Clinical Significance of Urine Heparanase in Bladder Cancer Progression1

Heparanase is an endo-β-glucuronidase capable of cleaving heparan sulfate (HS), an activity implicated in tumor metastasis. Heparanase expression is upregulated in primary human tumors, correlating with reduced post operative survival and elevated microvessel density. An ELISA method was used to quantify heparanase in urine from 282 individuals. Urine was collected from healthy volunteers (n = 41), patients diagnosed with noncancerous pathologic disorders (n = 90), and bladder cancer patients (n = 92). Fifty-nine bladder carcinoma patients after transurethral resection (TUR) with no evidence of disease (NED) were also included. Heparanase levels were significantly elevated in urine from bladder cancer patients compared with healthy controls (P < .001) and with noncancerous urinary disorders (P < .05). Heparanase elevation strongly correlated with tumor grade (P < .001) and stage (P = .027). An optimal cutoff value of 154 pg/ml was determined. Of 199 individuals enrolled (59 patients after TUR and 24 patients with recurring disease were excluded), 65 had heparanase levels above 154 pg/ml. Only 3 of 65 (4.6%) were healthy individuals. In contrast, 52.3% (34 of 65) of individuals with heparanase levels above 154 pg/ml were bladder cancer patients. The results indicate that urine heparanase levels are elevated during bladder cancer progression, suggesting that the ELISA method may be applied for bladder cancer diagnosis

Potential Refinement of Recurrence Score by pSTAT3 Status

The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (&lt;26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population

Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots

The importance of locating proteins in their context within cells has been heightened recently by the accomplishments in molecular structure and systems biology. Although light microscopy (LM) has been extensively used for mapping protein localization, many studies require the additional resolution of the electron microscope. Here we report the application of small nanocrystals (Quantum dots; QDs) to specifically and efficiently label multiple distinct endogenous proteins. QDs are both fluorescent and electron dense, facilitating their use for correlated microscopic analysis. Furthermore, QDs can be discriminated optically by their emission wavelength and physically by size, making them invaluable for multilabeling analysis. We developed pre-embedding labeling criteria using QDs that allows optimization at the light level, before continuing with electron microscopy (EM). We provide examples of double and triple immunolabeling using light, electron and correlated microscopy in rat cells and mouse tissue. We conclude that QDs aid precise high-throughput determination of protein distribution