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H Kamma

Publications and source records attributed to H Kamma.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effect of TNP-470 on cell proliferation and urokinase-type plasminogen activator and its inhibitor in human lung cancer cell lines.

The plasminogen activator system has been found to modulate neoplastic spread and angiogenesis in tumors. An angiogenesis inhibitor, TNP-470, has been shown to possess potent antitumor activities in various types of cancer cells. We therefore investigated the inhibitory effect of TNP-470 on cancer cell proliferation, and the suppressive effect of TNP-470 on urokinase-type plasminogen activator (u-PA) and its inhibitor (PAI-1), in human lung cancer cell lines in vitro. TNP-470 inhibited cell proliferation in a dose-dependent manner in both cell lines. u-PA and PAI-1 in culture supernatants were suppressed with the concentrations of TNP-470, in association with a decrease in viable cancer cells. Unchanged serum levels of u-PA and PAI-1 would be of great advantage to the diseased patients, since the plasminogen activator system has a crucial function in the process of distant metastasis.

Antibiotics, Antineoplastic↗
PubMed1995

Estimation of fetal hemoglobin levels in individual red cells via fluorescence image cytometry.

A method for estimating fetal hemoglobin (Hb F) levels in individual red blood cells was developed. Cell smears were prepared using a slide maker to ensure uniform thickness and were then stained with immunofluorescence. An antifading gel was applied to preserve a stable fluorescence. The total fluorescence intensities from the same number of red cells in different slide specimens correlated with their hemolysate Hb F levels, which were determined via column chromatography (R = 0.95). Hb F level in individual cells was estimated from fluorescence intensity and cell area, which were determined via image analysis techniques and the hemolysate Hb F level. Blood from a normal subject, a subject with hereditary persistence of fetal hemoglobin, and from sickle cell patients with varying Hb F levels was analyzed. Our analyses showed a wide distribution of Hb F among cells for the normal subject and a gaussian distribution with a peak at the hemolysate Hb F level for the subject with hereditary persistence of fetal hemoglobin. The Hb F distributions were unique to the patients with sickle cell disease. Because Hb F level in individual sickle cells is crucial to the inhibition of cell sickling, the unique hb F distribution may be important in determining the clinical course of this disease.

Anemia, Sickle Cell↗
PubMed1995

Heritable formation of neuroectodermal tumor in transgenic mice carrying the combined E1 region gene of adenovirus type 12 with the deregulated human renin promoter.

Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transcriptional regulation of viral and cellular promoters in infected and transfected culture cells and for transformation of primary rodent cells. Here, we established a line of transgenic mice carrying the E1 region gene of human adenovirus type 12 under the control of the human renin promoter, in which a neuroectodermal tumor derived from retroperitoneal, olfactory, and/or pelvic regions was heritably developed with varying degrees of incidence and the phenotype was successfully passed through six generations. The transgenes were located in the region E2-E3 bands of chromosome 7 with which no genetic linkage to neuroectodermal tumors was previously demonstrated, and expressed only in the tumors but not in another tissue examined. Notably, in addition to the expression of a neural marker gene N-CAM, the three nuclear oncogenes, c-, L-, and N-myc, were coexpressed in the tumors. These results suggest that E1A and E1B are cooperatively involved in the heritable formation of neuroectodermal tumors associated with co-expression of the three sets of myc family genes.

Adenovirus E1 Proteins↗
PubMed1995

Cell type-specific expression of hnRNP proteins.

HnRNP proteins are abundant nucleoplasmic pre-mRNA-binding proteins which have important roles in the biogenesis of mRNA. Although hnRNP proteins have been extensively characterized in cultured cell lines, little is known about their expression in animal tissues. Here, we have undertaken a systematic survey of the expression of major hnRNP proteins in mouse tissue using specific monoclonal antibodies. Immunohistochemical staining demonstrated that hnRNP proteins C, L, and U were localized to nuclei in all tissues examined. However, cytoplasmic expression of hnRNP A1, D, F/H, and K was also detected in several tissues, suggesting that these proteins have roles in the cytoplasm as well as the nucleus. Importantly, the relative amounts of different hnRNP proteins varied among cell types. This was especially striking in neuronal and reproductive cells. In the brain, certain neuronal cell types contained more hnRNP proteins than glial cells, perhaps reflecting increased levels of neuronal transcription and RNA processing. In the ovary, oocytes contained exceptionally high concentrations of hnRNP proteins as compared to follicular and stromal cells. In the testis, the expression of hnRNP proteins was generally high and was found to be tightly regulated during spermatogenesis. Specifically, hnRNP A1 was highly expressed only in early spermatogonia and absent in later stages. These findings demonstrate that hnRNP proteins do not exist in a fixed stoichiometry across different cell types. Furthermore, as the relative amounts of pre-mRNA-binding proteins (e.g., A1 and ASF/SF2) can affect alternative splicing patterns, the variations that we have observed could profoundly affect cell-specific gene expression.

