Teratomas

畸胎瘤
  • 文章类型: Journal Article
    生殖细胞肿瘤包括由生殖细胞谱系引起的广谱肿瘤,显示不同的组织学特征和临床表现。这些肿瘤包括一系列良性和恶性实体。虽然全球趋势提供了对其患病率的见解,特定的区域差异,比如印度西北部的那些,少探索。这项研究旨在通过检查三级癌症医院内生殖细胞肿瘤的患病率和特征来弥合这一知识鸿沟。在这个回顾性分析中,纳入了在指定三级癌症医院3年内诊断的所有生殖细胞肿瘤病例.排除记录不完整或病理资料不充分的病例。包括组织学亚型的数据,患者年龄分布,临床表现,收集并分析组织病理学特征。该研究包括145例生殖细胞肿瘤。畸胎瘤是最常见的亚型,成熟的畸胎瘤占大多数。最高的发病率发生在21-30岁年龄组,平均年龄为24.77岁。腹部肿块(56%)和腹痛(34%)是突出的临床表现。良性病例占多数85.5%。发现实体肿瘤(p<0.00001)和超过10厘米的肿瘤(p.029028)具有很高的恶性倾向,这被证明具有统计学意义。这项研究全面解释了生殖细胞肿瘤的患病率,临床特征,以及印度西北部一家三级癌症医院的组织病理学亚型。畸胎瘤占主导地位,特别是成熟的,与全球趋势保持一致。年龄分布和临床表现反映了共同的模式。不同的组织病理学表现强调了生殖细胞肿瘤的异质性。这项研究为临床管理和进一步的区域研究提供了有价值的见解。
    Germ cell tumors encompass a broad spectrum of neoplasms arising from germ cell lineage, demonstrating varying histological profiles and clinical presentations. These tumors encompass a range of benign and malignant entities. While global trends provide insights into their prevalence, specific regional variations, such as those within North-Western India, remain less explored. This study seeks to bridge this knowledge gap by examining the prevalence and characteristics of germ cell tumors within a tertiary cancer hospital. In this retrospective analysis, all cases of germ cell tumors diagnosed over a 3-year period in the specified tertiary cancer hospital were included. Cases with incomplete records or inadequate pathological data were excluded. Data encompassing histological subtypes, patient age distribution, clinical presentations, and histopathological features were collected and analyzed. The study comprised 145 cases of germ cell tumors. Teratomas were the most prevalent subtype, with mature teratomas accounting for the majority. The highest incidence occurred within the 21-30-year age group with a mean age of 24.77 years. Abdominal mass (56%) and abdominal pain (34%) were the prominent clinical presentations. Benign cases constituted the majority 85.5%. Solid tumors (p < 0.00001) and tumors more than 10 cm (p .029028) were found to have a high propensity to be malignant, which was proven to be statistically significant. This study comprehensively explains germ cell tumors\' prevalence, clinical features, and histopathological subtypes in a tertiary cancer hospital in North-Western India. The predominance of teratomas, particularly mature ones, aligns with global trends. The age distribution and clinical presentations reflect common patterns. The diverse histopathological appearances underscore the heterogeneous nature of germ cell tumors. This study offers valuable insights for clinical management and further regional research.
