Mass spectrometry-based proteomics: the road to lung cancer biomarker discovery.

Lung cancer is the leading cause of cancer death in men and women in Western nations, and is among the deadliest cancers with a 5-year survival rate of 15%. The high mortality caused by lung cancer is attributable to a late-stage diagnosis and the lack of effective treatments. So, it is crucial to identify new biomarkers that could function not only to detect lung cancer at an early stage but also to shed light on the molecular mechanisms that underlie cancer development and serve as the basis for the development of novel therapeutic strategies. Considering that DNA-based biomarkers for lung cancer showed inadequate sensitivity, specificity, and reproducibility, proteomics could represent a better tool for the identification of useful biomarkers and therapeutic targets for this cancer type. Among the proteomics technologies, the most powerful tool is mass spectrometry. In this review, we describe studies that use mass spectrometry-based proteomics technologies to analyze tumor proteins and peptides, which might represent new diagnostic, prognostic, and predictive markers for lung cancer. We focus in particular on those findings that hold promise to impact significantly on the clinical management of this disease.

Tracking the 2009 H1N1 influenza virus in the Italian region Campania.

A novel swine-origin influenza A (H1N1) virus affecting humans was detected in April 2009 in Mexico, Canada, and USA. The S-OIV infection caused a mild to severe febrile respiratory disease throughout the world. Here, we briefly review the main features of influenza A viruses, which caused also other pandemics in the past, and focus in particular on the epidemiology data of the H1N1 influenza in the Italian region Campania, which resulted the most affected by the S-OIV and the one with more lethal cases. In Campania, the peak of influenza preceded of about 2 weeks the incidence peak at the national level. Moreover, the percentage of H1N1-positive patients was much higher in the main town Naples, compared to the other Campania provinces. The age group from 7 months to 17 years was the most affected by the H1N1 infection (43.45%), similarly to what reported at the national level. Here, we discuss the possible reasons of the high H1N1 incidence in Campania and the implications that these findings could have on the future prevention campaigns.

The potential impact of the COVID-19 pandemic on child growth and development: a systematic review.

OBJECTIVE: This was a systematic review of studies that examined the impact of epidemics or social restriction on mental and developmental health in parents and children/adolescents. SOURCE OF DATA: The PubMed, WHO COVID-19, and SciELO databases were searched on March 15, 2020, and on April 25, 2020, filtering for children (0-18 years) and humans. SYNTHESIS OF DATA: The tools used to mitigate the threat of a pandemic such as COVID-19 may very well threaten child growth and development. These tools - such as social restrictions, shutdowns, and school closures - contribute to stress in parents and children and can become risk factors that threaten child growth and development and may compromise the Sustainable Development Goals. The studies reviewed suggest that epidemics can lead to high levels of stress in parents and children, which begin with concerns about children becoming infected. These studies describe several potential mental and emotional consequences of epidemics such as COVID-19, H1N1, AIDS, and Ebola: severe anxiety or depression among parents and acute stress disorder, post-traumatic stress, anxiety disorders, and depression among children. These data can be related to adverse childhood experiences and elevated risk of toxic stress. The more adverse experiences, the greater the risk of developmental delays and health problems in adulthood, such as cognitive impairment, substance abuse, depression, and non-communicable diseases. CONCLUSION: Information about the impact of epidemics on parents and children is relevant to policy makers to aid them in developing strategies to help families cope with epidemic/pandemic-driven adversity and ensure their children's healthy development.

Tumor liberated protein from lung cancer and perspectives for immunotherapy.

This review addresses peptide regions of human tumor liberated protein (TLP) complexes with antigenic activity. The review also deals with antibodies reacting with such proteins, to be used for diagnostic and clinical purposes. We identified peptide sequences of the TLP 100 kDa protein. Lung cancer cells were found positive with an immuno-histochemical test, by peroxidase-anti-peroxidase, using a specific antiserum. This test turned out negative in the presence of the synthesized peptide (blocking test). Several tumors were used to obtain antigens by various purification procedures (cell homogenization, ultracentrifugation at 100,000g, gel filtration and chromatography, preparative and analytical isoelectric focusing, IEF). The molecular weight on SDS-PAGE of an immunogenic peak detected on IEF was determined to be a value of 214,000 Da, with monomers of 54,000 Da. In vivo TLP yields delayed hypersensitivity reactions in both autologous and homologous hosts, and does not seem to have any nonspecific mytogenic activity, but does have mytogenic-specific activity since lymphocyte blastogenesis (TLP-induced in pre-sensitized patients), in the case of intradermal inoculation, could mean its ability to sensitize a lymphocytic clone.

