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Metastasis to the sinonasal tract from sigmoid colon adenocarcinoma

bin Sabir Husin Athar PP, bte Ahmad Norhan N, bin Saim L, bin Md Rose I, bte Ramli R

Ann Acad Med Singap, 2008 Sep;37(9):788-3.
PMID: 18989497

INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC).
CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC.
TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis.
CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

Matched MeSH terms: Carcinoembryonic Antigen/metabolism
Fulltext Selection and characterisation of Affimers specific for CEA recognition

Shamsuddin SH, Jayne DG, Tomlinson DC, McPherson MJ, Millner PA

Sci Rep, 2021 01 12;11(1):744.
PMID: 33436840 DOI: 10.1038/s41598-020-80354-6

Carcinoembryonic antigen (CEA) is the only blood based protein biomarker at present, used for preoperative screening of advanced colorectal cancer (CRC) patients to determine the appropriate curative treatments and post-surveillance screening for tumour recurrence. Current diagnostics for CRC detection have several limitations and development of a highly sensitive, specific and rapid diagnostic device is required. The majority of such devices developed to date are antibody-based and suffer from shortcomings including multimeric binding, cost and difficulties in mass production. To circumvent antibody-derived limitations, the present study focused on the development of Affimer proteins as a novel alternative binding reagent for CEA detection. Here, we describe the selection, from a phage display library, of Affimers specific to CEA protein. Characterization of three anti-CEA Affimers reveal that these bind specifically and selectively to protein epitopes of CEA from cell culture lysate and on fixed cells. Kinetic binding analysis by SPR show that the Affimers bind to CEA with high affinity and within the nM range. Therefore, they have substantial potential for used as novel affinity reagents in diagnostic imaging, targeted CRC therapy, affinity purification and biosensor applications.

Matched MeSH terms: Carcinoembryonic Antigen/metabolism*
Fulltext Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using In Vitro and In Vivo Models

Pramanik A, Xu Z, Shamsuddin SH, Khaled YS, Ingram N, Maisey T, et al.

ACS Appl Mater Interfaces, 2022 Mar 09;14(9):11078-11091.
PMID: 35196008 DOI: 10.1021/acsami.1c21655

Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.

Matched MeSH terms: Carcinoembryonic Antigen/metabolism*

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