Gastric adenocarcinoma with features of endodermal sinus tumor

Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here a case where a middle aged man presented with typical symptoms of gastric cancer. After extensive workup, which included blood work, CT abdomen scan, upper endoscopy, and endoscopic ultrasound, the patient was diagnosed with gastric cancer. However, due to very high blood levels of alpha-fetoprotein, the specimen was sent for special histochemical staining, which demonstrated that the tumor had features of both adenocarcinoma and endodermal sinus tumor. This is a very aggressive tumor with a very poor prognosis.

Primary Endodermal Sinus Tumor in the Posterior Cranial Fossa:Clinical Analysis of 7 Cases

Objective To clarify the clinical features,therapeutic method and outcomes of the primary endodermal sinus tumors(ESTs)in the posterior cranial fossa.Methods The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed.And a 4-year-old boy diagnosed with EST in our hospital was reported.The clinical manifestations,therapy,pathologic features,and prognosis of these cases were analyzed.Results Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review,including six cases searched from the PubMed and one case from our hospital.Six patients were boy and one patient’s gender was not available from the report.Ages ranged from 1 to 5 years(mean 3.14 years).The mean tumor size in our cohort was 4.4 cm.Six cases came from East Asia.Schiller-Duval bodies were found in all seven neoplasms.All tumors were positive for alpha-fetoprotein.The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy.The mean follow-up time was 24.4 months(range 5-52 months).Six tumors were totally removed,and four of them recurred.Three cases died including one whose tumor was partially removed.Conclusions The serum alpha-fetoprotein level is well correlated with the severity of the tumor.A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa.The prognosis of extragonadal intracranial EST is poor.

Roles of the Nanog protein in murine F9 embryonal carcinoma cells and their endoderm-differentiated counterparts

Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem （ES） cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.

Laparoscopic uncontained power morcellation-induced dissemination of ovarian endodermal sinus tumors:A case report

BACKGROUND Endodermal sinus tumors(ESTs),which arise primarily in children and adolescents,account for 20%of malignant ovarian germ cell tumors,but constitute only 1%of all ovarian malignancies.Treatment of ESTs consists of surgical staging with fertility-sparing surgery and chemotherapy.CASE SUMMARY A 15-year-old nulliparous patient was diagnosed with disseminated ovarian ESTs after laparoscopic unilateral salpingo-oophorectomy using uncontained power morcellation for treatment of a ruptured solid adnexal mass in another hospital.Exploratory laparotomy;total abdominal hysterectomy,right salpingooophorectomy,and lymphadenectomy were performed with optimal debulking,and surgical stage 3C was assigned to the patient.CONCLUSION In 2014,the Food and Drug Administration noted that power morcellation was probably associated with a risk of disseminating suspected cancerous tissue.Furthermore,the use of power morcellation to remove solid adnexal mass is considered a contraindication because of the potential for a malignant tumor.This case report aims to warn of the dangers of using uncontained power morcellation to treat solid adnexal masses.

Case Report of an Endodermal Sinus Vaginal Tumor in an Infant Girl

Case Report An female infant patient, aged 8 months old, suffered from irregular colporrhagia for a period of 1 month after which she was taken to our hospital on 30th April, 2003. A pelvic CT examination displayed a 6.5 cm×3.0 cm shadow of a soft-tissue tumor growing longitudinally in her supravaginal uterine area （Fig. 1）. The density of the shadow was uneven, in which there were irregular low-density loci, an indication of a compression of the colon and bladder and a diffuse boundary between the posterior wall of the urinary bladder and tumor. No abnormalities were found in either kidney or ovary, the liver or gall bladder. Also no obvious lesions were seen on the chest X-ray film, and routine blood and urine laboratory examinations were normal.

A Case of a Primary Endodermal Sinus Tumor of the Cerebellar Vermis

A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he had a ＂common cold＂, but treatment for 3 days produced no result. He was diagnosed as having viral encephalitis after an examination including an electroencephalogram （EEG）, blood biochemistry and lumbar puncture, etc. in a local hospital on November 15. After further treatment for 3 days his symptoms became aggravated showing instability of gait and involuntary movement of his head and extremities. Cranial CT showed： a 4.0 cm×4.0 cm×5.0 cm lump in the cerebellar vermis which intruded into the fourth ventricle inducing evident distention of the third and lateral ventricle. He was diagnosed with blastoma of the cerebellum.

Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm induction in zebrafish embryos

Development of animal embryos before zygotic genome activation at the mid blastula transition （MBT） is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a （Eomesa）, a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and rnxtx2 to activate their transcrip- tion. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.

Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm

Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.

Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids

Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases.In this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic organoids.We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology.Finally,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.

Endoderm contributes to endocardial composition during cardiogenesis

Heart formation commences from a single heart tube,which fuses from bilateral primordial heart fields.The developing heart tube is composed of outer-layer myocardial cells and inner-layer endocardial cells.Several distinct populations of precardiac cells contribute to cardiac morphogenesis.However,it still remains not very clear about the lineage of endocardium at gastrulation stage.Thereby,this study focused on ascertaining the correlation between the hypoblast in gastrulation and endocardium during cardiogenesis.Firstly,the fusing heart tube morphologically is closed to endoderm-derived pharynx floor,implying the possibility that pharynx floor might be wrapped into the formation of endoderm.Secondly,HNK1 is expressed in hypoblast strongly at gastrula stage and subsequently appeared in endocardium of cardiogenesis.Moreover,fate map data displayed that DiI labeled hypoblast was also present in endocardium later on.One more evidence is chick-quail chimera of hypoblast transplantation,in which quail-hypoblast derivative could be identified inendocardium of cardiogenesis by QCPN antibody.In sum,our current data suggests that endoderm in gastrula contribute at least partly to the formation of endocardium of cardiogenesis.

儿童小脑内胚窦瘤1例

男性患儿,2岁,间断头痛3天;既往无特殊病史及家族史。查体未见明显异常。实验室检查:血清甲胎蛋白(alpha-fetoprotein,AFP)2664 ng/ml。颅脑MRI:右侧小脑半球37 mm×39 mm×35 mm T1WI等-稍低信号占位,边界清晰(图1A),T2WI呈高信号内见条片状混杂低信号及多发小灶样更高信号(图1B),弥散加权成像(diffusion weighted imaging,DWI)呈等信号,表观弥散系数图呈稍高信号;周围见斑片状水肿,小脑蚓部及小脑扁桃体受压向前或前上移位,第四脑室受压变形、出口闭塞,幕上脑室系统扩张;增强后病变明显强化,内见条片状及灶状无强化。

Wnt信号通路与自身免疫调节因子共同参与胚胎干细胞向胸腺上皮祖细胞的分化

背景:自身免疫调节因子(autoimmune regulator gene,Aire)及Wnt信号通路在小鼠胚胎干细胞多能性的维持及分化中都发挥着重要作用,但Wnt信号与Aire是否参与了小鼠胚胎干细胞向胸腺上皮祖细胞的分化尚未可知。目的:探讨Wnt信号通路和自身免疫调节因子与胚胎干细胞分化的关系。方法:采用两步分化方法定向诱导小鼠胚胎干细胞分化为内胚层再分化为胸腺上皮祖细胞,然后用Aire shRNA慢病毒感染小鼠胚胎干细胞,嘌呤霉素筛选单克隆稳定株,再采用两步分化方法进行诱导分化,分别于定向诱导分化第0,3,10天,采用细胞免疫荧光、流式细胞术、Western blot、Real-Time qPCR检测相关基因及蛋白的表达变化。结果与结论:①定向诱导分化第0天,免疫荧光染色显示SSEA1、OCT4表达呈阳性;②定向诱导分化第3天,免疫荧光染色显示SOX17、FOXA2表达呈双阳性;③定向诱导分化第10天,流式细胞术结果显示EPCAM1、K5、K8表达呈阳性;④与未分化的小鼠胚胎干细胞相比,诱导分化的胸腺上皮祖细胞中Wnt7a、β-catenin、Gsk-3β蛋白表达升高,Aire蛋白表达降低;⑤与未分化的小鼠胚胎干细胞相比,诱导分化的胸腺上皮祖细胞中Wnt7a、β-catenin、Gsk-3β及Aire mRNA表达升高;⑥与正常培养的小鼠胚胎干细胞及其最终分化的胸腺上皮祖细胞相比,敲低Aire基因的小鼠胚胎干细胞及其最终分化的胸腺上皮祖细胞中Wnt7a、β-catenin、Gsk-3β蛋白表达水平降低。综上所述,Wnt信号通路和Aire共同参与了小鼠胚胎干细胞定向诱导分化为小鼠胸腺上皮祖细胞的过程。

