Subclinical cardiotoxicity following adjuvant dose-escalated FEC, high-dose chemotherapy, or CMF in breast cancer

We compared adjuvant chemotherapy-related myocardial damage by antimyosin scintigraphy in patients who received either nine cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (group I, n = 14), three cycles of FEC followed by high-dose chemotherapy with alkylating agents (CTCb) given with the support of peripheral blood stem cell transplantation (group II, n = 14), or six cycles of standard intravenous CMF (cyclophosphamide, methotrexate and fluorouracil; group III, n = 8). The cardiac uptake of In-111-antimyosin-Fab (R11D10) antibody was measured and the heart-to-lung ratio (HLR) calculated 8–36 months after the last dose of chemotherapy. Cardiac antimyosin antibody uptake was considerably higher among patients treated with nine cycles of dose-escalated FEC than among those who were treated with three cycles of FEC and high-dose CTCb (HLR, median 1.98; range 1.36–2.24 vs median 1.51; range 1.20–1.82;P< 0.001), or those treated with CMF (median 1.44; range 1.15–1.68;P< 0.001). The difference between groups II and III was not significant (P> 0.1). A linear association was found between the cumulative dose of epirubicin and the cardiac antimyosin uptake (P< 0.001). We conclude that subclinical cardiac damage caused by three cycles of conventional-dose FEC followed by one cycle of high-dose CTCb chemotherapy is small as compared with the damage caused by dose-escalated FEC. © 2000 Cancer Research Campaig

Further test of internal-conversion theory with a measurement in (197)Pt

Journals published by the American Physical Society can be found at http://publish.aps.org/We have measured the K-shell internal conversion coefficient, alpha(K), for the 346.5-keV M4 transition in (197)Pt to be 4.23(7). This result differs from a previous value, which disagreed significantly from theory. Our new value agrees well with Dirac-Fock calculations and removes the earlier discrepancy as a source of concern

Continuous-Time Classical and Quantum Random Walk on Direct Product of Cayley Graphs

In this paper we define direct product of graphs and give a recipe for obtained probability of observing particle on vertices in the continuous-time classical and quantum random walk. In the recipe, the probability of observing particle on direct product of graph obtain by multiplication of probability on the corresponding to sub-graphs, where this method is useful to determine probability of walk on complicated graphs. Using this method, we calculate the probability of continuous-time classical and quantum random walks on many of finite direct product cayley graphs (complete cycle, complete $K_n$, charter and $n$-cube). Also, we inquire that the classical state the stationary uniform distribution is reached as $t\longrightarrow \infty$ but for quantum state is not always satisfy.Comment: 21, page. Accepted for publication on CT

Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase III trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma

Background: In the phase III double-blind European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 trial, pembrolizumab improved recurrence-free and distant metastasis-free survival in patients with stage III cutaneous melanoma with complete resection of lymph nodes. In the pembrolizumab group, the incidence of grade I–V and of grade III–V immune-related adverse events (irAEs) was 37% and 7%, respectively. Methods: Patients were randomised to receive intravenous (i.v.) pembrolizumab 200 mg (N = 514) or placebo (N = 505) every 3 weeks, up to 1 year. On recurrence, patients could enter part 2 of the study: pembrolizumab 200 mg i.v. every 3 weeks up to 2 years, for crossover (those who received placebo) or rechallenge (those who had recurrence ≥6 months after completing 1-year adjuvant pembrolizumab therapy). For these patients, we present the safety profile and efficacy outcomes. Results: At the clinical cut-off (16-Oct-2020), in the placebo group, 298 patients had a disease recurrence, in which 155 (52%) crossed over (‘crossover’). In the pembrolizumab group, 297 patients completed the 1-year treatment period; 47 had a recurrence ≥6 months later, in which 20 (43%) entered the rechallenge part 2 (‘rechallenge’). In the crossover group, the median progression-free survival (PFS) was 8.5 months (95% confidence interval [CI] 5.7–15.2) and the 3-year PFS rate was 32% (95% CI 25–40%). Among 80 patients with stage IV evaluable disease, 31 (39%) had an objective response: 14 (18%) patients with complete response (CR) and 17 (21%) patients with partial response. The 2-year PFS rate from response was 69% (95% CI 48–83%). In the rechallenge group, the median PFS was 4.1 months (95% CI 2.6–NE). Among 9 patients with stage IV evaluable disease, 1 had an objective response (CR). Among the 175 patients, 51 (29%) had a grade I–IV irAE and 11 (6%) had a grade III–IV irAE. Conclusions: Pembrolizumab treatment after crossover yielded an overall 3-year PFS rate of 32% and a 39% ORR in evaluable patients, but the efficacy (11% ORR) was lower in those rechallenged

