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1.  Primary central nervous system lymphoma with preceding spontaneous pseudotumoral demyelination in an immunocompetent adult patient: A case report and literature review 
Oncology Letters  2014;7(6):1835-1838.
The rapid disappearance of primary central nervous system lymphomas (PCNSL) following steroid therapy is common; however, the spontaneous regression of PCNSL without any treatment is extremely rare. This study presented a rare case of PCNSL with preceding pseudotumoral demyelination and no previous steroid treatment, and the pitfalls of PCNSL diagnosis were discussed. A 70-year-old healthy male experienced memory and gait disturbances and showed multiple enhanced lesions with perifocal brain edema in the left cerebrum. The patient had no previous symptoms, no chronic lesions and negative oligoclonal immunoglobulin G bands in the cerebrospinal fluid. Histological examination of a brain biopsy specimen revealed predominantly destructive, demyelinating characteristics with infiltration of several T lymphocytes and foamy macrophages resulting in the diagnosis of multiple sclerosis. The patient received steroid therapy and demonstrated gradual improvement, multiple brain lesions had disappeared from the magnetic resonance imaging (MRI)scan two months after the biopsy. However, three months after the biopsy, the condition of the patient deteriorated. MRI indicated a homogeneous enhanced lesion in the right frontal lobe and a second biopsy was performed. Histological examination during the second biopsy revealed a diffuse large B-cell lymphoma. The patient received whole-brain radiation and steroid therapy, however, succumbed eight months following the initial diagnosis. In the current report a comparison between the our case and six previously reported cases is presented.
PMCID: PMC4049747  PMID: 24932243
multiple sclerosis; steroid; tumefactive; sentinel; biopsy
2.  Peroxiredoxin 4 Protects Against Nonalcoholic Steatohepatitis and Type 2 Diabetes in a Nongenetic Mouse Model 
Antioxidants & Redox Signaling  2013;19(17):1983-1998.
Aims: Consumption of a high-fructose diet (HFrD) can induce the development of a metabolic syndrome, manifesting as nonalcoholic steatohepatitis (NASH) and/or type 2 diabetes mellitus (T2DM), via a process in which oxidative stress plays a critical role. Peroxiredoxin 4 (PRDX4) is a unique and only known secretory member of the PRDX antioxidant family. However, its putative roles in the development of NASH and/or T2DM have not been investigated. Results: To elucidate the functions of PRDX4 in a metabolic syndrome, we established a nongenetic mouse model of T2DM by feeding mice a HFrD after injecting a relatively low dose of streptozotocin. Compared with wild-type (WT), human PRDX4 transgenic (Tg) mice exhibited significant improvements in insulin resistance, characterized by a lower glucose and insulin concentration and faster responses in glucose tolerance tests. The liver of Tg also showed less severe vesicular steatosis, inflammation, and fibrosis, along with lower lipid concentrations, lower levels of oxidative stress markers, more decreased expression of hepatic aminotransferase, and more reduced stellate cell activation than those in the WT liver, reminiscent of human early NASH. Hepatocyte apoptosis was also significantly repressed in Tg mice. By contrast, serum adiponectin levels and hepatic adiponectin receptor expression were significantly lower in WT mice, consistent with greater insulin resistance in the peripheral liver tissue compared with Tg mice. Innovation and Conclusion: Our data for the first time show that PRDX4 may protect against NASH, T2DM, and the metabolic syndrome by ameliorating oxidative stress-induced injury. Antioxid. Redox Signal. 19, 1983–1998.
PMCID: PMC3869472  PMID: 23477499
3.  Pleomorphic carcinoma of the breast associated with cyst formation: a unique surgical case focusing on cytological and immunohistochemical findings. Cystic breast PC 
Diagnostic Pathology  2013;8:75.
