Novel strategy for accurate tumor labeling:endogenous metabolic imaging through metabolic probes

Altered metabolism has long been recognized as a central hallmark of cancer;however,in the fluorescence imaging field,few studies have been conducted to label tumors by exploiting metabolic differences between cancer cells and normal cells.In this work,we successfully developed a metabolic probe MB-C for specific imaging of glutathione(GSH)dynamic metabolic pathways.GSH was endogenously metabolized to produce SO_(2)via Na_(2)S_(2)O_(3) and thiosulfate sulfurtransferase,equilibrating with sulfites/bisulfites.MB-C was allowed to be activated by GSH along with multi-fluorescence emission increased in red and green channels and further sequence-response metabolites(SO_(2))of GSH in significant fluorescence ratio change of red and green channels.Furthermore,such evident fluorescence ratio changes could be used to distinguish cancer cells from normal cells and identify tumor and normal tissues.Therefore,GSH metabolic imaging was successfully applied to accurately label tumors,which provides a new idea and practical case for the precise visualization of malignant tumors.

A New Glance on Energy Metabolism Investigation in Cultured Cells

The aim of the study was to analyze the input of cytosolic and oxidative pathways of energy metabolism in ATP production of cultured cells by using FLIM and routine biochemical techniques. Fluorescent imaging of endogenous cofactors NADH and FAD demonstrated a more pronounced oxidative redox status of fibroblasts compared to tumor cells and significant differences in metabolic processes in which FAD is involved. Analysis of glucose and lactate content and absorption showed that tumor cells not only absorb glucose more intensively from the environment, but also use it more intensively during anaerobic glycolysis. Lower energy efficiency of glycolysis and FAD oxidative path and greater energy consumption is the reason for the lower concentration of ATP in tumor cells. Presumably, the prevalence of glycolytic metabolism in tumor cells could be largely determined by their hypoxic reprogramming through the PI3K/AKT/mTOR signal pathway. The results of the study suggest that correlation between intracellular consumption of glucose and cytosolic concentration of NADH may contribute to the characteristic of energy metabolism state of cultured cells and serve as the biosensor of malignant cell transformation.

Metabolic reprogramming as an emerging mechanism of resistance to endocrine therapies in prostate cancer

Prostate cancer(PCa)is the second leading cause of cancer-related death in the US.Androgen receptor(AR)signaling is the driver of both PCa development and progression and,thus,the major target of current in-use therapies.However,despite the survival benefit of second-generation inhibitors of AR signaling in the metastatic setting,resistance mechanisms inevitably occur.Thus,novel strategies are required to circumvent resistance occurrence and thereby to improve PCa survival.Among the key cellular processes that are regulated by androgens,metabolic reprogramming stands out because of its intricate links with cancer cell biology.In this review,we discuss how cancer metabolism and lipid metabolism in particular are regulated by androgens and contribute to the acquisition of resistance to endocrine therapy.We describe the interplay between genetic alterations,metabolic vulnerabilities and castration resistance.Since PCa cells adapt their metabolism to excess nutrient supply to promote cancer progression,we review our current knowledge on the association between diet/obesity and resistance to anti-androgen therapies.We briefly describe the metabolic symbiosis between PCa cells and tumor microenvironment and how this crosstalk might contribute to PCa progression.We discuss how tackling PCa metabolic vulnerabilities represents a potential approach of synthetic lethality to endocrine therapies.Finally,we describe how the continuous advances in analytical technologies and metabolic imaging have led to the identification of potential new prognostic and predictive biomarkers,and non-invasive approaches to monitor therapy response.

Nonlinear optical endomicroscopy for label-free functional histology in vivo

This manuscript reports on the first two-photon,label-free,metabolic imaging of biological tissues in vivo at histological resolution on an extremely compact,fiber-optic endomicroscopy platform.This system provides new opportunities for performing noninvasive and functional histological imaging of internal organs in vivo,in situ and in real time.As a routine clinical procedure,traditional histology has made significant impacts on medicine.However,the procedure is invasive and time consuming,suffers random sampling errors,and cannot provide in vivo functional information.The technology reported here features an extremely compact and flexible fiber-optic probe~2 mm in diameter,enabling direct access to internal organs.Unprecedented two-photon imaging quality comparable to a large bench-top laser scanning microscope was achieved through technological innovations in double-clad fiber optics and miniature objective lenses(among many others).In addition to real-time label-free visualization of biological tissues in situ with subcellular histological detail,we demonstrated for the first time in vivo two-photon endomicroscopic metabolic imaging on a functioning mouse kidney model.Such breakthroughs in nonlinear endoscopic imaging capability present numerous promising opportunities for paradigm-shifting applications in both clinical diagnosis and basic research.