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2. Dill JA, Lee KM, Renne RA, Miller RA, Fuciarelli AF, Gideon KM, Chan PC, Burka LT, Roycroft JH: Alpha 2u-globulin nephropathy and carcinogenicity following exposure to decalin (decahydronaphthalene) in F344/N rats. Toxicol Sci; 2003 Apr;72(2):223-34
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  • (2) compare the kidney concentrations of decalin, 2-decalone, and alpha2u-globulin in males over 2 to 13 weeks of decalin exposure; and (3) correlate male rat nephropathy observed in the 13-week study with renal carcinogenicity in the two-year study.
  • Right kidneys were collected from male rats at weeks 2 and 6 and from both sexes at week 13, homogenates were prepared using the whole kidney, and these homogenates were analyzed for alpha2u-globulin, decalin, and 2-decalone.
  • Left kidneys were evaluated for histopathology and cell proliferation utilizing a proliferating cell nuclear antigen technique and counting proximal renal tubular epithelial cells to determine cell labeling indices.
  • Decalin exposure caused increases in kidney weight, urinalysis parameters (protein, AST, LDH), kidney alpha2u-globulin concentration, and proximal convoluted renal tubular cell proliferation in males.
  • These changes were accompanied by microscopic lesions (accumulation of hyaline droplets in cortical tubules, regeneration of proximal tubular epithelium, and granular casts in medullary tubules) clearly linked to alpha2u-globulin nephropathy.
  • Kidney concentrations of decalin, 2-decalone, and alpha2u-globulin in exposed females were negligible, while females excreted greater amounts of decalol metabolites in urine than males at weeks 2 and 6.
  • Chronic exposure induced a spectrum of nonneoplastic and neoplastic lesions in the renal cortex of males, ranging from regenerative lesions of chronic nephropathy to tubular carcinomas.
  • Incidences of renal tubular adenoma, tubular carcinoma, combined tubular adenomas and carcinomas, cortical tubular hyperplasia, hyaline droplet accumulation, hyperplasia of pelvic epithelium, and mineralization in renal papilla were increased in exposed males compared to controls.
  • It was concluded that the carcinogenic effect on the renal cortical epithelium of male rats exposed to decalin was related to increased turnover of this epithelium, resulting from the cytotoxic effects of alpha2u-globulin accumulation in the renal cortical tubular cell cytoplasm.
  • [MeSH-major] Adenoma / chemically induced. Carcinogens / toxicity. Carcinoma / chemically induced. Kidney / drug effects. Kidney Neoplasms / chemically induced. Naphthalenes / toxicity
  • [MeSH-minor] Administration, Inhalation. Alpha-Globulins. Animals. Carcinogenicity Tests. Cell Division / drug effects. Dose-Response Relationship, Drug. Female. Hyalin / metabolism. Kidney Tubules, Proximal / drug effects. Kidney Tubules, Proximal / pathology. Male. Organ Size / drug effects. Rats. Rats, Inbred F344. Sex Factors. Solvents

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  • (PMID = 12660359.001).
  • [ISSN] 1096-6080
  • [Journal-full-title] Toxicological sciences : an official journal of the Society of Toxicology
  • [ISO-abbreviation] Toxicol. Sci.
  • [Language] eng
  • [Grant] United States / NIEHS NIH HHS / ES / N01-ES-55392
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Alpha-Globulins; 0 / Carcinogens; 0 / Naphthalenes; 0 / Solvents; 0 / alpha 2u globulin; 88451Q4XYF / decalin
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3. Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M: PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol; 2002 Dec;26(12):1553-66
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  • [Title] PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21).
  • The reappraisal of genetically defined subsets of renal tumors can help to highlight the key pathologic features of specific neoplastic entities.
  • We report the morphologic, immunophenotypic, ultrastructural, and molecular features of 11 renal carcinomas bearing a t(X;1)(p11.2;q21) and/or the resulting PRCC-TFE3 gene fusion.
