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Biomedical subjects

I Sugano

Publications and source records attributed to I Sugano.

At least 37 records · Page 2Linked to original sources

Dipyridamole combined with tumor necrosis factor-alpha enhances inhibition of proliferation in human tumor cell lines.

In the search for cytokines whose antiproliferative action could be enhanced by combination with dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, the combination of tumor necrosis factor-alpha (TNF-alpha) with this agent was evaluated in various human tumor cell lines. Inhibition of the proliferation of human melanoma cell lines MM-1CB and HMV-1 by TNF-alpha (1-10(2) U/ml) was enhanced in culture dishes by combination treatment with dipyridamole (0.1-10 microM). The enhancement effect was also detected in other tumor cell lines: T98 (glioma), SCC-1CB (squamous cell carcinoma), HAC-2 (ovarian clear-cell carcinoma), HLE (hepatoma), HEC-1 (endometrial adenocarcinoma) and HOC-21 (ovarian serous cystadenocarcinoma). The incorporation of [14C]amino acids and [3H]uridine into acid-insoluble cell materials in the combination-treated cells was not significantly different from that in cells treated with TNF-alpha or dipyridamole. However, the incorporation of [3H]thymidine was specifically inhibited in all cell lines examined after more than 12 h of the TNF-alpha and dipyridamole combination treatment, although neither agent alone inhibited this incorporation. On the other hand, the growth of tumors induced by the injection of MM-1CB and HMV-1 cells into nude mice was more markedly inhibited by the subcutaneous administration of TNF-alpha in combination with orally administered dipyridamole than by either agent alone. The results presented suggested that dipyridamole is beneficial in assuring the effectiveness of anti-cancer cytokine therapy.

Amino Acids↗

Expression of insulin-like growth factor II by a gastric carcinoma associated with hypoglycaemia.

A gastric cancer with liver metastases was associated with low morning levels of plasma glucose (24 mg/dl), insulin (< 2.5 microU/ml) and growth hormone (0.23 ng/ml). Primary and metastatic tumour tissue stained positively with anti-insulin-like growth factor II (IGF-II) monoclonal antibody. Western immunoblot analysis revealed a high molecular weight IGF-II in the serum: 15 kDa (normal: 7.5 kDa). Postmortem reverse transcription polymerase chain reaction on mRNA from both sites revealed 471 base pairs size cDNA encoding prepro-IGF-II. These results suggest that the gastric carcinoma encoded, expressed, and secreted IGF-II, probably causing the extrapancreatic tumour hypoglycaemia.

Aged↗

Malignant melanoma within an intradermal nevus.

We describe a case of malignant "dermal" melanoma that arose within a preexisting intradermal nevus. Clinically, the lesion had recently enlarged. Histologically, two patterns were noted. One was an intradermal nevus in the upper portion of the dermis; the other was a deeper nodule composed of malignant neoplastic cells that extended into the reticular dermis. No melanocytic epidermal junctional activity was noted. Despite careful clinical investigation, no alternative primary source was found. Neoplastic transformation of the intradermal nevus without junctional activity is our proposed interpretation of the lesion's histology. Immunohistochemical stains demonstrated that the deeper dermal neoplastic cells were positive for both HMB-45 and PCNA, whereas the superficial nevoid-appearing cells were negative; these findings support our postulate that this melanoma arose within an intradermal nevus. It is important to distinguish this neoplasm from other diagnostic possibilities, including a metastatic lesion originating from another site.

Aged↗

Photoreceptor differentiation of retinoblastoma: an electron microscopic study of 29 retinoblastomas.

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photoreceptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas.

Cell Differentiation↗

[Cyst of the tunica albuginea testis: a case report].

The patient is a 75-year-old male presenting with a chief complaint of a left painless intrascrotal mass. The left testis was tense to palpation with induration inside. Ultrasonography demonstrated a 3.0 x 1.5 cm cystic space along the margin of the left testis. Left high orchiectomy was performed. Histopathological diagnosis was tunica albuginea cyst. Important differential diagnosis includes a simple testicular cyst and epidermoid cyst of the testis.

Aged↗

Intrahepatic cholangiocarcinoma with sarcomatous change. Clinicopathologic and immunohistochemical evaluation of seven cases.