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  • 文章类型: Journal Article
    人类诱导多能干细胞(iPSCs)在个性化医疗中具有广阔的前景,因为它们可以分化为特定的细胞类型,特别是间充质干细胞(MSCs)。因此,我们的研究旨在评估从人类iPSCs产生的畸胎瘤中获得MSCs的可行性。畸胎瘤作为模拟多谱系人类发育的模型,从而富集特定的体细胞祖细胞和干细胞。这里,我们发现了一个小的,MSCs在iPSC产生的畸胎瘤内的凝聚质量。之后,我们成功地从这个凝聚的物质中分离出了MSCs,这是畸胎瘤发展的副产品。评价iPSC来源的MSCs(iPSC-MSCs)的特性和细胞行为,我们使用qPCR进行了全面评估,免疫表型分析,和细胞增殖相关的测定。值得注意的是,iPSC-MSCs表现出类似于常规MSCs的免疫表型,它们表现出强大的增殖能力,与更高的多能干细胞来源的MSCs相似。此外,iPSC-MSC在体外表现出分化为多个谱系的能力。最后,我们使用骨软骨缺损模型评估了iPSC-MSCs的治疗潜力.我们的发现表明畸胎瘤是分离浓缩MSCs的有希望的来源。更重要的是,我们的结果表明,来自畸胎瘤的iPSC-MSCs具有组织再生能力,强调他们对未来治疗应用的承诺。
    Human induced pluripotent stem cells (iPSCs) hold great promise for personalized medicine, as they can be differentiated into specific cell types, especially mesenchymal stem cells (MSCs). Therefore, our study sought to assess the feasibility of deriving MSCs from teratomas generated from human iPSCs. Teratomas serve as a model to mimic multilineage human development, thus enriching specific somatic progenitors and stem cells. Here, we discovered a small, condensed mass of MSCs within iPSC-generated teratomas. Afterward, we successfully isolated MSCs from this condensed mass, which was a byproduct of teratoma development. To evaluate the characteristics and cell behaviors of iPSC-derived MSCs (iPSC-MSCs), we conducted comprehensive assessments using qPCR, immunophenotype analysis, and cell proliferation-related assays. Remarkably, iPSC-MSCs exhibited an immunophenotype resembling that of conventional MSCs, and they displayed robust proliferative capabilities, similar to those of higher pluripotent stem cell-derived MSCs. Furthermore, iPSC-MSCs demonstrated the ability to differentiate into multiple lineages in vitro. Finally, we evaluated the therapeutic potential of iPSC-MSCs using an osteochondral defect model. Our findings demonstrated that teratomas are a promising source for the isolation of condensed MSCs. More importantly, our results suggest that iPSC-MSCs derived from teratomas possess the capacity for tissue regeneration, highlighting their promise for future therapeutic applications.
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  • 文章类型: Journal Article
    在过去的14年中,随着诱导性多能干细胞的出现,多能干细胞研究彻底改变了现代时代。在此之前,科学家获得了人类和小鼠胚胎干细胞,主要用于基础研究,并尝试针对细胞疗法应用的谱系特异性分化。关于多能干细胞,表达bonafide标记蛋白,如Oct4,Nanog,Sox2,Klf4,c-Myc,和Lin28被认为是一个完美的多能干细胞读数,并使用分析流式细胞仪进行评估。除了细胞内标记,需要表面标记物,例如小鼠细胞的阶段特异性胚胎抗原-1和人细胞的SSEA-4,以分选纯干细胞群体,用于细胞治疗的进一步下游应用。表面标记SSEA-4最适合于获得人多能干细胞的纯群体。当使用生长因子或小分子以受控方式分化时,必须评估多能性标志物的下调(Oct4,Nanog,Sox2和Klf4),随后上调了阶段特异性分化标记。使用流式细胞术进行此类评估。多能干细胞在体内具有很高的畸胎瘤形成潜力。如果剩余在分化细胞池中,少量未分化的PSC可能在移植时导致危险的畸胎瘤。因此,流式细胞术对于分选具有畸胎瘤形成潜力的PSC群体至关重要。分化祖细胞的纯群体需要在将它们进一步分化以用于细胞治疗应用之前进行流式分选。例如,糖蛋白2是胰腺祖细胞的特异性细胞表面标志物,使人们能够分选从人PSC分化的胰腺祖细胞。一起来看,分析流式细胞术,和细胞分选为PSC研究和细胞治疗提供了不可或缺的工具。
    Pluripotent stem cell research has revolutionized the modern era for the past 14 years with the advent of induced pluripotent stem cells. Before this time, scientists had access to human and mouse embryonic stem cells primarily for basic research and an attempt towards lineage-specific differentiations for cell therapy applications. Regarding pluripotent stem cells, expression of bonafide marker proteins such as Oct4, Nanog, Sox2, Klf4, c-Myc, and Lin28 have been considered giving a perfect readout for pluripotent stem cells and assessed using an analytical flow cytometer. In addition to the intracellular markers, surface markers such as stage-specific embryonic antigen-1 for mouse cells and SSEA-4 for human cells are needed to sort pure populations of stem cells for further downstream applications for cell therapy. The surface marker SSEA-4 is the most appropriate for obtaining pure populations of human pluripotent stem cells. When differentiated in a controlled manner using growth factors or small molecules, it is mandatory to assess the downregulation of pluripotency markers (Oct4, Nanog, Sox2, and Klf4) with subsequent up-regulation of stage-specific differentiation markers. Such assessments are done using flow cytometry. Pluripotent stem cells have a high teratoma-forming potential in vivo. Small amounts of undifferentiated PSCs might lead to dangerous teratomas upon transplantation if leftover in the pool of differentiated cells. Hence, flow cytometry is essential for sorting out PSC populations with teratoma-forming potential. The pure populations of differentiated progenitors need to be flow-sorted before differentiating them further for cell therapy applications. For example, Glycoprotein 2 is a specific cell-surface marker for pancreatic progenitors that enables one to sort the pancreatic progenitors differentiated from human PSCs. Taken together, analytical flow cytometry, and cell sorting provide indispensable tools in PSC research and cell therapy.