  • Neoplastic cells were typically characterized by irregularly shaped nuclei with vesicular chromatin and small nucleoli not visible with a 10x objective, and cytoplasm that ranged from clear to densely granular and eosinophilic.
  • Ultrastructurally, all of the six neoplasms examined showed features consistent with conventional-type (clear cell) renal carcinoma, although two demonstrated distinctive intracisternal microtubules.
  • The differential diagnosis includes conventional-type papillary renal cell carcinoma, conventional-type (clear cell) renal carcinoma, and the ASPL-TFE3 renal carcinomas associated with the t(X;17)(p11.2;q25), with the latter two being morphologically the most similar to the t(X;1) renal carcinomas.
  • Aside from their distinctive clinicopathologic features described here, there is experimental evidence suggesting that these tumors may show differential sensitivity to certain chemotherapeutic agents.
  • [MeSH-major] Biomarkers, Tumor / genetics. Carcinoma, Renal Cell / pathology. Cell Cycle Proteins. Chromosomes, Human, Pair 1. DNA-Binding Proteins / genetics. Kidney Neoplasms / pathology. Neoplasm Proteins. Oncogene Proteins, Fusion / genetics. Proteins / genetics. Transcription Factors / genetics
  • [MeSH-minor] Adolescent. Adult. Basic Helix-Loop-Helix Leucine Zipper Transcription Factors. Child. DNA Primers. DNA, Neoplasm / analysis. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Karyotyping. Male. Middle Aged. Reverse Transcriptase Polymerase Chain Reaction

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  • (PMID = 12459622.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA 95785
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0 / Biomarkers, Tumor; 0 / Cell Cycle Proteins; 0 / DNA Primers; 0 / DNA, Neoplasm; 0 / DNA-Binding Proteins; 0 / Neoplasm Proteins; 0 / Oncogene Proteins, Fusion; 0 / PRCC protein, human; 0 / Proteins; 0 / TFE3 protein, human; 0 / Transcription Factors
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4. Hard GC: Significance of the renal effects of ethyl benzene in rodents for assessing human carcinogenic risk. Toxicol Sci; 2002 Sep;69(1):30-41
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  • [Title] Significance of the renal effects of ethyl benzene in rodents for assessing human carcinogenic risk.
  • In the two-year carcinogenicity study conducted by the National Toxicology Program (NTP) and reported in 1999, ethyl benzene administered by inhalation to Fischer 344 rats was associated with an increase in renal tubule tumors in males after standard evaluation of a single section of each rat's kidney, and in both males and females after evaluation of step-sectioned kidney.
  • In the present study, the kidneys of all rats in the NTP bioassay were histopathologically reevaluated with the purpose of attempting to define a mode of action underlying the development of the renal tumors.
  • In the reevaluation, the increases in renal tubule tumor incidence in the high-dose groups exposed to 750 ppm were confirmed, as well as increases in the precursor lesion, atypical tubule hyperplasia (ATH).
  • The vast majority of the proliferative lesions were of basophilic type and, apart from three carcinomas in the high-dose males, either small adenomas or foci of ATH.
  • Statistical analysis of the proliferative lesion and CPN data revealed a highly significant correlation between ATH/renal tumor incidence and end-stage CPN, and adjusting for end-stage CPN removed any statistically significant difference in renal tumor incidence between treated groups and controls.
  • Careful examination of renal tubules revealed no evidence of renal tubule injury or increased mitotic activity that would support sustained cytotoxicity/cell regeneration as a mode of action for tumor development.
  • An absence of granular casts and linear papillary mineralization discounted the possibility of alpha(2u)-globulin nephropathy as the primary underlying basis in male rats, even though subchronic studies revealed a modest accumulation of hyaline droplets in proximal tubules.
