Induction of cell differentiation by IMPDH antisense oligomer in HL-60 and K562 human leukemia cell lines.
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Base Sequence↗
Biomedical subjects
K Inai
Publications and source records attributed to K Inai.
Duplication polymorphism within the third intron of the p53 gene is a rare event in Japanese population.
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Alleles↗
Alteration in length of telomeric repeats in lung cancer.
We investigated the relationship between telomere length and various characteristics of tumor cells in 46 lung cancer specimens (40 primary lesions and six metastatic lesions). Three variant patterns of telomere length were observed in 16 cases (34.8%): reduction in 13 cases, elongation in two cases, and convergence in one case. These variant patterns were frequently observed in small cell carcinomas, in metastatic lesions, and in cases which possessed the S-type allele of the L-myc gene. All three cases with telomere elongation or convergence were associated with a poor prognosis. This is compatible with the previous report suggesting that telomerase activity may be an indicator of immortality in vitro. In adenocarcinoma, telomere reduction or elongation was also observed in the early stages with a low percentage of cells in the S-phase, while in cases with other histologic types, these changes were observed only in late stage, in metastatic lesions, or in cancerous tissues with a high percentage of cells in the S-phase. Although the reduction of telomere length in these tissues may be a result of many cell divisions, it may represent another stage of carcinogenesis in early-stage adenocarcinoma.
Aged↗
Tumorigenicity study of ferric citrate administered orally to mice.
Ferric citrate (FC) was orally administered at concentrations of 0.12 (maximum tolerated dose) or 0.06% in the drinking water to male and female B6C3F1 mice. Treatment was continued for 96 wk and the experiment was terminated at wk 100. There was no significant difference between treated and control groups in the tumour incidence or in the distribution of different types of tumour. Thus the long-term oral administration of FC to mice did not yield any evidence of chronic toxicity or tumorigenicity.
Administration, Oral↗
p53 mutations in lung cancers from Japanese mustard gas workers.
Mustard gas (MG) is a mutagenic and carcinogenic alkylating agent, and is a known risk factor for occupational lung cancer. Our hypothesis is that lung cancers from MG workers contain mutations (G:C to A:T transitions) as the result of MG-produced DNA promutagenic adducts in the p53 tumor suppressor gene. We analyzed 12 primary lung cancers from Japanese MG factory workers and 12 lung cancers from non-exposed individuals. Genomic DNA was isolated from archival paraffin-embedded tissues. Exons 5-8 were amplified by polymerase chain reaction using p53-specific primers, and sequenced by dideoxy termination methods. Six out of 12 lung cancers from MG workers contained a total of eight somatic point mutations: two cases had double G:C to A:T transitions; one had a G:C to T:A transversion; one case had an A:T to G:C transition; and two cases had single base deletions. Four of the six mutated purines occurred on the non-transcribed, DNA-coding strand. Out of 12 unexposed cases, there were six single base mutations in six cancers, and no double mutations. The p53 mutational frequency in the MG-exposed cases is similar to the non-exposed controls and the usual smoking-related lung cancers reported previously. However, the distinctive double mutations (G:C to A:T transition) observed in two cases are unusual and may be related to MG exposure.
Aged↗
[Carboplatin treatment by continuous infusion in combination for relapsed and refractory acute myeloid leukemia].
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Adult↗
Primary squamous cell carcinoma of the breast after cured Hodgkin's disease.
An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.
Adult↗
A case of Sturge-Weber syndrome with peculiar venous abnormalities.
A case of Sturge-Weber syndrome with poor filling of the deep cerebral venous system is reported. Usually in this syndrome, enlargement of the internal cerebral, basal Rosenthal, deep medullary, and subependymal veins is revealed by angiography. The abnormality of the deep cerebral venous system in this case corresponded to diffuse faint calcification of the right parietal parenchyma. This was accompanied by venous angioma in the left cerebellar hemisphere and poor filling of the left cerebellar veins-findings which are rare in this syndrome. Occlusion or maldevelopment of the cerebral venous system in the prenatal period may be one possible etiological cause of these venous abnormalities.
Calcinosis↗
Loss of VLA-2 collagen receptor in breast carcinoma, facilitating invasion and metastasis.
The integrin VLA-2 as a collagen receptor and VLA-5 as a fibronectin receptor were detected immunohistochemically in normal, benign tumor and carcinoma tissues of the breast. Both proteins were also detected by Western-blot analysis in some carcinoma cases. Epithelial and myoepithelial cells of both normal breast and benign tumor were in all cases immunoreactive for VLA-2 in the plasma membrane. Carcinoma cells in the invasive component were not immunoreactive for VLA-2 in 31 (46%) of 67 cases. Carcinoma cells in the intraductal components were negative for VLA-2 in only 4 (11%) of 36 cases, while 20 cases (56%) showed weak expression and 12 cases (33%) showed strong expression. Metastatic carcinoma cells in the lymph nodes of 6 cases showed no immunoreactivity except in one case, whereas, again with the exception of one case, the carcinoma cells in the primary tumors did show VLA-2 expression. With regard to VLA-5, there was no difference in its expression in the invasive components and the intraductal components. These findings suggest that the loss of VLA-2 plays a role in the invasion and metastasis of breast carcinoma.
