifies Uroplakin 1b as a putative diagnostic marker in surgical pathology

Abstract Introduction/Objective Uroplakin 1B (Upk1b) protein is relevant for stabilizing and strengthening epithelial cells that line the bladder. It helps to prevent urothelial cells from rupturing during bladder distension. Based on RNA expression studies Upk1b is expressed in a limited number of normal tissues. Methods/Case Report To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1b expression analysis, a tissue microarray containing 15,182 samples from 127 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results (if a Case Study enter NA) Upk1b positivity was found in 61 (48%) different tumor types including 50 (39%) with at least one moderately positive and 39 tumor types (31%) with at least one strongly positive tumor. The highest positivity rate and the highest levels of expression was found in urothelial neoplasms (58-95%), Brenner tumors of the ovary (92%), epitheloid mesothelioma (87%), serous carcinomas of the ovary (58%) and the endometrium (53%) as well as squamous cell carcinomas of various sites of origin. Immunostaining was infrequent in lung adenocarcinoma (0%) and largely absent in colorectal (0.7%) or prostatic adenocarcinoma (1.3%). In urothelial tumors cancer, low Upk1b expression was linked to high grade and invasive tumor growth (p<0.0001 each) as well as nodal metastasis (p=0.0006) but an unequivocal link to unfavorable tumor features was lacking in various other tumor entities. Conclusion In conclusion, the differential Upk1b expression in different tumor entities suggests potential diagnostic applications of Upk1b immunohistochemistry in panels for the distinction of malignant mesothelioma from adenocarcinoma of the lung, urothelial carcinoma from prostatic adenocarcinoma in the bladder, or pancreatico-biliary and gastro-esophageal from colorectal adenocarcinomas.

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Targeting Nodal and Cripto-1: Perspectives Inside Dual Potential Theranostic Cancer Biomarkers

Current Medicinal Chemistry ◽

10.2174/0929867325666180912104707 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1994-2050 ◽

Cited By ~ 4

Author(s):

Annamaria Sandomenico ◽

Menotti Ruvo

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Normal Development ◽

Cancer Biomarkers ◽

Normal Tissues ◽

Tumor Relapse ◽

Developmental Factors ◽

Theranostic Agents ◽

Tumor Types ◽

Embryonic Signaling

Background:Elucidating the mechanisms of recurrence of embryonic signaling pathways in tumorigenesis has led to the discovery of onco-fetal players which have physiological roles during normal development but result aberrantly re-activated in tumors. In this context, Nodal and Cripto-1 are recognized as onco-developmental factors, which are absent in normal tissues but are overexpressed in several solid tumors where they can serve as theranostic agents.Objective:To collect, review and discuss the most relevant papers related to the involvement of Nodal and Cripto-1 in the development, progression, recurrence and metastasis of several tumors where they are over-expressed, with a particular attention to their occurrence on the surface of the corresponding sub-populations of cancer stem cells (CSC).Results:We have gathered, rationalized and discussed the most interesting findings extracted from some 370 papers related to the involvement of Cripto-1 and Nodal in all tumor types where they have been detected. Data demonstrate the clear connection between Nodal and Cripto-1 presence and their multiple oncogenic activities across different tumors. We have also reviewed and highlighted the potential of targeting Nodal, Cripto-1 and the complexes that they form on the surface of tumor cells, especially of CSC, as an innovative approach to detect and suppress tumors with molecules that block one or more mechanisms that they regulate.Conclusion:Overall, Nodal and Cripto-1 represent two innovative and effective biomarkers for developing potential theranostic anti-tumor agents that target normal as well as CSC subpopulations and overcome both pharmacological resistance and tumor relapse.

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Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory?

Journal of Oncology ◽

10.1155/2012/376894 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 44

Author(s):

Paola Brescia ◽

Cristina Richichi ◽

Giuliana Pelicci

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Large Scale ◽

Molecular Mechanisms ◽

Cell Phenotype ◽

Multiple Tumor ◽

Early Results ◽

Tumorigenic Potential ◽

Tumor Types

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge.

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Expression of SSX-2 and SSX-4 Genes in Neuroblastoma

The International Journal of Biological Markers ◽

10.1177/172460080201700401 ◽

2002 ◽

Vol 17 (4) ◽

pp. 219-223 ◽

Cited By ~ 5

Author(s):

S.N. Chi ◽

N.-K.V. Cheung ◽

I.Y. Cheung

Keyword(s):

Cytolytic T Lymphocytes ◽

Rt Pcr ◽

Normal Peripheral Blood ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Stage 4 ◽

