scholarly journals A Panel of Four Anti-HSPG Monoclonal Antibodies Benefits in Increasing the Specificity in Detection of Colorectal Cancer

Author(s):  
Ei Khaing Mon ◽  
Rujurek Chaiwongsa ◽  
Phennapha Klangsinsirikul ◽  
Preeyanat Vongchan

Colorectal cancer (CRC) is the second leading with main cause of death is liver and lung metastasis. Using of a combination of genetic and epigenetic markers are addressed but the results have not been approved in clinical practice. A set of serum biomarkers has been proposed to increase accuracy in early diagnosis of CRC. In addition, non-invasive as well as the best prognostic panel of biomarkers and define predictive biomarkers for treatment of CRC are all aims of future research. HSPGs is an important biomolecule involving in cancer cell proliferation, differentiation, and migration. Membrane HSPGs shed into blood circulation and matrix in particular circumstance can be used as a specific biomarker for some cancer cells. In order to evaluate the benefit of a panel of anti-HSPGs monoclonal antibodies in increasing specificity to detect CRC, four clones of anti-HSPGs were studied for its specific reaction on various tumor cell lines by indirect immunofluorescent technique and analyzed by flow cytometer compared to normal white blood cells. A combination of two or more clones were focused. The results showed that all four clones presented a variation in reaction to all solid tumor cell lines tested but negative to normal white blood cells from different ABO blood groups. Interestingly, amongst those cells tested, HT29, a colorectal cancer cell lines were significantly reacted with all four monoclonal antibodies. Taken together, we proposed a panel of four anti-HSPGs monoclonal antibodies to be applied in various detection platforms to increase the specificity in screening of CRC. Keywords: Cancer biomarkers, Colorectal cancer, HSPG

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.


1993 ◽  
Vol 37 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Gail D. Lewis ◽  
Irene Figari ◽  
Brian Fendly ◽  
Wai Lee Wong ◽  
Paul Carter ◽  
...  

2003 ◽  
Vol 88 (11) ◽  
pp. 5537-5546 ◽  
Author(s):  
Ada Funaro ◽  
Anna Sapino ◽  
Bruna Ferranti ◽  
Alberto L. Horenstein ◽  
Isabella Castellano ◽  
...  

Abstract LH and human chorionic gonadotropin (hCG) control steroid production and gametogenesis. They also function as growth factors through interaction with a specific receptor that is a member of the seven-transmembrane receptor family coupled via G proteins to signal pathways involving cAMP and phospholipase C/inositol 3 phosphate. For this study, monoclonal antibodies (mAbs) were raised against the human LH receptor (LHR)/hCG receptor (hCGR), using Chinese hamster ovary LHR-transfected cells as the immunogen. Two reagents were then selected on the basis of their ability to recognize the full-length transmembrane re-ceptor expressed both by Chinese hamster ovary LHR-transfected cells and by a limited number of tumor cell lines. One of these mAbs reacts with the LHR/hCGR in tissue sections of both frozen and paraffin-embedded specimens. This unique feature allowed us to map the cytological distribution of LHR/hCGR in human breast tissues at different stages of development in physiological and benign pathological conditions. The same mAb proved to be agonistic: receptor ligation elicits signals that modulate the growth of selected breast tumor cell lines. This observation suggests that the mAb recognizes an epitope that is included in the domain of the receptor involved in the interaction with the natural ligand.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 524-524 ◽  
Author(s):  
Niels Frank Jensen ◽  
Rolf Soekilde ◽  
Jan Stenvang ◽  
Birgitte Sander Nielsen ◽  
Thomas Litman ◽  
...  

524 Background: Chemotherapy of metastatic colorectal cancer is based on 5-flourouracil combined with either oxaliplatin or irinotecan (active metabolite: SN-38). Identification of predictive biomarkers of drug response is needed to provide a better personalized treatment. In this study we aimed to identify microRNAs related to intrinsic resistance to oxaliplatin or irinotecan in a panel of ten colorectal cancer cell lines. Methods: Drug sensitivity towards oxaliplatin and SN-38 was determined for ten colorectal cancer cell lines (Colo-205, DLD-1, HCC-2998, HCT-15, HCT-116, HT-29, KM12, LoVo, LS-174T, and SW620), using the cell viability MTT assay and the cell death LDH assay. In addition, two cell lines (DLD-1 and LoVo) were exposed to the drugs for 6, 24 or 48 hours. MicroRNA expression profiles were generated using the Exiqon miRCURY LNA microarray platform (including 840 microRNAs), and four differentially expressed microRNAs were validated by independent qRT-PCR measurements. Results: The drug sensitivities of the ten colorectal cancer cell lines varied about 50 times between the least and most sensitive cell lines. Correlation of drug sensitivity data to microRNA expression data across the ten cell lines yielded about 25 microRNA biomarker candidates, for each of the drug/assay combinations. Following short-term drug treatment 10-20 microRNAs were altered for each drug/cell line combination. Validation by qRT-PCR showed a very good correlation to the microarray data. MicroRNAs identified by correlation to drug sensitivity and by short-term treatment were compared, and less than 10% were identified by both approaches, perhaps representing the most promising candidates. These candidates are for SN-38 miR-15a, miR-22, miR-24, miR-98, miR-142-3p, miR-1290, and let-7b, and for oxaliplatin miR-23b, miR-27a, miR-192, miR-200a, miR-222, miR-886-5p, and miR-1308. Conclusions: In the present study we identified a number of microRNAs that are potentially involved in intrinsic resistance and/or could be predictive biomarkers for either irinotecan or oxaliplatin.


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