Impact of immunohistochemistry-based molecular subtype on predicting chemotherapy response and survival in patients with T1 stage bladder cancer after bladder-preserving treatment.
- 作者列表："Lu J","Zhang Y","Wu C","Chu C","Liu Z","Cao Y
OBJECTIVE:To explore the immunohistochemistry-based molecular subtypes of bladder cancer, and their impact on the prognosis and the chemotherapy response between gemcitabine plus cisplatin intra-arterial chemotherapy and epirubicin-inducted intravesical chemotherapy, in patients with T1 stage bladder cancer after bladder-preserving treatment. METHODS:One hundred and seventy-six patients with T1 stage bladder cancer were selected for this study. Thirty-three patients underwent radical cystectomy, 43 received gemcitabine plus cisplatin intra-arterial chemotherapy and 100 received intravesical chemotherapy. The markers labeled with luminal (GATA3, Uroplakin II, CK20) and basal (CK5/6, CK14, CD44) phenotypes were chosen as candidate markers. RESULTS:One hundred and seventy-six patients were divided into 76 patients as basal/squamous (BASQ), 45 as the luminal A and 55 as the luminal B. Compared with the luminal B and BASQ tumors, the luminal A tumors showed a trend for better recurrence-free survival (P = 0.105) and progression-free survival (P = 0.093). The combination of CK20 and GATA3 was practical to identify the molecular phenotypes with total 84.9% accuracy and significantly associated with recurrence-free survival (P = 0.025) and progression-free survival (P = 0.004). The patient with BASQ tumors who received intravesical chemotherapy showed a trend for worse progression-free survival than the patient who received gemcitabine plus cisplatin intra-arterial chemotherapy or radical cystectomy. Furthermore, the patients with BASQ tumors experienced a significant improvement in progression-free survival after gemcitabine plus cisplatin intra-arterial chemotherapy compared with the patients who received intravesical chemotherapy (P = 0.011). CONCLUSIONS:The immunohistochemistry-based molecular subtypes could predict the patient's prognosis and clinically different chemotherapeutic survival outcomes in patients with T1 stage bladder cancer after bladder-preserving treatment.
目的: 探讨以免疫组化为基础的膀胱癌分子亚型，以及吉西他滨联合顺铂动脉内化疗与表柔比星膀胱灌注化疗对T1期膀胱癌患者保留膀胱治疗预后及化疗反应的影响。 方法: 选择T1期膀胱癌患者126例。33例患者接受根治性膀胱切除术，43例接受吉西他滨 + 顺铂动脉内化疗，100例接受膀胱内化疗。选择用luminal (GATA3，Uroplakin II，CK20) 和basal (CK5/6，CK14，CD44) 表型标记的标记作为候选标记。 结果: 126例患者分为基底/鳞状 (BASQ) 76例，管腔A 45例，管腔B 55例。与luminal B和BASQ肿瘤相比，luminal A肿瘤表现出更好的无复发生存期 (P = 0.105) 和无进展生存期 (P = 0.093) 的趋势。CK20和GATA3的组合对于鉴定分子表型是实用的，具有84.9% 的准确性，并且与无复发生存期 (P = 0.025) 和无进展生存期 (P = 0.004) 显著相关。与接受吉西他滨加顺铂动脉内化疗或根治性膀胱切除术的患者相比，接受膀胱内化疗的BASQ肿瘤患者显示出更差的无进展生存期趋势。此外，与接受膀胱内化疗的患者相比，吉西他滨联合顺铂动脉内化疗后，BASQ肿瘤患者的无进展生存期显著改善 (P = 0.011)。 结论: 基于免疫组织化学的分子亚型可以预测T1期膀胱癌患者保留膀胱治疗后的预后和临床不同的化疗生存结局。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.