The Family ◽

Prognostic Utility ◽

Stage 1 ◽

Cancer Testis

The SSX genes are members of the family of cancer/testis antigens that encode tumor-associated antigens recognizable by autologous cytolytic T lymphocytes. Their expression is common in tumors of diverse lineages and absent in normal tissues except testis and thyroid. In this study, sixty-seven neuroblastomas (NB) (12 stage 1, 13 stage 2, 12 stage 3, 12 stage 4S and 13 stage 4) were examined by RT-PCR and a sensitive chemiluminescent detection method for SSX-2 and SSX-4 expression. Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4. SSX-2 and SSX-4 positivity correlated with metastatic NB stage 4 (p=0.02 and p=0.006, respectively). Sensitivity experiments showed SSX-2 detection was one tumor cell in 106 normal cells, and one in 104 for SSX-4. All normal tissues (n=6), with the exception of testis, normal bone marrow (BM, n=12) and normal peripheral blood (PBL, n=10) were negative for SSX-2 and SSX-4 expression. Thirty-two BM and 14 PBL obtained from 35 stage 4 NB patients at 24 months from their diagnosis were evaluated for SSX-2 expression. Unlike another cancer/testis antigen, GAGE, only one BM sample was positive, and no prognostic utility could be established. Further investigation of SSX expression at other relevant time points is warranted.

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NaPi- II b as a potential diagnostic and prognostic biomarker in ovarian cancers

10.1101/394759 ◽

2018 ◽

Author(s):

Shoufeng Zhao ◽

Zhipeng Wang

Keyword(s):

Ovarian Cancer ◽

Cancer Cell Line ◽

Normal Tissues ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Tumor Types ◽

First Time ◽

Kaplan Meier Plotter ◽

Normal Controls

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.

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Liposomes

Advances in Medical Technologies and Clinical Practice - Novel Approaches for Drug Delivery ◽

10.4018/978-1-5225-0751-2.ch003 ◽

2017 ◽

pp. 52-87

Author(s):

Mangal Shailesh Nagarsenker ◽

Megha Sunil Marwah

Keyword(s):

Quality Control ◽

Large Scale ◽

Clinical Success ◽

Scale Production ◽

Large Scale Production ◽

Diagnostic Applications ◽

Set Up ◽

Insight Into ◽

Characterisation Techniques

The science of liposomes has expanded in ambit from bench to clinic through industrial production in thirty years since the naissance of the concept. This chapter makes an attempt to bring to light the impregnable contributions of great researchers in the field of liposomology that has witnessed clinical success in the recent times. The journey which began in 1965 with the observations of Bangham and further advances made en route (targeting/stealthing of liposomes) along with alternative and potential liposome forming amphiphiles has been highlighted in this chapter. The authors have also summarised the conventional and novel industrially feasible methods used to formulate liposomes in addition to characterisation techniques which have been used to set up quality control standards for large scale production. Besides, the authors have provided with an overview of primary therapeutic and diagnostic applications and a brief insight into the in vivo behaviour of liposomes.

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Detection of the 170 kDa P-Glycoprotein in Neoplastic and Normal Tissues

Tumori Journal ◽

10.1177/030089168907500605 ◽

1989 ◽

Vol 75 (6) ◽

pp. 542-546 ◽

Cited By ~ 10

Author(s):

Enrico Ronchi ◽

Ornella Sanfilippo ◽

Giovanni Di Fronzo ◽

Maria Rosa Bani ◽

Gabriella Della Torre ◽

...

Keyword(s):

Protein A ◽

Resistant Cell ◽

Nodal Metastasis ◽

Resistant Cell Line ◽

Resistant Variant ◽

Normal Tissues ◽

Immunoblotting Assay ◽

Human Solid Tumors

A membrane purification procedure and an immunoblotting assay have been designed to allow screening of human solid tumors for overexpression of the GP170 glycoprotein without employing a disaggregation method to obtain cell suspensions. The electrophoresed membrane proteins were probed, after Western Blotting, with the C219 monoclonal antibody and iodinated Protein A. The labeling intensity of the bands on the autoradioimmunoblots were quantified by densitometry. To test for the presence of GP170, we used membranes from the UV 2237 fibrosarcoma line and its adriamycin-resistant variant ADMR, grown in vitro or as solid tumor in mice. Membranes of human normal and tumor tissues obtained from previously untreated patients were also tested. An immunoreaction was observed in the adriamycin-resistant UV 2237 lines grown in vitro or in vivo. Quantitatively, the binding of the resistant cell line grown in vitro was higher than that observed in cells grown in mice. Bands in the GP 170 region were observed in 4/7 normal and in 7/7 tumor colon tissues and in the normal medulla from 2 patients with cancer of the renal cortex. No reaction could be found in samples from normal tissue, primary tumor or nodal metastasis from 7 patients with breast cancer.