  • Based on the close association of ATH and renal tumors with CPN, it was concluded that chemically induced exacerbation of CPN was the mode of action underlying the development of renal neoplasia, a pathway that is considered to have no relevance for extrapolation to humans.
  • [MeSH-major] Benzene Derivatives / toxicity. Carcinogens / toxicity. Kidney Diseases / chemically induced
  • [MeSH-minor] Adenoma / chemically induced. Adenoma / pathology. Animals. Carcinoma / chemically induced. Carcinoma / pathology. Chronic Disease. Disease Progression. Female. Humans. Hyperplasia / pathology. Kidney / pathology. Kidney Neoplasms / chemically induced. Kidney Neoplasms / pathology. Kidney Tubules / pathology. Male. Rats. Regeneration / drug effects. Risk Assessment

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  • (PMID = 12215658.001).
  • [ISSN] 1096-6080
  • [Journal-full-title] Toxicological sciences : an official journal of the Society of Toxicology
  • [ISO-abbreviation] Toxicol. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzene Derivatives; 0 / Carcinogens; L5I45M5G0O / ethylbenzene
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5. Fresini A, Rossiello L, Severino BU, Del Prete M, Satriano RA: Giant basal cell carcinoma. Skinmed; 2007 Jul-Aug;6(4):204-5
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  • [Title] Giant basal cell carcinoma.
  • The patient's history revealed mild hypertension, ischemic cardiopathy treated with percutaneous transluminal coronary angioplasty and anticoagulant drugs, and moderate chronic renal insufficiency.
  • Histologic examination of a biopsy specimen taken from the margin of the lesion displayed a superficial area of ulceration and invasion of the deeper dermis and subcutaneous tissue (Figure 2A and Figure 2B).
  • The tumor mostly showed an adenoid pattern: gland-like structures and cystic spaces sometimes containing amorphous or granular material, surrounded by strands of basaloid cells devoid of any peripheral palisading (Figure 2C).
  • Therefore, a diagnosis of basal cell carcinoma, adenoid subtype, was made.
  • Because the patient was taking anticoagulant drugs and had unstable renal and cardiac function, surgical treatment was at least temporarily excluded, and the patient was referred for radiation therapy.
  • [MeSH-major] Carcinoma, Basal Cell / pathology. Skin Neoplasms / pathology

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  • (PMID = 17618177.001).
  • [ISSN] 1540-9740
  • [Journal-full-title] Skinmed
  • [ISO-abbreviation] Skinmed
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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6. National Toxicology Program: NTP toxicology and carcinogenesis studies of decalin (CAS No. 91-17-8) in F344/N rats and B6C3F(1) mice and a toxicology study of decalin in male NBR rats (inhalation studies). Natl Toxicol Program Tech Rep Ser; 2005 Jan;(513):1-316
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  • Decalin was nominated for study by the National Cancer Institute because of its chemical structure, its potential for consumer exposure, and a lack of adequate testing of the chemical.
  • Male NBR rats do not produce alpha2u-globulin; the NBR rats were included to study the relationship of alpha2u-globulin and renal lesion induction.
  • Renal toxicity studies were performed in male F344/N and NBR rats.
  • The numbers of labeled cells and the labeling indices in the left kidney of 200 and 400 ppm F344/N male rats were significantly greater than those in the chamber controls.
  • Kidney weights of male F344/N rats exposed to 50 ppm or greater were significantly increased.
  • Exposure-related hyaline droplet accumulation, degeneration and regeneration of renal cortical tubules, and granular casts occurred in the kidney of exposed F344/N male rats.
  • 3-MONTH STUDY IN RATS: Groups of 25 male and 20 female F344/N rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 2 (five male renal toxicity rats), 6 (10 male and 10 female clinical pathology rats), or 14 (10 core study rats) weeks.
  • Urinalysis results indicated that decalin exposure caused increases in urine glucose and protein concentrations and enzyme activities that were consistent with the renal lesions observed microscopically.
