[Analysis of genomic alterations in neoplastic tumors by CGH and SKY].
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Chromosome Aberrations↗
Biomedical subjects
T Sakakura
Publications and source records attributed to T Sakakura.
Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine immunohistochemical detection of C3H strain-specific antigen and simple sequence length polymorphism analysis of DNA.
To determine the clonality and cellular origin of colon pre-neoplastic and neoplastic lesions, C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine (DMH) were investigated immunohistochemically using a specific antibody to C3H strain-specific antigen (CSA) enabling immunohistochemical discrimination of C3H cells in histological sections of chimeric mouse tissues. To confirm the results of immunostaining, simple sequence length polymorphism (SSLP) analysis was performed on DNA samples extracted from histological sections of adenocarcinomas. C3H/HeN<-->BALB/c chimeric mice were produced by an aggregation procedure and together with BALB/c and C3H/HeN animals were given weekly s.c. injections of 20 mg/kg body weight DMH for up to 20 weeks. At weeks 20 and 35 animals were killed and autopsied. In normal colonic mucosa of the chimeras, each gland was composed entirely of either CSA-positive or -negative cells and no mixed glands were found. Cells of all focal atypias in chimeric mice were, in each case, homogeneous for one or another of the parental types. Of 91 adenomas in chimeric mice, only one comprised both types of cell. Among 119 adenocarcinomas, 12 contained cells of both parental types. In these tumors, however, the 2 phenotypes were not mixed together at random but arranged in discrete areas, with intermingling limited to the junctions. SSLP analysis demonstrated DNAs extracted from CSA-positive and -negative tumors to exhibit the polymorphic patterns of C3H and BALB/c, respectively, while mixed CSA-positive and -negative tumors showed mixtures of both polymorphic DNA types.
1,2-Dimethylhydrazine↗
Overexpression of different members of the type 1 growth factor receptor family and their association with cell proliferation in periampullary carcinoma.
The expression of epidermal growth factor receptor (EGFR), c-erbB-2, and c-erbB-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type I growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c-erbB-3 was significantly higher than with overexpression of c-erbB-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c-erbB-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c-erbB-3 in pancreatic head carcinoma and overexpression of c-erbB-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c-erb-3 in pancreatic head carcinoma, c-erb-2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type I growth factor receptor family are overexpressed in different carcinomas of the periampullary region.
Adenocarcinoma↗
Deposition of PG-M/versican is a major cause of human coronary restenosis after percutaneous transluminal coronary angioplasty.
To clarify the mechanisms of restenosis, restenotic human tissue specimens obtained by directional coronary atherectomy (DCA) in 43 patients were immunohistochemically analysed for cell proliferation and deposition of PG-M/versican, an important extracellular matrix proteoglycan of the vessel wall. The patients were classified into five groups according to the period after percutaneous transluminal coronary angioplasty (PTCA): 0-1 month (N = 6), 1-3 months (N = 12), 3-6 months (N = 11), more than 6 months (N = 6) and de novo lesions (N = 8). The tissue specimens were of 35 restenotic lesions following PTCA and eight primary stenotic lesions with no prior PTCA. Total cell numbers in the atherectomy specimens increased significantly up to 3 months after PTCA. Most cells were alpha-smooth muscle actin (alpha-SMA)-positive. To evaluate cell proliferation, the specimens were immunostained for Ki-67 antigen (clone MIB-1). A significant increase in the positive ratio was observed up to 1 month after PTCA, although the labelling index was less than 1 per cent at every stage. The deposition of PG-M/versican, as analysed by immunohistochemistry, was greatest during the period 1-3 months after primary angioplasty, when restenosis detected by angiography progresses most actively. These results suggest that the peak of cell proliferation in the neointima occurs earlier than angiographic restenosis and that the deposition of PG-M/versican may be a major factor in restenosis following angioplasty.
Aged↗
An immunohistochemical and in situ hybridization study of the expression of tenascin in synovial membranes from human temporomandibular joints with internal derangement.
