muramidase and Intestinal-Neoplasms

Accumulating evidence has suggested a correlation of tumor infiltrating B cells (TiBcs) and a good prognosis of cancer diseases. In some cases, TiBcs appear to have experienced antigen stimulation since they have undergone class-switching and somatic hypermutation and formed tertiary lymphoid structures around tumors together with T cells. Assuming TiBcs include those that recognize some tumor antigens, we sought to investigate their possible usefulness for cell-mediated immunotherapies. To expand usually small number of TiBcs in vitro, we modified our B cell culture system: we transduced B cells with ERT2-Bach2 so that they grow unlimitedly provided with tamoxifen, IL-21 and our original feeder cells. Such cells differentiate into plasma cells and produce antibodies upon withdrawal of tamoxifen, and further by addition of a Bach2-inhibitor in vitro. As a preliminary experiment, thus expanded splenic B cells expressing a transgenic antigen receptor/antibody against hen egg lysozyme were intravenously injected into mice pre-implanted with B16 melanoma cells expressing membrane-bound HEL in the skin, which resulted in suppression of the growth of B16 tumors and prolonged survival of the recipient mice. To test the usefulness of TiBcs for the immunotherapy, we next used APCmin/+ mice as a model that spontaneously develop intestinal tumors. We cultured TiBcs separated from the tumors of APCmin/+ mice as above and confirmed that the antibodies they produce recognize the APCmin/+ tumor. Repeated injection of such TiBcs into adult APCmin/+ mice resulted in suppression of intestinal tumor growth and elongation of the survival of the recipient mice. Serum antibody from the TiBc-recipient mice selectively bound to an antigen expressed in the tumor of APCmin/+ mice. These data suggest a possibility of the novel individualized cancer immunotherapy, in which TiBcs from surgically excised tumor tissues are expanded and infused into the donor patients.

Topics: Animals; Antigens, Neoplasm; B-Lymphocytes; Basic-Leucine Zipper Transcription Factors; Cells, Cultured; Disease Models, Animal; Disease Progression; Immunohistochemistry; Immunotherapy; Interleukins; Intestinal Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Muramidase; Tamoxifen

The aim of this study was to investigate the differences between the clinicopathological findings in two histologic types of carcinoma of the papilla of Vater. We histologically classified carcinoma of the papilla into two types: 1) an intestinal type that resembles tubular adenocarcinoma of the stomach or colon, and 2) a pancreaticobiliary type that is characterized by papillary projections with scant fibrous cores. We examined 53 cases of resected carcinoma of the papilla. The intestinal-type carcinomas were similar to the intestinal mucosa in that they had lysozyme-containing, Paneth or argyrophil cells, as demonstrated by the immunohistochemically positive stainings for the anti-lysozyme antibody. Although both the sizes of the two types of carcinomas and the age distributions of cases with the two types of carcinoma were almost the same, the prognosis of the cases with the intestinal type was much better than that of the cases with the pancreaticobiliary type. Histological lymph node metastasis was found significantly more often in the pancreaticobiliary type. This result was supported by the fact that small carcinomas of the intestinal type showed little or no invasion into the surrounding interstitium, as opposed to the pancreaticobiliary type, which had a strong infiltrative tendency. The pathogenesis of carcinoma of the papilla of Vater should be further evaluated, taking into consideration the existence of these two histologic types.

Topics: Adult; Aged; Aged, 80 and over; Ampulla of Vater; Carcinoma; Common Bile Duct Neoplasms; Female; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Intestinal Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Muramidase; Neoplasm Invasiveness; Pancreatic Neoplasms; Prognosis; Staining and Labeling; Survival Analysis; Survival Rate

Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout the duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span of 120 d. Multi-label immunocytochemical studies of these lesions demonstrate patches of differentiated enterocytes, and scattered enteroendocrine, goblet and Paneth cells. Expression of endogenous marker genes within these differentiated cells can be directly correlated with the position occupied by the adenoma along the duodenal-to-colonic axis and mirrors the regional differentiation of the normal gut epithelium. The presence of multiple lineages in adenomas together with their retention of spatial information suggests that tumorigenesis in Min/+ mice may be initiated in a multipotent stem cell normally located at the base of intestinal crypts. To study the time-dependent properties of these tumors, genetic conditions were sought in which Min/+ animals could survive for up to 300 d. Min is fully penetrant in hybrids with either AKR/J or MA/MyJ. However, the hybrids demonstrate a reduction in the number of intestinal adenomas. Preliminary backcross analysis is consistent with a single major modifier locus unlinked to Min in both the AKR/J and MA/MyJ strains. The increased lifespan of the hybrid animals is also associated with the development of invasive tumors. New tumors do not arise continuously over the lifespan of these animals; instead all adenomas appear to be established by 100 d of age or sooner. These studies indicate that the Min/+ mouse is a powerful model system for analyzing the mechanisms that establish and maintain a balance between proliferation and differentiation in the continuously renewing gut epithelium and for an assessment of the multi-step hypothesis of intestinal neoplasia.

Topics: Adenoma; Animals; Carrier Proteins; Cell Differentiation; Crosses, Genetic; Epithelium; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Fatty Acids; Intestinal Mucosa; Intestinal Neoplasms; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Mucins; Muramidase; Mutation; Neoplasm Proteins; Neoplastic Stem Cells; Nerve Tissue Proteins; Phenotype; Serotonin

Immunologic studies have demonstrated that the vast majority of hematolymphoid neoplasms previously designated as "histiocytic" are lymphoid in origin. Consequently, malignancies of macrophage lineage are considered rare by most authors; indeed, their existence is doubted by some. Herein we report two cases of malignant histiocytic neoplasms (malignancies of macrophage lineage) of the small intestine. Both patients presented in the 7th decade with symptoms related to an abdominal mass. The polypoid tumors protruded into the intestinal lumen, extended through the entire thickness of the bowel wall, and involved regional lymph nodes. Microscopically, sheets of large pleomorphic histiocytic cells infiltrated around crypts and were associated with an admixture of bizarre giant cells and inflammatory cells. Mitotic figures were easily found. Ultrastructurally, the cells lacked desmosomes and had indented or kidney-shaped nuclei and cytoplasm containing mostly lysosomes and dense lipid droplets. In both cases, paraffin section immunohistochemistry revealed reactivity of tumor cells for CD45RB (LCA), CD45RO (A6), CD68 (KP1), CD15 (LeuM1), and lysozyme. Frozen section immunohistochemistry performed in one case further supported the macrophage phenotype. Southern blot studies of this case did not reveal immunoglobulin or T-cell receptor beta chain gene rearrangements. One patient initially treated by surgery only died of disease 3 years after diagnosis. The second patient is alive and disease-free 2 years following postoperative combination chemotherapy. The diagnosis of malignant histiocytic neoplasms requires the use of a panel of immunohistochemical markers and may be supported by electron-microscopic studies.

Topics: Antigens, CD; Biomarkers, Tumor; Blotting, Southern; Cell Transformation, Neoplastic; DNA, Neoplasm; Gene Rearrangement; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Macrophages; Male; Microscopy, Electron; Middle Aged; Muramidase

Histological material was studied in five unselected cases of intestinal large-cell non-Hodgkin's lymphoma, occurring in patients either with previously diagnosed coeliac disease, or with atrophic mucosa at the time of diagnosis. The morphological diagnosis in each case was centroblastic lymphoma: these tumours were composed of large cells with pale nuclei and prominent nucleoli. No phagocytosis was evident, but some cells showed considerable pleomorphism. Polykaryotic giant cells were infrequent. Immunohistochemical staining for lysozyme, alpha-1-anti-trypsin and alpha-1-anti-chymotrypsin failed to demonstrate any of these proteins in the tumour cells, although they were identified in accompanying reactive macrophages. There is thus no evidence for a histiocytic nature in these five cases. The tumours were immunoglobulin-negative. Again, polyclonal immunoglobulin could be demonstrated in reactive (plasma) cells in and near the tumour. The relevance of these immunological markers is discussed. We suggest that these tumours, and possibly some of those reported in a similar situation by other investigators, are in fact lymphocytic in origin. They are probably examples of centroblastic lymphoma, although T-cell lymphoma, rare in the gastrointestinal tract, cannot be ruled out by our immunohistological studies.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Celiac Disease; Cell Nucleolus; Cell Nucleus; Chymotrypsin; Histocytochemistry; Humans; Intestinal Neoplasms; Lymphocytes; Lymphoma; Macrophages; Male; Middle Aged; Muramidase; Plasma Cells