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  • 文章类型: Journal Article
    宫颈畸胎瘤是新生儿畸胎瘤的一种罕见形式,是新生儿宫颈肿块的不寻常原因。畸胎瘤是来自所有3个生殖细胞层的不寻常肿瘤:内胚层,中胚层,和外胚层,比例不同。宫颈畸胎瘤是一种罕见的实体。其预后主要取决于新生儿呼吸窘迫的风险,它的延伸和潜在的恶性肿瘤。手术治疗必须尽可能完整,以避免复发和恶性转化。我们报告了一例完全切除和治愈的婴儿宫颈未成熟畸胎瘤。没有复发的报道。我们研究的目的是回顾诊断,先天性宫颈畸胎瘤的治疗和预后.宫颈畸胎瘤虽然不常见,但在新生儿颈部肿块的鉴别诊断中应考虑。畸胎瘤是源自所有三个生殖细胞层的罕见肿瘤,占所有病例的3%。先天性宫颈畸胎瘤的早期完整手术方法可以取得良好的效果,并发症和复发率低。
    Cervical teratoma is a rare form of teratoma in neonates and is an unusual cause of cervical masses in them. Teratomas are unusual tumors derived from all 3 germs cell layers: endoderm, mesoderm, and ectoderm, with varying proportions. The cervical teratoma is a rare entity. Its prognosis mostly depends on the risk of neonatal respiratory distress, its extension and potential malignancy. Surgical management must be as complete as possible to avoid recurrences and malignant transformation. We report a case of a cervical immature teratoma in an infant with total excision and cure. No recurrence has been reported. The aim of our study is to review the diagnosis, management and outcomes of congenital cervical teratomas. Cervical teratoma although uncommon should be considered in the differential diagnosis of neck masses in neonates. Teratomas are rare tumors derived from all three germ cell layers affecting the neck in 3% of all cases. An early complete surgical approach to congenital cervical teratomas allows good results with low rates of complication and recurrence.
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  • 文章类型: Case Reports
    卵巢类癌是一种罕见的肿瘤,其中甲状腺(甲状腺肿)和类癌成分共存。该疾病通常被认为是边缘性恶性肿瘤,然而,已经描述了转移性疾病的病例。文献中没有数据可用于指导诊断和治疗。
    我们使用以下关键词对文献中发表的组织病理学证实的类癌病例进行了汇总分析和系统评价:“卵巢类癌”,“胸膜类癌病例报告”。在SpedaliCivili的肿瘤内科病房诊断并随访了一例树状类癌肿瘤(布雷西亚,意大利)也被描述和包括在内。
    确定了66篇合格出版物,提供来自117名患者的数据,加上我们机构确诊的病例.在介绍时,在88名有症状的患者中,37%的患者患有腹胀,49%的患者因腹部肿瘤肿块增大而疼痛,37%来自便秘(仅在其中9个中分析了肽YY,导致高于生理范围)。手术是99%患者的主要治疗方法。3例患者在诊断时患有转移性疾病,5例患者在根治性手术后复发。疾病复发时的组织学与两名患者的甲状腺成分有关,两名患者的类癌成分,一名患者的两种组织学。未达到该系列中的中位无病生存期和总生存期。
    卵巢类癌通常表现为良性行为,手术在大多数情况下是治愈性的。然而,由于甲状腺和神经内分泌(类癌)成分,一小部分患有这种疾病的患者可能会复发。因此,需要对彻底手术的患者进行随访,特别是那些在诊断时患有大量疾病的人。
    Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy.
