High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin.

BACKGROUND: Expression of the cold shock protein Y-box protein 1 (YB-1) is associated with deleterious outcome in various malignant diseases. Our group recently showed that the detection of an 18 kDa YB-1 fragment (YB-1/p18) in human plasma identifies patients with malignant diseases. We now tested the prevalence, clinical, and diagnostic value of YB-1/p18 detection in common tumors. METHODS: A newly established monoclonal YB-1 antibody was used to detect YB-1/p18 by immunoblotting in plasma samples from 151 unselected tumor patients, alongside established tumor markers and various diagnostic measures, during evaluation for a cancerous disease and in follow-up studies after therapeutic interventions. RESULTS: Circulating YB-1/p18 was detected in 78% of patients having a tumor disease. YB-1/p18 positivity was highly prevalent in all examined malignancies, including lung cancer (32/37; 87%), breast cancer (7/10; 70%), cancer of unknown primary (CUP; 5/5, 100%) or hematological malignancies (42/62; 68%). Positivity for YB-1/p18 was independent of other routine laboratory parameters, tumor stage, or histology. In comparison to 13 established tumor markers (cancer antigens 15-3, 19-9, 72-4, and 125; carcinoembryonic antigen; cytokeratin fragments 21-1; neuron-specific enolase; alpha-fetoprotein; beta-2-microglobulin; squamous cell carcinoma antigen; thymidine kinase; tissue polypeptide antigen; pro-gastrin-releasing peptide), YB-1/p18 detection within serum samples was the most sensitive general parameter identifying malignant disorders. YB-1/p18 concentrations altered during therapeutic interventions, but did not predict prognosis. CONCLUSIONS: Plasma YB-1/p18 detection has a high specific prevalence in malignancies, thereby providing a novel tool for cancer screening independent of the tumor origin.

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease.

BACKGROUND: Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. METHODS: We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n=33), patients with non-cancerous, mostly inflammatory diseases (n=60), hepatocellular carcinoma (HCC; n=25) and advanced solid tumors (n=20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. RESULTS: We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. CONCLUSIONS: Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.

Early clinical experiences with the new influenza A (H1N1/09).

BACKGROUND: Because of ongoing person-to-person transmission of the disease, the World Health Organization has declared a phase 6 pandemic alert for the new type of influenza A (H1N1/09). This means that the spread of the disease must be closely monitored. METHODS: At the Düsseldorf University Hospital, patients with flu-like symptoms and their contacts have been tested for the new type of influenza A since April 2009. RESULTS: The first patients that tested positive for H1N1/09 were treated on 20 May 2009. By mid-September, 3372 persons underwent PCR testing of a sample obtained by deep nasal swabbing, and the results were positive in 450 (13.3%). 379 of these 450 infections, or 84.2%, had been contracted abroad. Most patients came to the hospital with flu-like symptoms within three days of becoming ill. An analysis of the first 60 patients revealed a median core temperature of 37.8 degrees C and a mildly elevated C-reactive protein concentration. All patients were treated with oseltamivir. Most of the initially symptomatic patients were asymptomatic again within 3 days; the median duration of treatment was 5 days. The median time to the first negative deep nasal swab was 4 days. No oseltamivir resistance has been found to date in our patient collective. CONCLUSION: The clinical manifestations of the new type of influenza were still mild in the patient population that we studied up to mid-September 2009. At that time, the second wave of the pandemic had not yet begun in Germany. At present, however, the number of cases acquired within the country is on the rise.