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Volume 41(1); February 2007
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Original Articles
Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells.
Kyung Ryoul Kim, Min Young Park, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Dong Geun Lee, Myoung Jae Kang
Korean J Pathol. 2007;41(1):1-6.
  • 1,338 View
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AbstractAbstract PDF
BACKGROUND
The use of troglitazone (a PPARgamma ligand) and COX-2 inhibitor have been intensively studied for inhibition of tumor growth in cancer treatment, but the anti-tumor effect with a combination of these agents for cancer has not yet been studied. The aim of this study was to determine if low concentrations of troglitazone with COX-2 inhibitor in combination would cause significant cytotoxicity in glioma cells.
METHODS
The effects of co-treatment with troglitazone and COX-2 inhibitor on cell growth and apoptosis were assessed by use of trypan blue exclusion and a DNA fragmentation assay. A western blot was used to analyze the apoptotic signaling for the expression of bcl-2, bax, PARP and p21 proteins.
RESULTS
A low dose of troglitazone (5micrometer) and COX-2 inhibitor (5micrometer) strongly enhanced the cell growth inhibition and apoptosis in glioma cells when compared to a low dose of each drug alone. Western blotting analysis showed a decreased expression of bcl-2 and PARP proteins. In contrast, the bax protein level was increased.
CONCLUSIONS
The combination of troglitazone and COX-2 inhibitor in a low dose elicits synergistic cytotoxicity in glioma cells. Our study also demonstrates that down regulation of bcl-2, fragmentation of PARP protein and increased expression of bax protein were accompanied by co-treatment with troglitazone and the COX-2 inhibitor.
PPARgamma Ligand-Induced Decrease of in vivo Tumor Growth Accompanied by Increased Cytolytic Activity of Splenocytes.
Kyu Yun Jang, Ki Hoon Yu, Hak Yong Lee, Kyung Ryoul Kim, Ha Na Choi, Eun Jung Cha, Ho Sung Park, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee
Korean J Pathol. 2007;41(1):7-14.
  • 1,296 View
  • 19 Download
AbstractAbstract PDF
BACKGROUND
Recent studies have proposed the use of peroxisome proliferator activated receptor-gamma (PPARgamma) ligands as new chemotherapeutic agents for human malignant tumors. However the in vivo mechanism of PPARgamma ligands on cellular toxicity is not clear. Therefore we examined the anti-tumor effects of the PPARgamma ligand, rosiglitazone (ROS), in animal models.
METHODS
To evaluate the effect of RSO on splenocytes, an in vitro and in vivo study was performed. Cytolytic activity was measured by use of a 51Cr release assay. The splenic natural killer (NK) cell population and effector-target conjugation were measured by flow cytometric analysis.
RESULTS
In 9L glioma bearing rats, 30 mg/kg/d of ROS treatment induced a significant decrease of subcutaneous tumor growth accompanied by an increased cytolytic activity of splenocytes and of the splenic NKR-P1bright/CD3- NK cell population. In normal rats, systemic administration of ROS also increased the cytolytic activity of splenocytes, the splenic NK cell population, and effector-target conjugation. Moreover, we found that a concentration of 20micrometer ROS caused an increase in the cytolytic activity of splenocytes, and a concentration of 50micrometer ROS increased effector-target conjugation in vitro.
CONCLUSIONS
These results suggest that increased splenic cytolytic activity and NK cell population may contribute to the anti-tumor effects of PPARgamma ligands in vivo. However, the roles of NK cells in the PPARgamma ligand-induced anti-tumor activity should be further investigated.
Immunohistochemical Profile of Acute Cellular Rejection in Renal Allograft.
Jongha Park, Seung Woon Byun, Eunsil Yu, Su Kil Park, Duck Jong Han, Yong Mee Cho
Korean J Pathol. 2007;41(1):15-20.
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AbstractAbstract PDF
BACKGROUND
We wanted to find an adjunctive marker(s) in renal allograft biopsies for predicting acute cellular rejection (ACR), and so the expression patterns of immune-related molecules were compared between ACR, borderline ACR and non-ACR cases.
METHODS
The expression patterns of Fas ligand (FasL), HLA-DR, granzyme B, caspase-3, CD56, interferon stimulated growth factor-3 (ISGF-3), and CD53 were assessed via immunohistochemical study in 75 allograft biopsies from patients with ACR (n=19), borderline ACR (n=22), and non-ACR (n=34).
