Autopsy results of a case of ingestion of sodium hydroxide solution.

Sodium hydroxide is a strongly corrosive alkali. We describe herein a case of suicide by ingestion of sodium hydroxide. A man in his 80s was found dead with a mug and a bottle of caustic soda. Macroscopically, liquefaction and/or disappearance of esophagus, trachea and lung tissue and a grayish discoloration of the mucosa of the stomach were seen along with blackish brown coloration of the skin, mouth, and oral cavity. The contents of the gastrointestinal tract showed a pH level of 7-8 on pH indicator strips. Histopathologically, liquefactive necrosis of remnant lung tissue and the stomach were seen. As biological reactions such as vasodilatation and inflammation were not detected in these organs, only a short number of hours must have passed between ingestion and death. This human case provides valuable information concerning the direct irritation induced by systemic exposure to corrosive substances.

A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat.

Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.

Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats.

The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.

Autopsy report for chemical burns from cresol solution.

Cresol, which is used as a disinfectant and insecticide, has erosive effects on epidermal and epithelial tissues in the body. Oral exposure causes gastrointestinal corrosive injuries as a direct chemical burn. We report herein a case of suicidal poisoning by ingestion of cresol solution. An octogenarian man with depression was found dead approximately 14 h after exposure to less than 500 mL of saponated cresol solution. Macroscopically, corrosive lesions such as red-to-brown-colored epithelium and edematous thickening of walls were seen in the skin, mouth, oral cavity, esophagus, and stomach. Histopathologically, coagulative necrosis and vascular dilatation were detected from mucosal to muscular layers in the esophagus, stomach, and duodenum. Congestive edema of the lungs, edematous changes in the brain, and proximal tubular necrosis of the kidneys were seen, suggesting acute circulatory disturbance due to shock. This human case offers valuable information on the direct irritation and shock induced by systemic exposure to corrosive substances.

[A Case of Adenosquamous Carcinoma of the Ascending Colon].

We report a case of adenosquamous carcinoma of the colon. A 70-year-old woman underwent a colonoscopic examination because of a positive fecal occult blood test. Colonoscopy demonstrated a type 2 tumor of the ascending colon, and a biopsy specimen showed poorly-moderately differentiated tubular adenocarcinoma. We performed a right hemicolectomy with D2 lymphadenectomy. The histopathology of the tumor demonstrated adenosquamous adenocarcinoma. Primary adenosquamous carcinoma of the colon is relatively rare and has a poor prognosis. Therefore, adenosquamous carcinoma of the colon may require strict follow-up.

Granulocyte-colony stimulating factor producing anaplastic carcinoma of the pancreas treated by distal pancreatectomy and chemotherapy: report of a case.

Granulocyte-colony stimulating factor (G-CSF) producing pancreatic cancers are extremely rare. These tumors have an aggressive clinical course but no established treatment. We encountered a patient with a G-CSF-induced pancreatic cancer who was treated by surgical resection, followed by steroid treatment and chemotherapy. A 68-year-old Asian male presented at a local hospital with a 3-month history of fever, loss of appetite, and 10-kg weight loss. Laboratory data showed leukocytosis and elevation of C-reactive protein. Computed tomography (CT) revealed a 50-mm mass in the tail of the pancreas, but no signs of infective foci. He was transferred to our hospital for further evaluation. Contrast-enhanced CT showed rapid growth of this tumor over 1 week, and (18) F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) showed FDG accumulation in the tail of the pancreas (SUV max, 17.1) but at no other sites in his body. Magnetic resonance imaging showed a heterogeneous mass, similar to that observed by CT. Three weeks later, the patient underwent a distal pancreatectomy with splenectomy. The resected specimen was 154 mm in diameter, a threefold increase from the initial image. Histopathological examination identified the tumor as an anaplastic carcinoma of the pancreas. Following surgery, his leukocyte count and body temperature were reduced. He recovered well and was discharged from our hospital on postoperative day 18. Immunohistochemical expression of G-CSF in the resected specimen and elevated serum G-CSF concentration confirmed that the mass was a G-CSF producing anaplastic carcinoma of the pancreas. Subsequently, the patient experienced a high fever and loss of appetite. CT showed recurrence of cancer in the abdominal cavity, for which he was started immediately on tegafur-gimeracil-oteracil potassium combination S-1 and steroid. Unfortunately, he died on postoperative day 83. To our knowledge, this patient was the first with a G-CSF producing anaplastic carcinoma of the pancreas to be treated by surgical resection, steroid and adjuvant chemotherapy.

