glycogen and Esophageal-Neoplasms

Topics: alpha-Fetoproteins; Amines; Animals; Bombesin; Bronchi; Calcitonin; Calmodulin; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Bronchogenic; Chorionic Gonadotropin; Cytoskeletal Proteins; Esophageal Neoplasms; Glycogen; Growth Hormone; Hormones; Humans; Intestinal Neoplasms; Lung Neoplasms; Parathyroid Hormone; Physalaemin; Placental Lactogen; Precancerous Conditions; Somatostatin; Vasoactive Intestinal Peptide

Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal cancer and is often refractory to current therapies. Development of efficient therapeutic strategies against ESCC presents a major challenge. Glycogen synthase kinase (GSK)3β has emerged as a multipotent therapeutic target in various diseases including cancer. Here we investigated the biology and pathological role of GSK3β in ESCC and explored the therapeutic effects of its inhibition. The expression of GSK3β and tyrosine (Y)216 phosphorylation-dependent activity was higher in human ESCC cell lines and primary tumors than untransformed esophageal squamous TYNEK-3 cells from an ESCC patient and tumor-adjacent normal esophageal mucosa. GSK3β-specific inhibitors and small interfering (si)RNA-mediated knockdown of GSK3β attenuated tumor cell survival and proliferation, while inducing apoptosis in ESCC cells and their xenograft tumors in mice. GSK3β inhibition spared TYNEK-3 cells and the vital organs of mice. The therapeutic effect of GSK3β inhibition in tumor cells was associated with G0/G1- and G2/M-phase cell cycle arrest, decreased expression of cyclin D1 and cyclin-dependent kinase (CDK)4 and increased expression of cyclin B1. These results suggest the tumor-promoting role of GSK3β is via cyclin D1/CDK4-mediated cell cycle progression. Consequently, our study provides a biological rationale for GSK3β as a potential therapeutic target in ESCC.

Topics: Adult; Aged; Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Gene Expression; Glycogen; Glycogen Synthase Kinase 3 beta; Humans; Male; Mice; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Staging; Phosphorylation; Xenograft Model Antitumor Assays

Topics: Aged; Carcinoma, Squamous Cell; Chelation Therapy; Esophageal Neoplasms; Esophagoscopy; Esophagus; Glycogen; Humans; Lead Poisoning; Male

To investigate the structural changes at the molecular level and to assess the usefulness of Fourier-transform infrared (FTIR) spectroscopy in the diagnosis of esophageal cancer.. A pilot study was established of 10 consecutive patients with adenocarcinoma of the esophagus. Tissue samples from the diseased and normal sites of the resected specimens were analyzed and compared using FTIR spectroscopy and histopathology.. Specific changes were observed in the FTIR spectral features of esophageal cancer and thus spectral criteria were established for the detection of malignancy in esophagus tissues by FTIR spectroscopy. The spectral changes in cancer were the results of characteristic structural alterations at the molecular level in the esophageal cancer specimens. These alternations included an increase in the nuclei-to-cytoplasm ratio, an increase in the relative amount of DNA while a decrease in the relative amount of RNA, an enhancement in the phosphorylation of proteins, a decrease in the glycogen level, a loss of hydrogen bonding of the COH groups in the amino acid residues of proteins, a tighter intermolecular packing and a stronger intermolecular interaction among the DNA molecules, an increase in the distribution of protein segments with the conformation of beta-sheet and unordered turns and a tighter packing of the alpha-helical segments in overall tissue proteins, a decrease in the overall CH(3)-to-CH(2) ratio and an accumulation of triglycerides.. FTIR is an automated method that has shown promise in differentiating cancer in the esophagus and may play a role in surveillance programs in premalignant conditions.

Topics: Adenocarcinoma; Cell Nucleus; Cytoplasm; DNA; Esophageal Neoplasms; Glycogen; Humans; Hydrogen Bonding; Molecular Structure; Phosphorylation; Pilot Projects; Proteins; RNA; Spectroscopy, Fourier Transform Infrared; Triglycerides

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-microm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis.

Topics: Adenocarcinoma; Barrett Esophagus; Biopsy; Carcinoma, Squamous Cell; DNA, Neoplasm; Esophageal Neoplasms; Female; Glycogen; Humans; Lipid Metabolism; Male; Neoplasm Proteins; Precancerous Conditions; Spectrum Analysis, Raman

It was known that mucosal iodine staining could be used to improve the endoscopic visualization of esophageal premalignant lesion and cancer. However, the method was not used widely because of lacking clear mechanism. This study was designed to investigate the mechanism of esophageal epithelium staining with iodine and changes of glycogen or sacchariferous materials.. Esophageal epithelium was stained with iodine in endoscopic examination. According to color of tissue, the esophageal carcinoma and premalignant lesion were diagnosed. Glycogen from the esophageal mucous epithelium was extracted with beta-glycerophosphate buffer. The content of glycogen in the tissue speciman was detected by periodic acid-shiff staining (PAS). Protein in the esophageal mucous epithelium was extracted by tissue homogenate method.. After iodine staining, the normal epithelium became brown and easier to distinguish normal epithelium from precancerous of premalignant epithelium according to the change of color. Furthermore, normal epithelium slice stained by PAS technique had red reaction but it had no reaction after pretreatment by amylase. However, precancerous and premalignant epithelium tissue slices could not be stained whenever they were pretreated by amylase. The content of glycogen extracted from the esophageal epithelium was lower significantly than those of normal tissue (P < 0.01). But it was no deviation that protein contents of normal esophageal epithelium were compared with carcinoma tissue (P > 0.05).. These results demonstrated that glycogen and sacchariferous materials in esophageal carcinoma and premalignant lesion tissue decreased significantly and result in light yellow area by iodine staining. It may be helpful for diagnosis of esophageal carcinoma.

