X-linked Gene Expression Profiles by RNAi-Mediated BRCA1 Knockdown in MCF7 Cells

Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF 7 breast cancer cell line. The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF 7 cells after BRCA1 knockdown. The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1%) and 12 downregulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells.

Gonadoblastoma Overgrown by Dysgerminoma in Women with 46,XX Karyotype: A Report of Two Cases

Gonadoblastoma is a neoplasm containing an intimate mixture of germ cells and elements resembling immature granulosa or Sertoli cells. It has been considered as in situ germ cell malignancy that can be overgrown by more malignant germ cell neoplasms. The tumor has been reported to almost exclusively develop in various types of gonadal maldevelopment syndromes containing the Y chromosome, such as in pure or mixed gonadal dysgenesis and, less commonly, in male hermaphroditism. However, occurrences in phenotypically and chromosomally normal, menstruating women are exceptionally rare. We report two cases of gonadoblastoma overgrown by dysgerminoma occurring in the ovaries of phenotypically and cytogenetically normal menstruating women. One of the two cases showed an area composed of granulosa cell tumor-like elements. This type of combination has been very rarely described, and exemplified that gonadoblastoma may progress to sex cord-stromal tumors as well as to the malignant germ cell tumors.

Apoptosis Induced by Chemotherapeutic Agents in Differentiated HL-60 Human Leukemic Cell Line / 대한소아혈액종양학회지

PURPOSE: Chemotherapeutic agents are known to induce cell death in cancer cells by apoptotic mechanisms. This study was to investigate the influence of the differentiation on the apoptotic potential of chemotherapeutic agents. METHODS: Etoposide and cytosine arabinoside (Ara-C) were chosen as chemotherapeutic agents, and human promyelocytic leukemia cell line, HL-60, was used as target cells. RESULTS: Etoposide or Ara-C treated HL-60 cells showed cytoplasmic blebbing and nuclear condensation and fragmentation under fluorescence microscope when stained with acridine orange/ethidium bromide. In addition, the cellular DNA of HL-60 cells was found to cleave into internucleosomal fragments after treatment with chemotherapeutic agents. These findings were the characteristics of apoptosis and suggested the induction of apoptotic cell death of HL-60 cells by etoposide or Ara-C treatment. HL-60 cells are known to differentiate into myeloid or monocytic lineage by retinoic acid, phorbol 12-myristate acetate (PMA) and dimethyl sulfoxide (DMSO), and this differentiation itself can activate apoptosis program, so-called 'apoptosis by terminal differentiation'. The effect of terminal differentiation by PMA or DMSO on the apoptosis induced by etoposide or Ara-C was also investigated, utilizing qualitative and quantitative DNA fragmentation assay. HL-60 cells treated with PMA (100 nM) were adherent to culture dish and formed cellular processes. DMSO (1.25%) treated HL-60 cells instead recovered the ability to reduce nitroblue tetrazolium to blue-to-purple formazan, indicating its differentiation. After induction of differentiation by PMA or DMSO, differentiated HL-60 cells were treated with etoposide (10 muM) and Ara-C (50 muM) to compare its apoptotic potential with that of undifferentiated HL-60 cells. The ladder DNA induced by etoposide and Ara-C was decreased in differentiated HL-60 cells. On quantitative analysis of DNA fragmentation, PMA reduced DNA fragmentation induced by etoposide and Ara-C to 73% and 69%, respectively, and DMSO reduced it to 74% and 56%, respectively. In western blot analysis, the expression of Bcl-2, which is known to inhibit etoposide and Ara-C induced apoptosis, decreased significantly in HL-60 cells differentiated by PMA or DMSO. CONCLUSION: These results suggest that the differentiation of HL-60 cells by PMA or DMSO prevents apoptosis by etoposide and Ara-C, but bcl-2 proto-oncogene may have only minor role in inhibiting apoptosis by chemotherapeutic agents in differentiated HL-60 cell.