Romanowsky staining using liquid-based cytology: A pilot study using Cytolyt(®)/HESPANDER(®) processing solution for ThinPrep(®) preparations.

BACKGROUND: Liquid-based cytology (LBC) has been used to prepare and examine many types of samples. However, the use of Romanowsky stains for LBC has not yet been evaluated. Herein, we report a technique for the use of the Romanowsky May-Grünwald-Giemsa (MGG) stain using a ThinPrep(®) preparation technique (MGG-LBC). METHODS: KPL-1 breast cancer cells at a density of 1.25 × 10(5)/20 ml were compared in conventional smear and MGG-LBC preparations. Cell size, nucleus/cytoplasm (N/C) ratio, and morphological findings were investigated. Clinical samples including voided urine and pleural effusion were also examined in MGG-LBC preparations. RESULTS: Cellularity appeared lower with MGG-LBC compared with Papanicolaou-stained smears using the ThinPrep(®) method, though the cell size and N/C ratio showed similar tendencies. Reactive mesothelial cells, normal urothelial cells, urothelial carcinoma cells, crystals, and bacteria were all clear enough for diagnostic purposes after MGG-LBC. CONCLUSION: Romanowsky staining is necessary for the cytodiagnosis of some conditions. MGG-LBC may contribute to the cytodiagnostic results using LBC preparations.

Comparison of neutrophil infiltration between type 1 and type 2 autoimmune pancreatitis.

BACKGROUND: Characteristics of type 2 autoimmune pancreatitis (AIP) is granulocyte epithelial lesions, called idiopathic duct-centric pancreatitis (IDCP). To clarify pathogenesis of IDCP, we investigated mechanism of neutrophil infiltration in type 1 AIP, called lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. METHOD: This study was performed on resected pancreata from patients with alcoholic chronic pancreatitis (ACP, n = 10), LPSP (n = 10) and IDCP (n = 12). The number of neutrophils around the pancreatic ducts was counted. The expression of neutrophils chemoattractants granulocyte chemotactic protein-2 (GCP-2) and interleukin-8 (IL-8) in the pancreatic duct epithelia was examined using immunohistochemistry. The cell staining intensity is scored as negative (0), weak (1), moderate (2) or strong (3). RESULTS: The median number of neutrophils around the interlobular pancreatic ducts was significantly higher in IDCP (15.16; interquartile range [IQR]: 9.74-18.41) than in ACP (2.66; IQR: 1.33-4.33) (P < 0.05) and LPSP (3.16; IQR: 2.74-4.57) (P < 0.01). There was no significant difference in the median number of neutrophils around the intralobular pancreatic ducts among ACP (1.16; IQR: 0.33-3.41), LPSP (3.16; IQR: 0.74-5.5) and IDCP (3.00; IQR: 1.08-7.91). The median score of GCP-2 in the interlobular pancreatic duct epithelia was significantly higher in IDCP (1.5; IQR: 0.25-2) than in ACP (0; IQR: 0-0.75) (P < 0.05) and LPSP (0; IQR: 0-0.75) (P < 0.05). There was no significant difference in the median score of IL-8 in the interlobular pancreatic duct epithelia among ACP (0; IQR: 0-0.75), LPSP (1; IQR: 0-1.75) and IDCP (0.5; IQR: 0-1). CONCLUSIONS: Significantly increased neutrophil infiltration around the interlobular pancreatic duct in IDCP may depend on GCP-2.

Case of Primary Intraocular Lymphoma with Extraocular Extension.

