Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

Introduction  

Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas.     

Stuck bioprosthetic aortic valve--a new entity? A case report

We describe herein a case of bioprosthetic valve malfunction, which closely imitates a stuck valve. Although the term "stuck" was used originally for the immovable mechanical valve leaflets, the echocardiographic manifestation of this malfunction is similar to those of a mechanical one. The clinical presentation of the stuck bioprosthesis is, however, far more benign than a stuck mechanical valve. Familiarity with this entity is important.     

The familial Mediterranean fever (MEVF) gene as a modifier of Crohn's disease

OBJECTIVES: Crohn's disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation. AIMS: To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation. METHODS: Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi-non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens. RESULTS: The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3-10.5, p= 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3-11.5, p= 0.015). No differences were observed in disease location and disease severity. CONCLUSIONS: MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.     

Eosinophilic differentiation of the human promyelocytic leukemia cell line, HL-60

HL-60 promyelocytic leukemia cells differentiated to eosinophils and eosinophilic precursors when cultured under mildly alkaline conditions (pH 7.6-7.8) for 7 d without refeeding. New cytoplasmic granules appeared blue in the least mature cells and red in the most mature cells when stained with Wright-Giemsa. The granules also stained with Luxol-fast-blue, a characteristic of eosinophil granules. Furthermore, most cells contained the eosinophil major basic protein (MBP); the Charcot-Leyden Crystal (CLC) protein (lysophospholipase), eosinophil peroxidase, acid phosphatase, and arylsulfatase were also detected in a portion of these cells. The eosinophil major basic protein was found in a high proportion of undifferentiated cells, and thus may be constituitively produced. By examining finely banded chromosomes, translocation break points were demonstrated at q22 on one chromosome 16 and at q23 on the other homologue; abnormalities in this region of the long arm of 16 are a characteristic finding in the recently described syndrome of acute myelomonocytic leukemia (AMMoL) with abnormal bone marrow eosinophils. In common with the bone marrow eosinophils in these patients, the HL-60 eosinophil granules contained chloroacetate esterase and periodic-acid Schiff (PAS) reactive material; crystalloid inclusions were rare. Therefore, the HL-60 cell line appears to be an in vitro model for eosinophilopoiesis and may be specially suited for the study of the abnormal eosinophils seen in certain malignant conditions.     

Mass spectrometrical analysis of human serine racemase in foetal brain

Summary. We analysed human serine racemase for the first time from human foetal brain by mass spectrometrical methods, MALDI MS and MS/MS. The detection of human serine racemase from a transient area of human foetal brain, the perireticular nucleus, that is suggested to be mainly involved in guidance of corticofugal and thalamocortical fibers, may be a clue for the important role of this enzyme in neuronal migration and brain development via regulation of NMDA receptor activity.     

Medial dorsal superficial peroneal nerve studies in patients with polyneuropathy and normal sural responses

We studied medial dorsal superficial peroneal (MDSP) nerves in 52 patients with clinical evidence of mild chronic sensorimotor polyneuropathy and normal sural nerve responses, in order to assess the diagnostic sensitivity and usefulness of MDSP nerve testing in electrodiagnostic practice. To determine the effect of age on MDSP nerve parameters, 98 normal subjects were also examined. Electrodiagnostic evaluation involved studies of motor nerve conduction in tibial, peroneal, and median nerves; sensory nerve conduction in sural, MDSP, median, and radial nerves; tibial and peroneal nerve F waves; H reflexes from the soleus muscles; and needle electromyography of gastrocnemius and abductor hallucis muscles. Among the patients, 49% had low-amplitude sensory responses in MDSP nerves and 57% had either slowing of sensory conduction velocity or no sensory responses on proximal stimulation. MDSP nerve amplitude, tibial nerve motor velocity, and H reflexes were the most sensitive for detection of mild chronic symmetrical axonal sensorimotor polyneuropathy. MDSP nerve testing should be included in the routine electrodiagnostic evaluation of patients with suspected polyneuropathy and normal sural nerve responses.