3T3 Cells↗
PubMed1995

Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene.

The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.

Adenovirus E1 Proteins↗
PubMed1994

Neuroectodermal tumors expressing c-, L-, and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12.

Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transformation of primary cultured rodent cells. In order to investigate in vivo action of the E1 region, we established a line of transgenic mice carrying the oncogenic E1A and E1B genes of human adenovirus type 12 under control of the human angiotensinogen promoter. Histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying degrees of incidence. The transgene was expressed in the neuroectodermal tumors as well as in TNT-1 cells, a cell line established from the tumors, where the human angiotensinogen promoter was constitutively active. The high level expression of c-, L-, and N-myc without gene amplification was notable in the original tumors and TNT-1 cells, but not in another tissue examined. The co-expression of the three sets of myc family genes in both the original tumors and the established cell line provided the possibility that the target cells for transformation may belong to a specific cell type that expresses all these oncogenes during development.

3T3 Cells↗
PubMed1994

Comparative DNA analysis by image cytometry and flow cytometry in non-small cell lung cancer.

To determine whether image cytometry (ICM) is advantageous for clinical DNA analyses of tumor cells, nuclear DNA contents measured by ICM were compared with those by flow cytometry (FCM), using 46 samples of non-small cell lung cancers. ICM was performed on smear specimens of fresh materials (f-ICM) and cell suspensions obtained from paraffin-embedded tumors (p-ICM). The same cell suspensions were also analyzed by FCM (p-FCM). Aneuploid rates/coefficient of variation (CV) of f-ICM, p-ICM, and p-FCM were 76.1/4.90, 71.7/5.01 and 60.9/5.31%, respectively. There was a high correlation in the DNA indices between p-ICM and p-FCM (r = 0.80). In the comparative DNA analysis, there were seven discordant samples. Six of them were estimated as aneuploid by p-ICM, but they were miscounted as diploid or undefinable (impossible) by p-FCM. This was caused by measuring condensed nuclei or debris. All "impossible" samples in p-FCM were squamous cell carcinoma with necrosis. In cell cycle analysis, the S and S+G2/M phase fractions in diploid samples were higher in p-ICM than those in p-FCM (P < 0.005), because the G0/G1 phase (2N) fraction presented by FCM was composed of cancer and non-malignant cells in diploid cancers. In ICM, they can be separately measured by means of morphological selection. These findings indicated that ICM is superior to FCM, especially for the practical DNA measurement of a few cancer cells and in the evaluation of the proliferation rates.

Adult↗
PubMed1993

Encapsulated type II pneumocyte adenoma: a case report and review of the literature.

An unusual benign lung neoplasm, a papillary adenoma of type II pneumocytes, was resected from a 26-year-old man who showed no clinical symptoms. The tumor was 2.0 cm in diameter and was localized in the subpleural region of S7 of the right lung; the cut surface showed a spherical medullary mass encapsulated by a thin layer of connective tissue. Histologically, there were cuboidal to columnar epithelial cells with a little nuclear atypia showing a monotonous papillary pattern with a delicate stroma in most parts of the tumor. There was neither capsular invasion nor metastasis of tumor cells. Nuclear DNA analysis of the tumor cells showed a diploid pattern and a low S-phase fraction. The immunohistochemical study revealed that most tumor cells contained a large amount of surfactant apoprotein in the cytoplasm. Osmiophilic lamellar bodies characteristic of type II pneumocytes were frequently found by electron microscopy. These findings indicate that this was a benign adenoma of the lung arising from type II pneumocytes.

Adenoma↗
PubMed1992

Proliferative activity in thyroid tumors.

