Mature cystic teratoma of the pouch of Douglas containing multiple mobile spherules.
Explore the source record for details and available documents.
Dermoid Cyst↗
Biomedical subjects
K Kiguchi
Publications and source records attributed to K Kiguchi.
Reexamination of phenoloxidase in larval circulating hemocytes of the silkworm, Bombyx mori.
We have developed a modified method to detect phenoloxidase activity on hemocytes by using freshly prepared l-DOPA (1 mg/ml in 35% ethanol) to fix and incubate larval hemocytes. This method is more sensitive than the common method, in which hemocytes were fixed in 4% formaldehyde and then incubated with 2 mg/ml l-DOPA in water separately. Phenoloxidase assayed using this modified method can be inhibited by phenyltiourea (phenoloxidase inhibitor). After incubation with l-DOPA solution in ethanol, most prohemocytes, all plasmatocytes and young granulocytes are stained brown due to oxidation of l-DOPA into pigments, indicating that they have phenoloxidase. Oenocytoids are dimly stained because many of their cell inclusions have been released during the treatment. Large propidium-iodide-negative prohemocytes have strong phenoloxidase activity and are easily misunderstood as propidium-iodide-positive oenocytoids if the fluorescent method is not used for identification. Thus, in addition to oenocytoids and plasmatocytes, some prohemocytes and granulocytes in the silkworm also have phenoloxidase.
Animals↗
Establishment and characterization of two cell lines (HEC-155, HEC-180) derived from uterine papillary serous adenocarcinoma.
Uterine papillary serous adenocarcinoma (UPSC) is an uncommon histologic subtype of endometrial cancer that characteristically behaves aggressively with a poor prognosis. We established two novel cell lines derived from UPSC designated HEC-155 and HEC-180. Both cell lines have been growing steadily in monolayer cultures for over ten years. Overexpression of p53, Ki67 and p27 was detected in both cell lines by immunohistochemistry. Using a DNA sequencing technique, a point mutation of p53 was detected in exon 8, codon 286 in HEC-155 and in exon 6, codon 195 in HEC-180. These newly established cell lines should be useful for investigating the characteristics of UPSC.
Biopsy, Needle↗
WWOX, the FRA16D gene, behaves as a suppressor of tumor growth.
We recently reported the cloning of WWOX, a gene that maps to the common fragile site FRA16D region in chromosome 16q23.3-24.1. It was observed that the genomic area spanned by WWOX is affected by chromosomal translocations and homozygous deletions. Furthermore, the high incidence of allelic loss in breast, ovarian, prostate, and other cancers affecting this region suggests that WWOX is a candidate tumor suppressor gene. Expression of WWOX is highly variable in breast cancer cell lines, with some cases showing low or undetectable levels of expression. In this report, we demonstrate that ectopic WWOX expression strongly inhibits anchorage-independent growth in soft agar of breast cancer cell lines MDA-MB-435 and T47D. Additionally, we observed that WWOX induces a dramatic inhibition of tumorigenicity of MDA-MB-435 breast cancer cells when tested in vivo. We also detected the common occurrence of aberrant WWOX transcripts with deletions of exons 5-8 or 6-8 in various carcinoma cell lines, multiple myeloma cell lines, and primary breast tumors. These aberrant mRNA forms were not detected in normal tissues. Interestingly, we further observed that proteins encoded by such aberrant transcripts display an abnormal nuclear localization in contrast to the wild-type WWOX protein that localizes to the Golgi system. Our data indicate that WWOX behaves as a potent suppressor of tumor growth and suggest that abnormalities affecting this gene at the genomic and transcriptional level may be of relevance in carcinogenesis.
Alternative Splicing↗
Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma.
Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma in 100% of transgenic mice by 3 months of age. In addition, tumors developed in other parts of the biliary tree (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder appeared to arise via a stepwise process involving hyperplasia, adenoma formation, and then adenocarcinoma formation. Increased ErbB-2/epidermal growth factor receptor heterodimer formation, activation of mitogen-activated protein kinase, and up-regulation of cyclooxygenase-2 levels (mRNA and protein) were observed in gallbladder epithelium of these mice. These mice represent a unique new animal model for studying biliary tract carcinogenesis.
Adenocarcinoma↗
Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene.