绝经后妇女原发性子宫内膜卵黄囊瘤一例

报告1例绝经后妇女原发于子宫内膜的卵黄囊瘤病例。该患者为57岁女性,主要临床表现为绝经后阴道出血,伴有血清肿瘤标志物甲胎蛋白(alpha-fetoprotein,AFP)升高,妇科超声提示子宫内膜增厚并回声不均,可见较丰富血流,右侧宫腔占位病变;盆腔磁共振成像示子宫肌层及宫腔内异常信号影。该患者于2024年1月2日行经腹全子宫切除+双侧附件切除+盆腔及腹主动脉旁淋巴结清扫+大网膜切除术,术后病理提示子宫内膜卵黄囊瘤。截至2024年5月,患者已完成6次化疗,一般情况良好,未发现复发及转移。绝经后妇女原发性子宫内膜卵黄囊瘤恶性程度高、预后差,临床表现无特异性,确诊主要依靠病理学检查和免疫组织化学检查,早发现、早诊断并制定个体化的治疗方案是改善患者预后的关键。

DANCR在人胚胎干细胞向内胚层分化中的调控功能

【目的】探讨DANCR在人胚胎干细胞(hESC)向内胚层(DE)分化中的作用。【方法】建立体外诱导hESC向DE分化的体系,检测DANCR的表达水平与DE分化的相关性;利用慢病毒体系敲低hESC的DANCR表达水平,将敲低DANCR的hESC进行DE分化;用qPCR和Western blot方法检测DE分子标志物SOX17和FOXA2,以及原条分子标志物Brachyury(T),EOMES,MIXL1和GSC的表达水平;用Dual luciferase reporter assay和qPCR证明在DE分化过程中DANCR与WNT通路的相互作用。【结果】体外诱导hESC向DE分化的体系能够有效模拟体内DE分化,DANCR的表达水平随DE分化进程逐渐下降。建立敲低DANCR的hESC细胞株,DANCR表达水平相比对照组显著降低(P<0.001)。干扰DANCR表达使分化早期的原条分子标志物Brachyury(T),EOMES,MIXL1和GSC,以及分化后期的DE分子标志物SOX17和FOXA2的mRNA表达水平相比对照组显著降低(全部P<0.05)。并且,在DE分化过程中,敲低DANCR组的WNT通路的转录活性相比对照组显著降低(P<0.05),表现为WNT通路下游基因FZD5,FZD8,SFRP1,FRZB和ANKRD6 mRNA表达水平明显减少(P<0.05)。然而,敲低DANCR对TGFβ通路的SMAD2/3和p-SMAD2蛋白表达水平没有显著影响(P>0.05)。人为激活细胞内β-CATENIN蛋白活性,能够有效回补由于敲低DANCR导致的DE分化缺陷。【结论】DANCR在DE分化过程中逐渐下调并促进DE分化发生,DAN⁃CR可能通过与WNT通路相互作用参与调控hESC向DE分化。

彩色多普勒超声诊断卵巢内胚窦瘤

目的探讨彩色多普勒超声诊断卵巢内胚窦瘤的价值。方法分析51例经手术病理证实的卵巢内胚窦瘤患者的临床及彩色多普勒超声资料。结果本组卵巢内胚窦瘤15.69%为单房囊型,21.57%为多房囊型,39.22%为蜂窝型,23.53%为实质型,彩色多普勒超声显示实质型及蜂窝型血流信号丰富,阻力指数较低。结论卵巢内胚窦瘤的彩色多普勒超声声像图具有一定的特征性,紧密结合临床可明显提高该病的诊断率。

小儿骶前肿瘤的CT和MRI诊断

背景与目的:小儿骶前肿瘤有不同于成人骶前肿瘤的特征性影像学表现,而CT和MRI检查对于术前了解肿瘤的位置、内部成分、周围侵犯等情况有重要参考价值。本文分析小儿骶前肿瘤的CT和MRI表现,探讨CT和MRI对小儿骶前肿瘤的诊断价值。方法:搜集24例经手术病理证实的小儿骶前肿瘤的CT和MRI检查资料并进行回顾性分析。结果:24例骶前肿瘤中,囊性占位病变6例,病灶边界清楚,有完整包膜,病灶有多个囊腔;增强扫描囊壁强化,囊内容物无强化;病理证实均为良性病变。实性占位病变5例,肿块均表现为明显不均匀强化;病理证实均为恶性肿瘤。囊实混杂或实性成分内明显坏死囊变13例,其中7例为囊实性畸胎瘤,内可有条状钙化、软组织及脂肪密度,病理4例为良性肿瘤、3例为恶性肿瘤;5例为内胚窦瘤,呈蜂窝样强化;1例为神经母细胞瘤,肿瘤内部可见大片状坏死,肿瘤部分伸入椎管,骶骨受侵犯。肿瘤与周围组织界限不清楚者共5例,其中畸胎瘤3例,横纹肌肉瘤及内胚窦瘤各1例。侵犯骶骨者畸胎瘤、横纹肌肉瘤、神经母细胞瘤和淋巴管瘤各1例。结论:CT和MRI可清楚地显示小儿骶前间隙肿瘤的部位和范围,其中多数肿瘤可以定性。