In samples of 27 human temporomandibular joints (internal derangement, ankylosis and control specimens) the distribution of immunoreactive tenascin was restricted to the walls of blood vessels, at the perineurium, and at the surface of the disc. Tenascin staining was intense in the stroma of hypertrophic synovial membranes, particularly on the surface of severely hypertrophic synovial membranes with inflammation, proliferation, irregular lining structures and new capillary growth. In situ hybridization of fresh discs and synovial membranes demonstrated that synovial cells as well as fibroblasts and endothelial cells expressed tenascin mRNA. The expression of tenascin mRNA was most evident in synovial cells. It is concluded that synovial cells in the synovial membrane produce tenascin in the diseased human temporomandibular joint.
Adult↗
Combined analysis of expression of c-erbB-2, Ki-67 antigen, and tenascin provides a better prognostic indicator of carcinoma of the papilla of Vater.
Expression of the molecular biological factors (MBFs) c-erbB-2, Ki-67 antigen, and tenascin (TN) was assessed immunohistochemically in specimens from patients who had undergone surgery for carcinoma of the papilla of Vater. The MBFs were then analyzed by histological factors (v, d, panc, n, Stage), which have been demonstrated to be outcome predictors, and by patient outcome. None of the MBFs showed any significant correlation with the histological factors. There were significant differences (p < 0.05) in the expression of c-erbB-2, Ki-67 antigen, and TN between patients who survived >5 years and those who survived <5 years. The patients with greater expression of c-erbB-2, Ki-67 antigen, and TN had a poor prognosis, whereas those with less expression had a good prognosis. They were therefore considered independent predictors of outcome for carcinoma of the papilla of Vater. Combined analysis of both histological factors and MBFs was also performed, with the result that the combined analysis of MBFs yielded a better prediction of outcome in carcinoma of the papilla of Vater than analysis of either one histological factor or MBF.
Adult↗
[Chyluria treated with stripping of the renal pedicle: a case report].
A 54-year-old male was referred to our outpatient clinic because of milky urine. He had lived in Kumamoto, an area of endemic filariasis. There were no microfilaria found in his blood smear. Lymphangiography showed dilation of the retroperitoneal lymphatics and bilateral renal refluxes. The thoracic duct was obvious. The initial treatment consisted of irrigating the bilateral renal pelvis with silver nitrate solution, but was not successful and recurrent acute urinary retention developed. Therefore, we performed stripping and ligation of the bilateral renal lymphatics. Chyluria disappeared immediately after surgery. The etiology and various treatments for chyluria are discussed.
Chyle↗
[A case of oligozoospermia with marginal hyperprolactinemia due to pituitary microadenoma].
We present an infertility male with prolactin level of 37.5 ng/ml. The patient had pituitary microadenoma detected by Gd-DTPA enhanced magnetic resonance imaging (MRI). After bromocriptine was administrated for 4 months, the size of microadenoma decreased, and sperm density and mortality improved. His wife became pregnant after 6 months. Dynamic MRI is a useful modality for detection of pituitary microadenoma, and bromocriptine is also useful for treatment of oligospermic patients with marginal hyperprolactinemia.
Adenoma↗
Tenascin in breast cancer development--is epithelial tenascin a marker for poor prognosis?
(1) In mouse mammary gland development, immunoreactive tenascin (TN) is expressed in the dense mesenchyme surrounding the epithelial component of 14-day embryos, endbuds at puberty, and tumors. (2) Cells that produce TN are myofibroblastic and are characterized by nuclear invaginations, rough endoplasmic reticulum, and pinocytotic vesicles. These cells are not normally present in the stroma of mammary glands but present in cancer stroma, originating probably from fibroblasts differentiated under the influence of TGF-beta 1 stimulation. (3) Breast cancer cells are capable of synthesing TN under certain conditions. TN-non-producing MCF7 cells can produce TN when co-cultured with embryonic fibroblasts or with their conditioned medium. (4) Nine primary human breast cancers were examined for TN expression by in situ hybridization. TN mRNA was expressed in all nine cases in the stroma and in four cases in carcinoma cells as well. (5) Immunohistochemistry for TN was performed in human breast cancers, and it was found that the five-year survival after surgery was markedly lower in the group whose cancer cells were positive [corrected] for TN. TN expression in cancer cells appears to indicate poor prognosis.
Biomarkers, Tumor↗
Nodular scleroderma: focally increased tenascin expression differing from that in the surrounding scleroderma skin.