Actinomycosis in Urachal Sinus: A Case Report

Primary actinomycosis of the urachal remnants is rare disease, and was not reported in Korean literature. Wereport the fistulography and CT findings of a cases of actinomycosis in the urachal sinus in a 31 year-old man.

Expression of CD44 in Epithelial Ovarian Tumors

CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44H) as well as several CD44 variants isoforms are produced through alternative splicing. Alternatively spliced variants of the CD44 molecule have been found to be associated with invasive and metastatic potential of cancer cells and poor prognosis in several types of carcinoma. The purpose of the present study is to define the expression of CD44H and CD44v6 in ovarian tumors and to investigate whether the expression of these molecules is associated with adverse prognosis. We evaluated the expression of CD44 isoforms in 58 ovarian tumors by means of immunohistochemistry, and correlated between CD44 expression and the histologic types, tumor grade, peritoneal implants, pseudomyxoma peritonei and FIGO stage. While the CD44H was commonly expressed in ovarian tumors, the CD44v6 was expressed in a minor proportion of serous tumors in comparison with frequent expression of v6 isoform in mucinous tumors. The CD44H expression was significantly higher in stage I/II than in stage III. However, there was no correlation between the expression of CD44 and the presence of peritoneal implants or pseudomyxoma peritonei. These results suggest that CD44H could play an important role in the adhesive function in the lower stage of the ovarian tumor and reduced expression in the higher stage might be related to the metastasis and widespread invasion of ovarian carcinoma cells.

Intraabdominal Desmoplastic Small Round Cell Tumor: Report of Two Cases

Intraabdominal desmopl small round cell tumor is a rare neoplasm predominant in adolescent or young adult male. The tumor is characterized by widespread growht along the peritoneal surfaces of the abdomen and pelvis,typical histologic features, and a specific immunohistochemical staining pattern. We report the clinical,radiologic, and pathologc findings of intraabdominal desmoplastic small round cell tumor.

The Relationships of Pretreatment IGF-I SDS, Delay in Bone Age and Response to Recombinant Human Growth Hormone (rhGH) Therapy in Children with Growth Hormone Deficiency

PURPOSE: To assess whether pretreatment IGF-I SDS and pretreatmental bone age are useful indicators in the response of rhGH therapy in children with GH deficiency (GHD), the relationship between pretreatment IGF-I SDS, delay in bone age and the growth response during the first year of rhGH treatment was analyzed. METHODS: This study included 12 children with GHD. We measured IGF-I levels by RIA after acid-ethanol extraction at pretreatment and then calculated IGF-I SDS as follow: SDS = (IGF-I- mean IGF-I for normal subjects of the same age and sex)/SD of IGF-I for normal subjects of the same age and sex. GH levels were measured by immunoradiometric assay. All patients were treated with rhGH, 0.1IU/kg daily, 6 times a week for 1 year. RESULTS: Twelve patients (6 males and 6 females), age distribution from 4 to 16 years, were studed. The data is reported as the mean +/- SD. Height SDS for chronologic age of the group as a whole as -3.6 +/- 1.0 and bone age was 8.2 +/- 3.4 years. Pretreatment height velocity (HV) was 4.0 +/- 1.7cm/yr and the HV during each 3 months of therapy were 10.1 +/- 4.5cm/yr, 9.6 +/- 4.5cm/yr, 8.5 +/- 4.3cm/yr and 7.8 +/- 1.3cm/yr, respectively and therefore the HV during the first year of rhGH therapy increased to 9.3 +/- 2.9cm/yr (P=0.002). Pretreatmental IGF-I SDS was -2.2 +/- 0.9 (-0.4~-3.6). A significant negative correlation between pretreatmental IGF-I SDS and incremental height gain was obtained (r=-0.40, P<0.05). The height velocity of the group whose pretreatmental IGF-I SDS was below -2 (n= 8) as a whole increased significantly from 3.5 +/- 1.8cm/yr to 10.3 +/- 2.9cm/yr (P=0.001). Pretreatmental bone age delay was 3.1 +/- 1.9 (0.5-7.8) years. The height velocity of the group whose pretreatmental bone age delay above 2 years (n=9) increased significantly from 4.1 +/- 1.1cm/yr to 9.7 +/- 2.9cm/yr (P=0.001). CONCLUSION: The height velocity of GH deficient children whose pretreatmental IGF-I SDS below -2 or pretreatmental bone age delay above 2 years increased significantly after rhGH therapy. It suggests that the pretreatmental IGF-I SDS and pretreatmental bone age may be significant indicatiors in the response of GH therapy in children with GHD.

