Review

Authors: Anchit Bhagat, Herbert K Lyerly, Michael A Morse...

Carcinoembryonic antigen (CEA) is a glycosylated cell surface oncofetal protein involved in adhesion, proliferation, and migration that is highly upregulated in multiple carcinomas and has long been a promising target for cancer vaccination. This review summarizes the progress to date in the development of CEA vaccines, examining both pre-clinical and clinical studies across a variety of vaccine platforms that in aggregate, begin to reveal some critical insights. These studies demonstrate the ability of CEA vaccines to break immunologic tolerance and elicit CEA-specific immunity, which associates with improved clinical outcomes in select individuals. Approaches that have combined replicating viral vectors, with heterologous boosting and different adjuvant strategies have been particularly promising but, these early clinical trial results will require confirmatory studies. Collectively, these studies suggest that clinical efficacy likely depends upon harnessing a potent vaccine combination in an appropriate clinical setting to fully realize the potential of CEA vaccination.

Topics: Humans; Animals; Mice; Carcinoembryonic Antigen; Neoplasms; Genetic Vectors; Vaccination; Cancer Vaccines; Vaccines, Synthetic; Mice, Inbred C57BL

PubMed: 38087989
DOI: 10.1080/21645515.2023.2291857

Review

Authors: Emina H Huang, Howard L Kaufman

Carcinoembryonic antigen (CEA), the first tumor-associated antigen to be described, was cloned in 1987 and is expressed on nearly 50% of all human tumors. The identification of T-cell specific epitopes within the coding region of the CEA protein has led to the development of various vaccine strategies that target CEA and CEA-expressing tumors. These vaccines have shown evidence of therapeutic effectiveness in animal models and are being evaluated in early phase clinical trials. Although trials are not designed to elucidate clinical responses, they have provided important information about the ability of individual vaccines to induce CEA-specific immune responses through the use of newer in vitro monitoring assays. Continued clinical testing in patients with less advanced disease and the administration of vaccines in combination with other standard therapy will help define the role of CEA-based vaccines in the treatment and prevention of human cancer.

Topics: Animals; Carcinoembryonic Antigen; Cloning, Molecular; Dendritic Cells; Epitopes; Humans; Immunotherapy; Neoplasms; Vaccines; Vaccines, DNA; Vaccines, Subunit; Vaccines, Synthetic

PubMed: 12908512
DOI: 10.1586/14760584.1.1.49

Authors: Gyem Tshering, Palden Wangyel Dorji, Wanna Chaijaroenkul...

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

Topics: Bile Duct Neoplasms; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Cholangiocarcinoma; Humans; Sensitivity and Specificity

PubMed: 29637880
DOI: 10.4269/ajtmh.17-0879

Review

Authors: Jingjing Jiang, Jili Xia, Yang Zang...

Recently, electrochemistry- and photoelectrochemistry-based biosensors have been regarded as powerful tools for trace monitoring of carcinoembryonic antigen (CEA) due to the fact of their intrinsic advantages (e.g., high sensitivity, excellent selectivity, small background, and low cost), which play an important role in early cancer screening and diagnosis and benefit people's increasing demands for medical and health services. Thus, this mini-review will introduce the current trends in electrochemical and photoelectrochemical biosensors for CEA assay and classify them into two main categories according to the interactions between target and biorecognition elements: immunosensors and aptasensors. Some recent illustrative examples are summarized for interested readers, accompanied by simple descriptions of the related signaling strategies, advanced materials, and detection modes. Finally, the development prospects and challenges of future electrochemical and photoelectrochemical biosensors are considered.

Topics: Biosensing Techniques; Carcinoembryonic Antigen; Electrochemical Techniques; Electrochemistry; Humans; Immunoassay

PubMed: 34833818
DOI: 10.3390/s21227742

Review

Authors: Mihai Cătălin Roșu, Petrut Dinu Mihnea, Andrei Ardelean...

Tumour necrosis factor (TNF)-α plays an important role in inflammatory, infectious, and tumor processes, and it is closely related to the early stages of gastric cancer. It is a pro-inflammatory cytokine, produced not only by macrophages and monocytes but also by the lymphocytes, mast cells, neutrophils, keratinocytes, smooth muscle cells, and some tumor cell lines. Large amounts of TNF are released upon contact of macrophages, CD4 + T lymphocytes, and natural killer (NK) cells with lipopolysaccharides, bacterial products, and interleukin 1. TNF-alpha inducing protein (Tipa) is a unique carcinogenic factor of Helicobacter pylori, secreted into culture broth. The biological activities of TNF alpha and deletion mutant were studied. TNF alpha protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-a and chemokine gene expressions are induced by NF-jB activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between TNF alpha and cell-surface nucleolin causes a cancer-oriented microenvironment that increases the risk of gastric cancer. This paper discusses a mechanism of gastric cancer development and the clinical significance of tumor necrosis-alpha and carcinoembryonic antigen in gastric cancer.

Topics: Bacterial Proteins; Carcinoembryonic Antigen; Helicobacter pylori; Humans; Stomach Neoplasms; Tumor Microenvironment; Tumor Necrosis Factor-alpha

PubMed: 35186129
DOI: 10.25122/jml-2020-0098

Review

Authors: Michael A Turner, Thinzar M Lwin, Siamak Amirfakhri...