To clarify the proliferative activity of papillary thyroid carcinoma, the bromodeoxyuridine (BrdU) labeling index (LI) of 61 various thyroid tumors was investigated using an in vitro labeling technique and immunohistochemical staining with anti-BrdU monoclonal antibody. The mean LI (+/- standard deviation) of 31 papillary carcinomas, 12 adenomas, 10 adenomatous goiters, 3 follicular carcinomas, and 2 medullary carcinomas were 1.2% (+/- 1.3%), 0.6% (+/- 0.3%), 0.7% (+/- 0.6%), 1.5% (+/- 2.2%), and 0.7% (+/- 0.6%), respectively. The LI of the papillary carcinomas ranged from 0.1% to 4.6%, and approximately 66% of these showed less than a 1% similarity with almost all benign tumors. However, the LI of the two malignant lymphomas and the one anaplastic carcinoma were more than 13%. When the LI of the papillary carcinomas was compared with their various prognostic factors, there was no correlation with tumor size, nodal status, or morphologic features. However, the patients who were 50 years of age or older tended to have relatively high LI, and the LI of the papillary carcinomas correlated with patient age. According to these results, the biologic characteristics of papillary carcinomas vary with age and high proliferative activity may contribute to the poor prognosis of this tumor in elderly patients.

Adenoma↗
PubMed1992

[Quantitative DNA image cytometry by color image analyzer].

We developed a new method to analyze DNA quantitatively by a color image analyzer. A microscopic image of the nucleus stained with Feulgen's reaction, is taken by a CCD color camera and inputted in a color image analyzer. DNA quantity can be calculated directly from the RGB components of the color image instead of the monochrome image taken through band-pass filter, which is specific for the absorption of Feulgen's stain. It takes about 10 minutes to measure 500 nuclei by this method and its accuracy is almost the same as flow cytometry (CV = 3%). The nuclear color image can also be analyzed morphometrically. This method can select tumor cells in a usual cytologic specimen and measure their DNA contents.

Cytophotometry↗
PubMed1991

[Histopathological evaluation of the radiosensitizing effects of an intratumoral injection of BrdU for rectal cancer].

We delivered preoperative radiotherapy with intratumoral injection (ITI) of radiosensitizer, 5-bromodeoxyuridine for patients with locally advanced cancer originating in lower rectum. We identified immunohistochemically the tumor cells that incorporated BrdU, and evaluated the radiosensitizing effect of BrdU histopathologically. (1) BrdU-labeled nuclei of cancer cells were identified in twenty-three cases out of 24 (96%). Mean labeling index was 18.5%, and tended to decrease as time progressed. (2) The parameters representing volume of residual tumor nests (Tumor Nest Index) or degrees of tumor extension (Depth of Extramural Tumor and Depth of Extramural Fibrosis) for patients with ITI were compared to those for patients without ITI. Those parameters tended to decrease when ITI was combined with radiotherapy. However, the difference was not significant statistically. Intratumorally injected BrdU can incorporate with cancer cells, but a methodological invention is required for yielding clinically measurable radiosensitization.

Adenocarcinoma↗
PubMed1991

Pulmonary blastoma with a topographic transition from blastic to more differentiated areas. An immunohistochemical assessment of its embryonic nature using stage-specific embryonic antigens.

In order to investigate the probable embryonic nature of pulmonary blastoma, immunohistochemical studies were performed using stage-specific embryonic antigens (Ley, Lex, sialyl Lex-i) in case of pulmonary blastoma with a very wide spectrum of morphological features. The tumour presented a topographic transition from primitive blastic and embryonic areas to more differentiated areas showing diverse differentiation. Blastic areas composed of extremely immature cells were found in most peripheral parts of the tumour. Inside the blastic areas there were "embryonic" areas which morphologically resembled human embryo lungs in the pseudoglandular and canalicular stages. Most central parts of the tumour showed more differentiated features including chondrosarcomatous, leiomyosarcomatous and rhabdomyosarcomatous elements and the common type of adenocarcinomatous element. Electron microscopic observation suggested the blastic and embryonic nature of these immature cell elements. Ley was expressed in the blastic and pseudoglandular areas. Lex was expressed in the canalicular areas. These antigens were not expressed in the more differentiated areas. The topographic gradient in the tumour of morphology and antigen expression from the peripheral blastic areas to the central more differentiated areas suggests that the primitive cells gradually differentiated into more mature cells of various directions as the tumour grew in size.

Antigens↗
PubMed1991

Expression of MHC class II antigens in human lung cancer cells.

