Malignant mesothelioma

恶性间皮瘤
  • 文章类型: Journal Article
    恶性间皮瘤(MM)和腹膜假性黏液瘤(PMP)的腹腔内播散,在恶性细胞在上皮-间质(E/M)轴上重塑过程中激活的干性窗口方面特征不佳。为了深入了解这些罕见形式的腹膜转移(PM)的干性特性及其预后意义,通过醛脱氢酶1(ALDH1)和球体形成测定法分析了55例接受细胞减灭术和腹腔热化疗的患者的原发性肿瘤培养物的癌症干细胞(CSC)。和一组可塑性相关基因的表达来测量E/M转换(EMT)评分。还分析了瘤内异质性。包括来自结肠直肠癌PM的样品用于比较。使用主成分和聚类分析确认分子数据。使用Kaplan-Meier和Cox回归模型评估与生存的关联。乙酰水杨酸(ASA)的活性,一个stemness修饰符,在五种文化中进行了测试。ALDH1bright-cells鉴定的高级PMP的数量显著增加,并将两种形式的PM中的实体团块与腹水/粘蛋白包埋的肿瘤细胞区分开。上皮/早期混合EMT评分和与多能性因子相关的早期混合表达模式与早期腹膜进展显着相关(分别为p=.0343和p=.0339,对数秩检验)在多变量模型中。ASA在所有五种培养物中都损害了球状体的形成并增加了顺铂的敏感性。这些数据表明CSC亚群和混合E/M状态可能指导MM和PMP的腹膜扩散。Stemness可以被利用作为增加化学敏感性和改善患者预后的目标脆弱性。需要进一步的研究来证实这些初步数据。
    Intrabdominal dissemination of malignant mesothelioma (MM) and pseudomyxoma peritonei (PMP) is poorly characterized with respect to the stemness window which malignant cells activate during their reshaping on the epithelial-mesenchymal (E/M) axis. To gain insights into stemness properties and their prognostic significance in these rarer forms of peritoneal metastases (PM), primary tumor cultures from 55 patients selected for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were analyzed for cancer stem cells (CSC) by aldehyde dehydrogenase 1 (ALDH1) and spheroid formation assays, and for expression of a set of plasticity-related genes to measure E/M transition (EMT) score. Intratumor heterogeneity was also analyzed. Samples from PM of colorectal cancer were included for comparison. Molecular data were confirmed using principal component and cluster analyses. Associations with survival were evaluated using Kaplan-Meier and Cox regression models. The activity of acetylsalicylic acid (ASA), a stemness modifier, was tested in five cultures. Significantly increased amounts of ALDH1bright-cells identified high-grade PMP, and discriminated solid masses from ascitic/mucin-embedded tumor cells in both forms of PM. Epithelial/early hybrid EMT scores and an early hybrid expression pattern correlated with pluripotency factors were significantly associated with early peritoneal progression (p = .0343 and p = .0339, respectively, log-rank test) in multivariable models. ASA impaired spheroid formation and increased cisplatin sensitivity in all five cultures. These data suggest that CSC subpopulations and hybrid E/M states may guide peritoneal spread of MM and PMP. Stemness could be exploited as targetable vulnerability to increase chemosensitivity and improve patient outcomes. Additional research is needed to confirm these preliminary data.
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  • 文章类型: Journal Article
    背景:原发性肝内间皮瘤(PIHMM)的报道很少。其典型的临床表现,放射学特征和病理学尚未定义。这里,我们旨在总结其诊断和治疗。
    方法:对浙江大学医学院附属第一医院3例PIHMM病例进行回顾性分析,并复习现有文献,探讨PIHMM的临床病理特点及预后。
    结果:根据我们的案例系列和文献,PIHMM的平均年龄为59.7(41-83)岁.大多数患者表现为非特异性症状,如腹痛,发烧,减肥和虚弱。在成像方面,PIHMM通常表现为固体,非均质软组织肿块,边缘不规则,动脉期边缘显着增强。免疫组织化学标记物,如calretinin,细胞角蛋白(CK)5/6,D2-40,WT-1,间皮素CK和波形蛋白可能有助于诊断。3年无复发生存率(RFS)为51.85%,术后3年总生存率(OS)为83.33%,术后3年总生存率为100%。
    结论:PIHMM只能通过仔细的术后病理来诊断,由于其非特异性临床表现,血清学指标或影像学特征。免疫组织化学染色对于区分该肿瘤与其他肝肿瘤非常有用。手术是治疗的主要手段。
    BACKGROUND: Primary intrahepatic mesothelioma (PIHMM) has been rarely reported. Its typical clinical presentation, radiological features and pathology have not been defined. Here, we aimed to summarize its diagnosis and treatment.