RESULTS
Compared to those of the non-ACR group, the ACR group revealed an elevated number of FasL positive interstitial inflammatory cells, HLA-DR positive tubular inflammatory cells, cytoplasmic caspase-3 positive tubular epithelial cells, granzyme B positive interstitial mononuclear inflammatory cells and CD53 positive interstitial inflammatory cells. The expression patterns of the borderline ACR group were similar to those of non-ACR group, except for the intensity of FasL in the tubular epithelial cells.
CONCLUSIONS
Immunohistochemical investigations of the adjunctive markers FasL, HLA-DR, granzyme B, caspase-3 and CD56 can be useful for making the diagnosis of ACR.
Methylation Patterns of Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) Related to the Germ Cell Differentiation of Human Germ Cell Tumors.
Sun Young Jun, Kyu Rae Kim, Jene Choi, Jae Y Ro
Korean J Pathol. 2007;41(1):21-29.
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AbstractAbstract PDF
BACKGROUND
The histogenesis and interrelationship of the various types of germ cell tumors (GCTs) have been proposed. Dysgerminoma/seminoma (D/S) is a primitive GCT that has not acquired the potential for further differentiation, whereas other types of GCTs are in a dynamic process of differentiation towards a somatic or extraembryonal direction. A primordial germ cell giving rise to a GCT undergoes a developmentally regulated erasure and resetting of imprinted genes, but changes in the imprinting pattern in GCTs as the tumor differentiates have not been well defined. We aimed to investigate the changes of the SNRPN methylation pattern between the germinomas and non-germinomatous GCTs, as compared with the somatic methylation pattern.
METHODS
We used formalin-fixed paraffin-embedded tissue sections of 97 GCTs (18 Ds, 21 Ss, 17 yolk sac tumors (YSTs), 19 immature teratomas, and 22 mature teratomas). DNA methylation was evaluated after bisulfite modification, PCR amplification, and restriction enzyme digestion.
RESULTS
The SNRPN methylation pattern was changed in 53/74 (71.6%) of GCTs as non-somatic patterns. There were significant differences in the methylation pattern between the germinomas and non-germinomatous GCTs, the GCTs being frequently hypo- methylated in Ds/Ss (73.3%), in contrast to the frequent hypermethylation seen in the YSTs and teratomas (47.7%, p<0.05).
CONCLUSIONS
The methylation status of an imprinting gene may be involved in the mechanism causing cellular differentiation and tumorigenesis of GCTs.
Tetranucleotide Repeat Microsatellite Instability in Uterine Cervical Carcinomas.
Yoo Duk Choi, Ji Shin Lee, Chan Choi, Chang Soo Park, Sang Woo Juhng, Ho Sun Choi, Jong Hee Nam
Korean J Pathol. 2007;41(1):30-37.
  • 1,462 View
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AbstractAbstract PDF
BACKGROUND
Elevated levels of microsatellite alterations at selected tetranucleotide repeat regions (EMAST) have been recently described, and they are a distinct type of microsatellite instability (MSI). We investigated the prevalence of EMAST in squamous cell carcinoma (SCC) of the uterine cervix and we determined the correlation between EMAST and the clinicopathologic parameters, HPV infection and the p53 mutation.
METHODS
We examined the 3 mono-, 3 di-, and 5 tetranucleotide repeat markers in 47 cases of SCC, and we performed immunohistochemical staining for p53. HPV detection and genotyping was performed using a commercially available HPV DNA chip.
RESULTS
Thirteen out of 47 cases (27.7%) were EMAST(+) with at least one of five tetranucleotide repeat markers. However, MSI at mono- and dinucleo- tide markers was noted in only one case (2.1%). EMAST was not related with stage, size, lymph node metastasis, vascular/lymphatic invasion or the depth of invasion. Positive immunostaining for p53 was significantly more common in EMAST(+) tumors than in the EMAST(-) tumors (p=0.04). HPV-infection was positive in 32 cases. EMAST was not correlated with the state of HPV infection state or the HPV genotype.
CONCLUSIONS
27.7% of the invasive SCCs of the uterine cervix exhibited EMAST, and EMAST in the SCC of the uterine cervix was significantly associated with the p53 mutation.
Clinicopathological Analysis of Growth Patterns of Malignant Intraductal Papillary Mucinous Tumors of the Pancreas: Unusual Growth Pattern of Fistulous Extension.
Kee Taek Jang, Ghee Young Kwon, Geunghwan Ahn
Korean J Pathol. 2007;41(1):38-43.