A mammary nodular lesion was recognized one month before the surgery in the right upper breast of a 55-year-old female. The fine needle aspiration cytology specimens contained many individual bizarre, multi-nucleated, and/or giant cells having hyperchromatic pleomorphic nuclei, prominent nucleoli, and relatively abundant cytoplasm, admixed with numerous mitotic figures in a hemorrhagic or inflammatory background. A small amount of sheet-like or three-dimensional clusters of malignant cells coexisted. We first interpreted it as high-grade malignancy, such as invasive carcinoma, not otherwise specified. A right breast-conserving surgery was performed, and gross examination revealed a cystic cavity-formed and solid tumor lesion, measuring 35 × 35 × 25 mm and looking gray-yellowish to -whitish. On microscopic examination, the tumor was composed of a diffuse proliferation of highly atypical cells devoid of adhesive characteristics, including many multi-nucleated giant bizarre cells, in a haphazard fashion with stromal invasion, alternating with sarcomatoid features of spindle tumor cells. The cystic cavity was surrounded by hemorrhagic and inflammatory granulation tissue and lined by mostly denuded but atypical tumor cells or bland-looking flattened epithelial cells. Immunohistochemically, these tumor cells are specifically positive for all epithelial markers. Therefore, we made a conclusive diagnosis of pleomorphic carcinoma of the breast with cyst formation. We should be aware that, owing to its characteristic findings, cytopathologists can diagnose correctly, based on careful cytological examination of adequate samplings.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3772697  PMID: 23651662
Plemorphic carcinoma; Breast; Cytology; Cyst
4.  Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice 
Antioxidants & Redox Signaling  2012;17(10):1362-1375.
Aim: A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear. Results: To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4+/+/apoE−/−). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE−/− mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4+/+/apoE−/− mice than in apoE−/− mice. Bone marrow transplantation from hPRDX4+/+ donors to apoE−/− mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression. Innovation: In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE−/− mice fed a high-cholesterol diet. Conclusion: These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques. Antioxid. Redox Signal. 17, 1362–1375.
PMCID: PMC3437049  PMID: 22548251
5.  Invasive salivary duct carcinoma ex pleomorphic adenoma of the parotid gland: a teaching case giving rise to the genuine diagnostic difficulty on an inadequate cytology specimen 
Diagnostic Pathology  2012;7:61.
A history of a recent rapid increase in long-standing swelling mass was presented in the right parotid gland of an 85-year-old male. The inadequate cytologic specimens contained few small clusters of three-dimensional malignant epithelial cells having hyperchromatic pleomorphic nuclei and prominent nucleoli, adjacent to a cluster of benign monomorphic myoepithelial cells. We first interpreted it merely as an adenocarcinoma, not otherwise specified. A radical parotidectomy was performed, and gross examination revealed an encapsulated and firm tumor lesion, looking grayish-blue to yellowish-white, focally associated with extracapsular invasion. On microscopic examination, the tumor was predominantly composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, often arranged in a Roman-bridge appearance with foci of comedo necrosis, alternating with extensive infiltration to adjacent stroma in a trabecular or alveolar fashion with severe vessel permeation. Within the background of pleomorphic adenoma, the carcinoma cells sometimes replaced ductal luminal cells while retaining an intact-like myoepithelial layer. Therefore, we finally made a diagnosis of invasive salivary duct carcinoma ex pleomorphic adenoma. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate samplings.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3497703  PMID: 22647549
Salivary duct carcinoma; Carcinoma ex pleomorphic adenoma; Salivary gland; Cytology
6.  Duration of androgen deprivation therapy with maximum androgen blockade for localized prostate cancer 
BMC Urology  2011;11:7.
Primary androgen deprivation therapy (ADT) is a treatment option not only for advanced but also for localized prostate cancer. However, the appropriate duration for primary ADT for localized prostate cancer has not been defined and few studies have addressed this issue. In this study, we aimed to determine the appropriate duration of ADT for localized prostate cancer.
Sixty-eight consecutive patients with localized prostate cancer who underwent a prostatectomy following neoadjuvant ADT were retrospectively reviewed. Factors associated with pT0, which is regarded as serious cancer cell damage or elimination, were investigated.
Of the 68 males, 24 (35.3%) were classified as pT0. The median duration of neoadjuvant ADT in the pT0 and non-pT0 groups was 9 months and 7.5 months, respectively (p = 0.022). The duration of neoadjuvant ADT from when PSA reached < 0.2 ng/ml to surgery was longer in the pT0 group than that in the non-pT0 group (median 5 months against 3 months, p = 0.011). pT0 was achieved in 5 of 6 patients (83.3%) who received ADT for ≥10 months after PSA reached < 0.2 ng/ml. No other clinical characteristics predicted conversion to pT0.
