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1.

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
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Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.  相似文献   
6.
In an open, non-randomized 3-way cross-over study, the bioavailability of 2-oxo-pyrrolidine-1-acetamide (piracetam, Encetrop) from two solid oral formulations and one liquid formulation was tested in 8 healthy male volunteers. The area under the concentration time curve, which is defined to be a measurement for bioequivalence among the three tested galenic formulations correlated very well with the area under the effect intensity-time curve, which was estimated in the same volunteers using electro-physiological methods. The different methods of estimation of bioequivalence show similarity between both solid galenic formulations, while the liquid form exhibits superiority in respect to the oral solid formulations.  相似文献   
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Zusammenfassung Trotz der H?ufigkeit der Erkrankung liegen nur wenige gesicherte Erkenntnisse über die ?tiologie der chronischen Urtikaria vor. Bei 10 Patienten, bei denen keine anderweitige Ursache für die Erkrankung ermittelt werden konnte, führten wir eine Gastroskopie durch. Bei 8 der 10 Patienten konnte eine Besiedlung der Magenschleimhaut mit Helicobacter pylori gesichert werden. Die Urtikaria heilte innerhalb weniger Tage bei allen Patienten ab, nachdem wir eine Therapie mit Amoxicillin und Omeprazol einleiteten. Eingegangen am 6. Februar 1995 Angenommen am 12. Mai 1995  相似文献   
8.
Serum levels of IgE, anti-IgE autoantibodies (Abs), and IgE/IgG anti-IgE immune complexes (ICs) were measured in 110 children with asthma and 90 healthy control children. Significantly enhanced levels of IgE/anti-IgE IC were detected in children with asthma. However, only a weak correlation was found between anti-IgE auto-Ab serum levels and the degree of lung function abnormalities in children with asthma. However, children with asthma with low serum IgE levels had elevated IC serum levels of IgE/anti-IgE auto-Abs, suggesting that IgE might be hidden within these ICs and is therefore not measurable in vitro. The significant elevation of IgE/anti-IgE IC serum levels raises the question whether IgE within ICs is neutralized or might still be involved in immunologic mechanisms responsible for clinical symptoms of bronchial asthma.  相似文献   
9.
IgE fragments were detected by polyclonal and monoclonal anti-IgE antibodies using Western blot techniques and immunoassays. Other antibodies detected only intact IgE molecules. In the presence of IgE fragments, higher IgE levels were estimated, depending on the epitope specificity of the antibodies used in the IgE determination assays. IgE fragments have been found together with intact IgE in isolated material from different human sera and also from culture supernatant of an IgE-producing cell line. Our data demonstrate that IgE fragments may be assessed and represent a potential pitfall in diagnostic IgE determinations.  相似文献   
10.
Levels of "free" anti-IgE autoantibodies and IgE/anti-IgE immune complexes were measured in the sera of patients with atopic dermatitis before and after treatment, psoriasis patients, and nonatopic controls. In this measurement, we used two monoclonal antibodies with distinct in vitro functions (LE 27, BSW 17), directed against the epsilon CH3 and CH4 domains of the IgE Fc-fragment, in a novel immunobinding assay. In patients with atopic dermatitis, elevated levels of "free" anti-IgE antibodies and IgE/anti-IgE immune complexes were detected in comparison to psoriasis patients and controls. In addition, there was a positive correlation between total IgE and the amount of IgE/anti-IgE complexes detected by LE 27 ( r =0.7; P < 0.001) or BSW 17 ( r = 0.64; P < 0.001) in patients with atopic dermatitis. In contrast, an inverse correlation was observed between total IgE and "free" anti-IgE antibodies ( r =−0.34; P < 0.05) in atopic dermatitis. However, serum levels of anti-IgE autoantibodies before and after therapy in patients with atopic dermatitis did not differ, and levels of anti-IgE antibodies did not correlate with clinical severity, as evaluated by an established clinical scoring system. Our data clearly indicate that significantly elevated amounts of anti-IgE antibodies could be observed in patients with atopic dermatitis, which are directed against different epitopes on the IgE molecule. It is tempting to speculate that these autoantibodies exert different effects on IgE-receptor-bearing effector cells and may play an important role in IgE regulation.  相似文献   
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