Adult↗
A role of VLA-6 laminin receptor in invasion of breast carcinoma.
The integrin VLA-6 as a laminin receptor and laminin as a ligand for laminin receptor were detected immunohistochemically in normal, benign tumor and carcinoma tissues of the breast. Epithelial cells of both normal breast and benign tumor were in almost all cases strongly immunoreactive for VLA-6 in the plasma membrane. Carcinoma cells in 34 of 70 cases (49%) with an invasive component were not immunoreactive for VLA-6, and no carcinoma cells showed strong positivity. Although carcinoma cells in only four of 51 cases (8%) with intraductal components were negative for VLA-6, 37 cases (72%) showed weak expression of VLA-6 and 10 cases (20%) showed strong expression of VLA-6. A concordant expression of VLA-6 on carcinoma cells and laminin around carcinoma cell nests with an invasive component was observed, and VLA-6 expression in carcinoma cells was correlated to tubular formation in carcinoma cell nests as an indicator of differentiation. These findings suggest that loss of VLA-6 plays a role in the invasion of breast carcinoma, and that VLA-6 laminin receptor and laminin may contribute to tubular differentiation of breast carcinoma cells.
Breast Diseases↗
Distribution of laminin, type IV collagen and fibronectin in the invasive component of breast carcinoma.
Laminin, type IV collagen and fibronectin were examined immunohistochemically in the invasive component of breast carcinomas. Laminin was expressed around the invasive carcinoma cell nests in 38 (54%) of 71 cases. Immunoreactivity for type IV collagen was observed around the invasive carcinoma cell nests or the stroma apart from carcinoma cells in 44 (80%) of 55 cases. Fibronectin was strongly expressed in the stroma only in 75 (99%) of 76 cases. The expression of laminin significantly correlated with tubular formation in the invasive carcinoma cell nests and showed a tendency to be correlative to estrogen receptor (ER) and progesterone receptor (PgR) of carcinoma tissue, but no correlation among laminin expression, histological type, the age of patients, tumor size and lymph node metastasis was noted. Type IV collagen and fibronectin did not correlate to any clinicopathological factors such as histological type, grade of differentiation, the age of patients, tumor size, lymph node metastasis, ER and PgR status. No concordant expression of these extracellular matrices was seen.
Breast Neoplasms↗
Myxoma of the breast: report of a case with unique histological and immunohistochemical appearances.
A case of myxoma of the breast is reported. The patient, a 19 year old Japanese woman, showed a lump in the left breast which had enlarged gradually over 3 years. A tumor measuring 5 x 5 x 4.5 cm was located mainly in the mammary parenchyma, but partially involved the overlying subcutaneous tissue. Histologically the tumor was multinodular and each nodule consisted of an abundant myxoid substance with a few spindle or stellate mesenchymal cells. The presence of hyaluronic acid was observed in the myxoid area, and a few constituent cells showed immunoreactivities for S-100 protein and alpha 1-antichymotrypsin. Electron microscopic studies revealed that some constituent cells looked like undifferentiated mesenchymal cells, while others showed a differentiation similar to fibroblast or histiocyte. These findings suggest that the constituent cells might derive from totipotential primitive mesenchymal cells.
Adult↗
Malignant astrocytoma with extracranial metastases: a case report.
A 41-year-old man was referred to this hospital after being diagnosed as suffering from malignant astrocytoma. In spite of two operations and subsequent chemoradiation therapy, the patient died 20 months after the onset of disease. At autopsy, the authors found skin invasion of tumor at left temporal region, softening of the brain and subarachnoid hemorrhage at the base of the brain. Yellowish-white bulging lesions were found at the bottom of left lung, diaphragm and parietal pleura. Histologically, primary lesion showed features of anaplastic malignant astrocytoma. Subarachnoid dissemination was noted at the base of the brain and in the spinal canal. Invasion into the vessels were observed both at the primary site and at the base of the brain. Glial fibrillary acidic protein positive spindle-shaped tumor cells proliferation was seen in the metastatic lesions. This case was diagnosed as malignant astrocytoma with remote extracranial metastases.
Adult↗
Epithelial hyperplasia of the breast. Comparison of incidence between cases of breast carcinoma and control autopsy specimens with immunohistochemical observation of blood group antigens.
Epithelial hyperplasia in the duct, ductule or lobule of the breast is a very common lesion and has been considered to carry a risk of subsequent invasive carcinoma. However, it is not known whether epithelial hyperplasia can transform into carcinoma or whether malignant change occurs de novo. We analyzed the incidence of epithelial hyperplasia of the breast by making a comparison between cases of breast carcinoma and control autopsy specimens, and studied differences in the membrane antigens of the constituent cells using immunohistochemical staining of blood group antigens. It was found that the frequency of epithelial hyperplasia was higher in the cases of breast carcinoma. The lesions showed loss of A, B and H antigens at high frequency, and the proportion of lesions showing loss of these antigens became higher as the atypia of the lesion increased. On the other hand, expression of Lea antigen was observed more frequently in atypical epithelial hyperplasia or in situ carcinoma than in ordinary epithelial hyperplasia. These findings suggest possible transformation from epithelial hyperplasia to carcinoma, and indicate that atypical epithelial hyperplasia may be precancerous in nature.
