[Functioning lung tumor].
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ACTH Syndrome, Ectopic↗
Biomedical subjects
T Kameya
Publications and source records attributed to T Kameya.
Medullary carcinoma of the thyroid. An immunocytochemical and histochemical study of 25 cases using eight separate markers.
The current study was undertaken on 25 cases of thyroid medullary carcinoma to compare the diagnostic value of calcitonin with other peptides including PDN-21, the C-terminal flanking peptide of human calcitonin within the calcitonin precursor, and calcitonin gene-related peptide, CGRP. Antiserum raised to chromogranin, an acidic protein of 68,000 daltons, was also used to compare its diagnostic value as a general marker for neuroendocrine neoplasia with neuron-specific enolase (NSE) and Grimelius' argyrophil silver staining. Immunocytochemistry was performed using the peroxidase-antiperoxidase method at the light microscopic level and the immunogold staining procedure at the ultrastructural level. All tumors were reactive to calcitonin and CGRP antisera, whereas PDN-21 was present in 23 cases. It was also found that these peptides were colocalized in the majority of C-cells. The intensity and specificity of CGRP and PDN-21 immunoreaction was comparable to and in some cases even better than that obtained with calcitonin antiserum. In the majority of tumors, somatostatin and bombesin immunoreactivity was either absent, weak, or variable in intensity and distribution. The current study thus demonstrates that together with calcitonin, PDN and, in particular, CGRP antisera may be applied to corroborate immunocytochemical diagnosis in medullary carcinoma of the thyroid. With regard to general neuroendocrine markers, Grimelius' and chromogranin provided the most consistent results. NSE isoenzyme immunoreactivity, on the other hand, was more variable, probably reflecting the metabolic state of the tumor cells.
Bombesin↗
Peptide hormone production in primary lung tumors.
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Adenocarcinoma↗
Pancreatic endocrine tumours associated with WDHA syndrome. An immunohistochemical and electron microscopic study.
Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.
Adenoma, Islet Cell↗
S-100 protein-positive Langerhans cells in various human lung cancers, especially in peripheral adenocarcinomas.
The appearance of S-100 protein-positive Langerhans cells was studied in 90 cases of various lung cancers by an immunohistochemical method. S-100 protein-positive dendritic cells were frequently observed in many adenocarcinomas, especially in those subclassified as bronchiolar cell or type II alveolar cell type. However, no S-100 protein-positive cells were found in "goblet cell type" adenocarcinoma. In some cases of squamous cell carcinoma and large cell carcinoma, these dendritic cells were also observed though they were fewer in number. In all cases of small cell carcinoma, however, S-100 protein-positive dendritic cells were rare. Electron microscopic study of two adenocarcinomas clearly demonstrated many Birbeck granules in the cytoplasm of S-100 protein-positive dendritic cells and confirmed that S-100 protein-positive cells in lung cancer were identical with Langerhans cells.
Adenocarcinoma↗
Aromatic L-amino acid decarboxylase activities in human lung tissues: comparison between normal lung and lung carcinomas.
We measured the activity of aromatic L-amino acid decarboxylase with L-dihydroxyphenylalanine as a substrate (DOPA decarboxylase) in normal lung tissues and lung tumors obtained fresh at surgery. The activity in control human lung tissues was low and variable: 3.50 +/- 0.42 pmole/min/mg protein (n = 56, mean +/- SE, range 0.01-15), indicating the wide individual variations. Most of small cell carcinoma specimens showed very high activity, as compared with both control lung tissues and with other types of non-SCC lung cancers. Similar results were also obtained in the athymic mice heterotransplants of SCC. High activity was also observed using 5-L-hydroxytryptophan as a substrate (5-HTP decarboxylase) in nine SCC samples. Serotonin was not detected in any control lung tissues, but was detected in all the nine SCC samples, but dopamine was detected only in three out of nine SCC samples.
Animals↗
Nasopharyngeal carcinoma: immunohistochemical study for keratin, secretory component and leukocyte common antigen.
Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium.
Adolescent↗
Large cell carcinoma of the lung associated with marked eosinophilia. A case report.
A case of large cell carcinoma of the lung which produced eosinophil colony stimulating factor and eosinophil chemotactic factor was reported. A 52-year-old Japanese man with a tumor in the left upper lobe of the lung underwent left pneumonectomy. Marked eosinophilia persisted especially after recurrence, with a maximum peripheral leukocyte count of 161,000/mm3, of which 78% consisted of eosinophils. The patient died of pulmonary insufficiency 18 months after surgery. At autopsy, metastatic tumor tissues and almost all organs were markedly infiltrated with eosinophils, especially the spleen, and there was marked proliferation of eosinophils in the bone marrow. Eosinophil colony stimulating factor production by the transplanted tumor in a nude mouse was confirmed by use of a human bone marrow culture assay system. Eosinophil chemotactic factor production by metastatic tumor tissue also was proved by a modified micro-filter technique.