    METHODS: We conducted a retrospective analysis of three cases of PIHMM in the First Affiliated Hospital of Zhejiang University School of Medicine and reviewed the current literature to investigate the clinical and pathological characteristics and prognosis of PIHMM.
    RESULTS: Based on our case series and the literature, the mean age of PIHMM was 59.7 (41-83) years. Most patients present with nonspecific symptoms such as abdominal pain, fever, weight loss and weakness. On imaging, PIHMM usually presented as a solid, heterogeneous soft tissue mass with irregular margins and significant enhancement of the margins in the arterial phase. Immunohistochemical markers such as calretinin, cytokeratin (CK)5/6, D2-40, WT-1, mesothelin CK and vimentin may be useful for diagnosis. The 3-year relapse-free survival rate (RFS) was 51.85%, the 3-year overall survival (OS) rate was 83.33% and the 3-year postoperative overall survival rate was 100%.
    CONCLUSIONS: PIHMM can only be diagnosed by careful postoperative pathology, because of its nonspecific clinical presentations, serological indicators or imaging features. Immunohistochemical staining is very useful to distinguish this tumor from other liver tumors. Surgery is the mainstay of treatment.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    目的:恶性间皮瘤(MM)对患者及其家庭的躯体心理平衡有显著影响,包括身体,心理,和人际关系问题。本系统文献综述的目的是调查在全球范围内为MM患者及其护理人员提供哪些心理干预措施。
    方法:使用系统评价和荟萃分析的首选报告项目进行综述。通过文献检索,确定了12篇文章。结果分为五类。1.个人心理支持,2.团体心理支持,3.认知行为团体心理治疗,4.简短的精神分析小组,5.多家庭组。
    结果:干预措施在形式上有所不同,使用的持续时间和资源。他们中的大多数是基于群体和精神分析的,虽然也描述了个体和认知行为干预。尽管存在差异,干预措施似乎是促进处理与诊断相关的精神痛苦和愤怒的基础。
    结论:我们的研究表明,对MM患者及其照顾者的心理干预措施仍然很少。MM在患者和护理人员中的躯体化后果应鼓励机构和医疗保健专业人员开发评估和干预模型,以解决其痛苦的不同方面并促进其剩余活力。
    Malignant Mesothelioma (MM) has a striking impact on the somatopsychic balance of patients and their families, including physical, psychological, and interpersonal problems. The aim of this systematic literature review was to investigate what psychological interventions are offered to patients with MM and their caregivers worldwide.
    METHODS: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification of 12 articles. Results were categorized into five categories. 1. Individual psychological support, 2. Group psychological support, 3. Cognitive-behavioral group psychotherapy, 4. Brief psychoanalytic groups, 5. Multifamily group.
    RESULTS: The interventions differed in terms of form, duration and resources used. Most of them were group-based and psychoanalytically oriented, although individual and cognitive-behavioral interventions were also described. Despite the differences, the interventions appeared to be fundamental in facilitating the processing of mental pain and anger related to the diagnosis.
    CONCLUSIONS: Our study has shown that there are still few psychological interventions available for MM patients and their caregivers. The somatopsychic consequences of MM in patients and caregivers should encourage institutions and healthcare professionals to develop assessment and intervention models that address the different dimensions of their suffering and promote their residual vitality.
