Recent molecular analysis has revealed that L-myc has several domains of extremely conserved anino acid sequence homology with c-myc and N-myc, suggesting similarity of function. We tested the biologic activity of L-myc by using an expression vector containing a cDNA clone coding for the major open reading frame in the 3.9-kilobase mRNA of L-myc under the control of a strong promoter (Moloney long terminal repeat) and found that L-myc complemented an activated ras gene in transforming primary rat embryo fibroblasts. However, the efficiency of transformation was 1 to 10% of that seen with the c-myc and simian virus 40 (SV40) controls. The L-myc/ras transformants initially grew more slowly than c-myc or SV40 transformants, but once established as continuous cell lines, they were indistinguishable from cell lines derived from c-myc/ras or SV40/ras transfectants as determined by morphology, soft-agar cloning, and tumorigenicity in nude mice.
Under the auspices of the Belgian Society of Medical Oncology (BSMO).Background: New drugs are generally tested in patients with metastatic disease where bulky tumor mass is present. However, antiangiogenic compounds are probably more beneficial in the prevention of regrowth from tumors with small tumor load than in bulky tumors. This study wants to test the hypothesis that antiangiogenic compounds such as sunitinib are able to delay tumor progression after tumor mass reduction by taxanes, i.e. an objective response (PR or CR).Materials and methods: This is a dual-arm open-label randomized multicenter phase II clinical trial with 2:1 randomization evaluating the efficacy of sunitinib (study arm) versus no therapy (control arm, only for descriptive purposes) in patients with metastatic breast cancer after objective response to taxane chemotherapy. Eligible patients had metastatic HER2 negative breast cancer, had received 10 to 20 weeks of first- or second line taxane containing chemotherapy resulting in an objective response (RECIST). Patients received sunitinib (arm A) 50 mg/d po 4w/6 (amended to 37.5 mg continuously in 1-2008) or no therapy (arm B). Patients were stratified for disease free interval and dominant site of disease. Patients randomized to arm B were offered the opportunity to receive open-label sunitinib treatment upon development of disease progression. Treatment was pursued until disease progression or major intolerance or patients refusal. All patients who received at least day 1 of study treatment were evaluated for efficacy, toxicity and safety. The duration of response after taxane treatment in previous studies with metastatic breast cancer is around 7 months. Based on this, the median time interval between the end of chemotherapy and tumor progression was expected to be about 5 months in our study population. The primary endpoint was to determine the proportion of patients alive and without disease progression (PFS) at 5 months after study entry in arm A. If ≤ 18/36 patients are progression-free and alive at 5 months, sunitinib will be declared insufficiently active (beta 0.05); if ≥ 22 patients are progression-free and alive at 5 months, sunitinib will be declared active (alpha 0.05) and it will be recommended to continue the trial as a phase III design.Results: 10/36 patients (28%) reached 5 months PFS in arm A and 4/19 in arm B (21%). Median PFS was 3.4 months in Arm A and 3.1 months in Arm B. Toxicity and overall survival data will be reported at the meeting.Discussion: This study does not confirm the hypothesis that sunitinib can lead to a significant proportion of patients with PFS of ≥ 5 months after objective response to taxanes. This proof-of-principle study suggests that also the role of consolidation therapy with other (already approved) antiangiogenic treatments should be evaluated carefully in prospective clinical trials (high economic cost). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 203.
Recent molecular analysis has revealed that L-myc has several domains of extremely conserved amino acid sequence homology with c-myc and N-myc, suggesting similarity of function. We tested the biologic activity of L-myc by using an expression vector containing a cDNA clone coding for the major open reading frame in the 3.9-kilobase mRNA of L-myc under the control of a strong promoter (Moloney long terminal repeat) and found that L-myc complemented an activated ras gene in transforming primary rat embryo fibroblasts. However, the efficiency of transformation was 1 to 10% of that seen with the c-myc and simian virus 40 (SV40) controls. The L-myc/ras transformants initially grew more slowly than c-myc or SV40 transformants, but once established as continuous cell lines, they were indistinguishable from cell lines derived from c-myc/ras or SV40/ras transfectants as determined by morphology, soft-agar cloning, and tumorigenicity in nude mice.
