Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.
Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.
Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer. 相似文献
Here we report how the different types of regional muscle involvement, i.e. bulbar, ocular or generalized, in patients with myasthenia gravis (MG) influence the mental aspects of quality of life. Clinical examination according to Osserman was performed in 48 MG patients (45 women, three men; mean age 54, SD 12 years). Each patient was at the time for clinical evaluation asked to fill out the disease-specific Myasthenia Gravis Questionnaire (MGQ) and the Short-Form 36-item questionnaire for health survey (SF-36) as patient-oriented tools. We related the regional domains (generalized domain, bulbar domain and ocular domain) of the MGQ and the clinical findings, respectively, with mental quality of life as assessed by SF-36. Bulbar and generalized involvement results in impairment of mental aspects of quality of life, whereas ocular involvement does not. 相似文献
Summary Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of
cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted
apparent rates of onset of AN-132 (30 μmol/L) blocking were 0.051, 0.038, and 0.034 AF−1 at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting
potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related
receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the
inactivation process. 相似文献
A radioactive PCR test was developed that amplified the very virulent Marek's disease virus-1 (vvMDV-1) DNA sequence containing the 132 bp repeats. In apathogenic MDV-1 (CVI 988, Rispens), amplified DNA bands containing multiple copies of 132 bp repeats were identified. In the present study this PCR technique was used to monitor the passage level of vvMDV-1 in chicken embryo fibroblasts (CEF) in which the number of tandem 132 bp repeats was increased. It was found that at passage level 32 of vvMDV-1-B isolate, the 132 bp tandem repeat was already markedly amplified and its pattern resembled that of the MDV-1 (CVI 988, Rispens) vaccine virus DNA. In the vvMDV-1Z strain, amplification of the 132 bp repeat was not detectable at a similar passage level. The PCR test demonstrated that the apathogenic MDV-1 Md11/75c virus developed by extensive in vitro passaging has amplified 132 bp DNA repeats similar to those of the commercial vaccine virus (CVI 988, Rispense). It was also found that the pattern of viral RNA from infected cells detectable by Northern blot hybridization was markedly changed from a 2.4 kb RNA species in cells infected with vvMDV-1 viruses, to four RNA species (ranging from 2.2 to 4.4 kb) in cells infected with passage 32 of MDV-1-B strain, to a very large number of undefined RNA species synthesized in cells infected with attenuated MDV-1 viruses (CVI 988, Rispens and Md 11/75c). 相似文献
The genetic diagnosis of Gaucher disease by molecular methods is complicated by the existence of a highly homologous transcribed pseudogene (96% identity) that is found in close proximity to the true gene on chromosome 1q21. In addition, the pseudogene sequence can mimic disease-causing mutations in the true gene. Selective polymerase chain reaction (PCR) amplification of the true gene can be accomplished in extracted DNA from fresh-frozen samples by designing oligonucleotide primers to hybridize to defined regions that are not present in the pseudogene. This standard molecular approach, which entails amplification of relatively long segments of intact DNA, is not feasible in archival, paraffin-embedded, solid-tissue specimens in which the negative effects of chemical fixation result in DNA strand scission and breakdown of nucleic acid. A novel approach, specifically created for use with archival, fixative-treated tissue specimens, was developed for detection and characterization of common mutations of Gaucher disease. Three separate robust PCR reactions were formulated, 2 for selective amplification of portions of only the true gene exons 2 and 9, with a third reaction targeting exon 10, wherein both the true and pseudogene were coamplified. In the latter, DNA sequencing was used to determine the presence of true and pseudogene allele content in addition to identification of base sequence alterations. This method, requiring a single, 4-microm-thick histologic section, was successfully applied to archival paraffin block tissue specimens that had been in storage for up to 75 years. It was capable of accurately genotyping common Gaucher disease mutations as well as discovering a novel mutation and genetic polymorphism. We recommend our approach when only fixative-treated tis sue is available for molecular genotyping. 相似文献