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Predicting STAT1 as a prognostic marker in patients with solid cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920917558 ◽

2020 ◽

Vol 12 ◽

pp. 175883592091755

Author(s):

Jinguo Zhang ◽

Fanchen Wang ◽

Fangran Liu ◽

Guoxiong Xu

Keyword(s):

Ovarian Cancer ◽

Prognostic Value ◽

Renal Carcinoma ◽

The Cancer Genome Atlas ◽

Solid Cancer ◽

Lower Grade ◽

High Grade ◽

Large Tumor ◽

Normal Tissues ◽

Tumor Types

Background: Aberrant activities of signal transducer and activator of transcription 1 (STAT1) have been implicated in cancer development. However, the prognostic value of STAT1 remains unclear. This report identified the role of STAT1 in prognosis in patients with solid cancer through open literature and The Cancer Genome Atlas (TCGA) database. Methods: Published articles were obtained from PubMed, Web of Science, and Embase databases according to a search strategy up to October 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the prognostic factors of patients. TCGA datasets were used to explore the prognostic value of STAT1 in various cancers. Results: A total of 15 studies incorporating 2839 patients with solid cancers were included. Pooled data showed that overexpressed STAT1 favored long overall survival (OS) (HR = 0.604, 95% CI = 0.431–0.846, p = 0.003) and disease-specific survival (DSS) (HR = 0.650, 95% CI = 0.512–0.825, p = 0.000). In subgroup analyses, highly expressed STAT1 was correlated with long OS of patients with high-grade serous ovarian cancer and oral squamous cell carcinoma. Data extracted from TCGA datasets unveiled that STAT1 expression was significantly higher in 12 cancers (e.g. bladder and breast) than their adjacent normal tissues. Again, highly expressed STAT1 favored long OS of patients with ovarian cancer as well as rectum adenocarcinoma, sarcoma, and skin cutaneous melanoma. However, in renal carcinoma, brain lower grade glioma, lung adenocarcinoma, and pancreatic cancer, highly expressed STAT1 was correlated with poor OS of patients. Particularly in renal carcinoma, increased STAT1 expression was associated with high grade, later stage, large tumor size, and lymph node and distant metastasis. Conclusion: STAT1 has been identified to have prognostic value in patients with solid cancer. Highly expressed STAT1 may predict prognosis in cancer patients based on their tumor types.

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Production of Monoclonal Antibodies against a New Carcinoma-associated Marker in View of Developing a Serological Test

The International Journal of Biological Markers ◽

10.1177/172460089000500302 ◽

1990 ◽

Vol 5 (3) ◽

pp. 109-117 ◽

Cited By ~ 4

Author(s):

E. Tagliabue ◽

F. Centis ◽

A. Mastroianni ◽

S. Martignone ◽

S. Ménard ◽

...

Keyword(s):

Lung Carcinoma ◽

Serological Test ◽

Small Cell Lung Carcinoma ◽

Metastatic Breast ◽

Cell Lung Carcinoma ◽

Normal Tissues ◽

Diagnostic Applications ◽

Low Sensitivity ◽

Nsclc Patients ◽

And Control

By immunizing a mouse with human metastatic breast tumor cells from patient effusions and infiltrated lymph nodes, a monoclonal antibody (MLuC2), which identifies a new carcinoma-associated marker, was raised. The reactivity of this reagent was studied by immunohistochemistry on live and fixed cells from tumor cell lines and on frozen sections from surgical specimens. Besides reacting with 73% of breast carcinomas, MLuC2 also reacted with 93% of non-small cell lung carcinoma (NSCLC) and with a few normal tissues. The MLuC2-recognized molecule (CaMLuC2), whose MW was 90 KDa according to immunoblotting experiments, was found to be detectable in the serum and could therefore be of particular interest for serological diagnostic applications. Since the CaMLuC2 epitope was not polyexpressed on the bearing molecule, we produced a new generation of MAbs in order to define epitopes coexpressed with CaMLuC2 on the same 90 KDa molecule, and which are therefore suitable to develop a double-determinant immunoradiometric assay (DDIRMA) for the detection of this marker in the sera of lung carcinoma patients. Different analyses by immunohistochemistry, binding inhibition tests and DDIRMA, proved that the two new reagents developed, MLuC8 and MLuC9, recognize the same or closely related epitopes, which are however different from CaMLuC2, but which are all present on the same molecule. Preliminary immunoradiometric tests performed on sera from lung cancer and control patients showed a good specificity but a low sensitivity. In fact, only 42% of the 28 tested sera samples from NSCLC patients scored positive despite the fact that more than 90% of the NSCLC expressed the relevant antigen

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Trisomy 21 and Down syndrome: a short review

Brazilian Journal of Biology ◽

10.1590/s1519-69842008000200031 ◽

2008 ◽

Vol 68 (2) ◽

pp. 447-452 ◽

Cited By ~ 20

Author(s):

CA. Sommer ◽

F. Henrique-Silva

Keyword(s):

Gene Expression ◽

Down Syndrome ◽

Large Scale ◽

Molecular Mechanisms ◽

Global Gene Expression ◽

Short Review ◽

Complex Disorder ◽

Expression Studies ◽

Gene Expression Studies ◽

Chromosome Segments

Even though the molecular mechanisms underlying the Down syndrome (DS) phenotypes remain obscure, the characterization of the genes and conserved non-genic sequences of HSA21 together with large-scale gene expression studies in DS tissues are enhancing our understanding of this complex disorder. Also, mouse models of DS provide invaluable tools to correlate genes or chromosome segments to specific phenotypes. Here we discuss the possible contribution of HSA21 genes to DS and data from global gene expression studies of trisomic samples.

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