Continuous ADT for ≥10 months after PSA reached < 0.2 ng/ml induced serious prostate cancer cell damage in most patients (> 80%) and may be sufficient to treat localized prostate cancer.
PMCID: PMC3116482  PMID: 21569574
7.  Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway 
PLoS ONE  2010;5(12):e15330.
Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway.
PMCID: PMC3009728  PMID: 21203463
8.  Rectal Carcinoma with Heterotopic Bone: Report of a Case 
Case Reports in Gastroenterology  2010;4(3):351-355.
Heterotopic bone is rarely present in malignant tumors of the gastrointestinal tract. We herein report a case of rectal adenocarcinoma with heterotopic bone. A 46-year-old Japanese male presented to our hospital with abdominal distension and constipation. Colonoscopic examination showed an ulcerated polypoid tumor of the rectum which nearly obstructed the rectal lumen. Abdominal computed tomography showed a tumor of the rectum with calcified deposits. Low anterior resection with lateral lymph node dissection was performed under the tentative diagnosis of rectal cancer. Histological examination of the resected specimen showed mucinous carcinoma of the rectum with heterotopic bone. One of the metastatic lymph nodes dissected also showed heterotopic bone. In the present report, we describe this rare tumor and briefly review the pertinent literature regarding rectal cancer with heterotopic bone.
PMCID: PMC2974998  PMID: 21060699
Rectum; Adenocarcinoma; Osseous metaplasia
9.  C5a promotes migration, proliferation, and vessel formation in endothelial cells 
Inflammation Research  2010;59(8):659-666.
The goal of this paper is to investigate the effects of activated complement C5a on vascular endothelium during vessel formation.
A human microvascular endothelial cell line (HMEC-1) derived from post-capillary venules in skin was used to measure DNA synthesis, proliferation and cell-cycle progression. In vitro ring-shaped formation by the cells was assessed by using type I collagen gel matrix and a cell-migration assay using the Chemotaxicell chamber. A Matrigel plug assay was performed to confirm the effect of C5a in vivo.
C5a progressed the cell cycle of HMEC-1 into G2/M phases, and induced DNA synthesis and proliferation in a dose-dependent manner. C5a efficiently induced migration and ring-shaped structure formation both in vitro and in vivo. Furthermore, a C5a receptor antagonist (W-54011) suppressed all HMEC-1 activities including proliferation and migration.
Proliferation, migration, and ring-shaped formation by HMEC-1 cells was induced by C5a. The actions were efficiently inhibited by a specific antagonist against C5a. Our results implicated C5a in vessel formation and as a potent target for management of inflammatory diseases.
PMCID: PMC2902742  PMID: 20217457
C5a; Angiogenesis; Endothelial cell; Inflammatory diseases; Activated complement
10.  Total anomalous pulmonary vein drainage: Report of an autopsy case associated with atresia of the common pulmonary vein and left superior pulmonary vein 
Pathology International  2011;61(2):93-98.
We describe the clinicopathological features of a case of total anomalous pulmonary vein drainage (TAPVD) associated with atresia of the common pulmonary vein (ACPV). A male Japanese infant born at 37 weeks of gestation demonstrated apnea and severe respiratory acidosis immediately after delivery. The patient died of hypoxemic respiratory failure 6 days after birth despite the initiation of artificial ventilation and administration of a surfactant. Autopsy showed the bilateral inferior pulmonary veins joined with a blind confluence, representing ACPV, accompanied by atresia of the left superior pulmonary vein. Moreover, the anomalous and small right superior pulmonary vein drained into the superior vena cava, consistent with partial and supracardiac type TAPVD. A histological examination of the lungs exhibited diffuse dilation of the lymphatic channels in the peribronchial, interlobular, hilar and focally, subpleural areas. The channels were lined with flattened endothelium which was immunohistochemically positive for D2-40. These findings conformed to a secondary form of pulmonary lymphangiectasis due to the congenital cardiovascular anomalies, including TAPVD and ACPV. To the authors' knowledge, this is the first case of TAPVD associated with ACPV, atresia of left superior pulmonary vein and pulmonary lymphangiectasis.
PMCID: PMC3047006  PMID: 21255186
atresia of the common pulmonary vein (ACPV); atresia of the left superior pulmonary vein; neonate; pulmonary lymphangiectasis (PL); total anomalous pulmonary vein drainage (TAPVD)

Results 1-10 (10)