Toksični učinci olova u profesionalno izložene indijske obitelji

This article describes an entire family manufacturing lead acid batteries who all suffered from lead poisoning. The family of five lived in a house, part of which had been used for various stages of battery production for 14 years. Open space was used for drying batteries. They all drank water from a well located on the premises. Evaluation of biomarkers of lead exposure and/or effect revealed alarming blood lead levels [(3.92±0.94) µmol L-1], 50 % reduction in the activity of δ-aminolevulinic acid dehydratase [(24.67±5.12) U L-1] and an increase in zinc protoporphyrin [(1228±480) µg L-1]. Liver function tests showed an increase in serum alkaline phosphatase [(170.41±41.82) U L-1]. All other liver function test parameters were normal. Renal function tests showed an increase in serum uric acid [(515.81±86.29) µmol L-1] while urea and creatinine were normal. Serum calcium was low [(1.90±0.42) mmol L-1 in women and (2.09±0.12) mmol L-1 in men], while blood pressure was high in the head of the family and his wife and normal in children. Lead concentration in well water was estimated to 180 µg L-1. The family was referred to the National Referral Centre for Lead Poisoning in India, were they were received treatment and were informed about the hazards of lead poisoning. A follow up three months later showed a slight decrease in blood lead levels and a significant increase in haemoglobin. These findings can be attributed to behavioural changes adopted by the family, even though they continued producing lead batteries.Olovo je sveprisutni metal s mnogo namjena, a čovječanstvo ga rabi već više od 6000 godina. Danas je olovo među najrasprostranjenijim toksinima u okolišu, a drugi je na popisu toksičnih metala, odmah iza arsena. Mnogi još nisu svjesni njegova toksičnoga djelovanja te se i dalje izlažu olovu. Ovdje je opisana obitelj koja proizvodi olovne akumulatore i koja je pretrpjela trovanje olovom zahvaljujući svojoj neobaviještenosti. Ova peteročlana obitelj živjela je u jednome kućanstvu čiji je dio namijenjen različitim fazama proizvodnje akumulatora već 14 godina. Akumulatori su se sušili na otvorenome. Na imanju je bio i bunar s pitkom vodom. Mjerenja biopokazatelja izloženosti olovu i njegova djelovanja u svih pet članova obitelji dovela su do alarmantnoga saznanja o razinama olova u krvi [(3,92±0,94) µmol L-1], 50 %-tnom padu aktivnosti dehidrataze δ-aminolevulinske kiseline [(24,67±5,12) U L-1] te povišenom cinkovu protoporfirinu [(1228±480) µg L-1]. Jetrene probe otkrile su povišene razine alkalne fosfataze u serumu [(170,41±41,82) U L-1]. Ostali su parametri jetrene funkcije bili normalni. Testovi funkcije bubrega otkrili su povišene razine mokraćne kiseline u serumu [(515,81±86,29) µmol L-1], dok su razine ureje i kreatinina bile normalne. Također je zabilježen pad razina kalcija u serumu [(1,90±0,42) mmol L-1 u žena te (2,09±0,12) mmol L-1 u muškaraca]. Povišeni krvni tlak zamijećen je u glave obitelji i njegove supruge, dok je u djece bio normalan. Koncentracija olova u bunarskoj vodi bila je izrazito visoka, prema procjeni 180 µg L-1. Obitelj je upućena u indijski Državni referalni centar za otrovanje olovom (National Referral Centre for Lead Poisoning) gdje je primila lijekove i bila upoznata s činjenicama vezanim uz otrovanje olovom. Tromjesečno je praćenje pokazalo blagi pad razina olova u krvi te značajan porast hemoglobina. Ovi se nalazi mogu pripisati promjenama u ponašanju obitelji, bez obzira na to što je nastavila proizvoditi akumulatore

Gene expression profiling in sinonasal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.</p> <p>Methods</p> <p>To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.</p> <p>Results</p> <p>Among the genes with significant differential expression we selected <it>LGALS4, ACS5, CLU, SRI and CCT5 </it>for further exploration. The overexpression of <it>LGALS4, ACS5, SRI</it>, <it>CCT5 </it>and the downregulation of <it>CLU </it>were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.</p> <p>Conclusion</p> <p>Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.</p