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  • 文章类型: Journal Article
    背景:2006年,国际癌症研究机构(IARC)得出结论,无石棉滑石的致癌性证据不足(第3组),而会阴使用滑石粉被归类为可能致癌(2B组)。
    目的:评估后续研究是否提供了有关无石棉滑石粉和滑石粉致癌风险的更可靠信息以及更好的暴露特征。
    方法:系统评价。
    方法:对接触无石棉滑石粉的滑石粉矿工和磨坊进行队列研究,以及从2006年起发表的报告滑石粉消费者癌症风险的队列和病例对照研究通过PubMed和参考列表进行了鉴定.包括汇总分析,但不是评论和荟萃分析。在反复报告研究的情况下,选取随访时间最长或观察病例数量最多的文章进行数据抽象.注意到分别报告并包括在汇总分析中的研究。
    结果:符合纳入标准的出版物是:2项关于滑石粉矿工和磨坊的队列研究,10项关于滑石粉使用者的队列研究(其中4项评估卵巢癌风险),和14个病例对照研究(13个卵巢和1个子宫内膜癌)的滑石粉使用的风险。在无石棉滑石粉矿工和磨坊主中,没有报告过重的癌症死亡率。病例对照研究始终导致与使用会阴滑石粉相关的卵巢癌过度估计(比值比高达1.5)。大多数量化暴露的研究也提供了剂量-反应关系的证据。个体队列研究估计风险比(HR)略高于1。在对总共3,112例病例的汇总队列的分析中,生殖道未闭女性的HR为1.13(95CI1.01-1.26),HR与使用频率之间存在相关性(p为趋势0.03).在所有队列研究中,在随访的早期阶段,会阴使用滑石粉仅测量一次,从而产生不准确的累积暴露量。关于其他器官癌症风险的流行病学研究结果有限且不一致。
    结论:在IARC2006年评估后更新或发表的流行病学研究表明:无石棉滑石粉矿工和磨坊主的癌症风险没有增加;在会阴使用商业滑石粉后,卵巢癌的风险增加。许多研究表明,使用量指标与癌症风险之间存在相关性。在这些研究中考虑的滑石粉的组成是未知的。
    in 2006, the International Agency for Research on Cancer (IARC) concluded that the evidence of carcinogenicity for asbestos-free talc was inadequate (group 3), whereas perineal use of talcum powder was classified as possibly carcinogenic (group 2B).
    to assess whether later studies provide more solid information on the carcinogenic risk from asbestos-free talc and talcum powder and a better characterization of exposure.
    systematic review.
    cohort studies of talc miners and millers exposed to asbestos-free talc, as well as cohort and case-control studies reporting cancer risk in talc powder consumers published from 2006 onwards were identified through PubMed and reference lists. Pooled analyses were included, but not reviews and meta-analyses. In the case of repeatedly reported studies, the article with the longest follow-up or the largest number of observed cases was selected for data abstraction. Notice was taken of studies which were both reported individually and included in pooled analyses.
    publications meeting inclusion criteria were: 2 cohort studies on talc miners and millers, 10 cohort studies on talcum powder users (4 of which estimated ovarian cancer risk), and 14 case-control studies (13 on ovarian and 1 on endometrial cancer) on the risk from talcum powder use. No excess cancer mortality has been reported among asbestos-free talc miners and millers. Case-control studies consistently led to estimates of ovarian cancer excesses associated with the use of perineal talcum powder (odds ratios up to 1.5). Most studies quantifying exposure also provided evidence of a dose-response relationship. Individual cohort studies estimated hazard ratios (HR) just above 1. In an analysis of pooled cohorts for a total of 3,112 cases, the HR for women with patent reproductive tract was 1.13 (95%CI 1.01-1.26) with a correlation between HR and frequency of use (p for trend 0.03). In all cohort studies, the perineal use of talcum powder was measured only once in the early phases of follow-up, thus producing an inaccurate measure of cumulative exposure. Results of epidemiological studies regarding cancer risk in other organs are limited and inconsistent.
    epidemiological studies updated or published after IARC 2006 evaluation indicate that: no increase in cancer risk is apparent among miners and millers of asbestos-free talc; risk for ovarian cancer increases following the perineal use of commercial talcum powder. A correlation between indicators of quantity of use and cancer risk is suggested by a number of studies. The composition of talcum powders considered in such studies is not known.
