Innovative Diagnostic Peptide-Based Technologies for Cancer Diagnosis: Focus on EGFR-Targeting Peptides.

Active targeting using biological ligands has emerged as a novel strategy for the targeted delivery of diagnostic agents to tumor cells. Conjugating functional targeting moieties with diagnostic probes can increase their accumulation in tumor cells and tissues, enhancing signal detection and, thus, the sensitivity of diagnosis. Due to their small size, ease of chemical synthesis and site-specific modification, high tissue penetration, low immunogenicity, rapid blood clearance, low cost, and biosafety, peptides offer several advantages over antibodies and proteins in diagnostic applications. Epidermal growth factor receptor (EGFR) is one of the most promising cancer biomarkers for actively targeting diagnostic and therapeutic agents to tumor cells due to its active involvement and overexpression in various cancers. Several peptides for EGFR-targeting have been identified in the last decades, which have been obtained by multiple means including derivation from natural proteins, phage display screening, positional scanning synthetic combinatorial library, and in silico screening. Many studies have used these peptides as a targeting moiety for diagnosing different cancers in vitro, in vivo, and in clinical trials. This review summarizes the progress of EGFR-targeting peptide-based assays in the molecular diagnosis of cancer.

Immunometabolism in biofilm infection: lessons from cancer.

BACKGROUND: Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host. MAIN BODY OF THE MANUSCRIPT: It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode. CONCLUSION: Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.

A novel chimeric protein with enhanced cytotoxic effects on breast cancer in vitro and in vivo.

In our previous study, we reported the design and recombinant production of the p28-apoptin as a novel chimeric protein for breast cancer (BC) treatment. This study aimed to evaluate the inhibitory activity of the chimeric protein against BC cells in vitro and in vivo. We developed a novel multifunctional protein, consisting of p28, as a tumor-homing killer peptide fused to apoptin as a tumor-selective killer. The chimeric protein showed significantly higher toxicity in BC cell lines dose-dependently than in non-cancerous control cell lines. IC50 values were 1.41, 1.38, 6.13, and 264.49 µM for 4T1, MDA-MB-468, Vero, and HEK293 cells, respectively. The protein showed significantly enhanced uptake in 4T1 cancer cells compared with non-cancerous Vero cells. We also showed that the p28-apoptin chimeric protein binds significantly higher to human breast cancer tumor sections than the normal human breast tissue section. Also, significant apoptosis induction and tumor growth inhibition were observed in established tumor-bearing mice accompanied by a decreased frequency of metastases. Our results support that the chimeric protein has inhibitory activity in vitro and in vivo, making it a promising choice in targeted cancer therapy.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers.

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.

Nucleic acid aptamers in diagnosis of colorectal cancer.

Nucleic acid aptamers are promising recognition ligands for diagnostic applications. They are short DNA or RNA molecules isolated from large random libraries through the Systematic Evolution of Ligands by EXponential enrichment (SELEX) procedure. These molecules, with a particular three-dimensional shape, bind to a wide range of targets from small molecules to whole cells with high affinity and specificity. The unique properties of nucleic acid aptamers including high binding affinity and specificity, thermostability, ease of chemical production, ease of chemical modification, target adaptability, simple storage, resistance to denaturation, low immunogenicity, and low cost make them potential diagnostic tools for clinical use. Colorectal cancer is one of the most common types of cancer in humans and the third leading cause of cancer deaths in the world. Due to low response rate to current therapies in advanced stages of the disease, early detection of CRC can be useful in disease management. This review highlights recent advances in the development of nucleic acid aptamer-based methods for diagnosis, prognosis, and theranosis of colorectal cancer.