BACKGROUND: Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. METHODS: Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin-biotin-peroxidase complex method were performed on these cases. RESULTS: The tumor showed both mucin-producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease-free for 3 years after surgery. CONCLUSIONS: These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Adenocarcinoma, Mucinous↗

Degeneration of anterior horn cell in neuronal type of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type II): a Golgi study.

A morphological study using the Golgi impregnation method was carried out on the anterior horn cells at cervical (C), thoracic (Th), and lumbar (L) levels of the spinal cord in a patient with neuronal type of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type II) and an age-matched control. The present study demonstrated an uneven cell body surface, loss of cells (particularly large cells), loss of dendrites, reduced dendritic extent and an irregular surface and shape of dendrites at the C and L levels. In contrast, hematoxylin and eosin and Klüver-Barrera staining showed only simple atrophy or no change. The Th level of the patient showed none of these changes. Our results suggest that the degeneration or loss of dendrites of anterior horn cells by the Golgi staining method, which is most severe at the L level, is closely related to clinical findings such as muscle atrophy and weakness in neuronal type of Charcot-Marie-Tooth disease.

Aged↗

Occurrence of sequential intraocular tumors: malignant medulloepithelioma subsequent to retinoblastoma.

A 13-year-old boy, whose bilateral retinoblastoma had been treated by enucleation (OD) and irradiation (OS), developed anterior staphyloma (OS) necessitating the second enucleation. Histopathological, immunohistochemical and electron microscopic studies revealed malignant teratoid medulloepithelioma of the ciliary body, with demonstrated multipotential histogenesis. This is the first report which demonstrates the development of a second malignant intraocular tumor in an eye previously affected by hereditary retinoblastoma. Careful monitoring of patients who have had hereditary retinoblastoma is necessary because of the potential for a second malignancy.

Adolescent↗

Hepatic inflammatory lesions manifested as a pseudotumor. Report of two cases with different characteristics.

We report two surgical cases of inflammatory conditions of the liver that, on imaging studies, closely resembled a neoplasm. Under the diagnoses of hepatic malignant neoplasms, both patients underwent hepatic resections. Histologically, one case was found to be a hepatic xanthogranuloma (an inflammatory pseudotumor) that consisted of foamy histiocytes, plasma cells, lymphocytes, and fibroblasts, while the other case was found to be an epithelioid cell granuloma with a central area of coagulative necrosis. Although their exact pathogenesis remained obscure, cholangitis in the former case and tuberculosis in the latter were assumed to be possible causal factors. Special attention should be paid to these unusual conditions in terms of the differential diagnosis of hepatic mass lesions.

Aged↗

Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells.

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.

Animals↗

Biliary cystadenocarcinoma of the liver. A clinicopathologic and histochemical evaluation of nine cases.

Nine cases of biliary cystadenocarcinoma of the liver were studied, with emphasis on its clinicopathologic features, mucin profiles, and immunohistochemical characteristics. In general, the cystic tumors had protrusions that consisted of well-differentiated papillary adenocarcinoma cells with or without benign-appearing epithelial elements. In invading or metastatic foci, the carcinoma cells tended to show distinctive anaplastic changes. Tumor growth was confined to the cystic lesions in five cases (noninvasive type), whereas in four cases it extended to the hepatic parenchyma or neighboring organs (invasive type). There was a considerable difference between the two groups in terms of prognosis. In fact, the patients included in the group with the noninvasive type had no sign of tumor recurrence after an appropriate surgical procedure. With mucin histochemical and immunohistochemical approaches, positive reactions with carcinoembryonic antigen, tissue polypeptide antigen, carbohydrate 19-9, and Dupan-2 and the predominance of sialomucin were observed in most cases of biliary cystadenocarcinoma, indicating a similar cellular nature of cholangiocarcinoma.

Adenoma, Bile Duct↗

Hepatocellular carcinoma containing endocrine cells. An autopsy report of triplecancer involving the liver, kidney and thyroid.

An autopsy case of triplecancer (hepatocellular carcinoma of the liver, renal cell carcinoma of the kidney, and papillary carcinoma of the thyroid) was reported. Histological features of primary hepatic tumor suggested undifferentiated hepatocellular carcinoma (Edmondson-Steiner's Grade IV). However, certain tumor cells showed distinctive argyrophilic reactions and electron microscopy revealed small round granules resembling electron dense endocrine secretory granules in their cytoplasm. Immunohistochemistry demonstrated that tumor cells showed a positive reaction for AFP while some others were positive for chromogranin-A. Immunohistochemical demonstration of AFP production by tumor cells indicated their hepatocyte origin. No endocrine syndrome had been present and no alternative primary source of the endocrine tumor was detected. Tumors of the kidney and thyroid were considered to be incidentally combined.