The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease (ADPKD), the most common human genetic disorder. Rats with a germline inactivation of one allele of the Tsc2 tumor suppressor gene developed early onset severe bilateral polycystic kidney disease, with similarities to the human contiguous gene syndrome caused by germline codeletion of PKD1 and TSC2 genes. Polycystic rat renal cells retained two normal Pkd1 alleles but were null for Tsc2 and exhibited loss of lateral membrane-localized polycystin-1. In tuberin-deficient cells, intracellular trafficking of polycystin-1 was disrupted, resulting in sequestration of polycystin-1 within the Golgi and reexpression of Tsc2 restored correct polycystin-1 membrane localization. These data identify tuberin as a determinant of polycystin-1 functional localization and, potentially, ADPKD severity.
Alleles↗
Absolute configuration of (6S,9S)-roseoside from Polygonum hydropiper.
From Polygonum hydropiper L., a C13-norisoprenoid glucoside was isolated and its absolute configuration was established to be (6S,9S)-roseoside (1) by spectroscopic evidence and X-ray crystallographic analysis of its acetate derivative (2). In addition, the stereostructure of roseoside from Canthium subcordatum was revised to the (6S,9S) configuration.
Glucosides↗
New approach for the establishment of mouse early embryonic stem cells and induction of their differentiation.
Eleven early embryonic stem (EES) cell lines were established using a new novel method. Two cell stage embryos from the ddY mouse strain were cultured in alpha-MEM supplemented with 10% fetal calf serum (FCS) and embryotrophic factors (ETFs) and allowed to develop to the trilaminal germ disc embryonic stage. Only small round cells (EES cells) were isolated by the colony isolating technique and subsequently cultured in the same medium containing the ETFs and leukemia inhibitory factors (LIF-10 ng/ml). The newly established embryonic stem (ES) cells isolated from inner cell mass of blastocysts differentiated from two cell stage embryo in culture. The EES and ES cell lines were maintained in an undifferentiated state using Ham's F12 medium supplemented with 10% FCS and 1 ng/ml of LIF. The EES cells maintained their normal genetic and morphological features as well as their potential to differentiate into a broad spectrum of cell types as well as their ability to contribute to all cell lineages in chimeric mice. Moreover, these cell lines changed and differentiated into various kinds of cells by removing LIF and by the addition of ETFs to the vitro culture system. All 11 EES cell lines and 3 ES cell lines formed embryoid bodies; however, cell line EES-4 formed tube-like structures which extended, anastomosed with each other, and finally formed networks when the LIF were absent. Primitive germ organ-like structures composed of 3 germ layers were recognized in the cultures following the administration of ETFs. In conclusion, the new method devised by us is a novel, easy and reliable technique for establishing EES cell lines.
Animals↗
Constitutive expression of erbB2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development.
The erbB family of receptor tyrosine kinases, which consists of the epidermal growth factor receptor (EGFr/erbB1), erbB2 (neu), erbB3 and erbB4, has been shown to be important for both normal development as well as neoplasia. The expression of rat erbB2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter. Overexpression of wild type rat erbB2 in the basal layer of epidermis led to alopecia, follicular hyperplasia and sebaceous gland enlargement as well as hyperplasia of the interfollicular epidermis. Spontaneous papillomas, some of which converted to squamous cell carcinomas, arose in homozygous erbB2 transgenic mice as early as 6 weeks of age with >90% incidence by 6 months. Analysis of several proliferation/differentiation markers indicated that erbB2 overexpression led to epidermal hyperproliferation and a possible delay in epidermal differentiation. Transgenic mice were also hypersensitive to the proliferative effects of the skin tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA) and were more sensitive to two-stage carcinogenesis. Elevations in EGFr and erbB2 protein as well as erbB2:EGFr and erbB2:erbB3 heterodimers were observed in skin of the erbB2 transgenic mice. Phosphotyrosine levels of the EGFr, erbB2 and erbB3 proteins were also elevated. These results indicate an important role for erbB2 signaling in epidermal growth, development and neoplasia. Oncogene (2000) 19, 4243 - 4254
Animals↗
Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice.
Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice >/=6 months of age (38 mice total) was 50%. The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
Animals↗
Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion.
Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in the basal layer of skin epidermis were generated using the bovine keratin 5 promoter (BK5). Neonatal transgenic mice were slightly smaller at birth and exhibited early ear unfolding, wrinkled and thickened skin, and slightly enlarged ears compared with nontransgenic littermates. Morphological evaluation of the skin revealed that persistent overexpression of IGF-1 in the basal layer of the epidermis resulted in epidermal hyperplasia, hyperkeratosis, and an increased labeling index that persisted in adult mice. Phenotypic changes observed in skin were associated with transgene expression in the basal layer of the epidermis and activation of the IGF-1 receptor. Squamous papillomas (some of which converted to carcinomas) developed in a significant proportion (approximately 50%) of older BK5.IGF-1 mice. Treatment of BK5.IGF-1 transgenic mice with multiple topical applications of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, in the absence of tumor initiation led to the development of additional skin papillomas. Furthermore, treatment of BK5.IGF-1 transgenic mice with an initiating dose of 7,12-dimethylbenz[a]anthracene only led to the formation of additional papillomas in the absence of promotion. In two-stage carcinogenesis experiments, BK5.IGF-1 transgenic mice developed 7-fold more papillomas than nontransgenic littermates. Phosphatidylinositol-3-kinase and protein kinase B (Akt) activities were elevated (3-4-fold), and mitogen-activated protein kinase activity was elevated approximately 1.7-fold in the epidermis of transgenic mice compared with nontransgenic mice. In addition, UV light-induced epidermal apoptosis was significantly suppressed in BK5.IGF-1 transgenic mice. These data suggest that persistent activation of IGF-1 receptor signaling pathways in basal epithelial cells leads to spontaneous tumor promotion and that up-regulation of both mitogenic and cell survival signaling pathways may play an important role in the action of IGF-1 in this model system.
Animals↗
Intramolecular electron-transfer reaction within a diprotein complex of cytochrome c with ferrylmyoglobin modified with diethylenetriaminepentaacetic acid.
Horse heart metmyoglobins modified with diethylenetriaminepentaacetic acid, metMb(DTPA)n (n=1, 2, 4, and 5), were characterized by a MALDI-TOF mass spectrometry, amino-acid sequence analysis, and UV-Vis and CD spectroscopies. The DTPA-binding sites on metMb were Lys47, Lys50, Lys87, Lys145, and Lys147 for metMb(DTPA)5, Lys47, Lys87, Lys145, and Lys147 for metMb(DTPA)4, Lys87 and Lys145 for metMb(DTPA)2, and Lys87 for metMbDTPA, respectively. The modified metMb(DTPA)n showed cytochrome c peroxidase-like activity more efficiently than native metMb: metMb(DTPA)5>metMb(DTPA)4>metMb(DTPA)2> metMbDTPA approximately equals native metMb. The first-order rate constants for the reactions of ferrylMb(DTPA)n (n=2, 4, and 5) with reduced cytochrome c [cyt c(II)] were saturated with concentrations of cyt c(II), suggesting that the electron transfer (ET) occurs within a diprotein complex. The intramolecular ET rate constants in the diprotein complex increased with increasing the number of DTPA ions. The reactions of native ferrylMb and ferrylMbDTPA with cyt c(II) obeyed a second-order rate law. A possible ET mechanism is proposed; cyt c(II) binds the DTPA-linked anionic patch around Lys87, Lys145, and Lys147 region of ferrylMb(DTPA)n.
Animals↗
Human papillomavirus types 56 and 59 in novel cervical cancer cell lines.
Explore the source record for details and available documents.
Female↗
Effects of embryotrophic factors on the embryogenesis and organogenesis of mouse embryos in vitro.
In order to study embryogenesis and organogenesis in vitro, two cell mouse embryos were cultured with alpha-MEM supplemented 10% FCS and embryotrophic factors (ETFs). The ETFs were separated from the conditioned medium of a SKG-II-SF cell line derived from a human uterine cervical epidermoid carcinoma. IL-1 beta, IL-6, IL-8, EGF, GH, PDGF-AB, basic FGF, VEGF were also detected in the conditioned media of this cell line. Using ETFs and a 10% FCS supplemented culture medium, 23% of the mouse two cell stage embryos developed to the bilaminar disc stage, 13% to the trilaminar germ disc stage, 9% were observed with blood islets in the yolk sac, and the heart beat was noted in 7% (28 embryos) of the embryos. Furthermore, primordial organs, such as the liver, heart, kidney, notochord, retina-like structure, etc. were observed. Usually, structures associated with the primordial streak stage (bilaminar germ disc embryo) developed in vitro using ETFs from two cell stage embryos. These closely resemble structures found at the same stage in the normal embryo in vivo. After the primordial streak stage, the cultured embryos showed no resemblance to the same stage in normal embryos. None of the external appearances of these embryos appeared normal. On the other hand, trilaminar disc stage embryos never developed when using only a 10% FCS supplemented culture system.
Animals↗
Enhancement of susceptibility to diverse skin tumor promoters by activation of the insulin-like growth factor-1 receptor in the epidermis of transgenic mice.