Nodular scleroderma is a rare variant of the disease, whose pathogenesis is uncertain. Tenascin is a recently cloned extracellular matrix protein which is thought to be a marker for tissue remodelling. To further investigate the pathogenesis of nodular scleroderma, we have followed up a case of this disease and studied tenascin expression in the nodular lesions and surrounding progressive systemic sclerosis skin. Previously, we demonstrated a long-lasting intermediate level of dermal tenascin expression in progressive systemic sclerosis; morphea and hypertrophic scar lesions showed strong but short-lived tenascin expression. In our current patient, high levels of tenascin were found in the nodules, which rapidly resolved. Thus, the time course of the clinical and histopathological findings together with the tenascin expression were more suggestive of hypertrophic scar than progressive systemic sclerosis. These findings imply that nodular scleroderma has a supplementary pathogenesis, such as itching, in addition to the proceeding systemic sclerosis.
Adult↗
Generation of 28 sequence-tagged sites (STSs) from yeast artificial chromosome (YAC) clones anchored at human chromosome 21q22.1 region.
Twenty-eight sequence-tagged sites (STSs) were newly generated from the DNA sequences of vector-insert junctions from yeast artificial chromosomes (YACs) anchored at chromosome 21q22.1 region. The insert DNAs adjacent to vector arms were specifically amplified through inverse PCR method to clone into pUC19 vector for sequencing. Sixty DNA junctions from 44 CEPH YAC clones were cloned and sequenced. Of these DNA sequences of junctions between vector-arms and DNA inserts, twenty-eight STSs were finally obtained to show the accurate amplification, which is specific for human chromosome 21. The sets of 28 STSs were useful to build fine YAC contigs by STS-mediated YAC walking at the 21q22.1 region.
Animals↗
[Radiological diagnosis of renal oncocytoma].
Eight patients (nine tumors) with histologically proven renal oncocytoma are presented. In all cases, differential diagnosis between renal oncocytoma and renal cell carcinoma could not be done on ultrasonography. On selective renal angiography, extended arteries surrounding the tumor margin was demonstrated in six of seven tumors without a spoke-wheel arterial supply. A sharp and smooth margin with capsule (lucent rim) could be found in five cases, and a spoke-wheel configuration of vessels could be seen in only two cases. A spoke-wheel pattern might be found with tumor growth. All tumors on computed tomography (CT scan) have a distinct margin, a smooth contour and a homogeneous appearance on contrast enhanced CT scan. The capsule and the presence of a central scar were clearly seen on T1 and T2 weighted images of magnetic resonance imaging (MRI). It is helpful to differentiate the oncocytoma from renal cell carcinoma. The modality of MRI may be useful in the preoperative diagnosis of oncocytoma.
Adenoma, Oxyphilic↗
Tenascin expression in cancer cells and stroma of human breast cancer and its prognostic significance.
Sections of formalin-fixed, paraffin-embedded tissues from 210 human breast cancers were immunohistochemically examined using the mAb against human tenascin (TN) RCB1. Immunoreactive TN was detected in the breast cancer stroma in 77 (36.7%) cases, whereas the remaining 133 (63.3%) were negative. Of the 77, 12 (5.7%) cases also showed positive staining in the carcinoma cell cytoplasm. The positive cells were often observed in the margin of the cancer nests at the site adjacent to the stroma. According to the staining pattern of TN, the breast cancer cases were classified into the three groups of cancer cell TN(+)/stromal TN(+), cancer cell(-)/stromal TN(+), and cancer cell(-)/stromal TN(-). Analysis of the relationship of these TN patterns with various clinicopathological characteristics of the tumors and the patient outcome revealed that, in comparison to the cancer cell(-)/stromal TN(-) group, the cancer cell TN(+)/stromal TN(+) group exhibited increased frequency of lymph node metastasis and exceptionally poor outcome, and the cancer cell(-)/stromal TN(+) group also showed more frequent metastasis and poorer outcome. Most of the cancer cell TN(+)/stromal TN(+) cases were c-erbB-2 positive and estrogen receptor negative. Furthermore, in situ hybridization of freshly obtained breast cancer tissues demonstrated that both cancer cells and stromal cells express TN mRNA. These results indicate that the TN in breast cancer is produced by cancer epithelial cells as well as by stromal mesenchymal cells, and that cancer cell TN might be involved in cancer spreading, resulting in unfavorable patient prognosis.
