Anticancer Activity and Mechanisms of Action of MAPK pathway inhibitors


LANHAM JE, BARRIE T, KOHNER EM. had suffered general aching and malar rashes on her face 4 months before, at which time leukocyte count was 3.20109/L on routine examination at a private clinic. The visual loss began suddenly, and the skin lesions were aggravated several days before admission. She first visited the Division of Ophthalmology and was referred to the Rheumatology Department to exclude connective tissue diseases. At admission, she looked acutely ill, but her vital signs were normal. On ophthalmologic examination, the visual acuity of both eyes was considerably decreased, the BMS-754807 visual acuity of the right eye being 0.14/5 and that of the left eye FC20 (finger count 20cm). On physical examination, erythematous elevated eruptions were noted on the fingertips, knuckle areas, arms, and malar rash was developed on areas of the face, and 2nd, 3rd and 4th proximal interphalangeal joints of both hands were swollen slightly (Figure 1). These skin lesions were tender on pressure. Open in a separate window Figure 1. Cutaneous lesions of SLE. Initial laboratory findings revealed mild anemia, with a hemoglobin value of 11.7 gm/dL. The white blood cell count was 5.10109/L, with 45.5% neutrophils, 43.8% lymphocytes and 8.2% monocytes, and the platelet count was 149109/L. Blood urea nitrogen and creatinine concentrations were normal. C-reactive protein was 0.3 mg/dL (normal 0.8 mg/dL) and the erythrocyte sedimentation rate was 32 mm/h (normal 20 mm/h) by the Wintrobe method. Urinalysis revealed normal findings without blood or casts. The results of immunologic tests were as follows: antinuclear antibody 1:1280 with a speckled pattern; anti-Sm antibody, VDRL, and anti-Ro/La negative, anticardiolipin antibody IgM 6.2 MPL U/mL (normal 7 U/mL); IgG 8.3 GPL U/mL (normal 10 U/mL); anti-ds DNA antibody 5.15 IU/ml (normal 5.3 I U/mL); C3 69.5 mg/dL (normal range 55120 mg/dL); and C4 10.5 mg/dL (normal range 2050 mg/dL). On admission, the ophthalmoscopic examination with mydriasis showed multiple retinal hemorrhages and cotton-wool spots in GLB1 the right eye. The retinal arteries were constricted, and tortuous veins were surrounded by exudates. In the left eye, there was profuse vitreous and disc hemorrhage and ghost vessels (Figure 2). Retinal fluorescein angiography showed ischemic changes secondary to venous nonperfusion and leakage of dye from the retinal vessels. These features strongly suggested the clinical diagnosis of vaso-occlusive disease secondary to ocular SLE. Open in a separate window Figure BMS-754807 2. Fundoscopic examination showed multiple hemorrhages and cotton-wool spots in both eyes. Panretinal argon laser photocoagulation therapy was done on the first, second and fourth day after admission but, on 6th day, the signs and symptoms of both eyes were unchanged. She was treated with pulsed methylprednisolone, 1 gm/day for 3 consecutive days and subsequently received oral prednisone (1 mg/kg per day) and hydroxychloroquine 400 mg/day. On the 22nd day of treatment, the retinal status was stable and her visual acuity was considerably recovered. Prednisone was gradually tapered to 15 mg/day. We added oral warfarin 5 mg daily to prevent recurrence of retinal vaso-occlusion. Five months later, the vitreous and disc hemorrhage in the left eye had disappeared and the vessels had a more normal appearance (Figure 3). At present, the vision of both eyes is much improved (right 0.3 and left 0.14/5), and she is being maintained BMS-754807 on prednisone 15 mg/day, hydroxychloroquine 400 mg/day and warfarin 5 mg/day in the outpatient department. Open in a separate window Figure 3. View of both eyes after 5 months.