Surgical specimens of lung cancers were examined immunopathologically for the expression of major histocompatibility complex class II (MHC-II) antigens in the tumor cells and their relationship to the lymphocytic infiltration. A lymphocytic infiltrate was frequently observed in the tumor tissue, though its intensity differed among the various histological types. MHC-II antigens were often demonstrated in tumors with a lymphocytic infiltrate. They were detected predominantly in the cytoplasm of tumor cells and to a lesser extent on the cell membranes. The emergence of the MHC-II-positive tumor cells was closely related to a local infiltration by lymphocytes including interferon-gamma (IFN-gamma)-producing T-cells. On the basis of the histological findings, an in vitro experiment was carried out. Four types of lung cancer cells were incubated with recombinant IFN-gamma in order to induce MHC-II antigens. MHC-II antigens (HLA-DR as well as HLA-DQ and HLA-DP antigens) were elicited in three cancer cell lines depending on the concentration of IFN-gamma. Immunoelectron microscopic study revealed that they were expressed on the surface of the cell membrane, though to a lesser extent than in the cytoplasm. It was considered that MHC-II antigens could be induced in some tumor cells in the immunological environment where IFN-gamma was secreted from T-cells and concentrated locally.

HLA-DQ Antigens↗
PubMed1991

Clinical significance of serum levels of a carbohydrate antigen, sialyl SSEA-1, in patients with fibrosing lung disease.

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Adrenal Cortex Hormones↗
PubMed1991

[Pathological findings as determinant factors of prognosis of renal cell carcinoma].

Clinicopathological studies were made on 105 patients with renal cell carcinoma who visited us from January 1978 to August 1989. The results were as follows: 1. Overall 3, 5 and 10-year survival rates were 60.4%, 49.8% and 44.5%, respectively. 2. Patients in Robson stage I survived longer than those in stage III, and patients in stage II survived longer than those in stage IV with a significant difference. 3. A significant difference did not exist between patients in stages lower than pT2 and those in pT3a, while patients in pT3a survived longer than those in stages higher than pT3b. 4. Patients with grade 1 tumors survived longer than those with grade 2 tumors, and patients with grade 2 tumors survived longer than those with grade 3 tumors with a significant difference. 5. Patients with clear cell subtype survived longer than those with granular cell subtype and mixed subtype with a significant difference, while a significant difference did not exist between patients with granular cell subtype and those with mixed subtype. 6. Patients with INF alpha tumors survived longer than those with INF beta tumors with a significant difference. There was the same significant difference in patients with grade 2 tumors.

Adult↗
PubMed1989

Lung cancer-associated monoclonal antibody 15 that recognizes cell growth-related membrane antigens gp85/45 and its growth-inhibitory effect on human lung cancer cells in vitro.

In order to find lung cancer-specific markers, monoclonal antibody 15 (MAb15) was produced against a variant-type cell of small cell lung carcinoma. Its gp85/45 antigens were demonstrated in 70% of lung cancers, and particularly in the proliferating zone of cancer cell nests, but they are scarcely detected in noncancerous tissues. Immunoelectron microscopy revealed that gp85/45 antigens were expressed alternatively on the cell membrane of living cancer cells according to their biological states. MAb15 added to the culture medium inhibited the proliferation of lung cancer cells, depending on its concentration, but cell death rate did not increase. The growth inhibition by MAb15 was reevaluated by a colonogenic assay. On DNA histogram, MAb15 decreased the number of DNA-synthesizing cells in the S phase with an elevation of the G1 peak, indicating a G1-S boundary block in the cell cycle. gp85/45 detected by this lung cancer-associated monoclonal antibody could be a functional membrane unit, such as a growth factor receptor, which is related to the cell proliferation of lung cancer. The growth inhibition by MAb15 may be caused by the blocking of a growth factor receptor which is specific to lung cancer.

Antibodies, Monoclonal↗
PubMed1989

A case of metastasis from gastric cancer to the thyroid gland.

Metastatic tumors in the thyroid gland are rarely seen in clinical practice. This report describes a case of metastasis from gastric cancer to the thyroid, found five years after removal of the primary gastric lesion. The patient had a large thyroid mass extending to the mediastinum, but there were no obvious metastatic lesions anywhere except in the thyroid. Subtotal thyroidectomy was performed and histological examination revealed the same findings a those of the original gastric cancer. Of additional interest are the findings that led us to believe this metastatic tumor produced alpha-fetoprotein. Seven months following the operation, the patient dies suddenly and, although it is difficult to say whether the patient's survival was prolonged, we believe that the thyroid surgery gene him considerable palliation.

Adenocarcinoma↗