Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.
Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity. 相似文献
Abstract – The aim of this study was to investigate mechano-sensory responses of injured and uninjured incisor teeth. Twenty-five children who had experienced dental trauma, together with age- and gender-matched controls, were studied prospectively. Touch thresholds of incisor teeth from both groups were determined using calibrated sets of von Frey hairs (force range 0.5–10.0 g in 0.5 g increments) using a forced choice staircase method. Forces were applied perpendicular to the buccal enamel surfaces along the midline, 2 mm from the incisal edge. Touch threshold was defined as the lowest force detected in three out of the five occasions. Following statistical analysis, P < 0.05 was considered significant. At initial examination, the touch threshold values of 25 traumatised teeth were significantly greater than the untraumatised controls ( P < 0.001), and these values approached those of the control teeth over 3–12 months ( P > 0.05). Dental trauma was associated with increased touch thresholds in permanent incisor teeth, with recovery toward healthy control values usually occurring between 3–12 months. 相似文献
Changes on serial assessments of brain MRI lesion load are used for monitoring therapeutic efficacy in patients with multiple
sclerosis (MS). We assessed the accuracy and reliability of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences
for measurement of lesion volume using a semiautomated contour technique. Cranial CSE and FSE examinations of 18 patients
with secondary progressive MS were studied. The mean lesion load was slightly higher with the CSE sequence (p = 0.002). Intraobserver
variability was significantly higher for FSE than for CSE, according to both the coefficient of variation between two measurements
(mean 2.48 % and 1.35 % respectively, p < 0.05) and back-transformed 95 % limits of agreement (1.005–1.060 for FSE; 0.988–1.019
for CSE). Although FSE sequences are quicker and the total lesion volume measurements are similar to those obtained with CSE,
the poorer reproducibility raises doubts about the use of FSE to replace CSE in clinical trials.
Received: 26 March 1996 Accepted: 4 April 1996 相似文献
The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis. 相似文献
We report the case of a 6-year-old girl with granuloma annulare (GA) possibly related to antitetanus vaccinations. The first episode occurred 2 months after the girl had been vaccinated but the lesions were not located at the vaccination site. After 1 year of being free of lesions, she had a second episode unrelated to vaccination. After another 6-month lesion-free period, the girl was administered another antitetanus vaccination and a solitary lesion developed at the vaccination site within 3 days. A few lesions developed on her legs in the 2 months following the appearance of the initial plaque. The literature includes two reports of cases with papular lesions limited to the hepatitis B vaccination site, both histopathologically consistent with necrobiotic granuloma, but clinically not suggestive of GA. To the best of our knowledge, GA following antitetanus vaccination and occurring at the vaccination site has not been reported before. Either the trauma alone from the injection or a vaccine-induced immunological reaction might have triggered the necrobiosis of collagen through some unexplained mechanisms. 相似文献
A rehabilitation program including foot sensory stimulation, balance and gait training with limited vision was performed in 24 patients with clinically defined sensory ataxia. There were 15 patients with bilateral somatosensory loss related to chronic neuropathy and nine patients with unilateral loss-related to multiple sclerosis. After training, balance control assessed using the Berg Balance Test improved similarly in both groups, and Romberg's sign disappeared in some patients, suggesting an improvement in dynamic balance and in the proprioceptive contribution. Conversely, balance assessed on a static force platform remained similar in the open-eyes condition and improved in the closed-eyes condition only in patients with unilateral sensory loss. These results show that ataxic patients can improve their balance with better results in dynamic conditions and that the relative contribution of proprioceptive and visual inputs may depend on the extent of somatosensory loss. 相似文献