Biological Assay↗
Enolase distribution in human brain tumors, retinoblastomas and pituitary adenomas.
The cellular localization of alpha-, beta- and gamma-subunits of enolase isoenzyme was studied immunohistochemically in various human brain tumors, retinoblastomas and pituitary adenomas (total, 91 cases). The alpha-subunit was found in almost all brain tumors except in medulloblastoma cases. A case of medullomyoblastoma contained beta-subunit-positive myoblastic cells, which was also positive for human myoglobin. The gamma-subunit was frequently observed in medulloblastomas, retinoblastomas and pituitary adenomas. However, gamma-subunit was also present in some non-neuronal brain tumors such as astrocytomas and oligodendrogliomas. Enzyme immunoassay technique also confirmed the presence of gamma-subunit in a medulloblastoma and two retinoblastomas.
Adenoma↗
Concomitant production of immunoreactive gastrin-releasing peptide and calcitonin in medullary carcinoma of the thyroid.
Immunoreactive gastrin-releasing peptide (IR-GRP) was found to be present in medullary carcinoma of the thyroid (MCT) by use of a radioimmunoassay (RIA) specific for the carboxyl-terminal portion of GRP. Immunohistochemical studies revealed IR-GRP in the MCT tumor cells, indicating that the tumor cells produce IR-GRP. Immunoreactive GRP was also detected in macroscopically normal thyroid tissue of patients with multiple endocrine neoplasia type II (MEN II, or Sipple's syndrome) and in areas of C cell hyperplasia and micronodules in the thyroids of patients with MCT. When these tissue extracts were examined with a bombesin RIA that recognizes bombesin but not GRP, no IR-bombesin was detected, suggesting that the IR-GRP detected in these tissues is more similar to GRP than to bombesin. IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was elevated to 130 to 780 pg/mL (normal: undetectable, less than 62.5 pg/mL) in three patients with metastatic MCT, and both calcium and tetragastrin increased the plasma levels of IR-GRP. Sephadex G-50 gel filtration of the MCT extracts revealed two peaks, one coeluted with porcine GRP (1-27) and the other eluted just after its carboxyl-terminal (14-27) fragment. There was a significant correlation (P less than 0.01) between the concentration of IR-GRP and that of IR-calcitonin in MCT tumor tissue and in macroscopically normal portions of thyroid tissue from two patients with MEN II, although the concentration of IR-GRP was only about 0.1% of that of IR-calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)
Bombesin↗
A prolactin producing tumor originated in the sphenoid sinus.
The case presented is a prolactin producing tumor originated in the sphenoid sinus of a 40-year-old woman. Histologically this tumor is a typical chromophobe adenoma of the pituitary gland. Human prolactin was immunohistochemically detected in the cytoplasm of most tumor cells. The tumor invaded around the pituitary gland and in the nasal cavity without distant metastasis. Clinically the patient showed hyperprolactinemia and amenorrhea.
Adenoma↗
Interconversion of biological characteristics of small cell lung cancer depending on culture conditions.
Two distinct cell lines were obtained from a single heterotransplanted tumor which had originated from a primary focus of small cell carcinoma of the lung (SCCL). They were maintained separately from the beginning in culture media with and without fetal calf serum supplementation. Cells in the serum-free medium grew mostly floating in loose aggregates and showed poor cell cohesiveness, scanty cytoplasm and a few intracytoplasmic small dense-cored granules; all of these features are characteristics of oat cell type SCCL. On the other hand, cells in the serum-supplemented medium grew mostly floating in flatter and more closely associated clumps, were larger, and showed increased cell cohesiveness, occasional tubular structures, better developed organelles including dense-cored granules, and an increased number of cell attachments; these features are characteristics of intermediate cell type SCCL. The modal number of chromosomes differed from each other. Neuron-specific enolase (gamma enolase) and aromatic L-amino acid decarboxylase (ADC) activities in cell pellets were significantly higher in both lines than in control non-small cell lung cancer cell lines. The alpha/gamma type enolase ratio was lower, as was the ADC activity, in serum-free cultures than in serum-supplemented cultures. Interchange of the culture medium induced changes of the growth pattern and cell type from "oat cell type" to "intermediate cell type" and vice versa. The chromosomal number also partially changed. These findings suggest that cultured cells of SCCL alter their growth pattern and cell type depending on the culture conditions and that the selective growth of one cell type might then take place.
Animals↗
Peripheral lung carcinoid tumor producing predominantly gastrin-releasing peptide (GRP). Morphologic and hormonal studies.