  • 1,297 View
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AbstractAbstract PDF
BACKGROUND
Usually, a malignant intraductal papillary mucinous tumor (IPMT) of the pancreas shows invasive carcinoma. Recently, IPMT with an unusual growth pattern of a fistulous extension was reported. However, little is known about malignant IPMTs with a different growth pattern of invasion and fistulous extension.
METHODS
Malignant IPMTs were classified into invasive (colloid or tubular type) carcinomas and the fistulous extension type according to their growth patterns. Their clinicopathological characteristics were compared.
RESULTS
Among a total of 68 cases of IPMT, there were 16 cases with malignant IPMT; eight, six and two of the colloid, tubular, and fistulous extension types, respectively. The immunohistochemical (IHC) expression of MUC1 was found in seven out of eight colloid and five out of six tubular types, but there was no IHC expression of MUC1 in the fistulous extension type. The IHC expression of MUC2 was noted in one of the eight colloid, one of the six tubular and in both cases with the fistulous extension type. There was no difference in the tumor recurrence rates bet- ween the different growth patterns.
CONCLUSIONS
IPMT with the fistulous extension type has a peculiar extension pattern consisting of multiple fistulous tracts without a mass. Although most of the epithelium in the fistulous tract show moderate to severe dysplasia, only the fistulous extension should be considered to be an unusual growth pattern of malignant IPMT. The clinical significance of this unusual type of IPMT remains to be determined.
Case Reports
Kikuchi's Disease of the Mesenteric Lymph Nodes Presenting as Acute Appendicitis.
Kyueng Whan Min, Ki Seok Jang, Si Hyong Jang, Young Soo Song, Woong Na, Soon Young Song, Seung Sam Paik
Korean J Pathol. 2007;41(1):44-46.
  • 1,374 View
  • 14 Download
AbstractAbstract PDF
Kikuchi's disease is a benign self-limiting necrotizing lymphadenitis that occurs most commonly in young women, and is usually found in the cervical lymph nodes. When there is an unusual location of involved lymph nodes, the diagnosis can be difficult. We recently treated a patient with Kikuchi's disease who had ileocecal mesenteric lymph node involvement; the patient presented with symptoms of acute appendicitis in an 11-year old boy. Although mesenteric lymph node involvement of Kikuchi's disease is very rare, Kikuchi's disease should be added to the differential diagnosis of acute appendicitis in patients with enlarged ileocecal mesenteric lymph nodes on radiological evaluation.
Restrictive Dermopathy In Two Siblings.
Tae Jung Kim, Youn Soo Lee, Hyun Young Ahn, Ahwon Lee, Kyo Young Lee, Jong Sup Park
Korean J Pathol. 2007;41(1):47-50.
  • 1,266 View
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AbstractAbstract PDF
Restrictive dermopathy (RD) is a rare and lethal autosomal recessive skin disorder that presents with rigid and tense skin, multiple joint contractures and fixed facial expression. We report herein two siblings from consecutive pregnancies affected with RD. Both siblings died of respiratory insufficiency at a day after birth. An autopsy for the first baby and a skin necropsy for the second baby were performed. The gross findings of both were characterized by thin, translucent skin with prominent vessels, multiple joint contractures resulting in hyperflexed position, and a typical facial appearance with a fixed open mouth in the O-position. Such manifestations are typical features of RD. At the autopsy of the first baby, no internal organ abnormality was found. The histologic findings of the skin of the second baby revealed a thin dermis consisting of a flat dermal-epidermal junction, hypoplastic skin appendages and compactly arranged collagen bundles. Elastic tissue stain showed markedly decreased elastic fibers.
Intraneural Perineurioma in the Tongue: A Case Report.
Jun Kang, Shin Kwang Khang, Jene Choi, Jeong Won Kim, Eul Ju Seo, Bu kyu Lee, Eunsil Yu
Korean J Pathol. 2007;41(1):51-54.
  • 1,568 View
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AbstractAbstract PDF
We report a case of an intraneural perineurioma that developed in an unusual location, the tongue. A 16-year-old male presented with a 1 cm sized protruding submucosal mass in his tongue without any sensory or motor signs or symptoms. The mass was excised. The mucosa was intact, with an ill-defined firm mass measuring 1.0 x 0.8 x 0.6 cm in the submucosa and muscle. The cut surface of the mass was pinkish gray and fibrotic. Microscopically, the mass contained tortuous and thickened peripheral nerve bundles in the submucosa, showing onion bulb like structures. The onion bulb like structures consisted of centrally located S-100 protein positive Schwann cells surrounded by Glut-1 positive perineurial cells. The FISH study did not reveal any genetic aberrations in chromosome 22.