Abstract. This text outlines the main features of two educational programmes of the International Astronomical Union (IAU): the International Schools for Young Astronomers (ISYA) and the Teaching for Astronomy Development programme (TAD), developed since 1967.The main goal of the International Schools for Young Astronomers (ISYA) is to support astronomy (education and research) in developing countries in organizing a 3-week School for students with typically M.Sc. degrees.The context in which the ISYA were developed changed drastically during the last decade. From a time when access to large telescopes was difficult and mainly organized on a nationbasis, nowadays the archives of astronomical data have accumulated at the same time that many major telescope become accessible, and they are accessible from everywhere, the concept of virtual observatory reinforcing this access.A second programme of the IAU, Teaching for Astronomy Development (TAD), partially based on a School, but also of shorter duration (typically one week) has a complementary objective. It is dedicated to assist countries that have little or no astronomical activity, but that wish to enhance their astronomy education. The fast development of the TAD programme over the past years is emphasized.
Purpose: Grade II breast cancers have been clinically attributed either to low risk or high risk groups based on the degree of cellular proliferation assessed by genomic grading index [1] or Ki67 labeling index. This differentiation is clinically important as the medical management of these two groups are different. Non-invasive MR Spectroscopy (MRS) based choline quantification enables assessment of cellular proliferation in-vivo. The aims of our study were to check whether (1) total choline (tCho) quantified with MRS correlated with tumor grading and (2) in grade II tumors, the differentiation into high and low risk groups could be made based on tCho values. Methods: The preliminary results concerning the first 14 patients included in a prospective ongoing study are discussed here. Patients who had tumor of at least 1.5cm dimension in all the three planes and who underwent mastectomy or wide excision were studied on a 1.5 T scanner (Philips Intera, Nederland) by in-vivo MR mammography protocol including MRS, which is a PRESS single voxel sequence (TE/ 270 ms, TR 2000ms). Post-processing was done using jMRUI 4.0. The AMARES algorithm was used to quantify tCho using water as the internal reference [2]. Operated tumor specimens were immunostained for Ki67 with MIB-1 antibody. Estimated tCho values were correlated with tumor grades and Ki67 index. Results: Among the 14 patients, 8 were grade II and 6 were grade III tumors. Table 1: Patient/tumor characteristicsAge (years)[Cho] (mmol/kg)Size (cm)GradeKi67 (%)ERPRHER2 Gene550,18811.7251++_671,13413.126,7+++580,00001.5210++_730,77154.1250__+720,00002.125++_610,00002.9250+__550,05054.625++_620,00003.0225++_540,07892.6326++_612,35772.8350++_620,45312.0330++_740,71802.1330___622,51252.8361++_710,60333.33NA__+(NA: not available) Ki67 could not be assessed in one grade III sample as it had extensive necrotic tissue. Strongly elevated tCho with a maximum of 2.53 mmol/kg was measured in grade III tumors. Mean tCho values were significantly different between Grade II and III tumors (t test, p = 0.05). There is a linear correlation between tCho and tumor grades (r = 0.54, p <0.05). There was a general correlation between Ki67 index and tCho, significant only in Grade III tumors (r = 0.98, p< 0.05). However, in grade II tumors, by taking the mean tCho (0.234mmol/kg) as the cut-off value, a rough delineation could be observed: a group of tumors (n = 6) with absent or very low(< 0.2mmol/kg) tCho and another group with a detectable tCho (n = 2). These two cases with detectable tCho were HER2 amplified. Conclusion: This feasibility study indicates significant correlation of tCho determined by MRS with tumor grades and a relatively weak correlation with Ki67 labeling index. This in turn offers a utilizing basis for further exploration of MRS based tCho estimation in the accurate in vivo assessment of breast tumor grades. These are preliminary results of an on-going study which will be further validated against the genomic grade index in a larger number of patients. References :[1]Ignatiadis M et al. Pathobiology.2008[2]Begley JKP et al. Breast Cancer Research 2012. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-02-02.
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