High Aldehyde Dehydrogenase Levels Are Detectable in the Serum of Patients with Lung Cancer and May Be Exploited as Screening Biomarkers.

OBJECTIVES: Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk represents an area of intense investigation. Tumor liberated protein (TLP) has been previously described as a tumor-associated antigen (complex) present in the sera from lung cancer patients. Here, we set out to identify the nature of TLP to develop this as a potential biomarker for lung cancer screening. MATERIALS AND METHODS: Beginning from the peptide epitope RTNKEASI previously identified from the TLP complex, we produced a rabbit anti-RTNKEASI serum and evaluated it in the lung cancer cell line A549 by means of immunoblot and peptide completion assay (PCA). The TLP sequence identification was conducted by mass spectrometry. The detected protein was, then, analyzed in patients with non-small cell lung cancer (NSCLC) and benign lung pathologies and healthy donors, by ELISA. RESULTS: The anti-RTNKEASI antiserum detected and immunoprecipitated a 55 kDa protein band in the lysate of A549 cells identified as aldehyde dehydrogenase isoform 1A1, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened blood samples from a non-tumor cohort of 26 patients and 45 NSCLC patients with different disease stages for the presence of ALDH1A1 and global ALDH. This analysis indicated that serum positivity was highly restricted to patients with NSCLC (ALDH p < 0.001; ALDH1A1 p=0.028). Interestingly, the global ALDH test resulted positive in more NSCLC samples compared to the ALDH1A1 test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. CONCLUSION: Our data indicate that ALDH levels are elevated in the sera of NSCLC patients, even with early stage disease, and may thus be evaluated as part of a marker panel for non-invasive detection of NSCLC.

Papillary thyroid microcarcinoma (Black Ink).

We report a case of a 58-year-old Caucasian woman affected by papillary thyroid microcarcinoma (PTMC) of the left-lobe of the gland with very small size (Ø 0.3 cm). The characteristics with the Diagnostic Imaging using Ultrasonography, ADF (Advanced Dynamic Flow), and fine-needle-aspiration cytology (FNAC) are discussed, comprising a very small micro-focus of radial shape, with markedly hypoechoic echostructure, irregular margins, supplemented by peripheral vessel formation. It acquires an image which appears similar to a brisk visualization of a dark ink stain in the normal thyroid weave. We call such a pattern "Black Ink" with ultrasonographic image and believe consistent with the infiltrating variant of papillary thyroid microcarcinoma if associated with malignant cytology after FNA.

Biomolecular markers of breast cancer.

Here, the structure, function, biological and pathological significance and clinical utility of the principal biomolecular markers of breast cancer is reviewed. Each marker was scored for clinical utility using a recently developed tumor marker utility grading system (TMUGS). Among the tissue markers, ERs and PRs are important prognostic/predictive factors and the only tissue markers routinely determined. ER cross-talks with other growth factors while co-regulatory factors enhance (co-activators) or decrease (co-repressors) its transcriptional activity. C-erbB-2 and Ki67/MIB-1 select for adjuvant chemotherapy a subgroup of lymph-node negative patients at a high risk of relapse. Monoclonal antibodies (trastuzumab, gefitinib, erlotinib and bevacizumab) targeting tissue markers and involved in tumor growth and metastasization (EGFR, C-erbB-2, VEGF) have been developed; they showed therapeutical single agent activity as well as potent synergy with chemotherapy agents in metastatic cancer. Among circulating markers, some are potentially useful in the early detection and monitoring of metastatic disease; nevertheless, none is routinely recommended. To suspect distant metastases, CEA-TPA-CA15.3 panel attained accuracy of about 90%. ECD HER2-neu, p53 and nucleophosmin antibodies seem suitable candidates for different associations. Preliminary observations suggest that an early detection with tumor markers and successive treatment of relapses significantly prolongs disease-free and overall survival in selected patients. In conclusion, biomolecular markers are improving understanding of biology and management of breast cancer.