Topics: Epithelium; Esophageal Neoplasms; Esophagus; Glycogen; Humans; Iodine; Staining and Labeling

Extraskeletal Ewing's sarcoma is a rare tumor. The most common sites of occurrence are on the trunk, extremities, and retroperitoneum. This type of tumor is well characterized by recurrent chromosomal translocation such as t (11;22) (q24;q12) (EWSR1/FLI1) or t (21;22) (q22;q12) (EWSR1/ERG) and overexpression of MIC2/CD99 on tumor cell membrane. We describe the first reported case of an esophageal extraskeletal Ewing's sarcoma with confirmation from immunohistochemical and molecular diagnoses. A 56-year-old man developed a polypoid tumor located in the lower part of the esophagus. The tumor was composed of small-sized round cells showing prominent fibrillar cytoplasmic processes. Intracytoplasmic glycogen was detected in all the tumor cells. Immunoreactivity for MIC2/CD99 was positive on the membrane of all tumor cells. A reverse transcriptase-polymerase chain reaction followed by sequencing revealed an EWSR1/ERG chimeric transcript, which combined EWSR1 exon 10 with ERG exon 6. The present report added a new entity of esophageal small round cell tumor.

Topics: 12E7 Antigen; Antigens, CD; Bone Neoplasms; Cell Adhesion Molecules; DNA, Neoplasm; Esophageal Neoplasms; Glycogen; Humans; Immunoenzyme Techniques; Male; Middle Aged; Oncogene Proteins, Fusion; Proto-Oncogene Protein c-fli-1; Reverse Transcriptase Polymerase Chain Reaction; RNA-Binding Protein EWS; Sarcoma, Ewing; Transcription Factors; Translocation, Genetic

To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II, normal greenish brown staining; grade III, less intense staining; and grade IV, unstained. Most of the grade IV lesions were invasive carcinomas, carcinomas in situ, or severe dysplasia. The carcinomas in situ and the intraepithelial extension of the carcinomas, which were difficult to detect, were clearly shown as grade IV. On the other hand, moderate to mild dysplasia or atrophy showed grade III staining. Grade IV lesions showed well-demarcated sharp margins, whereas grade III lesions showed ill-demarcated dull margins. The grade III carcinomas, however, by the Lugol test, showed well-demarcated margins. Histologic evaluation disclosed that the staining intensity reflected well the thickness of the glycogen-containing cell layer in the lesion. The sharpness of the margin reflected the abrupt or gradual change from the glycogen-containing to non-containing cell layers. These findings suggest 1) the usefulness of the staining pattern of the Lugol test for the diagnosis of esophageal lesions such as squamous cell carcinoma and severe dysplasia, and 2) the usefulness of the Lugol test for precise delineation of the proximal resection line during surgery of esophageal carcinomas with unexpected wide extension.

Topics: Atrophy; Carcinoma in Situ; Carcinoma, Squamous Cell; Esophageal Diseases; Esophageal Neoplasms; Esophagitis; Esophagus; Glycogen; Humans; Iodides; Staining and Labeling

The development of hepatocellular tumors was investigated with histological, histochemical, and morphometrical methods in male Sprague-Dawley rats continuously administered N-nitrosodiethylamine (DEN) or N-nitrosomorpholine (NNM) in the drinking water at low doses (0.5 mg DEN/100 ml; 1 mg NNM/100 ml). Groups of control, DEN-, and NNM-treated rats were investigated at 5-week intervals. Similar results were obtained in DEN- and NNM-treated rats. Two types of areas composed of basophilic or glycogenotic hepatocytes were observed preceding the appearance of hepatocellular adenomas and carcinomas. Besides their cytologic differences, the basophilic and glycogenotic areas induced displayed distinct histochemical features. Both types of areas were detected simultaneously and increased in parallel with time to a similar incidence, but basophilic areas reached larger sizes than the glycogenotic ones. Furthermore, each type of area, which clustered around and along efferent veins, was differently linked to tumorigenesis. Basophilic areas frequently developed into basophilic adenomas and trabecular carcinomas through a characteristic sequence. Early basophilic areas consisted of hepatocytes with lamellar cytoplasmic hyperbasophilia and exhibited the normal laminar liver structure. With time, an increasing number of basophilic areas also contained hepatocytes with powdered diffuse hyperbasophilia, which frequently were arranged in thick trabeculae, showed abundant mitotic figures, and invaded efferent veins. Neither such signs of malignancy nor conversion into basophilic areas or tumors could be established for areas of clear and acidophilic glycogenotic hepatocytes. However, a few small glycogenotic adenomas probably developed from glycogenotic areas. Our data thus underline the central role of basophilic areas for hepatocarcinogenesis. Moreover, taking into account the data from other experiments, it seems likely that although glycogenotic areas may be associated with the application of some carcinogens at high doses, they are not obligatory precursors of hepatocellular tumors.

Topics: Adenoma; Administration, Oral; Animals; Carcinogens; Diethylnitrosamine; Dose-Response Relationship, Drug; Esophageal Neoplasms; Glycogen; Histocytochemistry; Incidence; Liver; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Nitrosamines; Papilloma; Rats

Topics: Aged; Autopsy; Carcinoma, Squamous Cell; Epithelium; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Female; Glycogen; Humans; Hyperplasia; Hypertrophy; Leukoplakia; Male; Middle Aged; Precancerous Conditions

Topics: Animals; Carcinoma, Squamous Cell; Connective Tissue; Esophageal Neoplasms; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hydrolases; In Vitro Techniques; Lyases; Neoplasms, Experimental; Oxidoreductases; Rats