  • Renal toxicity studies were performed on rats sacrificed at 2 and 6 weeks and at the end of the study.
  • In kidney tissue examined for cell proliferation, the numbers of PCNA-labeled cells and labeling indices were generally significantly greater than those of the chamber controls in exposed groups of rats at all three time points.
  • Concentrations of alpha2u-globulin in the kidney as well as the alpha2u-globulin/soluble protein ratios were significantly increased at week 2 in all exposed groups and in the 200 and 400 ppm groups at week 6 and at the end of the study.
  • Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm or greater were increased.
  • Incidences of renal tubule regeneration and granular casts in the medulla of the kidney in exposed male rats were increased, and the severities of hyaline droplets generally increased with increasing exposure concentration.
  • Incidences of renal tubule adenoma and adenoma or carcinoma (combined) and of benign or malignant pheochromocytoma (combined) of the adrenal medulla in 100 and 400 ppm males were significantly increased.
  • Nonneoplastic lesions related to decalin exposure occurred in the kidney of male rats.
  • CONCLUSIONS: Under the conditions of these studies, there was clear evidence of carcinogenic activity of decalin in male F344/N rats based on increased incidences of renal tubule neoplasms.
  • Exposure of male rats to decalin resulted in nonneoplastic lesions of the kidney characteristic of alpha2u-globulin accumulation.
  • [MeSH-minor] Administration, Inhalation. Animal Feed / analysis. Animals. Atmosphere Exposure Chambers. Body Weight / drug effects. Female. Genitalia, Male / pathology. Kidney Diseases / chemically induced. Kidney Diseases / pathology. Male. Mice. Mice, Inbred Strains. Mutagens / toxicity. Organ Size / drug effects. Rats. Rats, Inbred F344. Reproduction / drug effects

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  • (PMID = 15891779.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Mutagens; 0 / Naphthalenes; 88451Q4XYF / decalin
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7. Lazzeri M, Vannucchi MG, Zardo C, Spinelli M, Beneforti P, Turini D, Faussone-Pellegrini MS: Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder. Eur Urol; 2004 Dec;46(6):792-8
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  • The aim of this study is to identify, by immunohistochemistry, the cell types expressing TRPV1 in the human urinary bladder.
  • MATERIAL AND METHODS: Specimens, obtained from normal urinary bladder by multiple biopsy and from ureter at the time of radical nefrectomy for renal cell carcinoma, were fixed and frozen.
  • In the urothelial cells, the labelling was slightly granular.
  • [MeSH-major] Receptors, Drug / analysis. Urinary Bladder / chemistry

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  • (PMID = 15548449.001).
  • [ISSN] 0302-2838
  • [Journal-full-title] European urology
  • [ISO-abbreviation] Eur. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Receptors, Drug; 0 / TRPV Cation Channels; 0 / TRPV1 receptor
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8. Gollob JA, Veenstra KG, Mier JW, Atkins MB: Agranulocytosis and hemolytic anemia in patients with renal cell cancer treated with interleukin-12. J Immunother; 2001 Jan-Feb;24(1):91-8
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  • [Title] Agranulocytosis and hemolytic anemia in patients with renal cell cancer treated with interleukin-12.
  • In this article, the authors describe two patients with renal cell cancer in whom grade 4 neutropenia and grade 3 hemolytic anemia developed, respectively, during treatment with twice-weekly intravenous recombinant human interleukin-12 (rhIL-12) during a phase 1 trial.
  • The severe neutropenia was associated with bone marrow agranulocytosis and a preponderance of large granular lymphocytes in the peripheral blood, whereas the hemolytic anemia was negative for the Coombs test and associated with splenomegaly.
  • These findings indicate that rhIL-12 can induce unique hematologic toxic effects that can be reversed with immunosuppressive drugs.
