Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 66-year-old man, who had been diagnosed with vasculitis 1 year previously, presented at our hospital with edema of the left leg and erythema of more than 1 year's duration (Fig. 1). He had been diagnosed with dermatitis and vasculitis in another hospital without being biopsied, and had been treated with topical steroids, oral antihistamines, antibacterials, hydrochlorothiazide, and Radix Salviae Miltiorrhizae, which provided some temporary benefit. He had no other complaints and denied any family history of breast cancer. No history of radiation therapy to the chest or hormone therapy was elicited. After biopsy of the skin lesion in our hospital, a breast mass was found, followed by lumpectomy for pathologic examination. The results of a physical examination showed a well-developed and well-nourished man. There was a 2-cm, palpable subareolar mass in the left breast with inguinal lymph node and axillary lymph node swelling; no discharge or tenderness was evident on breast mass palpation. The skin and nipple overlying the breast mass were normal. The right breast was unremarkable. Examination revealed solitary, nonpitting edema of the left thigh and buttock with erythema. Laboratory tests showed normal plasma alpha-l-fucosidase (AFU) and alpha-fetoprotein (AFP) and a carcinoembryonic antigen (CEA) level of 145.9 microg/L. Ultrasonography showed normal resonance in the prostate, bladder, liver, spleen, pancreas, and kidney, but abnormal resonance beside the aorta. Computed tomography (CT) showed lymph node swelling in the mediastina. The skin biopsy from the erythema of the left thigh revealed metastatic carcinoma (atypical cells in the lymphatic vessel). Pathologic examination of the breast mass revealed intraductal carcinoma (Figs 2 and 3). The breast mass was positive for presenilin-2 (PS2), c-erbB-2, and cytokeratin (CK), but negative for estrogen receptor (ER) and progesterone receptor (PR). The cutaneous metastasis was positive for CK but negative for PR, ER, PS2, and c-erbB-2.
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PMID:A case report of remote cutaneous metastasis from male breast carcinoma. 1761 6

CI-1033 (canertinib) is an irreversible inhibitor of the erbB family of transmembrane tyrosine kinase receptors, including the epidermal growth factor (EGF) receptor. Various inhibitors of the EGF receptor, including CI-1033, have resulted in cutaneous toxicity in humans as a common adverse event. In a chronic toxicity study in rats, CI-1033 produced cutaneous lesions with morphologic characteristics similar to that reported in man. Here the authors describe in detail the dermal changes observed, along with other noteworthy findings of that study. Male and female Wistar rats (15/sex/group) were administered CI-1033 for 27 weeks at 2.5, 5, or 10 mg/kg (15, 30, or 60 mg/m(2), respectively) by gavage. Control animals (15/sex) received vehicle alone (aqueous 0.5% methylcellulose) in a dose volume of 5 mL/kg. Six animals/sex/dose were included for toxicokinetic evaluations. Skin lesions were the primary drug-related toxicity and occurred at > or = 2.5 mg/kg in a dose-dependent fashion. The major gross lesions were papules that evolved into crusts and scales that were first observed in weeks 1 and 3, respectively. Alopecia developed in conjunction with the papular eruptions. Skin changes were most pronounced in females, possibly due to higher drug levels. In week 13, CI-1033 plasma AUC(0-24) values were 527 to 1980 ng.h/mL in males and 844 to 2920 ng x h/mL in females at 2.5 to 10 mg/kg. Microscopic changes could be described as 3 patterns that affected the tail and body (haired skin). Pattern 1 consisted of epidermal changes that started as a superficial, perivascular spongiotic dermatitis with evolving epidermal hyperplasia, scale-crusts, and areas of ulceration. Areas of hyperplasia on the tail were often associated with the development of new hair follicles. Pattern 2 was characterized by a suppurative to pyogranulomatous infundibular folliculitis. Pattern 3 consisted of abnormally oriented hair follicles with malformed hair shafts that were associated with a deeper (isthmic) folliculitis; this correlated with alopecia. Elevations in bone marrow myeloid counts correlated with a peripheral leukocytosis, consistent with inflammatory changes in the dermis. In addition, hepatic cholestasis and epithelial atrophy in the gastrointestinal tract and vagina occurred at > or = 2.5 mg/kg. In conclusion, CI-1033 produced cutaneous lesions involving the epidermis and hair follicle, and the morphologic characteristics were similar to that reported in clinical studies with various inhibitors of the EGF receptor. These changes are consistent with pharmacologic inhibition of the EGF receptor in these tissues and demonstrate that the rat can serve as an animal model for investigating the mechanisms for this toxicity.
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PMID:Cutaneous lesions in the rat following administration of an irreversible inhibitor of erbB receptors, including the epidermal growth factor receptor. 1846 88