Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fields. However, with the wide application and increasing production of CNTs, their potential risks have led to concerns regarding their impact on environment and health. The shape of some types of CNTs is similar to asbestos fibers, which suggests that these CNTs may cause characteristic pleural diseases similar to those found in asbestos-exposed humans, such as pleural plaques and malignant mesothelioma. Experimental data indicate that CNTs can induce lung and pleural lesions, inflammation, pleural fibrosis, lung tumors, and malignant mesothelioma upon inhalation in the experimental animals. In this review, we focus on the potential of MWCNTs to induce diseases similar to those by asbestos, molecular and cellular mechanisms associated with these diseases, and we discuss a method for evaluating the pleural toxicity of MWCNTs.

Tumor research has largely relied on xenograft models created by the engraftment of cultured cell lines derived from tumor tissues into immunodeficient mice for in vivo studies. Like in vitro models, such models retain the ability of tumor cells to continuously proliferate, so they have been used to predict the clinical relevance of studies on proliferating cells. However, these models are composed of a limited population of tumor cells, which include only those tumor cells that are able to adapt to culture conditions, and thus they do not reflect the diversity and heterogeneity of tumors. This, at least in part, explains the poor predictivity of non-clinical data in the research and development of molecularly targeted drugs. Recently, research focus has been directed towards patient-derived xenograft (PDX) models created by directly engrafting tumor tissues, which have not been cultured in vitro, into immunodeficient mice. PDX models reflect the diversity and heterogeneity of tumors, and the evidence they provide can be verified in the patient tissues from which they were derived originally. PDX models are anticipated to efficiently bridge non-clinical and clinical data in translational research. Based on the evidence obtained from our research experience, this review describes the characteristics of PDX models for acting as tumor models, and elucidates the points to consider when attempting to establish these models.

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus, and hypertension is considered to be a risk factor for DPN in patients with type 1 diabetes (T1DM). However, the morphological effects of hypertension on DPN are unclear. In this study, we investigated the effect of hypertension on DPN by investigating the changes in unmyelinated and myelinated nerve fibers in hypertensive rats with alloxan (AL)-induced T1DM. Thirteen-week-old WBN/Kob rats with AL-induced diabetes were allocated to receive tap water only (AL group), tap water containing 0.5% saline (0.5AN group), or tap water containing 0.75% saline (0.75AN group) for 15 weeks. Hyperglycemia was maintained for 15 weeks, and the animals were euthanized at 28 weeks. By 23 weeks of age, the systolic blood pressure was significantly higher in the 0.75AN and 0.5AN groups than in the AL group and was unchanged in all groups at 28 weeks. The number of intraepidermal sensory unmyelinated nerve fibers was significantly smaller in the 0.75AN and 0.5AN groups than in the AL group. The axonal size in the myelinated tibial and sural nerve fibers was significantly smaller in the 0.75AN group than in the AL group. Furthermore, luminal narrowing and endothelial hypertrophy were observed in the endoneurial tibial nerve vessels in the 0.75AN group. These findings suggest that superimposing hypertension on hyperglycemia may accelerate a reduction in the number of small unmyelinated sensory nerve fibers in the skin and induce mild axonal atrophy in myelinated tibial and sural nerve fibers in rats with AL-induced T1DM.

A mass was detected in the right tympanic cavity of a 15-week-old male Crl:CD(SD) rat. Histological examination revealed papillary or tubular proliferations of epithelial cells including ciliated cells that produce mucus and have an abundant eosinophilic matrix. The malignancy of this tumor was revealed by its destructive proliferation, cellular polymorphism, and high proliferative activity. The tumor was diagnosed as a middle ear adenocarcinoma due to its location and histological characteristics. This is the first report of a middle ear adenocarcinoma in rats and the first middle ear tumor accompanied by eosinophilic matrix observed in either humans or animals. The eosinophilic matrix was positive for periodic acid-Schiff and periodic acid-silver methenamine stains and for laminin and collagen Type IV, immunohistochemically, but negative for Congo red, which suggested that this matrix was a basement membrane substance.

Here, we reported a spontaneous case of membranoproliferative glomerulonephritis observed in a young ICR mouse. A 5-week-old female mouse was euthanized owing to abdominal swelling and increased body weight. At necropsy, generalized subcutaneous edema, and clear, colorless, non-viscous ascites were observed. Histologically, the kidneys showed diffuse, bilateral glomerular lesions. The lesions were characterized by thickening and double contour of the basement membrane and an increase in mesangial cells and matrix, resulting in the narrowing of the capillary lumen. Additionally, eosinophilic hyaloid material accumulated in the subendothelial areas and Bowman’s space. The material was positive for periodic acid-Schiff, complement component C3, or immunoglobulin G, stained red by Masson’s trichrome, and stained blue by phosphotungstic acid-hematoxylin stain and was considered to be plasma due to glomerular leakage. The glomerular lesion was diagnosed as membranoproliferative glomerulonephritis, and an uncertain endothelial injury was suspected as the cause.

We examined a 110-week-old RccHan^TM: WIST Wistar male rat from a carcinogenicity study. No clinical signs were observed, and the rat was sacrificed at the end of the study. Macroscopically, within the midline of the sphenoid bone, was a 10 mm, non-infiltrative, soft, heterogeneous mass. Microscopic evaluation showed an expansile, cystic proliferation, consisting of two patterns of epithelial lining: well-differentiated areas lined by a single layer to a pseudostratified, ciliated-cuboidal epithelia with Goblet cells compatible with Rathke’s cleft cyst; and poorly differentiated ones that formed irregular papillary projections, covered by atypical epithelia with squamous differentiation and hyperkeratosis compatible with areas of craniopharyngioma. Pleomorphisms were high in atypical areas with up to 2–3 mitotic figures per high power field. Within the cystic cavities, there was abrupt keratinization, mucus, cholesterol clefts, and foci of foamy macrophages. Immunohistochemistry revealed strong pancytokeratin immunolabelling of neoplastic cells confirming the epithelial origin. Well-differentiated epithelial lining showed cytokeratin-20 and cytokeratin-8 immunoreactivity, whereas the atypical squamous epithelium presented with a loss of cytokeratin-20 positive signal and weak to moderate positivity with cytokeratin-8. Areas compatible with a Rathke’s cleft cyst and craniopharyngioma were considered to co-exist in the same mass.

The Sprague Dawley (SD) and Han Wistar (HW) are the two most commonly used rat strains in Europe and the US, with the Han Wistar increasing in popularity because of its greater longevity and lower tumor burden. This survey was undertaken at Covance CRS (Huntingdon and Eye) to compare in-house longevity and common spontaneous tumor profiles of the two strains with published data. Data were compiled from 104-week studies started between 2010 and 2017. Mean survival was greater for both sexes of HWs when compared with SDs. Pituitary tumors were the commonest in both strains, with slightly higher incidences and more malignant tumors in SDs of both sexes. Mammary tumors were the second most common tumor in both strains; the incidence being greater in SDs compared to HWs. Benign pheochromocytomas of the adrenal and fibromas of the skin/subcutis were commoner in male SDs than in HWs. Granular cell tumors of the uterine tract were recorded only in SDs, but uterine stromal and glandular tumors were more common in HWs, which also displayed a higher incidence of granulosa cell tumors of the ovaries. Vascular tumors of the mesenteric lymph nodes, thymomas and follicular cell tumors of the thyroids were recorded at a higher incidence in HWs than in SDs. Tumor profiles of other common tumors were broadly similar between the two strains. The results of this survey correlate closely with similar comparisons made at other laboratories, and with data compiled at our laboratories 10 years ago and published as a poster.