Drug-Induced Cutaneous Toxicity

The skin is the largest organ in the body and is continually exposed to external stimuli, such as chemical and environmental substances. Cutaneous toxicity can be broadly classified according to the mechanism of onset, namely: contact dermatitis, i.e., damage resulting from contact with a substance (irritant dermatitis, allergic contact dermatitis, chemical burns); photosensitivity, i.e., caused by combined effects of a substance and ultraviolet light (phototoxic dermatitis, photoallergic contact dermatitis); contact urticaria; chemical-induced acne; pigmentary disturbance; drug rash; hair disturbance; nail disturbance; or tumor-induced. This review outlines the function and structure of the skin, outlining characteristics of these types of cutaneous toxicity. In recent years, advances have been made in the development of pharmaceutical products targeting specific molecules or genes and nanotechnology-based pharmaceutical products, raising concerns about the onset of toxicity by novel mechanisms involving new pharmaceutical products. Therefore, it is important to understand the basic toxicity-related changes described herein

A Case Report of Lipid-Rich Carcinoma of the Breast Including Histological Characteristics and Intrinsic Subtype Profile

A 57-year-old Japanese woman with schizophrenia, who had received long-term treatment with neuroleptics, noticed a painless, pea-sized lump in her right breast. She was admitted to our hospital and a malignant tumor was diagnosed. The patient underwent a conservative radical mastectomy (Patey's operation). The excised tumor measured 2.0 × 1.2 × 1.1 cm in diameter, and its cut surface was grayish-white. Histologically, tumor cells with clear to foamy cytoplasm were invariably Oil Red O-positive and periodic acid Schiff-negative with or without diastase digestion. The tumor was diagnosed as a lipid-rich carcinoma accompanied by an in situ component. Neuroleptics increase serum prolactin levels by interfering with dopaminergic inhibition of prolactin secretion. Immunohistochemical analysis revealed that, although prolactin was not detected, the tumor cells expressed prolactin receptor, indicating prolactin as the genesis of this neoplasm. In immunohistochemical intrinsic subtype analysis, the tumor was negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 1 and 2, and basal cytokeratins (CK5, CK6, and CK14), indicating an unclassified (all-marker negative) subtype. Axillary lymph nodes were free of metastasis (stage I), and the patient has been well for 20 years without any evidence of recurrence

A Case of Multiple Pilosebaceous Cysts

Multiple pilosebaceous cysts include the entities of steatocystoma multiplex and eruptive vellus hair cysts (EVHCs). Multiple pilosebaceous cysts are proposed to be one entity originating in the pilosebaceous duct, since steatocystoma multiplex and EVHCs are frequently present concomitantly and are caused by a cystic change in the same pilosebaceous duct. Here, we describe a patient with yellowish papules, 3–8 mm in diameter, on the neck and skin-colored or light-brown papules, 1–3 mm in diameter, on the neck, chest and upper abdomen. The smaller cysts were histopathologically diagnosed as EVHCs. The larger cysts had both features of EVHCs and steatocystoma multiplex. Therefore, a diagnosis of these lesions was made as multiple pilosebaceous cysts. Our case supports the proposition that multiple pilosebaceous cysts are a more appropriate diagnosis than the terms of EVHCs and steatocystoma multiplex

Well-Differentiated Liposarcoma, an Atypical Lipomatous Tumor, of the Mesentery: A Case Report and Review of the Literature

Mesenteric liposarcoma is a rare neoplasm. Here, we report the case of a 73-year-old Japanese man with a well-differentiated (WD) liposarcoma of the mesentery. Due to rapid growth of the abdominal mass and abdominal insufficiency, a tumorectomy was performed. The excised tumor was 12.4 × 9.6 cm in size and weighed 548 g. Cut sections showed a lobulated yellow and/or grayish-colored appearance. The histological features were predominantly those of the sclerotic and lipoma-like variants of WD liposarcoma. The cytoplasm of most spindle cells was diffusely immunoreactive for CD34, while fat cells were positive for S-100 protein. Some spindle cell nuclei were positive for CDK4, and a few were positive for MDM2. The average Ki-67 proliferation index in tumor cells was 10%, and androgen receptor expression was detected in tumor cell nuclei. The present case and 11 cases identified from a literature search were reviewed. The WD mesenteric liposarcomas developed in patients in the fourth to seventh decades of life (mean age 57.9 years). The patients consisted of 7 men and 5 women. All tumors were larger than 10 cm in diameter at the time of surgery. Complete resection might be the only curative therapy for WD liposarcomas of the mesentery, but long-term follow-up is needed because of the possibility of a local recurrence of the tumor

N -Ethyl- N -Nitrosourea Induces Retinal Photoreceptor Damage in Adult Rats

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p