Insulin-like growth factor-1 (IGF-1) and its receptor are believed to play an important role in mitogenesis and neoplastic transformation. The purpose of this study was to further examine the role of IGF-1 during tumor promotion in mouse skin. HK1.IGF1 transgenic mice, which overexpress IGF-1 in epidermis via the human keratin 1 promoter, were previously shown to be hypersensitive to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). We examined these mice for their sensitivity to diverse classes of tumor-promoting agents. HK1.IGF-1 transgenic mice initiated with 7,12-dimethylbenz[a]anthracene were more sensitive to treatment with a wide variety of tumor promoters, including chrysarobin, okadaic acid, and benzoyl peroxide, which resulted in more rapid development of tumors and a dramatic increase in the number of tumors per mouse compared with corresponding non-transgenic mice treated with the same compounds. Histological analyses of skin from HK1.IGF-1 mice treated with various tumor promoters revealed that these mice were also more sensitive to the induction of epidermal hyperplasia and cell proliferation. Analysis of the IGF-1 receptor (IGF-1r) and epidermal growth factor (EGFr) in the epidermis of TPA-treated HK1.IGF-1 transgenic and non-transgenic mice revealed that both receptors were activated (hyperphosphorylated on tyrosine residues), and the level of activation was higher in transgenic mice. The mechanism for the increased sensitivity of HK1.IGF-1 mice to tumor promoters may involve cooperation between the IGF-1r and EGFr signaling pathways. Our data suggest that IGF-1r signaling may play an important role in the process of tumor promotion by diverse classes of tumor promoters.
Animals↗
Tumor angiogenesis factors produced by cancer cells.
Tumor angiogenic activity from tumor angiogenesis factors (TAFs) produced by 25 cell lines was assayed onto chorioallantoic membranes (CAMs). Neovascularization occurred prominently in such cell lines, as HTBOA (poorly differentiated ovarian carcinoma), HUOCA-II (poorly differentiated clear cell adenocarcinoma), HWUA (poorly differentiated endometrial adenocarcinoma), HKUS (uterine cervical small cell carcinoma), and in HOTHC (anaplastic thyroid carcinoma). The cell lines which secreted TAF showed high heterotransplantability in nude mice and produced rapidly growing tumors which were rich in blood vessels. The TAFs polypeptides of 14,000 and 78,000 molecular weight, were extracted and purified from the conditioned medium of HUOCA-II or W3UF (sub-line of HUOCA-II) lines, respectively. TAFs at concentrations of 10 ng/ml and 100 ng/ml promoted proliferation of the endothelial cells and induced tube formation. Microsequencing analysis revealed that TAF of 78,000 molecular weight has sequence identity with human hepatocyte growth factor (hHGF).
Angiogenesis Inducing Agents↗
Establishment and characterization of human uterine poorly differentiated adenocarcinoma cell line (HHUABM).
The cell line designated HHUABM was established from the metastatic region (left Bartholin gland) of human endometrial adenocarcinoma. The cell line grew well, multilayering rapidly without contact inhibition, and 72 serial passages were successively done within 25 months. The cultured cells of HHUABM line were round and spindle in shape, and showed a pavement-like arrangement. The distribution of chromosome number varied narrowly at the diploid range, and the modal chromosome number was 46. The 90% of metaphase cells showed normal karyotype. The HHUABM cells were transplanted easily into the subcutis of BALB/c nude mice and produced poorly differentiated adenocarcinoma resembling the original tumor. The conditioned medium promoted the proliferation of CPAE (endothelial cells). The estradiol-17 beta and progesterone receptors were not detected.
Adenocarcinoma↗
Establishment and characterization of human choriocarcinoma cell line derived from a metastatic focus of a testicular mixed germ cell tumor.
A human testicular choriocarcinoma cell line HKRT-II was established by the single-cell cloning method from a mixed cell culture system derived from a retroperitoneal metastatic germ cell tumor composed of a yolk-sac tumor, a choriocarcinoma, and an immature teratoma. Its primary tumor rose from the testis and was comprised of a seminoma, a yolk-sac tumor, a choriocarcinoma and an immature teratoma. The HKRT-II cells were spindle or polygonal in shape and contained multi-nucleated giant cells showing neoplasticity and pleomorphism. The cells proliferated in a stable manner, and the population doubling time was 42 hours. The chromosome numbers showed a wide distribution of aneuploidy, while the mode was in the hypertetraploid range. Double minute chromosomes and homogeneously staining regions were recognized in about 5% to 10% of the metaphase plates, respectively. Heterotransplantation was not difficult. Subcutaneous transplantation of 1 x 10(7) cells into nude mice formed a tumor composed of only a choriocarcinoma. The most noteworthy characteristics of the cell line were that it produced human chorionic gonadotropin (hCG) in an in vitro culture system and in in vivo grafted cells, and that the N-myc gene was amplified about 10 times.
Adult↗