human epidermal growth factor receptor type 2

人表皮生长因子受体 2 型
  • 文章类型: Journal Article
    犬前列腺癌(cPC)是一种预后不良的泌尿生殖系统肿瘤,尚未建立有效的治疗方法。最近,已经显示人表皮生长因子受体2型(HER2)在cPC细胞中过度表达;然而,HER2靶向治疗的疗效尚不清楚.
    研究拉帕替尼对HER2阳性cPC细胞系的抗肿瘤作用。
    从两只患有cPC的狗中建立了两种细胞系(muPC和bePC),并研究了拉帕替尼治疗对细胞增殖的影响,凋亡,和HER2下游信号进行了研究。此外,muPC用于产生荷瘤小鼠,并在体内检查了拉帕替尼的抗肿瘤作用。
    拉帕替尼治疗抑制Erk1/2和Akt的增殖和磷酸化,它们是HER2的下游信号。此外,TUNEL分析显示拉帕替尼诱导两种细胞系的细胞凋亡.muPC移植的裸小鼠模型显示,与媒介物治疗组相比,拉帕替尼显著抑制肿瘤生长并增加坏死肿瘤组织的面积。
    拉帕替尼通过抑制HER-2信号对cPC细胞发挥抗肿瘤作用。
    UNASSIGNED: Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that human epidermal growth factor receptor type 2 (HER2) is overexpressed in cPC cells; however, the efficacy of HER2-targeted therapy remains unclear.
    UNASSIGNED: Investigate the anti-tumour effect of lapatinib on HER2-positive cPC cell lines.
    UNASSIGNED: Two cell lines (muPC and bePC) were established from two dogs with cPC and the effects of lapatinib treatment on cell proliferation, apoptosis, and HER2 downstream signalling were investigated. Furthermore, muPC was used to generate tumour-bearing mice, and the anti-tumour effects of lapatinib were examined in vivo.
    UNASSIGNED: Lapatinib treatment inhibited the proliferation and phosphorylation of Erk1/2 and Akt, which are downstream signals of HER2. Furthermore, the TUNEL assay showed that lapatinib induced apoptosis in both cell lines. The muPC-engrafted nude mouse model showed that lapatinib significantly inhibited tumour growth and increased the area of necrotic tumour tissue compared to the vehicle-treated groups.
    UNASSIGNED: Lapatinib exerts anti-tumour effects on cPC cells by inhibiting HER-2 signalling.
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  • 文章类型: Journal Article
    探讨吡唑替尼联合不同放疗方式在人表皮生长因子受体2(HER2)阳性乳腺癌(BC)脑转移(BM)患者中的疗效和安全性。
    本研究是对2018年11月至2023年4月期间接受吡罗替尼治疗的BM患者的回顾性分析。共有66例患者接受放疗联合吡唑替尼(A组),26例患者接受了吡唑替尼作为独立治疗(B组)。A组内,18例患者行常规分割放疗(2Gy/F),48例患者接受超分割放疗(HFRT)(≥3Gy/F)。主要终点是颅内无进展生存期(IC-PFS)和总生存期(OS)。次要终点是客观缓解率(ORR)和临床获益率(CBR)。
    A组的ORR为54.5%(36/66),B组ORR为34.6%(9/26)(P=0.047)。A组CBR为89.4%(59/66),B组为69.2%(18/26)(P=0.041)。A组和B组的IC-PFS分别为12个月和8个月,分别为(P<0.001),OS分别为20个月和16个月,分别为(P=0.065)。A组,常规分割放疗组与HFRT组的IC-PFS和OS分别为10个月和12个月,分别为(P=0.001)、16个月和24个月,分别(P<0.001)。A组和B组未观察到严重不良反应。
    对于患有BM的HER2阳性BC患者,建议采用HFRT联合吡唑替尼的治疗模式,能提高患者的局部控制力和生存率。
    UNASSIGNED: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM).
    UNASSIGNED: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR).
    UNASSIGNED: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B.
    UNASSIGNED: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.
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  • 文章类型: Clinical Trial, Phase II
    OBJECTIVE: Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown.
    METHODS: Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled.
    RESULTS: Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%).
    CONCLUSIONS: Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.
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  • 文章类型: Case Reports
    Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) - positive breast cancer. Patients with HER2- positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS.
    Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells.
    A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases.
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  • 文章类型: Journal Article
    胃癌是世界上最致命的癌症之一,尽管在治疗方面有许多进步和选择。因为它通常被诊断为晚期,预后较差,中位总生存期少于12个月.化疗仍然是这些患者的主要治疗方法,但它仅具有中等的生存优势。仍然需要新的靶向治疗选择和更好地定义将受益于这些药物的患者群体的方法。在过去的几年里,对生物学有了更好的理解,分子谱分析,和胃癌的异质性。我们不断增长的知识导致了胃癌亚型的鉴定和新的靶向治疗剂的开发。现在有两个新的目标特工,曲妥珠单抗和雷莫珠单抗,最近被批准用于治疗晚期和转移性胃癌。还有许多其他积极调查的目标,包括表皮生长因子受体,磷酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶途径,c-Met,聚ADP-核糖聚合酶,和免疫检查点抑制。在这次审查中,我们讨论了当前晚期胃癌的治疗方法以及新兴的靶向治疗和免疫疗法.
    Gastric cancer is one of the most lethal cancers worldwide despite many advances and options in therapy. As it is often diagnosed at an advanced stage, prognosis is poor with a median overall survival of less than twelve months. Chemotherapy remains the mainstay of treatment for these patients but it confers only a moderate survival advantage. There remains a need for new targeted treatment options and a way to better define patient populations who will benefit from these agents. In the past few years, there has been a better understanding of the biology, molecular profiling, and heterogeneity of gastric cancer. Our increased knowledge has led to the identification of gastric cancer subtypes and to the development of new targeted therapeutic agents. There are now two new targeted agents, trastuzumab and ramucirumab, that have recently been approved for the treatment of advanced and metastatic gastric cancer. There are also many other actively investigated targets, including epidermal growth factor receptor, the phosphatadylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, c-Met, poly ADP-ribose polymerase, and immune checkpoint inhibition. In this review, we discuss the current management of advanced gastric cancer as well as emerging targeted therapies and immunotherapy.
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  • 文章类型: Journal Article
    BACKGROUND: The aim of this study was to evaluate the significance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers.
    METHODS: Of 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined.
    RESULTS: Receiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUVmax) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUVmax ≤ 3.8 and 91.6% for patients with a tumor of SUVmax > 3.8 (p < 0.001). High value of SUVmax was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUVmax (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUVmax ≤ 8.6 and 42.9% for patients with a tumor of SUVmax > 8.6 (p = 0.002), and high SUVmax was the only significant independent prognostic factor (p = 0.047).
    CONCLUSIONS: FDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.
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