A Case of Gastric Inverted Hyperplastic Polyp Associated with Gastritis Cystica Profunda and Early Gastric Carcinoma.
Min Sung Choi, So Young Jin, Dong Won Kim, Dong Wha Lee, Sang Mo Park
Korean J Pathol. 2007;41(1):55-58.
  • 1,495 View
  • 31 Download
AbstractAbstract PDF
A gastric inverted hyperplastic polyp is characterized by downward growth of the hyperplastic mucosal components into the submucosa. Lesions are composed of hyperplastic foveolar-type glands, and sometimes coexist with gastritis cystica profunda (GCP). Adenocarcinoma frequen- tly can coexist, but the relationship is not clear. A 71-year-old male was admitted to hospital because of dyspepsia for one month. He underwent a wedge resection of the stomach, after endoscopic biopsies. The gross finding showed a slightly elevated papillary lesion with central depression. Microscopically, the elevated lesion was composed of hyperplastic fundic glands and foveolar cells, and the central depressed lesion showed a nodular inverted proliferation of normal appearing gastric epithelium and glands in the submucosa. An additional proximal gastrectomy specimen exhibited marked GCP and a minute adenocarcinoma at the proximal margin with p53 protein overexpression.
A Sertoli-Leydig Cell Tumor in a Patient with Complete Androgen Insensitivity Syndrome: A Case Report.
Min Sung Choi, Dong Won Kim, So Young Jin, Sang Mo Park, Dong Wha Lee
Korean J Pathol. 2007;41(1):59-62.
  • 1,347 View
  • 18 Download
AbstractAbstract PDF
Complete androgen insensitivity syndrome (CAIS) is a rare disorder sometimes referred to as male pseudohermaphroditism. This syndrome is characterized by a 46,XY karyotype with internal bilateral testes, female external genitalia, absence or scantiness of pubic and axillary hair and normal breast development. A variety of gonadal tumors can develop in individuals with CAIS. A 57-year-old patient was admitted to urology with intermittent gross hematuria for one month. CT revealed a left ureteric mass, measuring 2.5 x 2 cm. Ureteroscopic biopsy was performed and the result was a diagnosis of high grade urothelial carcinoma. The patient underwent laparotomy which revealed slightly enlarged gonads in the pelvic cavity. However, a uterus and fallopian tubes were not identified. Left nephroureterectomy and bilateral gonadectomy were performed. The right gonad measured 3.9 x 2.5 x 2 cm and the cut surface showed a well circumscribed, firm, brownish gray colored 2 x 1.8 cm sized nodule. Microscopically, this nodule consisted of uniform and solid tubules containing immature Sertoli cells and Leydig cells which were both positive for alpha-inhibin. The left gonad measured 3.5 x 2 x 1.9 cm and showed atrophic testicular tissue.
Pure Immature Teratoma with Increase of Serum alpha-fetoprotein: A Case Report.
Bohng Hee Kim
Korean J Pathol. 2007;41(1):63-65.
  • 3,266 View
  • 112 Download
AbstractAbstract PDF
In the immature teratoma with increased serum alpha-fetoprotein (AFP), a complete pathologic examination is especially required because coexistence with other germ cell tumors is associated with a poor prognosis. If the case is proved to be a pure immature teratoma in spite of a thorough examination, the source of AFP should be found as an AFP-producing pure immature teratoma is not associated with a poor prognosis. In this case of a grade III-immature teratoma in an ovary of a 12-year old girl, serum AFP was increased. On pathologic examination, there was no evidence of a yolk sac tumor or embryonal carcinoma. On an AFP immunohistochemical stain, immature liver tissue, digestive and respiratory epitheliums were positive.
Ceruminous Gland Adenocarcinoma of External Ear Canal: A Case Report.
Jung Weon Shim
Korean J Pathol. 2007;41(1):66-68.
  • 1,537 View
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AbstractAbstract PDF
Ceruminomas are rare tumors arising from the ceruminous gland, which is a modified apocrine gland in the skin of the external ear canal. There is controversy about these rare tumors regarding their histological classification, their origin and the importance of wide excision, and there is also terminological confusion for making the diagnosis. Ceruminous adenocarcinoma is a malignant subtype of ceruminoma. We report here on a case of adenocarcinoma of the ceruminous gland in a 71-year-old male patient.

JPTM : Journal of Pathology and Translational Medicine