  • [MeSH-major] Anemia, Hemolytic / immunology. Carcinoma, Renal Cell / drug therapy. Interleukin-12 / adverse effects. Interleukin-12 / therapeutic use. Kidney Neoplasms / drug therapy. Neutropenia / immunology
  • [MeSH-minor] Aged. Female. Humans. Injections, Intravenous. Male. Middle Aged. Recombinant Proteins / administration & dosage. Recombinant Proteins / adverse effects. Recombinant Proteins / therapeutic use

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  • (PMID = 11211153.001).
  • [ISSN] 1524-9557
  • [Journal-full-title] Journal of immunotherapy (Hagerstown, Md. : 1997)
  • [ISO-abbreviation] J. Immunother.
  • [Language] eng
  • [Publication-type] Case Reports; Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Recombinant Proteins; 187348-17-0 / Interleukin-12
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9. National Toxicology Program: NTP technical report on the toxicology and carcinogenesis studies of Stoddard Solvent IIC (Cas No. 64742-88-7) in F344/N rats and B6C3F1 mice (inhalation studies). Natl Toxicol Program Tech Rep Ser; 2004 Sep;(519):1-274
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  • It is used as a dry cleaning agent; as an extraction, cleaning, and degreasing solvent; and as a solvent in aerosols, paints, wood preservatives, asphalt products, lacquers, and varnishes.
  • The relative kidney, liver, and testis weights of all exposed groups of males and the absolute kidney weights of males exposed to 550 mg/m3 or greater were increased.
  • The incidences of renal tubule granular casts were significantly increased in males exposed to 550 mg/m3 or greater, and the severities of renal tubule hyaline droplet accumulation, granular casts, and regeneration increased with increasing exposure concentration in males.
  • The incidences of goblet cell hypertrophy of the nasal respiratory epithelium in males and females exposed to 2,200 mg/m3 were significantly increased.
  • The incidences of hematopoietic cell proliferation of the spleen in all exposed groups of females were greater than that in the chamber controls.
  • Additional groups of 10 males and 10 females were exposed to the same concentrations for 3 months for renal toxicity analyses.
  • Cell proliferation analyses were performed in the left kidney of males and females after 3 months of exposure.
  • The amount of alpha2u-globulin in the right kidney of males increased with increasing exposure concentration.
  • Also, the incidences of granular casts and cortical tubule degeneration and regeneration were generally increased in exposed males, as was the severity of hyaline droplets.
  • Due to increased incidences of renal tubule hyperplasia in males at 2 years, extended kidney evaluations were conducted; a slightly increased incidence of renal tubule adenoma occurred in the 1,100 mg/m3 group.
  • Nonneoplastic lesions related to Stoddard solvent IIC exposure occurred in the kidney of males.
  • However, the incidences of hepatocellular adenoma or carcinoma (combined) and hepatocellular carcinoma alone in exposed males and females were not significantly increased.
  • CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of Stoddard solvent IIC in male F344/N rats based on increased incidences of adrenal medulla neoplasms; the slightly increased incidences of renal tubule adenoma may have been related to Stoddard solvent IIC exposure.
  • Exposure of male rats to Stoddard solvent IIC resulted in nonneoplastic lesions of the kidney characteristic of alpha2u-globulin accumulation.
  • [MeSH-minor] Adrenal Gland Neoplasms / chemically induced. Adrenal Gland Neoplasms / pathology. Animals. Carcinogenicity Tests. Female. Growth / drug effects. Humans. Inhalation Exposure / adverse effects. Kidney Diseases / chemically induced. Male. Mice. Mice, Inbred Strains. Mutagenicity Tests. Neoplasms / chemically induced. Neoplasms / pathology. Occupational Exposure / adverse effects. Pregnancy. Rats. Rats, Inbred F344. Reproduction / drug effects. Teratogens / toxicity. Time Factors

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  • (PMID = 15625557.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article; Technical Report
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Hydrocarbons; 0 / Solvents; 0 / Teratogens; 8052-41-3 / Stoddard solvent
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