Identification of stemness-related glycosylation changes in head and neck squamous cell carcinoma.

BACKGROUND: Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors. METHODS: Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed. RESULTS: Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential. CONCLUSIONS: A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified.

Lectin-nanoparticle concept for free PSA glycovariant providing superior cancer specificity.

BACKGROUND: Using lectins to target cancer-associated modifications of PSA glycostructure for identification of clinically significant prostate cancers, e.g., Gleason score (GS) ≥ 7, from benign and indolent cancers (GS 6), is highly promising yet technically challenging. From previous findings to quantify increased PSA fucosylation in urine, we set out to construct a robust, specific test concept suitable for plasma samples. METHODS: Macrophage galactose-binding lectin (MGL) coupled to 100 nm Eu3 + -nanoparticles was used to probe PSA captured from cancer cell lines, seminal plasma, and plasma samples from 249 patients with a clinical suspicion of prostate cancer onto 3 mm dense spots of free PSA antibody fab fragments. Results were compared to four kallikrein tests: tPSA, fPSA, iPSA and hK2. RESULTS: The fPSAMGLglycovariant provided superior discrimination of the GS ≥ 7 and benign + GS 6 groups (p 0.0003) compared to fPSA (NS). The corresponding AUC in ROC analysis was 0.70 compared to 0.66 for tPSA. In contrast to all four kallikrein tests, the fPSAMGLGV was independent of prostate gland volume. Using a logistic regression analysis the fPSAMGLGV significantly improved on the four-kallikrein model. CONCLUSIONS: Due to Eu-nanoparticles and a dense fPSA capture spot, the fPSAMGL glycovariant identifies an fPSA subform with the highest cancer specificity compared to the four conventional kallikreins.

Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.

OBJECTIVE: Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. METHODS: Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. RESULTS: We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. CONCLUSION: Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.

Comparative evaluation of parasitology and serological tests in the diagnosis of visceral leishmaniasis in India: a phase III diagnostic accuracy study.

In this phase III trial for diagnostics for visceral leishmaniasis (VL) in India, we compared parasitological diagnosis with several serological tests: direct agglutination test (freeze dried; DAT-FD), rK-39 strip test, rK-26 strip test and a latex agglutination test for antigen detection in urine (KAtex) in 452 subjects from the endemic regions of Bihar, India. The subjects were segregated into four categories: 230 confirmed patients, 52 probable cases, 70 non-cases and 100 healthy endemic controls. The first two groups were used for estimating sensitivity, the latter two for specificity. Sensitivity of DAT-FD was 98.9%, rK-39: 98.9%, KAtex: 67.0% and rK-26: 21.3%. Sensitivity of DAT-FD on blood taken on filter paper (DAT-FDF) was 99.3%, which was comparable with that using serum. Specificity of serological tests was comparable and high (DAT-FD and DAT-FDF: 94%, rK-39 strip test: 97%, KAtex: 99% and rK-26 strip test: 100%). The classical 'gold standard' parasitological demonstration in splenic smear performed poorly as it missed 18.4% of cases that benefited from VL treatment. Reproducibility of the serological tests between field and central laboratories was excellent (kappa = 1.0, 0.99, 0.96 and 0.94 respectively for microscopy, DAT-FD, rK-39 strip test and rK-26 strip test). A high degree of agreement was observed between DAT-FD and rK-39 strip test (kappa = 0.986). Although DAT-FD and rK-39 strip test were highly sensitive with excellent specificity, the ease of use of the latter makes it most suitable for the diagnosis of VL in the field conditions.