scholarly journals Tumor-Targeted Fluorescence Imaging and Mechanisms of Tumor Cell-Derived Carbon Nanodots

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 193
Author(s):  
Taotao Huo ◽  
Wenshuai Li ◽  
Dong Liang ◽  
Rongqin Huang
Keyword(s):  
Tumor Cell ◽  
Fluorescence Imaging ◽  
Carboxyl Groups ◽  
Carbon Nanodots ◽  
Large Neutral Amino Acid ◽  
Normal Tissues ◽  
Specific Tumor ◽  
Tumor Tissues ◽  
Diagnostic Probe ◽  
New Vision

An ideal cancer diagnostic probe should possess precise tumor-targeted accumulation with negligible sojourn in normal tissues. Herein, tumor cell-derived carbon nanodots (C-CNDU87 and C-CNDHepG2) about 3~7 nm were prepared by a solvothermal method with stable fluorescence and negligible cytotoxicity. More interestingly, due to the differences in gene expression of cancers, C-CND structurally mimicked the corresponding precursors during carbonization in which carbon nanodots were functionalized with α-amino and carboxyl groups with different densities on their edges. With inherent homology and homing effect, C-CND were highly enriched in precursor tumor tissues. Mechanistic studies showed that under the mediation of the original configuration of α-amino and carboxyl groups, C-CND specifically bound to the large neutral amino acid transporter 1 (LAT1, overexpressed in cancer cells), achieving specific tumor fluorescence imaging. This work provided a new vision about tumor cell architecture-mimicked carbon nanodots for tumor-targeted fluorescence imaging.

scholarly journals ALPPL2 is a highly specific and targetable tumor cell surface antigen

2020 ◽  
Author(s):  
Yang Su ◽  
Xin Zhang ◽  
Scott Bidlingmaier ◽  
Christopher R. Behrens ◽  
Nam-Kyung Lee ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Surface Antigen ◽  
Tissue Specificity ◽  
Surface Antigens ◽  
Cell Surface Antigen ◽  
Cell Surface Antigens ◽  
Normal Tissues ◽  
Specific Tumor ◽  
Therapy Development

AbstractIt has been challenging to identify tumor-specific cell surface antigens as the vast majority of tumor-associated antigens are also expressed by some normal tissues. In the course of our study on mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, incurable and categorized into three histological subtypes, epithelioid, biphasic and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counter-selection on normal cells, and identified a panel of human antibodies that bind all subtypes of mesothelioma but not normal mesothelium. One of the antibodies, M25, showed high specificity, and we hereby report the identification of the M25 antigen as ALPPL2. We performed immunohistochemistry on normal human tissues and found that ALPPL2 is expressed only on placental trophoblasts but not any other normal tissues. This exquisite tissue specificity and broad tumor type coverage suggests that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, we developed an ALPPL2-targeted antibody-drug conjugate and demonstrated potent and specific tumor killing in vitro and in vivo against both epithelioid and sarcomatoid mesothelioma. Thus ALPPL2 belongs to a rare class of cell surface antigens that can be said as being truly tumor specific and is well suited for therapy development against ALPPL2 expressing tumors.

Calreticulin is Differentially Expressed in Invasive Ductal Carcinoma: A Comparative Study

2019 ◽  
Vol 16 (2) ◽  
pp. 148-155
Author(s):  
Asma Tariq ◽  
Rana Muhammad Mateen ◽  
Iram Fatima ◽  
Muhammad Waheed Akhtar
Keyword(s):  
Invasive Ductal Carcinoma ◽  
Tumor Tissue ◽  
Ductal Carcinoma ◽  
Tissue Level ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Two Dimensional Gel Electrophoresis ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Grade Ii