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  • 文章类型: Case Reports
    我们报告了一例69岁的女性,其胸膜间皮瘤出现在后纵隔,最大直径为25厘米。她患有慢性咳嗽,胸部X光检查发现胸腔积液。对积液的检查显示高透明质酸水平,和间皮瘤被怀疑。胸部计算机断层扫描显示纵隔巨大肿块,导致呼吸衰竭和心脏受压的快速进展。死亡前无法获得足够的组织样本。患者在初次就诊后约1个月死亡,并进行了病理尸检。诊断为恶性胸膜间皮瘤。恶性胸膜间皮瘤与巨大的后纵隔肿块,如在这种情况下是相当罕见的;然而,它是该疾病的一种快速发展形式,在本文中被报道为纵隔肿瘤的重要鉴别诊断。
    We report a case of a 69-year-old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X-ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours.
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  • 文章类型: Journal Article
    基于吲哚的药物经常用于几种癌症的靶向或支持疗法。在这项研究中,我们研究了最初合成的新型吲哚啉-2-酮衍生物(6a-d)对恶性间皮瘤的抗癌特性,乳腺癌,和结肠癌细胞。我们的结果表明,所有衍生物都通过抑制ERK1/2,AKT,和STAT3信号通路呈浓度依赖性。此外,这些变体诱导细胞周期停滞在S期,伴随着p21和p27表达水平的升高。衍生物还通过上调Bax和下调Bcl-2蛋白引发线粒体凋亡,在暴露的细胞中导致caspase3的激活和PARP裂解。值得注意的是,三种吲哚啉-2-酮衍生物对乳腺癌和结肠癌细胞显示出显著的选择性,化合物6d有望成为所有癌细胞系的最有效和最宽光谱的化合物。
    Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl-2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin-2-one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines.
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  • 文章类型: Case Reports
    恶性间皮瘤(MM)是一种罕见的侵袭性肿瘤,存在于胸膜和腹膜中。已报道了几例心包和阴道膜睾丸中的MM。此外,原发性发生在中庭极为罕见。这种肿瘤的视觉外观与常见的心房粘液瘤相似,这使得临床医生和放射科医生诊断和治疗这种疾病具有挑战性。
    一名18岁女性出现胸痛症状,呼吸急促,咳嗽,并咳痰7天。对患者进行了超声心动图检查,显示心房肿块。粘液瘤是鉴别诊断之一。肿瘤是一个有尖端的椭圆形肿块,切割表面像果冻一样,类似于粘液瘤。手术后,活检肿瘤的病理检查证实为上皮型MM。术后随访期间,未观察到肿瘤复发。
    源自中庭的MM被认为极为罕见。因此,临床医生很容易将心房MM误诊为粘液瘤。此外,为了确认诊断,组织病理学活检,组织形态学特征,免疫组织化学,分子基因检测是必需的.因此,MM的临床诊断和治疗具有挑战性。
    UNASSIGNED: Malignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis have been reported. Moreover, primary occurrence in the atrium is extremely rare. The visual appearance of this tumor is similar to that of a common atrial myxoma, which makes it challenging for clinicians and radiologists to diagnose and treat this disease.
    UNASSIGNED: An 18-year-old woman presented with symptoms of chest pain, shortness of breath, cough, and expectoration for 7 days. Echocardiography was performed on the patient, which revealed an atrial mass. Myxoma was one of the differential diagnoses. The tumor was an elliptical mass with tips, and the cut surface was jelly-like, similar to myxoma. After surgery, a pathologic examination of the biopsied tumor confirmed epithelial-type MM. During postoperative follow-up, no recurrence of the tumor was observed.