Aged↗

Case report 685: Ossifying fibromyxoid tumor of the soft parts of the upper arm.

We report an unusual case of an ossifying tumor arising in the deep soft tissue adjacent to the humerus of a 72-year-old woman. The tumor exhibited sarcoma-like features histologically, although its clinical course unexpectedly differed from that of a malignant tumor. We diagnosed this particular case as an ossifying fibromyxoid tumor of soft parts, which has been recently described by Enzinger et al.. This is another example of an ossifying soft-tissue tumor which simulates a malignant sarcoma.

Aged↗

Lobular involvement in human breast carcinoma.

One hundred twenty-nine cases of breast carcinoma were examined in order to clarify the occurrence of lobular involvement with regard to stromal invasion. Lobular involvement was clearly recognized in 56 cases (43%) having discernible portions of intraductal carcinoma components. The process of lobular involvement was first recognizable as an extension of a few carcinoma cells from intralobular ducts into the acinar lumina. Progressive accumulation of the carcinoma cells resulted in marked swelling and distortion of the involved lobules. During the process, perilobular myoepithelial cells (actin-positive cells) were stretched and disappeared. Subsequently, breaks in the basement membranes were also observed, resulting in stromal invasion of carcinoma cells. The lobular involvement was classified into common and round varieties, possibly reflecting different growth activities of the carcinoma cells. The stromal invasion was initiated by peripheral budding or focal necrosis of the involved lobules. The latter pattern was often observed in comedo carcinoma. It was thus revealed that in breast carcinomas the terminal ductal-lobular units are quite often involved and can become sites of extraductal invasion.

Actins↗

[Charcot-Marie-Tooth disease associated with dilated cardiomyopathy: an autopsy case report].

This is a clinical report of a rare case of Charcot-Marie-Tooth disease associated with dilated cardiomyopathy. A seventy-seven-year-old Japanese male first visited our outpatient clinic with a ten-year history of muscular weakness in his bilateral lower extremities and gait disturbance characterized by classical features of peroneal muscular atrophy and inverted champagne bottle legs. Biopsy findings of the m. quadriceps femoris and the n. gastrocnemius revealed clustered atrophy of myofibrils and segmental demyelinization mingled with remyelinization. Because of his other problem of dilated cardiomyopathy, he had been treated with salt restriction, digitalis, diuretics and vasodilators, until his third hospitalization, when he developed terminal stage of severe congestive heart failure. Despite our intensive cardiac care, the patient died because of profound pump failure. Autopsy findings disclosed a remarkably dilated left ventricular chamber and an increased total heart weight of 600 grams. Grossly, the cross sectional view of the left ventricle revealed diffuse, but not homogenous fibrosis that was most prominent in the posterior wall. On light microscopic examination, the left ventricular myocardium revealed diffusely scattered muscular degeneration interlaced with fibrosis. Although large epicardial coronary arteries revealed only mild intimal atheromatous thickening, most of the small intramuscular coronary arteries were free from atherosclerosis. Neither diabetic nor amyloid lesions could be detected. It has been well known that cardiomyopathy is often associated with various forms of muscular dystrophy and Friedreich's ataxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy↗

Enhancement of an anti-tumor effect of interferon by dipyridamole in established human malignant melanoma cell lines.

Enhancement of the anti-proliferative effect of human interferon (HuIFN) preparations (alpha, beta and gamma) by dipyridamole was detected in a human malignant melanoma cell line, MM-ICB, which we originally established. Cell growth was inhibited by HuIFN alone, but a marked increase in inhibition was noted in vitro and in vivo when dipyrydamole was added. Cellular DNA synthesis, as determined by 3H-deoxythymidine incorporation into the acid-insoluble cellular fraction, was more inhibited by combined treatment than by any of the agents used alone. Two other melanoma cell lines that we established, MM-2CB and MM-3CB, also exhibited sensitivity to combined treatment both in vitro and in vivo. Furthermore, the HMV-I and SEKI melanoma cell lines were susceptible to the combination. Even non-cytotoxic concentrations of dipyridamole could enhance the effect of HuIFN on MM-ICB, MM-2CB, and SEKI cells.

Aged↗