Adult↗
Susceptibility of tenascin to degradation by matrix metalloproteinases and serine proteinases.
The degradation of tenascin purified from human melanoma cells was examined by treatment with matrix metalloproteinases (MMPs) and serine proteinases. Among eight different types of proteinases examined, MMP-1, -3, and -7, cathepsin G and leukocyte elastase could digest tenascin, but MMP-2, MMP-9 and thrombin did not. This suggests that tenascin may be readily catabolized by extracellular matrix-degrading proteinases found in the pathophysiological conditions.
Cathepsin G↗
Clonal analysis of glandular stomach carcinogenesis in C3H/HeN<==>BALB/c chimeric mice treated with N-methyl-N-nitrosourea.
The clonal growth of gastric carcinomas was investigated immunohistochemically in C3H<==>BALB/c chimeras using a strain specific antibody. C3H, BALB/c and chimeric mice were given N-methyl-N-nitrosourea 0.5 mg/mice once a week for a total of 10 times by intragastric intubation and observed until week 50. In normal gastric mucosa of the chimeras, each gland was composed entirely of C3H strain specific antigen (CSA)-positive or -negative cells and no mixed glands were found. Cells of all adenomatous hyperplasias and adenocarcinomas in chimeric mice were, in each case, homogeneous for one or other of the parental types, while comprising both surface mucous cell and pyloric gland cell forms. The results clearly suggest that individual cancers are derived from single cells with multi-potential activities and that cellular differentiation of gastric cancer cells occurs secondarily.
Adenocarcinoma↗
The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C.
We have isolated a cDNA encoding mouse tenascin-X (TN-X), a new member of the family of tenascin genes. The TN-X gene lies in the major histocompatibility complex (MHC) class III region, as it is the case for its human counterpart. On Northern blots we detected a TN-X mRNA of approximately 13 kb in most tissues analyzed, whereas in various mouse cell lines mRNAs of approximately 11 and 13 kb were detected, suggesting the possibility of alternative splicing of TN-X transcripts. We raised antibodies against mouse TN-X fragments expressed in bacteria and used these antibodies to identify the TN-X protein in heart cell extracts and in the conditioned medium of a renal carcinoma cell line. The subunit molecular size of TN-X is approximately 500 kD, suggesting that the protein may contain up to 40 fibronectin type III repeats, making it the largest tenascin family member known yet. TN-X in conditioned medium, as well as the purified protein bind to heparin, but no binding to tenascin-C (TN-C), fibronectin, laminin or collagens could be detected. Thus the heparin-binding activity may be a common feature of the tenascins. The TN-X mRNA as well as the protein are predominantly expressed in heart and skeletal muscle, but the mRNA is found in most tissues at a low level. Immunostaining showed the protein to be associated with the extracellular matrix of the muscle tissues and with blood vessels in all of the tissues analyzed. Although the TN-X gene lies in the MHC class III locus, it is not expressed in the lymphoid organs analyzed, except for the staining around blood vessels. In skin and tissues of the digestive tract often a reciprocal distribution of TN-X and TN-C was observed.
Amino Acid Sequence↗
Sarcomatoid carcinoma of the urinary tract.
Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation. Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematuria. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors with myxoid stroma or malignant fibrous histiocytoma-like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical and/or electron-microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months' follow-up, respectively, constant careful monitoring is recommended.
Aged↗
[Clinical evaluation of intracavernous self-injection of vasoactive drugs for impotence: a long-term follow-up observation].
From December 1989 to September 1992, nine patients with impotence were instructed to perform intracavernous self-injection of vasoactive drugs. At first 40 mg of papaverine hydrochloride was used in all patients and the response on erection was evaluated. If the response did not show sufficiently functional erection, a mixture of 40 mg of papaverine hydrochloride and 1 mg of phentolamine mesylate or 20 mg of prostaglandin E1 was reinjected. Eight patients had achieved full erections and vaginal penetrations without noteworthy complications during the follow-up period. Out of eight patients, three patients were able to ejaculate and one patient showed recovery of erection. No major side effects were seen. In conclusion, intracavernous self-injection is a useful modality for impotence.
Adult↗