Objective: The aim of the present study was to build protein profiles of untreated breast cancer patients of invasive ductal carcinoma grade II at tissue level in Pakistani population and to compare 2-D profiles of breast tumor tissues with matched normal tissues in order to evaluate for variations of proteins among them. Materials & Methods: Breast tissue profiles were made after polytron tissue lysis and rehydrated proteins were further characterized by using two-dimensional gel electrophoresis. On the basis of isoelectric point (pI) and molecular weight, proteins were identified by online tool named Siena 2-D database and their identification was further confirmed by using MALDI-TOF. Results: Among identified spots, 10 proteins were found to be differentially expressed i.e.; COX5A, THIO, TCTP, HPT, SODC, PPIA, calreticulin (CRT), HBB, albumin and serotransferrin. For further investigation, CRT was selected. The level of CRT in tumors was found to be significantly higher than in normal group (p < 0.05). The increased expression of CRT level in tumor was statistically significant (p = 0.010) at a 95% confidence level (p < 0.05) as analyzed by Mann-Whitney. CRT was found distinctly expressed in high amount in tumor tissue as compared to their matched normal tissues. Conclusion: It has been concluded that CRT expression could discriminate between normal tissue and tumor tissue so it might serve as a possible candidate for future studies in cancer diagnostic markers.

scholarly journals Comparative analysis ofBRAF,NRASandc-KITmutation status between tumor tissues and autologous tumor cell-lines of stage III/IV melanoma

2014 ◽  
Vol 24 (1) ◽  
pp. 70-73 ◽  
Author(s):  
Anne-Chantal Knol ◽  
Marie-Christine Pandolfino ◽  
Audrey Vallée ◽  
Frédérique Nguyen ◽  
Virginie Lella ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Tumor Cell ◽  
Cell Lines ◽  
Stage Iii ◽  
Autologous Tumor Cell ◽  
Autologous Tumor ◽  
Tumor Cell Lines ◽  
Tumor Tissues

scholarly journals Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 428
Author(s):  
Emma Renard ◽  
Estel Collado Camps ◽  
Coline Canovas ◽  
Annemarie Kip ◽  
Martin Gotthardt ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Fluorescence Imaging ◽  
Ex Vivo ◽  
Growth Factor Receptor ◽  
Nuclear Imaging ◽  
A431 Cells ◽  
Site Specific ◽  
Variable Domains ◽  
Diagnostic Probe

Variable domains of heavy chain only antibodies (VHHs) are valuable agents for application in tumor theranostics upon conjugation to both a diagnostic probe and a therapeutic compound. Here, we optimized site-specific conjugation of the chelator DTPA and the photosensitizer IRDye700DX to anti-epidermal growth factor receptor (EGFR) VHH 7D12, for applications in nuclear imaging and photodynamic therapy. 7D12 was site-specifically equipped with bimodal probe DTPA-tetrazine-IRDye700DX using the dichlorotetrazine conjugation platform. Binding, internalization and light-induced toxicity of DTPA-IRDye700DX-7D12 were determined using EGFR-overexpressing A431 cells. Finally, ex vivo biodistribution of DTPA-IRDye700DX-7D12 in A431 tumor-bearing mice was performed, and tumor homing was visualized with SPECT and fluorescence imaging. DTPA-IRDye700DX-7D12 was retrieved with a protein recovery of 43%, and a degree of labeling of 0.56. Spectral properties of the IRDye700DX were retained upon conjugation. 111In-labeled DTPA-IRDye700DX-7D12 bound specifically to A431 cells, and they were effectively killed upon illumination. DTPA-IRDye700DX-7D12 homed to A431 xenografts in vivo, and this could be visualized with both SPECT and fluorescence imaging. In conclusion, the dichlorotetrazine platform offers a feasible method for site-specific dual-labeling of VHH 7D12, retaining binding affinity and therapeutic efficacy. The flexibility of the described approach makes it easy to vary the nature of the probes for other combinations of diagnostic and therapeutic compounds.

scholarly journals Validation of MicroRNA-188-5p Inhibition Power on Tumor Cell Proliferation in Papillary Thyroid Carcinoma

2020 ◽  
Vol 29 ◽  
pp. 096368972091830 ◽  
Author(s):  
Ping Zhou ◽  
Andrew Irving ◽  
Huifang Wu ◽  
Juan Luo ◽  
Johana Aguirre ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Tumor Cell ◽  
Cellular Proliferation ◽  
Tumor Cell Proliferation ◽  
Papillary Thyroid ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
And Function

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.