Wegener's Granulomatosis Involving Lung and Middle Ear: A case report

A case of Wegener's granulomatosis is described, with special attention focused on the typical histologic findings and involvement of both middle ear and lung. The patient is a 37-year-old man presented with four-month history of cough and sputum. He had a past history of surgery of both ears because of otitis media followed by left facial palsy. Chest radiographs showed variable sized ill defined nodules in both lower lobes with internal airspace consolidation. Histologic preparations of the open lung biopsy specimens demonstrated a diffusely scattered palisading micro and macrogranulomas with central focus of neutrophils and necrotic collagen surrounded by histiocytes, histiocytic giant cells. Fibrinoid necrosis involved blood vessels and lung parenchyma. Chronic inflammation, diffuse granulation tissue formation and irregular fibrosis are also found in the lung parenchyma. The histologic findings of middle ear which was previously biopsied showed scattered palisading ill defined microgranulomas mixed with fibrotic tissue.

The Degree of TGF-beta1 and alpha-SMA Expression in Liver Tissues with its Prognostic Value for the Therapeutic Efficacy of Interferon in Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of alpha-interferon (IFN) on liver histology as well as on activation of hepatic stellate cell ( HSC) and trans for ming growth fact or beta-1 (TGF beta-1) expression. We had also investigated the clinical usefulness of TGFbeta-1 and alpha-smooth muscle actin (alpha-SMA) expression in liver tissue for predicting a response to alpha-IFN therapy in chronic hepat it is B. METHODS: We studied the expression of TGFbeta-1 and alpha-SMA in liver biopsys pecimens from 51 chronic hepatitis B pat ients. Using immunohistochemical staining and a semiquant it ative scoring met hod, we also evaluated TGF-beta1 and alpha-SMA expression in liver stellate cells before and after alpha-IFN therapy in liver tissue from rebiopsys pecimen of the 12 chronic hepatitis B pat ients. Recombinant IFN alpha-2b (Intron A) in doses of 6 MU/ d was given to patients intramus cularly three times per week for 6 months (total doses , 432 MU). The patients were divided into two groups according to serum alanine aminotransferase levels as well as HBV- DNA and HBeAg s eroconversion stat e. Histological grading and staging scores were according to modified Histological Activity Index (HAI) grading systems of Ishak (1995). RESULTS: The index of portal inflammation and total scores of HAI grading significantly decreased in biopsies after alpha-IFN treatment, but the scores of fibrosis staging showed no significant change in biopsies after IFN treatment. A significant decrease in alpha-SMA expression, especially in periportal area, was found, but the change of TGFbeta-1 expression was not significant. The immunoreactivity of alpha-SMA was significantly lower in responders than in non-responders, whereas the diffference of immunoreactivity of TGF-beta1 between these two groups was not found. CONCLUSIONS: These findings suggest that alpha-IFN therapy may reduce the necroinflammatory activity in liver tissues of chronic B viral hepatitis and that the degree of alpha-SMA expression before treatment may be employed as a pottent predicting indicator for the therapeutic efficacy of IFN-alpha.

