Improving colorectal cancer screening programs

In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology.They suggest policies for more effective colorectal screening.Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening.Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps.However,colonoscopy is an invasive process,and fecal tests such as the current hemoglobin immunodetection were developed,followed by endoscopy,as the general tool for population screening,avoiding logistical and economic problems.Even so,participation and adherence rates are low.Different screening options are being developed with the idea that if people could choose between the ones that best suit them,participation in population-based screening programs would increase.Blood tests,such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA,showed a similar accuracy rate to stool tests for cancer,but were less sensitive for advanced precancerous lesions.At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer,novel immune system-related biomarkers and information on patients’immune parameters,such as cell counts of different immune populations,were studied for the early detection of colorectal cancer,since they could be effective in asymptomatic people,appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood.sCD26,for example,detected 80.37%of advanced adenomas.To reach as many eligible people as possible,starting at an earlier age than current programs,the direction could be to apply tests based on blood,urine or salivary fluid to samples taken during routine visits to the primary health system.

Specific Antigens to Distinguish <i>M. tuberculosis</i>from <i>M. avium</i>

To distinguish Mycobacterium tuberculosis from Mycobacterium avium, specific M. tuberculosis antigens had been studied for improving the early differential diagnosis effect of tuberculosis caused by different Mycobacterium. The rabbit anti-M. avium sera and anti-M. tuberculosis sera were analyzed for antibody-based reactivity by matrix-assisted laser desorption-ionization mass spectrometry (MALDI-TOF Mass) against M. tuberculosis proteins. The immunoreactive spots, which were attributed to the proteins HspX, GroES and CFP-10, were mostly located at 10 - 60 kDa and PI 4 - 6, subsequently Western blotting result proved that HspX and CFP-10 were specific to M. tuberculosis and ELISA testing result of 30 M. avium positive sera showed that GroES were cross-reactive to M. avium. Lastly, positive and negative tuberculosis reference sera and based on the mechanism of indirect ELISA, the specificity and the sensitivity of the methods targeting the antibodies HspX, GroES or CFP-10 were evaluated at 37% and 26%, 12% and 97%, 81% and 98%, respectively. The combination of these three antibody detection methods allowed to reached a specificity of 42%, and of 39% without taken into account of the method targeting the GroES antibody. Using proteomics approach, we found three M. tuberculosis specific antigens showed good potential in tuberculosis diagnosis, providing basic study for serodiagnosis of tuberculosis.

IgY technology: Methods for developing and evaluating avian immunoglobulins for the in vitro detection of biomolecules

The term“IgY technology”was introduced in the literature in the mid 1990s to describe a procedure involving immunization of avian species,mainly laying hens and consequent isolation of the polyclonal IgYs from the“immune”egg yolk(thus avoiding bleeding and animal stress).IgYs have been applied to various fields of medicine and biotechnology.The present article will deal with specific aspects of IgY technology,focusing on the currently reported methods for developing,isolating,evaluating and storing polyclonal IgYs.Other topics such as current information on isolation protocols or evaluation of IgYs from different avian species are also discussed.Specific advantages of IgY technology(e.g.,novel antibody specificities that may emerge via the avian immune system)will also be discussed.Recent in vitro applications of polyclonal egg yolk-derived IgYs to the field of disease diagnosis in human and veterinary medicine through in vitro immunodetection of target biomolecules will be presented.Moreover,ethical aspects associated with animal well-being as well as new promising approaches that are relevant to the original IgY technology(e.g.,development of monoclonal IgYs and IgY-like antibodies through the phage display technique or in transgenic chickens)and future prospects in the area will also be mentioned.

Synthesis of Gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] Utilizing a UV-Photoactivated Gemcitabine Intermediate: Cytotoxic Anti-Neoplastic Activity against Chemotherapeutic-Resistant Mammary Adenocarcinoma SKBr-3

Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell carcinoma, cervical epitheliod carcinoma, or leukemia/lymphoid neoplastic cell types based on their reported sensitivity to gemcitabine and gemcitabine covalent conjugates.