The RAV12 Monoclonal Antibody Recognizes the N-Linked Glycotope RAAG12: Expression in Human Normal and Tumor Tissues

2009 ◽  
Vol 133 (9) ◽  
pp. 1403-1412
Author(s):  
Suzanne K. Coberly ◽  
Francine Z. Chen ◽  
Mark P. Armanini ◽  
Yan Chen ◽  
Peter F. Young ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Antigen Expression ◽  
Subcellular Location ◽  
Carbohydrate Antigen ◽  
Cytoplasmic Staining ◽  
Safety Issues ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Associated Proteins

Abstract Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts. Objective.—To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues. Design.—Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression. Results.—More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non–tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation. Conclusions.—High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.

TOXOHORMONE IN BACTERIA-FREE TUMORS

1966 ◽  
Vol 44 (8) ◽  
pp. 1069-1087 ◽  
Author(s):  
J. C. Nixon ◽  
B. Zinman
Keyword(s):  
Gel Filtration ◽  
Human Kidney ◽  
Metastatic Carcinoma ◽  
Exchange Chromatography ◽  
Human Spleen ◽  
Normal Tissues ◽  
Highly Active ◽  
Normal Human Kidney ◽  
Tumor Tissues ◽  
Normal Human

Toxohormone was extracted from bacteria-free human tumors and normal tissues, and assayed for activity by measuring the decrease in serum iron levels of rats 12 hours after injection of the extracts. In contrast with the findings of others, the results of the present study demonstrated that active toxohormone could be isolated from bacteria-free tumor tissues. Bacteria-free normal human kidney and spleen also yielded active toxohormone extracts, whereas extracts of normal human- and rat-skeletal muscle and rat liver had no activity.Four active toxohormone extracts were purified by ion-exchange chromatography followed by gel filtration. Human leukemic spleen, metastatic carcinoma of the cecum, and normal human spleen and kidney yielded several highly active purified fractions.

scholarly journals miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

2018 ◽  
Vol 51 (4) ◽  
pp. 1969-1981 ◽  
Author(s):  
Xiangyu Zhu ◽  
Si-ping Ma ◽  
Dongxiang Yang ◽  
Yanlong Liu ◽  
Yong-peng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Nude Mice ◽  
Colony Formation ◽  
Tumor Cell Growth ◽  
Rt Pcr ◽  
Tumor Tissues

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.

scholarly journals Identification of key genes related to macrophage infiltration in gastric cancer based on WGCNA

2020 ◽  
Author(s):  
Haiyan Chen ◽  
Cangang Zhang ◽  
Shuai Cao ◽  
Meng Cao ◽  
Nana Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Accurate Diagnosis ◽  
Marker Genes ◽  
Hub Genes ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
New Strategy ◽  
Tumor Environment ◽  
Advanced Stages

Abstract Background: Gastric cancer (GC) is rampant around the world. Most of the GC cases are detected in advanced stages with poor prognosis. The identification of marker genes for early diagnosis is of great significance. Studying the tumor environment is helpful to acknowledge the process of tumorigenesis, development, and metastasis.Methods: In GEO, 22 kinds of immune cell infiltration were calculated by CIBERSORT. Macrophages were discovered remarkably infiltrated higher in GC compared with normal tissues. WGCNA was utilized to construct the network and then identify key modules and genes related to macrophages in TCGA.Results: Finally, 18 hub genes were verified. In the PPI bar chart, the top 3 genes were chosen as hub genes involved in most pathways. On the TIMER and THPA websites, it is verified that the expression levels of CYBB, CD86 and C3AR1 genes in tumor tissues were higher than those in normal tissues.Conclusion: These genes may work as biomarkers or targets for accurate diagnosis and treatment of GC in the future. Our findings may be a new strategy for the treatment of GC.

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