Congenital Sialoblastoma: A case report and review

A congenital salivary gland tumor, sialoblastoma, is extremely rare. A sialoblastoma of the parotid gland, occurring in a 28-week old fetus, is described. The histologic, immunohistochemical, and ultrastructural features of this tumor were studied. The tumor was characterized by solid nests or sheets of tumor cells intermingled with ductal structures lined by a columnar cells. Some of the tumor cells showed squamous differentiation. Immunohistochemically, these epidermoid cells reacted positively with anti-cytokeratin. But anti-S-100, anti- vimentin, anti-smooth muscle actin, anti-GFAP positive cells were not found. The ultrastructure was characterized by primitive epithelial cells. Although various names have been proposed, we favored the term "sialoblastoma". The histogenesis of this tumor is also discussed.

A Case of Endometrial Adenocarcinoma in a Double Uterus / 대한산부인과학회잡지

Endometrial adenocarcinoma in a double uterus has rarely been reported.We had a very rare case of double uterus with endometrial adenocarcinoma involving onehemiuterus and endometrial hyperplasia involving another hemiuterus. By report this case, wewant to share our experiance. The abnomal anatomy of the uterine cavities could have madeadequate biopsy difficult and endometrial cancer is clinically suspected but histology fails toconfirm the diagnosis.

A Case of Pulmonary Siderosis / 대한내과학회지

Pulmonary siderosis is one kind of pneumoconiosis caused by the long term inhalation of iron dust. Iron is deposited in the lungs, usually in the form of iron oxides. Iron oxides are relatively inert particles with a minimal fibrotic response. It occurs in a number of occupations including welding, steel rolling and grinding, casting, iron ore mining and oxyacetylene cutters. We have experienced the first case of pulmonary siderosis in Korea. A 42-year-old woman who had engaged in a metalware manufacturing factory as a manager for 7 years was admitted because of dyspnea on exertion. A pulmonary function test disclosed a mildly obstructive ventilatory defect. Open lung biosy revealed deposition of iron-laden macrophages in most alveolar spaces by which confirmed the diagnosis of pulmonary siderosis. We report a case of pulmonary siderosis with a review of the literature.

Mixed hepatoblastoma in an adult--a case report and literature review

Hepatoblastoma is thought to originate from embryonal hepatic tissue, and most of these tumors occur in children under the age of 2 years. Hepatoblastoma in adults is extremely rare, and the prognosis is much worse than the mixed hepatoblastoma of childhood. We experienced a case of mixed hepatoblastoma in a 51 year old female patient. She had been suffering from a mild pain and a palpable lump in the epigastric area. Serum AFP was 43,850 ng/ml. Computerized tomography and selective abdominal angiography showed a large low-density mass. With a suspicion of hepatocellular carcinoma of the left lobe, a left lateral segmentectomy was performed. The external surface showed a huge protruding mass and the capsule was previously ruptured. On section, the tumor was a 11 x 7 cm sized expanding mass which had a variegated surface composed of yellow-white friable tissue with multifocal hemorrhagic areas. Microscopic examination revealed a tumor consisted of epithelial and mesenchymal elements. The mesenchymal cells were spindle in shape and proliferated over the whole tumor with focal osteosarcomatous differentiation. The epithelial components showed well-differentiated hepatocellular carcinoma-like areas, poorly differentiated acinar or tubular structures.

Atypical Polypoid Adenomyomas of the Endometrium: 2 case reports

Atypical polypoid adenomyoma(APA) is a rare benign polypoid tumor arising in the uterine endometrium which was first designated by Mazur in 1981. Microscopic examination reveals architecturally and cytologically atypical endometrial glands separated by intersecting fascicles of smooth muscle cells. The tumor can be misdiagnosed as endometrial adenocarcinoma with myometrial invasion, especially on microscopic examination of a curettage specimen. However a granulation tissue-like stromal response is absent and the smooth muscle in APA is more cellular than that of normal myometrium. We are reporting 2 cases of APA of the uterine endometrium which are 1.5 cm and 1.7 cm in size, respectively, in a 30 and a 22 year-old women. This is the first report in Korean literature using the immunohistochemical staining for smooth muscle actin and desmin.