小鼠胚胎心流出道的形态发生与呼吸内胚层发育耦联

目的探讨小鼠胚胎心发育过程中前肠呼吸内胚层与第一生心区和第二生心区及胚胎心流出道的形态发生关系。方法胚龄7.5～13d小鼠胚胎心各3个,连续石蜡切片,用抗胰岛素增强子结合蛋白1(ISL-1)、抗心肌肌球蛋白重链(MHC)、抗α-平滑肌肌动蛋白(α-SMA)、抗Nkx2.5和抗增殖细胞核抗原(PCNA)抗体进行免疫组织化学或免疫荧光染色。结果胚胎发育7.5d,ISL-1在生心板心肌前体细胞表达并与发育中的第二生心区ISL-1阳性细胞连续。胚胎发育第10～13天,可见ISL-1强阳性的前肠腹侧呼吸内胚层细胞增生,排列不规则,失去极性,细胞间间隙明显,变为间充质样细胞,与周围ISL-1阳性间充质细胞无明确界限。紧邻动脉囊背侧壁,局部增生的内胚层向动脉囊方向生长,形成实心细胞索,ISL-1阳性间充质细胞围绕前肠腹侧呼吸内胚层及细胞索形成特征性锥体样结构。结论第一和第二生心区是连续结构,ISL-1同时是两个生心区心肌前体细胞的标记蛋白。呼吸内胚层和内胚层细胞索可能诱导第二生心区的扩展,并通过上皮-间充质转化,保持第二生心区细胞数量稳定。

61例儿童睾丸卵黄囊瘤的诊断与治疗

目的：分析儿童睾丸卵黄囊瘤的诊断与治疗，以提高其临床诊治水平。方法回顾性分析本院1995年至2014年收治的61例儿童睾丸卵黄囊瘤患儿的临床资料。结果61例均以阴囊包块就诊，其中60例无痛；61例体查均有阴囊沉重感，透光试验均为阴性；3例提睾反射消失，6例误诊为鞘膜积液，4例初诊腹股沟疝，2例睾丸炎症，1例误诊为腺瘤。术前AFP值均增高，超声检查提示实性包块，CDFI提示84．8％睾丸肿块血流丰富。阴囊X线片均未见确切钙化影。60例行瘤睾高位切除术，1例行睾丸肿瘤剥除术，11例加行腹股沟区淋巴结清扫术。病理检查多见疏网状、腺泡样以及乳头样结构。2009年以前术后化疗采用博来霉素＋长春新碱，近5年采用PEB（顺铂＋足叶以带＋博来霉素）方案、PVB（顺铂＋长春新碱＋博来霉素）方案或二者交替化疗。术后1～2个月随访AFP值多降至正常，无一例复发或死亡。结论儿童睾丸卵黄囊瘤多因无肿痛性肿块就诊，体查包块有沉重感，AFP值升高，超声检查可见实质性包块。胸片和腹部超声可协助肿瘤临床分期。手术方案主要为高位瘤睾切除术，术中冰冻切片能协助术者选择手术范围，术后配合化疗，患儿临床预后效果好。

小儿骶尾部内胚窦瘤的治疗

目的探讨骶尾部内胚窦瘤的治疗和预后。方法回顾性分析1999年1月-2005年12月收治12例骶尾部内胚窦瘤患儿。该组病例术前经B超、CT或MRI检查发现骶尾部肿瘤,经检测血清甲胎蛋白均升高,采用手术切除全部或大部分肿瘤,所有患儿均采用BEP（顺铂十足叶乙甙＋博来霉素）方案化疗。结果该组病例术前经B超或CT检查发现骶尾部肿瘤,经检测血清甲胎蛋白（AFP）均升高,采用手术切除全部或大部分肿瘤,病理证实为内胚窦瘤。患儿均采用BEP（顺铂＋足叶乙甙＋博来霉素）方案化疗。随访6年,生存9例,死亡3例,复发5例。结论以顺铂为基础的联合化疗可改善内胚窦瘤疗效,AFP检测及B超联合应用对小儿内胚窦瘤诊断及复发监测有重要意义,选择恰当的手术方式并辅以联合化疗可提高患儿长期生存率。