    We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: \"strumal carcinoid of the ovary\", \"strumal carcinoid case report\". A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included.
    Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained.
    Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.
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  • 文章类型: Journal Article
    Retrorectal or presacral tumors are rare lesions located in the presacral area and considered as being derived from multiple embryological remnants. These tumors are classified as congenital, neurogenic, osseous, inflammatory, or miscellaneous. The most common among these are congenital benign lesions that present with non-specific symptoms, such as lower back pain and change in bowel habit. Although congenital and developmental tumors occur in younger patients, the median age of presentation is reported to be 45 years. Magnetic resonance imaging plays a crucial role in treatment management through accurate diagnosis of the lesion, the evaluation of invasion to adjacent structures, and the decision of appropriate surgical approach. The usefulness of preoperative biopsy is still debated; currently, it is only indicated for solid or heterogeneous tumors if it will alter the treatment management. Surgical resection with clear margins is considered the optimal treatment; described approaches are transabdominal, perineal, combined abdominoperineal, and minimally invasive. Benign retrorectal tumors have favorable long-term outcomes with a low incidence of recurrence, whereas malignant tumors have a potential for distant organ metastasis in addition to local recurrence.
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  • 文章类型: Case Reports
    几种肿瘤产生于纵隔内的不同结构。尽管每种类型的纵隔肿瘤都有特定的区室,可以发生从一个隔室到另一个隔室的生长进程。前纵隔是几种肿瘤的部位,对胸外科医师提出了有趣的诊断和治疗挑战。前纵隔是纵隔内大多数肿瘤生长的所在地。胸腺瘤和淋巴瘤是前纵隔最常见的病理。间质起源的肿瘤(血管瘤,淋巴管瘤,脂肪瘤)及其恶性对应物可能发生在任何纵隔区。前纵隔区不太常见的肿瘤是异位甲状腺和甲状旁腺肿瘤,生殖细胞肿瘤,间充质起源肿瘤,血管瘤,和宫颈纵隔积液。大多数纵隔生长通常在临床上保持沉默,直到它们变大并引起压迫症状。这里,我们介绍了一系列五个前纵隔肿瘤,包括孤立性良性畸胎瘤,纤维良性肿瘤,恶性纤维肉瘤,错构瘤软骨瘤,还有恶性胸腺瘤.
    Several tumors arise from different structures within the mediastinum. Although each type of mediastinal tumor has a predilection for a specific compartment, the progression of growth from one compartment to another can occur. The anterior mediastinum is the site of several tumors that pose interesting diagnostic and therapeutic challenges to thoracic surgeons. The anterior mediastinum is the seat of the majority of neoplastic growths within the mediastinum. Thymomas and lymphomas are the most common pathologies of the anterior mediastinum. Tumors of mesenchymal origin (hemangioma, lymphangioma, lipomas) and their malignant counterparts may occur in any of the mediastinal compartments. Less common tumors of the anterior mediastinal compartment are ectopic thyroid and parathyroid tumors, germ cell tumors, mesenchymal origin tumors, hemangiomas, and cervicomediastinal hygromas. Most of the mediastinal growths usually remain clinically silent until they become large and cause compressive symptoms. Here, we present a case series of five anterior mediastinal tumors consisting of solitary benign teratoma, fibrous benign tumor, malignant fibrosarcoma, hamartomatous chondroma, and malignant thymoma.
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  • 文章类型: Journal Article
    The Ter mutation in Dead-End 1 (Dnd1), Dnd1Ter, which leads to a premature stop codon, has been determined to be the cause for primordial germ cell deficiency, accompanied with a high incidence of congenital testicular germ cell tumors (TGCTs) or teratomas in the 129/Sv-Ter mice. As an RNA-binding protein, DND1 can bind the 3\'-untranslated region (3\'-UTR) of mRNAs and function in translational regulation. DND1 can block microRNA (miRNA) access to the 3\'-UTR of target mRNAs, thus inhibiting miRNA-mediated mRNA degradation and up-regulating translation or can also function to degrade or repress mRNAs. Other mechanisms of DND1 activity include promoting translation initiation and modifying target protein activity. Although Dnd1Ter mutation causes spontaneous TGCT only in male 129 mice, it can also cause ovarian teratomas in mice when combined with other genetic defects or cause germ cell teratomas in both genders in the WKY/Ztm rat strain. Furthermore, studies on human cell lines, patient cancer tissues, and the use of human cancer genome analysis indicate that DND1 may possess either tumor-suppressive or -promoting functions in a variety of somatic cancers. Here we review the involvement of DND1 in cancers, including what appears to be its emerging role in somatic cancers.