Analysis of Histological Findings and Estrogen and Progesterone Receptor Status in Luteal Phase Defect Caused by Delayed Ovulation and Clomiphen Treatment

Luteal phase defect (LPD) is an ovulatory disorder of considerable clinical importance that leads to delayed endometrial maturation and inadequate endometrium for blastocyst implantation. This disorder is implicated in infertility and recurrent spontaneous abortion. We analyzed the endometrial histological maturation, and the estrogen receptor(ER) and progesterone receptor(PR) status in patients with unexplained delayed ovulation, and in patients with ovulation induction by clomiphen citrate. The purpose of this study was to determine whether the length of the follicular phase influences the endometrial histological maturation and the hormonal receptor status, and to know the effect of clomiphen citrate on the endometrium. In the delayed ovulation group, the endometrium was characterized by an irregular outpouching and dilated lumina of the glands, a decreased secretory activity and predecidualization, and a decreased number of granulocytes in the stroma. In the clomiphen citrate-ovulation induction group, glandular proliferation was markedly diminished with poorly convoluted and narrow glands, secretory activity was decreased, stroma was undecidualized, and there was an absence of granulocytes. ER expression was increased in the glandular epithelium in the delayed ovulation group, and both ER and PR expressions were markedly decreased in the glandular epithelium and stromal cells in the ovulation induction group. Endometrial maturation and differentiation may be diminished by increased estrogenic and relatively deficient progesterone effects in patients with delayed ovulation. The hormonal receptor status might also be influenced by hormonal changes. Clomiphen citrate successfully induced ovulation in patients with delayed ovulation, however, endometrial proliferation and maturation were markedly suppressed. This might be related to the lower pregnancy rate and higher abortion rate in patients with clomiphen citrate induced ovulation.

Effects of Progesterone Treatment on the Squamous or Morular Metaplasia Associated with Endometrial Hyperplasia

During evaluation of follow-up curettage of endometrial hyperplasia after progesterone treatment, we have noticed that the foci of squamous or morular metaplasia are persistent or even markedly increased after the hyperplastic glands have all disappeared. These observations have led us to study the histological changes of squamous or morular metaplasia in the hyperplastic endometrium after progesterone treatment and to examine the changes of estrogen receptors(ER) and progesterone receptors(PR) to find out, if there is any pathogenetic role of progesterone administration on the squamous or morular metaplasia. Squamous or morular metaplasia was associated in 21 cases (13.5 %) out of 156 endometrial hyperplasia during the study periods and all of them were associated with complex hyperplasia, but not associated with simple hyperplasia. At follow-up curettage after progesterone treatment, squamous metaplasia newly appeared in 3 cases(20 %), markedly increased in 4 cases(26.7%), persisted in 4 cases(26.7%) and decreased in 4 cases(26.7%), even after hyperplastic glands have all disappeared or were markedly decreased. On immunohistochemical staining, metaplastic foci showed ER- and PR- in 13 cases (87 %) in contrast to the surrounding endometrium and the remaining 2 cases showed minimal ER+ and PR+ confined to several nuclei. Intensity or staining pattern of ER and PR in metaplastic foci were not changed with progesterone treatment. In the background endometrium, intensity of glandular ER+ and PR + was higher than that of the stroma at the initial curettage, however, progesterone treatment predominantly down-regulated glandular ER+ more than stromal ER+. Increment or persistence of squamous metaplasia along the progesterone treatment seemingly would implicate hormonal influences as playing a significant role in the formation of squamous or morular metaplasia and the absence of cellular receptors for these hormones in the metaplastic foci may suggest qualitative changes in the receptors.