A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon's ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.

Topics: Humans; Carcinoembryonic Antigen; Neoplasms; Animals; Fluorescent Dyes; Antibodies

PubMed: 34944463
DOI: 10.3390/biom11121819

Review

Authors: Patrizia Bonsignore, Johannes W P Kuiper, Jonas Adrian...

Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), is one of the fastest-evolving human proteins. In this focused review, we will try to resolve the conundrum why a conserved process such as phagocytosis is conducted by a rapidly changing receptor. Therefore, we will first summarize the biochemical and structural details of this immunoglobulin-related glycoprotein in the context of the human CEACAM family. The function of CEACAM3 for the efficient, opsonin-independent detection and phagocytosis of highly specialized, host-restricted bacteria will be further elaborated. Taking into account the decisive role of CEACAM3 in the interaction with pathogenic bacteria, we will discuss the evolutionary trajectory of the CEACAM3 gene within the primate lineage and highlight the consequences of CEACAM3 polymorphisms in human populations. From a synopsis of these studies, CEACAM3 emerges as an important component of human innate immunity and a prominent example of a dedicated receptor for professional phagocytosis.

Topics: Animals; Bacteria; Biological Evolution; Carcinoembryonic Antigen; Humans; Immunity, Innate; Phagocytosis; Primates

PubMed: 32117212
DOI: 10.3389/fimmu.2019.03160

Authors: Si Liu, Li Chen, Yunxiao Shang...

OBJECTIVES

Asthma, a prevalent chronic disease, poses significant health threats and burdens healthcare systems. This study focused on the role of bronchial epithelial cells in asthma pathophysiology.

METHODS

Bioinformatics was used to identify key asthmarelated genes. An ovalbumin-sensitized mouse model and an IL-13-stimulated Beas-2B cell model were established for further investigation.

RESULTS

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a crucial gene in asthma. CEACAM5 expression was elevated in asthmatic mouse lung tissues and IL-13-stimulated Beas-2B cells, primarily in bronchial epithelial cells. CEACAM5 induced reactive oxygen species (ROS), lipid peroxidation, and ferroptosis. Interfering with CEACAM5 reduced ROS, malondialdehyde levels, and enhanced antioxidant capacity, while inhibiting iron accumulation and autophagy. Overexpression of CEACAM5 in IL-13-stimulated cells activated the JAK/STAT6 pathway, which was necessary for CEACAM5-induced autophagy, ROS accumulation, lipid peroxidation, and ferroptosis.

CONCLUSION

CEACAM5 promotes ferroptosis and autophagy in airway epithelial cells via the JAK/STAT6 pathway, exacerbating asthma symptoms. It represents a potential target for clinical treatment.

Topics: Asthma; Animals; Ferroptosis; Autophagy; Mice; Epithelial Cells; Humans; STAT6 Transcription Factor; Janus Kinases; Reactive Oxygen Species; Signal Transduction; Disease Models, Animal; Carcinoembryonic Antigen; GPI-Linked Proteins

PubMed: 39844719
DOI: 10.1080/13510002.2024.2444755

Review

Authors: Rui Zheng, Aochun Wu, Jiyue Li...

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Topics: Humans; Biomarkers, Tumor; Lung Neoplasms; Biosensing Techniques; Electrochemical Techniques; Carcinoembryonic Antigen; Nanocomposites; Graphite

PubMed: 38999110
DOI: 10.3390/molecules29133156

Meta-Analysis Review

Authors: Mitra Ahadi, Shahrzad Tehranian, Bahram Memar...

BACKGROUND AND STUDY AIMS

There is a common misconception that malignant ascites is equivalent to peritoneal carcinomatosis. It seems that malignancy-related ascites is a more appropriate description of malignant ascites, which is difficult to confirm. Carcinoembryonic antigen, a glycoprotein tumor marker shed by malignant cells, increases in a wide range of gastrointestinal malignancies. We carried out the current meta-analysis to determine carcinoembryonic antigen accuracy in the diagnosis of malignancy-related ascites.

PATIENTS AND METHODS

Pubmed/Medline and SCOPUS were searched using these search terms: malignan* AND ascites AND (CEA OR carcinoembryonic). The outcome of interest was carcino-embryonic antigen accuracy in the differentiation of malignancy-related ascites and nonmalignant ascites.

RESULTS

Seven studies were included in this systematic review. Pooled diagnostic indices using random-effects model were as follows: sensitivity 43.1% [381-48.3]; specificity 95.5% [93-97.3]; LR+ (positive likelihood ratio) 7.33 [4.58-11.73]; LR- (negative likelihood ratio) 0.6 [0.54-0.68]; and DOR (diagnostic odds ratio) 12.93 [7.58-22].

CONCLUSIONS

Carcinoembryonic antigen of the ascitic fluid does not seem to be sensitive enough to diagnose malignancy-related ascites. However, due to high specificity, the positive predictive value of this marker is high and the higher the level of carcino-embryonic antigen, the more likely it is to be malignancy-related. Nevertheless, a negative test result cannot definitely rule out the malignancy.

Topics: Ascites; Ascitic Fluid; Carcinoembryonic Antigen; Humans; Liver Neoplasms; Peritoneal Neoplasms

PubMed: 25682632
DOI: No ID Found