PURPOSE: To describe a case of primary intraocular lymphoma (PIOL) with an extension through the sclera that was confirmed to be part of the PIOL by histopathological examinations. CASE: An 89-year-old woman was referred to a local clinic with a 1-year history of persistent blurred vision in her left eye. After 2 years without aggressive treatments, she had a marked reduction of vision and pain in her left eye. The clinical diagnosis was panophthalmitis, and the eye was enucleated and submitted for histopathological study. RESULTS: Light microscope examination showed that atypical lymphocytic cells had infiltrated into both the intraocular and extraocular areas. The anterior chamber angle was blocked by infiltrating tumor cells, which were also detected around the optic nerve. The tumor cells destroyed Bruch's membrane and infiltrated around the perineural and perivascular areas within the sclera. Immunohistochemistry showed that the tumor cells were positive for B-lymphocyte surface antigen (CD20), B-cell antigen receptor complex-associated protein alpha chain (CD79-alpha), and had a high positive rate for anti-Ki-67 antibody. CONCLUSION: The finding in our case indicates that early diagnosis and treatment are important for eyes with PIOL because the tumor can spread and penetrate the sclera and invade extraocular tissues.

Diagnosis of intraocular lesions using vitreous humor and intraocular perfusion fluid cytology: Experience with 83 Cases.

OBJECTIVE: The objective of the study was to evaluate the use of vitreous humor and/or intraocular perfusion fluid (IPF) from pars plana vitrectomy as a diagnostic and therapeutic procedure for intraocular diseases. METHODS: The cytologic findings with respect to the clinical data, the anatomical findings, and the final diagnosis in 83 cases that underwent intraocular cytologic examinations at the Kansai Medical University Takii Hospital were evaluated. For cytologic examination, the Papanicolaou stain, Giemsa stain, and in some cases, molecular biology and immunocytochemical techniques were used. RESULTS: Most of the clinical diagnoses were uveitis or endophthalmitis. Sixty-eight cases (81.9%) were negative on cytodiagnosis, while 15 cases (18.9%) were positive or suspicious for malignancy. Negative cases included infections and intraocular sarcoidosis (IOS), and all of the positive or suspicious cases were intraocular lymphomas. Some of these latter cases were also diagnosed using immunocytochemical staining or molecular biological procedures as ancillary techniques, performed using vitreous body cytology from IPF. CONCLUSIONS: An early diagnosis and treatment of intraocular diseases is necessary to maintain an acceptable degree of quality of life. For an accurate diagnosis, it is necessary to understand the anatomy of the eye. Giemsa staining is recommended in addition to Papanicolaou staining for cytologic diagnostic evaluation of intraocular diseases. Furthermore, for the diagnosis of clonality in intraocular lymphomas, it is often necessary to use ancillary molecular biological procedures, using vitreous fluid.

Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma.

BACKGROUND: Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC. METHODS: We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting. RESULTS/CONCLUSION: High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.

Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis.

BACKGROUND: High serum immunoglobulin G4 (IgG4) levels and IgG4-positive plasma cell infiltration are characteristic of type 1 autoimmune pancreatitis (AIP). It is unclear whether innate immunity is a cause of type 1 AIP; the possible involvement of microbial infection has been suggested in its pathogenesis. To clarify the pathogenesis of type 1 AIP, we investigated Toll-like receptors (TLRs) in type 1 AIP patients. METHODS: We studied nine cases of type 1 AIP with ten cases of alcoholic chronic pancreatitis (ACP) and three of the samples from non-tumorous lesion of neuroendocrine tumor (NET) as control subjects. We counted the number of TLR1-11-positive cells immunohistochemically stained with anti-TLR1-11 antibodies. To identify TLR-positive cells in pancreata from type 1 AIP patients, we used a double-immunofluorescence method and counted the numbers of identifiable CD68-, CD163-, CD123-, and CD20-positive cells. RESULTS: In type 1 AIP, TLR7 (8.815 ± 1.755), TLR8 (3.852 ± 1.489), and TLR10 (3.852 ± 0.921) were highly expressed. Only the ratio of TLR7 per monocyte was significantly higher in type 1 AIP (0.053 ± 0.012) than in ACP (0.007 ± 0.004; p < 0.01) and non-tumorous lesion of NET (0.000 ± 0.000; p < 0.01). In type 1 AIP, the CD163 to TLR7 ratio (0.789 ± 0.031) was significantly higher both than that of CD123 to TLR7 ratio (0.034 ± 0.006; p < 0.001) and CD20 to TLR7 ratio (0.029 ± 0.010; p < 0.001). CONCLUSIONS: TLR7 might be key pattern-recognition receptors involved in the development of type 1 AIP.

Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo.

The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells.

Horrifying Basal cell carcinoma: cytological, immunohistochemical, and ultrastructural findings.

Basal cell carcinoma (BCC) is a slow-growing and frequently occurring tumor of the eyelids. Among BCC cases, there is a subtype of aggressive cases called horrifying BCC (HBCC). There are also rare BCC cases that show neuroendocrine differentiation. Here, we describe a case of HBCC with neuroendocrine differentiation. The patient, a 41-year-old woman, presented with abnormal left eye tearing and left cheek pain. On computed tomography imaging, a tumor that extended to the left orbit was detected in the left cheek. On cytological examination of fine-needle aspiration (FNA) samples, the tumor cells were observed as sheet-like clusters and single bare nuclei with a clear background; peripheral palisading was not clearly seen. On examination of the biopsy specimen taken after FNA, the tumor was found to be composed of cancer cell nests with scattered peripheral palisading in the dermis. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and CD56 and were negative for CK20, synaptophysin, and chromogranin A. Membrane-bound dense-core granules were detected on ultrastructural study. A HBCC case with neuroendocrine differentiation has not been previously reported. The correlation between the presence of neuroendocrine differentiation in HBCC and patient prognosis should be further studied.

Green tea extract suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats.

BACKGROUND: Retinitis pigmentosa (RP) is a group of inherited neurodegenerative human diseases characterized by the loss of photoreceptor cells by apoptosis and eventual blindness. A single intraperitoneal (ip) injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor cell apoptosis within 7 days in rats. Green tea extract (THEA-FLAN 90S; GTE) is a common herbal supplement with pluripotent properties including antioxidant activity. The purpose of the present study was to evaluate the efficacy of GTE against photoreceptor apoptosis in 7-week-old female Sprague-Dawley rats that received a single ip injection of 40 mg/kg MNU. METHODS: The oral administration of 250 mg/kg/day GTE was initiated 3 days prior to MNU injection and continued once daily throughout the experiment. Rats were sacrificed at 12, 24, and 72 h and 7 days after MNU injection, and the eyes were examined morphologically and morphometrically. The photoreceptor cell ratio, retinal damage ratio, and retinal preservation ratio were used to determine the structural and functional alterations. The number of apoptotic photoreceptor cells per mm(2) was determined in situ by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL). Our results indicated that oral administration of GTE significantly suppressed the loss of photoreceptor cells morphometrically 7 days after MNU injection. The number of TUNEL-positive cells per mm(2) in MNU-exposed rat central retina with or without GTE administration was 981 vs. 2056 at 24 h after MNU injection. CONCLUSIONS: GTE structurally and functionally suppressed MNU-induced photoreceptor cell apoptosis. These findings indicate that GTE may help to ameliorate the onset and progression of human RP.

Multifocal adenomatous oncocytic hyperplasia of the parotid gland.

Multifocal adenomatous oncocytic hyperplasia (MAOH) is a non-neoplastic lesion that is classified as oncocytosis. MAOH is a rare entity of the parotid gland and accounts for approximately 0.1% of salivary gland lesions. Here, we report a case of MAOH of the parotid gland. The patient was a 71-year-old woman who presented with discomfort at the left side of her neck. Fine-needle aspiration cytology of the parotid gland revealed a loose sheet-like cluster of round to polygonal cells with granular cytoplasm against a hemorrhagic background. The cells had round to oval, centrally located nuclei with granular chromatin and without distinct nucleoli. Histologically, the lesion was formed of many variable-sized nodules, comprising oncocyte-like cells with small round nuclei and eosinophilic granular cytoplasm that was positive for mitochondrial antibodies. The diagnosis of MAOH is difficult to make by cytology alone, because the findings overlap with those of other oncocytic lesions. In particular, the cytological findings of MAOH have not been sufficiently reported to date. A correlation of cytology and histology was expected.