Metastatic Gestational Trophoblastic Disease in the Lung Occuring with Hydatidiform-mole in Tubal Pregnancy: A case report

Gestational trophoblastic disease associated with the tubal pregnancy is uncommon, and the incidence has been described as 1/5000 tubal pregnancy. We have experienced a case of metastatic gestational trophoblastic disease(GTD) in the lung occuring with complete hydatidiform mole arising in tubal pregnancy. The patient was a 39-year-old, G4P2A2L2 woman with amenorrhea for 5 weeks. Ectopic pregnancy in the right fallopian tube was suspected on transvaginal ultrasonogram. A right adnexectomy was performed. The fallopian tube was markedly dilated and ruptured. The right ovary and a round hematoma had adhered to the external surface of the fallopian tube. On gross examination, no molar tissue was identified. On microscopic examination, the lumen of the dilated fallopian tube was filled with blood clots admixed with several chorionic villi showing hydropic swelling and marked proliferation of atypical trophoblasts. Proliferating syncytio-and cytotrophoblasts invaded the wall of the blood vessels of the fallopian tube and sheets of trophoblasts and some villi were identified in the lumen of blood vessels. Multiple pulmonary nodules thought to be metastatic nodules were identified in the chest X-ray and serum beta-HCG had increased 2 weeks later. This case indicates that a careful pathological examination in the ectopic pregnancy is mandatory, because tubal GTD is not clinically distinguishable from ordinary tubal pregnancy.

Xanthoma of the liver in a patient with multiple myeloma associated with hyperlipidemia: A case report

A case of xanthoma of the liver in a 61-year-old Korean woman with multiple myeloma, hyperlipidemia and xanthoma of the skin is described. Microscopically, the liver showed a multiple xanthomatous collection of foamy histiocytes as well as diffuse sinusoidal infiltration of the foam cells. This hepatic accumulation of foam cells seems to be related to hyperlipidemia of the patient. The mechanism of hyperlipidemia in multiple myeloma is discussed.

roded Polypoid Hyperplasia of the Rectosigmoid Colon: Report of 2 cases with special reference to its relation to mucosal prolapse syndrome

Polypoid prolapse of mucosal folds can occur at various sites and in various conditions predominantly associated with strain during defecation. There are two well known types of mucosal prolapse syndrome(MPS), the inflammatory cloacogenic polyp(ICP) and the mucosal redundant polyp associated with diverticular disease(N4RPD). ICP is a mucosal prolapse of the anorectal junction and MRPD is a proximal analogue involving the sigmoid colon. We experienced two cases of eroded polypoid hyperplasia(EPH) of the rectosigmoid colon which manifested as a huge gyriform mass simulating the gross features of gastrointestinal lymphomas or other malignant tumors. The EPH consisted of confluent polypoid mucosal folds with rolled-up submucosa to form stalk, The polypoid lesion represented hyperplastic epithelium, erosion of the mucosal surface and congestive vascular ectasia of lamina propria and submucosa. To explain the whole morphologic features, the initial phenomenon should be the mucosal prolapse. Vascular stretching with ischemic erosion of the mucosal surface and compensatory epithelial hyperplasia ensue as the result. The ominous endoscopic and gross features of EPH should be kept in mind to avoid erroneous radical surgery.

Clinicopathologic comparison of eroded polypoid hyperplasia and solitary rectal ulcer syndrome

We experienced two unusual cases of tumor-like polypoid lesions involving the rectosigmoid colon. They could not be readily classified into any well known polypoid tumors of the rectosigmoid colon, but appeared to have some similarities to the previously documented "eroded polypoid hyperplasia (EPH)". A collective review of our seven cases of solitary rectal ulcer syndrome (SRUS), which proved to be due to paradoxically over-reactive muscle tone of the puborectalis, was performed, and clinicopathologic comparisons between EPH and SRUS were carried out. They shared histopathologic characteristics such as vascular congestion, crypt hyperplasia, and eroded surface, but they were different from each other in clinical symptoms, location of lesions and gross features. Furthermore, in one EPH case there was an altered much profile which was similar to that seen in SRUS and complete rectal prolapse. Conceivably, the pathological features of both EPH and SRUS were thought to have a possible connection with mucosal prolapse syndrome (MPS). Considering that MPS is a group of diseases encompassing SRUS and the related disorders of the colorectum and the anus, it is speculated that EPH of the rectosigmoid colon might be the proximal analogue of SRUS, a mucosal prolapse of the more distal colon.