Evaluation of the Expression of HER2 and c-KIT Proteins as Prognostic Markers in Superficial Bladder Urothelial Carcinoma.

BACKGROUND: The roles of c-KIT and HER2 protein expression in bladder cancer are still debated, and the prognostic value of these proteins as markers of tumor progression is inconclusive. OBJECTIVE: To assess the impact of HER2 and c-KIT protein expressions in the progression of non-muscle-invasive bladder cancer. METHODS: All patients undergoing transurethral resection of bladder tumors for non-muscle-invasive urothelial carcinoma, with standard regimen of BCG, between January 2017 and November 2019, were evaluated pathologically and immunohistochemically for HER1 and c-KIT proteins in urothelial carcinoma cells. Follow-up cystoscopy was performed for 100 patients every 3 months for the first 2-years and any recurred tumors were excised and examined pathologically, as well as stained for HER2 and c-KIT protein expression. RESULTS: HER2 and c-KIT positive expressions were detected in 49% and 38% of cases, respectively. After a mean follow-up of 26.4±7.2 months, the overall recurrence and progression rates were significantly correlated with overexpression of HER2 and c-KIT. In high-grade non-invasive muscle neoplasms, tumor cells showed weak expression for both HER2 and c-KIT proteins, but with progression to muscle-invasion, tumor cells strongly expressed HER2 and lost expression to c-KIT. In the multivariate model, overexpression of HER2 rather than c-KIT protein significantly predicted increased progression. CONCLUSION: Recurrence and progression of non-muscle-invasive bladder cancer correlate with overexpression of HER2 and c-KIT proteins in tumor cells.

High yield single stage conversion of glucose to hydrogen by photofermentation with continuous cultures of Rhodobacter capsulatus JP91.

Photofermentative hydrogen (H(2)) production from glucose with the photosynthetic bacterium Rhodobacter capsulatus JP91 (hup(-)) was examined using a photobioreactor operated in continuous mode. Stable and high hydrogen yields on glucose were obtained at three different retention times (HRTs; 24, 48 and 72 h). The H(2) production rates, varying between 0.57 and 0.81 mmol/h, and optical densities (OD(600 nm)) were similar for the different HRTs examined. However, the rate of glucose consumption was influenced by HRT being greater at HRT 24h than HRTs 48 and 72 h. The highest hydrogen yield, 9.0 ± 1.2 mol H(2)/mol glucose, was obtained at 48 h HRT. These results show that single stage photofermentative hydrogen production from glucose using photobioreactors operated in continuous culture mode gives high, nearly stoichiometric yields of hydrogen from glucose, and thus is considerably more promising than either two stage photofermentation or co-culture approaches.

Strategies for improving biological hydrogen production.

Biological hydrogen production presents a possible avenue for the large scale sustainable generation of hydrogen needed to fuel a future hydrogen economy. Amongst the possible approaches that are under active investigation and that will be briefly discussed; biophotolysis, photofermentation, microbial electrolysis, and dark fermentation, dark fermentation has the additional advantages of largely relying on already developed bioprocess technology and of potentially using various waste streams as feedstock. However, the major roadblock to developing a practical process has been the low yields, typically around 25%, well below those achievable for the production of other biofuels from the same feedstocks. Moreover, low yields also lead to the generation of side products whose large scale production would generate a waste disposal problem. Here recent attempts to overcome these barriers are reviewed and recent progress in efforts to increase hydrogen yields through physiological manipulation, metabolic engineering and the use of two-stage systems are described.

Photofermentative hydrogen production from wastes.

In many respects, hydrogen is an ideal biofuel. However, practical, sustainable means of its production are presently lacking. Here we review recent efforts to apply the capacity of photosynthetic bacteria to capture solar energy and use it to drive the nearly complete conversion of substrates to hydrogen and carbon dioxide. This process, called photofermentation, has the potential capacity to use a variety of feedstocks, including the effluents of dark fermentations, leading to the development of various configurations of two-stage systems, or various industrial and agricultural waste streams rich in sugars or organic acids. The metabolic and enzymatic properties of this system are presented and the possible waste streams that might be successfully used are discussed. Recently, various immobilized systems have been developed and their advantages and disadvantages are examined.

Metabolic engineering in dark fermentative hydrogen production; theory and practice.

Dark fermentation is an attractive option for hydrogen production since it could use already existing reactor technology and readily available substrates without requiring a direct input of solar energy. However, a number of improvements are required before the rates and yields of such a process approach those required for a practical process. Among the options for achieving the required advances, metabolic engineering offers some powerful tools for remodeling microbes to increase product production rates and molar yields. Here we review the current metabolic engineering tool box that is available, discuss the current status of engineering efforts as applied to dark hydrogen production, and suggest areas for future improvements.