N -Methyl- N -nitrosourea-induced Renal Tumors in Rats: Immunohistochemical Comparison to Human Wilms Tumors.

N-Methyl-N-nitrosourea (MNU)-induced renal tumors in rats and Wilms tumors in humans were compared. Renal mesenchymal tumors (RMTs) and nephroblastomas (blastemal and epithelial components) in female Lewis rats treated with a single intraperitoneal injection of 50 mg/kg MNU at birth and Wilms tumors (blastemal, epithelial and mesenchymal components) in humans were analyzed for the expression of pancytokeratin (CK), vimentin, p63, α-smooth muscle actin (SMA), desmin, S-100, CD57, CD117/c-kit, Wilms tumor 1 protein (WT1) and ß-catenin. The mesenchymal components of rat RMTs and human Wilms tumors expressed vimentin, SMA and ß-catenin. The blastemal components of rat nephroblastomas and human Wilms tumors expressed vimentin, CD117/c-kit and ß-catenin. The epithelial components of rat nephroblastomas and human Wilms tumors expressed vimentin and ß-catenin. WT1 was expressed in different cellular components of rat tumors as compared with human Wilms tumors; the expression was seen in mesenchymal tumors and blastemal components of nephroblastomas in rats and epithelial components in human Wilms tumors. CK, p63 and CD57 were not expressed in rat RMTs or nephroblastomas, while CK and WT1 were expressed in epithelial components and CD57 was expressed in blastemal and epithelial components of human Wilms tumors. Rat and human tumors were universally negative for the expression of desmin and S-100. The immunohistochemical characteristics of rat renal tumors and human Wilms tumors may provide valuable information on the differences in renal oncogenesis and biology between the two species.

Curcumin suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats.

AIM: Retinitis pigmentosa is a group of inherited neurodegenerative human diseases characterized by the loss of photoreceptor cells by apoptosis and lead to eventual blindness. A single intraperitoneal (i.p.) injection of N-methyl-N-nitrosourea (MNU), an alkylating agent, causes photoreceptor cell apoptosis within seven days in rats. Curcumin is a polyphenolic natural product with pluripotent properties including antioxidant activity. The purpose of the present study was to evaluate the efficacy of curcumin against photoreceptor apoptosis in a MNU-induced retinal degeneration rat model. MATERIALS AND METHODS: Seven-week-old female Sprague-Dawley rats received a single i.p. injection of 40 mg/kg MNU. Three days prior to MNU injection, daily i.p. injections of 100 or 200 mg/kg curcumin were started, and the injections were continued once daily until sacrifice. Rats were sacrificed at 6, 12, 24 and 72 h, and 7 days after MNU, and their eyes were examined morphologically and morphometrically to evaluate the photoreceptor cell ratio and retinal damage ratio in hematoxylin and eosin-stained sections. Retinal 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were quantified by enzyme-linked immunosorbent assay (ELISA), and the apoptotic cell ratio in photoreceptor cells was determined in situ by TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL). RESULTS: Curcumin (200 mg/kg) significantly (p<0.01) suppressed the loss of photoreceptor cells, as determined by the photoreceptor cell ratio at the central retina seven days after MNU, and this effect was dose-dependent. At 12 h after MNU injection, when the oxidative DNA damage caused by MNU peaked, curcumin significantly reduced the level of 8-OHdG (0.78 vs. 0.50 ng/ml) (p<0.05) and the percentage of TUNEL-positive photoreceptor cells (17.5% vs. 10.8%) (p<0.05) as compared with MNU-exposed, curcumin-untreated retina, respectively. CONCLUSION: Curcumin inhibited MNU-induced photoreceptor cell apoptosis by suppressing DNA oxidative stress. These findings indicate that curcumin may help to suppress the onset and progression of human retinitis pigmentosa.