Adolescent↗
Ovarian sex cord tumor with annular tubules--a case report and review of the literature in Japanese.
A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 41-year-old female is reported. The patient's chief complaint was menstrual irregularity, but the serum values of estradiol and testosterone were not elevated. On gross examination, the left ovary measured 8 x 7 x 6 cm in size and its cut surface was yellowish gray or yellow and solid with no cystic area. Histologically, the tumor was composed of simple and complex annular tubules, lined by columnar cells containing abundant lipid droplets. Eosinophilic materials in the center of the annular tubules were continuous with the basement membrane in the periphery, and showed immunoreactivity for type IV collagen. Also, hollow tubules, consisting of columnar cells with a truncated luminal surface and elongated trabeculae, composed of columnar cells with clear cytoplasm, were noted. These structures were reminiscent of Sertoli cell tumor. Based on these histological observations, it appears that SCTAT is a sex cord/stromal tumor made up of cells with differentiation in the direction of Sertoli cells rather than granulosa cells.
Adult↗
Elastosis in breast--correlation with epithelial proliferation in benign disease and carcinomatous growth.
Elastosis in the breast is an unusual phenomenon and its morphogenesis has not yet been fully ascertained. The degree of elastosis in the breast associated with benign diseases, including fibroadenoma and fibrocystic disease as well as with breast carcinoma, was examined with special reference to the correlation between the degree of epithelial proliferation and elastosis. Using the immunohistochemical method, the presence of elastase (EL) and alpha 1-antichymotrypsin (ACT), one of the protease inhibitors, in these epithelial cells was also investigated to elucidate the role of an imbalance in these enzymes in the morphogenesis of the elastosis. Consequently, it was shown that there is a tendency in fibroadenoma and fibrocystic disease, for epithelial proliferation to be related to the degree of elastosis, and that the lack of EL in proliferated epithelial cells might play a role in the occurrence of elastosis, although ACT has no significant correlation. On the contrary, in our study noninvasive carcinoma showed marked periductal elastosis but no stromal elastosis, while invasive carcinoma showed various degrees of periductal and stromal elastosis. In invasive carcinoma, especially scirrhous carcinoma, the degree of ACT in cancer cells correlated well with stromal elastosis, although there was no correlation with EL. These findings suggest that an imbalance of the protease-antiprotease system, produced by epithelial cells of the breast, contribute to the morphogenesis of elastosis, although the physiological event, aging, is only marginally related to elastosis. Further investigation of the cells producing elastin and regulatory factors may be necessary.
Adult↗
Quantitative risk assessment of carcinogenicity of urethane (ethyl carbamate) on the basis of long-term oral administration to B6C3F1 mice.
A carcinogenicity study of urethane was performed for quantitative assessment of its risk in humans. Three hundred 6-week-old male B6C3F1 mice were divided into 6 groups, each consisting of 50 mice, and urethane was given ad libitum in drinking water at levels of 0 (control), 0.6, 3, 6, 60 and 600 ppm for 70 weeks. The tumors with a clear dose-response relationship were lung tumor (alveolar/bronchiolar adenoma or carcinoma) and liver tumor (hemangioma or angiosarcoma). The incidences of these two types of tumor were applied to estimation of the virtually safe dose (VSD) at the level of 10(-6) by using four mathematical models (Logit, Probit, Weibull and Multistage models). The VSD based on the incidences of lung tumor by using the Logit model was estimated to be 1.8 x 10(-4) mg/kg body weight/day. On the other hand the VSD based on those of liver tumor by using the Weibull model was 7.2 x 10(-5) mg/kg body weight/day. Thus, the VSDs based on the incidences of the two different types of tumor using the most compatible mathematical model in each case, as judged from the P-values, were similar.
Adenoma↗
Malignant islet cell tumor of the pancreas with multiple hormone production and expression of CEA and CA19-9. Report of an autopsy case.
An autopsy case of malignant islet cell tumor of the pancreas is presented. The patient, a 64-year-old woman showed severe hypoglycemia as the initial symptom, and hyperinsulinemia was demonstrated by laboratory examinations. Metastatic tumors in the liver were found by abdominal computed tomography. Autopsy revealed a tumor measuring 6.5 x 3 x 2 cm occupying the pancreas from the body to the tail. From the results of histological and immunohistochemical studies, this was diagnosed as a malignant islet cell tumor producing multiple hormones such as insulin, glucagon, somatostatin and pancreatic polypeptide, as well as expressing the tumor-related antigens CEA and CA19-9. These findings suggested that the tumor cells showed differentiation to both endocrine cells and pancreatic duct cells.
Adenoma, Islet Cell↗