    UNASSIGNED: MM originating in the atrium is considered to be extremely rare. Consequently, clinicians can easily misdiagnose atrial MM as a myxoma. Moreover, to confirm the diagnosis, histopathologic biopsy, histomorphological characterization, immunohistochemistry, and molecular genetic testing are required. Therefore, clinical diagnosis and treatment of MM are challenging.
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  • 文章类型: Journal Article
    乳酸脱氢酶A(LDH-A)催化糖酵解的最后一步:向细胞快速但低效地提供ATP。许多肿瘤,包括恶性间皮瘤(MM),LDH-A的高表达,这与癌症侵袭性有关。我们的目的是确定吉西他滨/卡铂(Gem+Carbo)组合的疗效,广泛用于治疗这种疾病,可以通过抑制LDH-A(通过NHI-2)来增加。为了这个目标,我们分析了多种组合对胸膜和腹膜MM的生长抑制。
    使用72小时磺罗丹明B测定(SRB)来测试吉西他滨(0.1-400nM)和卡铂(0.01-40μM)的组合的细胞毒性固定浓度的NHI-2(在IC25)。我们使用了胸膜(H2452)和原发性腹膜(STO,MESO-II)MM细胞系,在常氧条件下培养。
    NHI-2在腹膜MM细胞系中不增加100nM吉西他滨和10µM卡铂的组合的细胞毒性。三重组合后的细胞生长抑制比Gem+Carbo处理小10%。
    在常氧条件下,LDH-A的抑制并未增加吉西他滨和卡铂在MM中的功效。
    UNASSIGNED: Lactate dehydrogenase A (LDH-A) catalyzes the last step of glycolysis: supplying cells rapidly but inefficiently with ATP. Many tumors, including malignant mesothelioma (MM), have a high expression of LDH-A, which is associated with cancer aggressiveness. We aimed to determine whether the efficacy of the gemcitabine/carboplatin (Gem + Carbo) combination, widely used to treat this disease, could be increased by inhibition of LDH-A (by NHI-2). To this aim, we analyzed the growth inhibition of pleural and peritoneal MM by multiple combinations.
    UNASSIGNED: The 72 h sulforhodamine B assay (SRB) was used to test the cytotoxicity of the combination of gemcitabine (in the range 0.1 - 400 nM) and carboplatin (0.01 - 40 µM) with a fixed concentration of NHI-2 (at IC25). We used pleural (H2452) and primary peritoneal (STO, MESO-II) MM cell lines, cultured at normoxic conditions.
    UNASSIGNED: NHI-2 did not increase the cytotoxicity of the combination of 100 nM gemcitabine and 10 µM carboplatin in peritoneal MM cell lines. The cell growth inhibition was 10% smaller after the triple combination than the Gem + Carbo treatment.
    UNASSIGNED: Inhibition of LDH-A did not increase the efficacy of gemcitabine and carboplatin in MM under normoxic conditions.
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  • 文章类型: Journal Article
    背景:胸膜间皮瘤(PM)的发病率和死亡率反映了石棉的生产和消费随时间的变化。然而,尽管当前全球关注,这些数据还有待了解。
    目的:我们的目的是对2014年至2020年之间的一些葡萄牙数据库中的PM病例和死亡率进行描述性分析。
    方法:2014年至2020年进行了一项回顾性观察性研究。PM病例数的数据由葡萄牙癌症登记处提供,死亡率数据来自葡萄牙死亡证明信息系统。
    结果:在2014年至2020年期间,报告了315例PM,男性222人(70.5%)。患者的平均年龄为72.1,年龄>70岁的患者的病例数最高(n=198;62.9%)。2018年报告的病例数最高(n=62;19.7%)。关于死亡率,报告有169人死亡,有126名(74.6%)男性,主要是年龄>70岁的个体(n=109;64.5%)。据估计,大约有520年的潜在寿命丧失。死亡人数最多的是2015年(n=33;19.5%)。
    结论:必须加强对监测计划的需求,使我们能够收集真实可靠的数据并消除与石棉有关的疾病。
    BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.
    OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.
    METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.
    RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).
    CONCLUSIONS: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.
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