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  • 文章类型: Journal Article
    细胞重编程是成年分化细胞失去其身份并转化为多能干细胞的过程,被称为诱导多能干细胞(iPS)。该过程可以在体外和体内实现,并且与包括再生医学和癌症在内的许多领域有关。细胞重编程通常由Oct4,Sox2,Klf4和Myc(缩写为OSKM)组成的转录因子混合物的异位表达诱导,其效率和动力学强烈依赖于Myc的存在。这里,我们描述了一种基于使用腺相关病毒(AAV)载体的体内研究重编程的通用方法,它允许靶向特定的器官和细胞类型。此方法可用于测试Myc突变或可能替代Myc的基因,或与不同的Myc调节器结合使用。体内重编程可以通过畸胎瘤的存在和体内iPS的分离来评分,从而为Myc在去分化和干性中的功能提供了简单的替代。我们的方案可分为五个步骤:(1)静脉内接种AAV载体;(2)监测动物直至畸胎瘤出现;(3)畸胎瘤分析;(4)小鼠器官的组织病理学分析;(5)从畸胎瘤中分离体内产生的iPS细胞,血,还有骨髓.该体内测试平台获得的信息可能提供有关Myc在组织再生中的作用的相关信息,stemness,和癌症。
    Cellular reprogramming is a process by which adult differentiated cells lose their identity and are converted into pluripotent stem cells, known as induced pluripotent stem (iPS) cells. This process can be achieved in vitro and in vivo and is relevant for many fields including regenerative medicine and cancer. Cellular reprogramming is commonly induced by the ectopic expression of a transcription factor cocktail composed by Oct4, Sox2, Klf4, and Myc (abbreviated as OSKM), and its efficiency and kinetics are strongly dependent on the presence of Myc. Here, we describe a versatile method to study reprogramming in vivo based on the use of adeno-associated viral (AAV) vectors, which allows the targeting of specific organs and cell types. This method can be used to test Myc mutations or genes that may replace Myc, or be combined with different Myc regulators. In vivo reprogramming can be scored by the presence of teratomas and the isolation of in vivo iPS, thereby providing a simple surrogate for the function of Myc in dedifferentiation and stemness. Our protocol can be divided into five steps: (1) intravenous inoculation of AAV vectors; (2) monitoring the animals until the appearance of teratomas; (3) analysis of teratomas; (4) histopathological analysis of mouse organs; and (5) isolation of in vivo-generated iPS cells from teratomas, blood, and bone marrow. The information obtained by this in vivo testing platform may provide relevant information on the role of Myc in tissue regeneration, stemness, and cancer.
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  • 文章类型: Journal Article
    In response to signals from the embryonic testis, the germ cell intrinsic factor NANOS2 coordinates a transcriptional program necessary for the differentiation of pluripotent-like primordial germ cells toward a unipotent spermatogonial stem cell fate. Emerging evidence indicates that genetic risk factors contribute to testicular germ cell tumor initiation by disrupting sex-specific differentiation. Here, using the 129.MOLF-Chr19 mouse model of testicular teratomas and a NANOS2 reporter allele, we report that the developmental phenotypes required for tumorigenesis, including failure to enter mitotic arrest, retention of pluripotency and delayed sex-specific differentiation, were exclusive to a subpopulation of germ cells failing to express NANOS2. Single-cell RNA sequencing revealed that embryonic day 15.5 NANOS2-deficient germ cells and embryonal carcinoma cells developed a transcriptional profile enriched for MYC signaling, NODAL signaling and primed pluripotency. Moreover, lineage-tracing experiments demonstrated that embryonal carcinoma cells arose exclusively from germ cells failing to express NANOS2. Our results indicate that NANOS2 is the nexus through which several genetic risk factors influence tumor susceptibility. We propose that, in the absence of sex specification, signals native to the developing testis drive germ cell transformation.
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