glycogen and Urinary-Bladder-Neoplasms

Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis--two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist.

Topics: Glycogen; Humans; Urinary Bladder Neoplasms

Urothelial carcinomas of the bladder are a heterogeneous group of tumours, although some histological sub-variants are rare and sparsely reported in the literature. Diagnosis of sub-variants from conventional urothelial carcinoma can be challenging, as they may mimic the morphology of other malignancies or benign tumours and therefore their distinction is important. For the first time, the spectral pathology of some of these sub-variants has been documented by infrared microspectroscopy and an attempt made to profile their biochemistry. It is important not only to identify and separate the cancer-associated epithelial tissue spectra from common tissue features such as stroma or blood, but also to detect the signatures of tumour sub-variants. As shown, their spectroscopic signals can change dramatically as a consequence of differentiation. Example cases are discussed and compared with histological evaluations.

Topics: Algorithms; Biopsy; Carcinoma; Cell Differentiation; Cluster Analysis; Diagnostic Imaging; Glycogen; Humans; Neoplasm Metastasis; Phenotype; Principal Component Analysis; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Support Vector Machine; Urinary Bladder Neoplasms; Urothelium

We have applied Raman spectroscopy to discriminate between nontumor and tumor bladder tissue and to determine the biochemical differences therein. Tissue samples from 15 patients were collected, and frozen sections were made for Raman spectroscopy and histology. Twenty-five pseudocolor Raman maps were created in which each color represents a cluster of spectra measured on tissue areas of similar biochemical composition. For each cluster, the cluster-averaged spectrum (CAS) was calculated and classified as tumor and nontumor in accordance to pathohistology. Unguided hierarchical clustering was applied to display heterogeneity between and within groups of nontumor and tumor CAS. A linear discriminant analysis model was developed to discriminate between CAS from tumor and nontumor. The model was tested by a leave-one-patient-out validation, 84 of the 90 CAS (93%) were correctly classified with 94% sensitivity and 92% specificity. Biochemical differences between tumor and nontumor CAS areas were analyzed by fitting spectra of pure compounds to the CAS. Nontumor CAS showed higher collagen content while tumor CAS were characterized by higher lipid, nucleic acid, protein, and glycogen content. Raman spectroscopy enabled effective discrimination between tumor and nontumor bladder tissue based on characterized biochemical differences, despite heterogeneity expressed in both tumor and nontumor CAS.

Topics: Cluster Analysis; Collagen; Discriminant Analysis; Frozen Sections; Glycogen; Humans; Linear Models; Lipids; Models, Biological; Nucleic Acids; Proteins; Sensitivity and Specificity; Spectrum Analysis, Raman; Urinary Bladder; Urinary Bladder Neoplasms

The focus of my study was the immunohistological expressions of bladder tumour cells when stained by several antigens, those being; Carcinoembryonic antigen (CEA), Ferritin, Beta 2 Microglobulin (beta 2-MG), Keratin and Glycogen. There were 59 cases of bladder cancer studied using the Peroxidase-antiperoxidase technique (PAP) of staining. Specimens were formalin-fixed, paraffin embedded, and then sectioned. Some correlation was found between histological grade, stage and CEA incidence but was not found in the Ferritin or beta 2-MG. Keratin and Glycogen were detected in all cases. These staining patterns were mosaic according to higher grade and stage. It is believed this demonstrates that immunohistochemical expressions of staining with CEA, Keratin, and Glycogen may be a sensitive indicator of histological grade, stage.

Topics: Adult; Aged; Aged, 80 and over; beta 2-Microglobulin; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Female; Ferritins; Glycogen; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Urinary Bladder Neoplasms

The focus of my study was the immunohistochemical studies of tumour cells induced by ADM intravesical instillation therapy when stained by several antigens, those being; Carcinoembryonic antigen (CEA), Ferritin, Beta 2 Microglobulin (beta 2-MG), Keratin and Glycogen before and after the therapy. Then I discussed as to their value in indicating therapeutic efficacy. There were 18 cases of bladder cancer studied using the Peroxidase-antiperoxidase technique (PAP) of staining. Data indicated a 44.4% response rate following therapy with intravesical ADM. Immunohistochemical evaluation showed improvement as indicated by not staining with CEA. Also observed was no change and slightly diffuse staining with Keratin: and a decrease in all layers of Glycogen expression: However this could not be observed with the Ferritin or beta 2-MG. It is believed this demonstrates that immunohistochemical expressions of staining with CEA, Keratin, and Glycogen may be a sensitive indicator of a therapeutic response to intravesical ADM.

Topics: Administration, Intravesical; beta 2-Microglobulin; Biomarkers, Tumor; Carcinoembryonic Antigen; Doxorubicin; Drug Evaluation; Female; Glycogen; Humans; Immunohistochemistry; Keratins; Male; Urinary Bladder Neoplasms

The activities of glycogen synthase and phosphorylase were measured and compared to the growth-related variations of glycogen accumulation in three cultured human tumor cell lines: HT-29 (colon carcinoma); MeWo (malignant melanoma); and RT-4 (carcinoma of the urinary bladder). A similar pattern of variations in the enzyme activities was found in the three cell lines. The activities of the a + b forms of glycogen phosphorylase increased throughout the culture period. Maximal activity of phosphorylase a coincided with low intracellular concentrations of glycogen during the period of exponential growth. When the rate of cell division decreased, phosphorylase a activity also decreased while the glycogen levels increased. Glycogen synthase was almost entirely in b form during the entire culture period, i.e., in both the exponential and the stationary phases. In vitro incubation of the cellular extracts without NaF showed, however, that the enzyme could be partially converted to the a form by the endogenous phosphatases. The A0.5 values of the enzyme for glucose-6-phosphate (Glc-6-P) were of the same order of magnitude as the intracellular Glc-6-P concentrations which ranged from 2.2 to 5.4 mM (almost 10 times those reported in normal cells). Similar Glc-6-P values were obtained by two different extraction methods controlled by the intracellular ATP and ADP concentrations. The Km values for uridine-5'-diphosphoglucose were always 2 to 3 times lower than the intracellular uridine-5'-diphosphoglucose concentrations. These results suggest that: (a) in these tumor cells, glycogen is essentially synthesized by glycogen synthase b via an allosteric activation by intracellular Glc-6-P; (b) there is no obvious growth-related control of glycogen synthase activity; and (c) the activity of glycogen phosphorylase seems to be growth dependent with maximal phosphorylase a activities associated with the period of high division rate.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Cell Line; Colonic Neoplasms; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Synthase; Humans; Kinetics; Melanoma; Neoplasms; Uridine Diphosphate Glucose; Urinary Bladder Neoplasms

Topics: Cell Nucleolus; Cell Nucleus; Cytoplasm; DNA, Neoplasm; Glycogen; Histocytochemistry; Humans; Lipids; Neoplasm Proteins; Papilloma; Polysaccharides; RNA, Neoplasm; Urinary Bladder Diseases; Urinary Bladder Neoplasms

Topics: Amylases; Carcinoma, Transitional Cell; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hyaluronoglucosaminidase; Mucins; Neuraminidase; Periodic Acid; Polysaccharides; Staining and Labeling; Urinary Bladder Neoplasms

Topics: Glycogen; Humans; Kidney Neoplasms; Male; Neoplasms; Testicular Neoplasms; Testis; Urinary Bladder Neoplasms