A carcinoid tumor of the peripheral lung producing gastrin-releasing peptide (GRP), a peptide hormone known to be present in the endocrine cells of fetal bronchial epithelium, is reported. Brain-gut peptide hormones in this tumor were assayed by radioimmunoassays, localized by immunohistochemistry and characterized by gel filtration. Electron microscopic study revealed that tumor cells resembled P-cells of normal human fetal bronchial epithelium. While GRP-containing cells were predominant in this tumor, calcitonin-containing cells were also found in some areas. Difference in distribution of hormones according to histologic features was noted in the tumor. A greater portion of the tumor showed spindled cells that predominantly contained GRP, and a smaller portion of the tumor showed cells arranged in tubular or trabecular patterns that mainly contained calcitonin. The gel-filtration pattern of the tumor extracts consisted of two peaks, one of these corresponded to the synthetic replicate of porcine GRP, and another was considered to correspond to C-terminal fragments of the peptide.
Adult↗
Peptide hormone production by adenocarcinomas of the lung; its morphologic basis and histogenetic considerations.
The cell source of peptide hormone production and the morphological differentiation were investigated in 18 adenocarcinomas of the lung by immunohistochemistry and/or by electron microscopy. These tumors were found by radioimmunoassay of tumor extracts to contain either one or more of 7 peptide hormones, i.e. adrenocorticotropin (ACTH), beta- and gamma-melanocyte stimulating hormones (MSH), somatostatin (SS), vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and calcitonin (CT). In a combined adeno- and small cell carcinoma, a considerable number of small tumor cells were positively stained for ACTH, beta- and gamma-MSHs and GRP. In a poorly differentiated adenocarcinoma with mucin and CT production, these products were localized in some single cells. Electron microscopy revealed secretory granules indistinguishable from exocrine or endocrine types. In another mucin-positive adenocarcinoma with high SS and CT contents, some tumor cells were stained for SS and/or CT. Two distinct exocrine and endocrine type secretory granules were found in the same cells. In tumors with 100 ng or less of the peptides/g tissue, most tumor cells were not stained for the peptides but a small number showed morphological endocrine differentiation. In conclusion, a considerable proportion of the adenocarcinomas of the lung may show heterogeneous differentiation in both endocrine and exocrine directions.
Adenocarcinoma↗
Production of gastrin releasing peptide by medullary carcinoma of the thyroid. An immunohistochemical study.
Forty medullary carcinomas of the thyroid (MCT) with documented calcitonin (CT) production were studied immunohistochemically for the production of gastrin releasing peptide (GRP), a mammalian counterpart of amphibian bombesin. GRP-positive cells, revealed by an unlabelled peroxidase-antiperoxidase immunoenzyme histochemistry were found in 81% (34/40) of the MCTs. Variable numbers of tumor cells in positive MCTs were immunostained for GRP. In 3 cases with Sipple's syndrome, cells in scattered microscopic MCT nodules and hyperplastic intrafollicular C cells of the thyroid were frequently positive for GRP as well as for CT. Non-neoplastic C cells (or CT-positive cells) of the human thyroids were also positive for GRP. In the neoplastic and non-neoplastic C cell system, some cells were confirmed to be immunoreactive with both anti-GRP and anti-CT. All these findings indicate that GRP and CT are closely associated peptide hormones produced by the C cell system.
Calcitonin↗
[Prolactin producing cells in human pituitary adenomas. Observation by consecutive semithin-thin section method].
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Adenoma↗
Production of immunoreactive pancreatic growth hormone-releasing factor in small cell carcinoma of the lung.
A specific and sensitive radioimmunoassay for human pancreatic growth hormone-releasing factor (hpGRF) was developed. Using this radioimmunoassay, it was found that immunoreactive hpGRF (which is present in hypothalamic tissues) of at least two different molecular sizes is often produced by small cell carcinoma of the lung.
Breast Neoplasms↗
In vivo and in vitro biological activities of two human cell lines derived from anaplastic lung cancers.
Cell lines Lu-65 and SK-Luci-6 were established from two patients with anaplastic (non-oat cell) lung cancers. These cell lines showed in vivo and in vitro functional activities that could explain the paraneoplastic syndromes which were clinically manifested. In both patients, elevated white blood cell counts occurred in the absence of any evidence of sepsis. Tumor fragments taken directly from one patient and transplanted to nude mice produced a progressive leukocytosis in the mice. Tissue culture-derived cells from both cell lines enhanced white blood cell numbers following heterotransplantation to nude mice. Cell-free extracts from both cell lines were found to enhance granulocyte-macrophage colony formation in soft agar. Greater colony formation was consistently found with the cell line (SK-Luci-6) that was derived from the patient manifesting the more marked leukocytosis. These data suggest that the tumor cells release colony-stimulating activities. Coincidently, one cell line (Lu-65) synthesized and released large amounts of prostaglandin E2 with little or no other prostaglandin product; the other cell line produced no prostaglandins. When the tumor cell lines were cocultured with explanted fetal rat bones, enhanced bone resorption with excessive calcium release occurred. Bone-resorbing activity correlated with tumor prostaglandin synthesis for the cell line releasing prostaglandin E2. An osteolytic factor that was neither prostaglandin nor parathyroid hormone was released by the SK-Luci-6 cell line. Hypercalcemia was a persistent feature only in the patient from whom the latter tumor line was derived.
Adult↗