The potential impact of the COVID-19 pandemic on child growth and development: a systematic review

Abstract Objective This was a systematic review of studies that examined the impact of epidemics or social restriction on mental and developmental health in parents and children/adolescents. Source of data The PubMed, WHO COVID-19, and SciELO databases were searched on March 15, 2020, and on April 25, 2020, filtering for children (0-18 years) and humans. Synthesis of data The tools used to mitigate the threat of a pandemic such as COVID-19 may very well threaten child growth and development. These tools — such as social restrictions, shutdowns, and school closures — contribute to stress in parents and children and can become risk factors that threaten child growth and development and may compromise the Sustainable Development Goals. The studies reviewed suggest that epidemics can lead to high levels of stress in parents and children, which begin with concerns about children becoming infected. These studies describe several potential mental and emotional consequences of epidemics such as COVID-19, H1N1, AIDS, and Ebola: severe anxiety or depression among parents and acute stress disorder, post-traumatic stress, anxiety disorders, and depression among children. These data can be related to adverse childhood experiences and elevated risk of toxic stress. The more adverse experiences, the greater the risk of developmental delays and health problems in adulthood, such as cognitive impairment, substance abuse, depression, and non-communicable diseases. Conclusion Information about the impact of epidemics on parents and children is relevant to policy makers to aid them in developing strategies to help families cope with epidemic/pandemic-driven adversity and ensure their children's healthy development.

Lung cancer proteomics: recent advances in biomarker discovery.

Lung cancer is the most common cause of cancer death in both men and women in Western countries, with a 5-year survival rate of 15%, which is among the lowest of all cancers. The high mortality from lung cancer is due not only to the late stage diagnosis but also to the lack of effective treatments even for patients diagnosed with stage I lung cancer. Therefore, there is an urgent need to identify new markers for early diagnosis and prognosis that could serve to open novel therapeutic avenues. Proteomics can represent an important tool for the identification of biomarkers and therapeutic targets for lung cancer since DNA-based biomarkers did not prove to have adequate sensitivity, specificity, and reproducibility. In this paper we will describe studies focused on the identification of new diagnostic, prognostic, and predictive markers for lung cancer, using proteomics technologies.

Early diagnosis of lung cancer by detection of tumor liberated protein.

Tumor liberated protein (TLP) is a protein that can be used to reveal the early development of a tumor. Besides being formed in the tumor, TLP is released in the blood when a patient starts producing cancer cells, which in turn enables the physician to intervene at a stage when the cancer is operable. To date, the available studies of tumor markers in lung cancer patients are CEA, NSE, TPA, Chromogranine, CA125, CA19-9, and Cyfra 21-1. The sensitivity and specificity for serum markers ranges between 50 and 90%, depending on the study and the clinical samples analyzed. Most of these markers show an increased rate of positivity as the stage advances. There are very limited data on TLP to draw any firm conclusion regarding the diagnostic value of this marker. TLP has been detected in 53.1% of non-small cell lung cancer (NSCLC) patients (N = 534) with 75% being positive in the early stage (stage I) and dropping to 45% in the late stage (stage IV). However, 7.6% blood donor sera and 17.4% chronic lung disease sera have also tested positive. In a confirmation study, the specificity was 89.94% and the sensibility was 63.63% from stage III to IV NSCLC patients. In an initial study of TLP as a marker for early detection in stage I, NSCLC patients showed a sensitivity of 66.7% and a specificity of 80% for TLP compared to a sensitivity of 33.3% for CA19-9, 11.1% for Cyfra 21-1 and CA125, and 0% for CEA; the specificity for all four of the latter markers was 100%. Using immunohistochemical analysis with peroxidase anti-peroxidase (PAP), we observed that NSCLC cells were positive; we used the specific rabbit antiserum to TLP, which turned out negative in the presence of 1 mg/ml of the synthetized peptide. The pre-serum was also negative. The same reactivity was found early in the modified epithelial cells of interstitial lung fibrosis and might be a predictive marker of cell transformation. The site of the peroxidase positivity was cytoplasmic, of diffuse and/or granular type.