Normal and metaplastic gastrointestinal mucosa obtained at surgical resection were studied by light microscopy, using the unlabelled antibody enzyme method for immunohistochemical staining of lysozyme, pancreatic endoproteases, and pancreatic secretory trypsin inhibitor (PSTI). Paneth cells in the mucosa of normal small intestine, gastric mucosa with intestinal metaplasia, and colonic metaplastic mucosa were found to contain anionic trypsin, cationic trypsin, lysozyme, and PSTI immunoreactivity, but not chymotrypsin and elastase immunoreactivity. Normal gastric and colonic mucosa and some goblet cells in the small intestine showed positive PSTI immunoreactivity but no endoprotease immunoreactivity. The presence of immunoreactive trypsin and immunoreactive PSTI in the Paneth cells, which are of secretory type, probably indicates an important extrapancreatic source of these proteins rather than a storage of endocytosed material.

Topics: Adenoma; Colitis, Ulcerative; Gastric Mucosa; Humans; Immunoelectrophoresis; Immunoenzyme Techniques; Intestinal Mucosa; Intestinal Neoplasms; Muramidase; Pancreas; Peptide Hydrolases; Trypsin; Trypsin Inhibitors

Topics: Celiac Disease; Female; Humans; Intestinal Neoplasms; Lymphoma; Male; Muramidase

One hundred one lymphoproliferative lesions of the gastrointestinal tract (66 malignant lymphomas, 20 pseudolymphomas, and 5 borderline lesions) were reviewed. The pathologic features were compared to the clinical findings, with reference to differential diagnosis and prognosis. Special attention was paid to immunohistochemical features. The gross appearance was diagnostic in only a limited number of cases. Endoscopic biopsy alone was also of limited value because only a diagnosis of probability could be made in several cases. In most of them the definitive diagnosis had to be based on histologic examination of the resected specimen. Immunohistochemical examination was found to be very useful as an ancillary diagnostic technique. Malignant lymphomas displayed either cytoplasmic immunoglobulins with a monoclonal pattern (47.1 per cent) or a negative reaction, whereas the pseudolymphomas were generally characterized by polyclonal immunoglobulins. Ninety per cent of malignant lymphomas with cytoplasmic immunoglobulins contained lambda chains. The survival probability was found to be related to the size of the lesion, the depth of infiltration, and the immunohistochemical characteristics of the tumors. The histologic type of the lymphomas was of limited value as a predictor of prognosis in the present series.

Topics: Animals; Cytoplasm; Female; Gastrectomy; Gastrointestinal Neoplasms; Humans; Immunoglobulins; Intestinal Neoplasms; Lymph Nodes; Lymphoma; Male; Middle Aged; Mortality; Muramidase; Plasma Cells; Rabbits

Topics: Humans; Immunoenzyme Techniques; Intestinal Neoplasms; Lymphatic Diseases; Muramidase

Serum lysozyme levels were significantly raised in a group of eight patients with malabsorption associated with gastrointestinal lymphomas of a type recently characterised as malignant histiocytosis of the intestine. In four of the cases, levels were markedly raised. In contrast there was no significant difference between groups of patients with uncomplicated adult coeliac disease and healthy controls. The estimation of serum lysozyme is a simple test to perform and may be valuable in the diagnosis of malignant histiocytosis of the intestine, in particular differentiating it from uncomplicated adult coeliac disease.

Topics: Adolescent; Adult; Aged; Celiac Disease; Female; Humans; Intestinal Neoplasms; Lymphatic Diseases; Male; Middle Aged; Muramidase

Topics: Animals; Appendicitis; Biological Evolution; Cell Division; Colitis, Ulcerative; Colonic Neoplasms; Crohn Disease; Ethionine; Gastritis; Germ-Free Life; Histocytochemistry; Humans; Intestinal Neoplasms; Intestines; Metaplasia; Microscopy, Electron; Muramidase; Peutz-Jeghers Syndrome; Puromycin; Rats; Stomach Neoplasms; Stomach Ulcer; Triparanol; Whipple Disease; Zinc