ovarian carcinoma

卵巢癌
  • 文章类型: Journal Article
    卵巢癌向胃转移极为罕见。最常见的转移到胃的肿瘤包括黑色素瘤,乳房,肺,和食道癌,而卵巢癌仅占所有胃转移性肿瘤的0.013-1.6%。这项研究的目的是提出一例罕见的卵巢癌异时性胃转移病例,一位59岁的女士。一名59岁的女士在腹部和骨盆的MRI成像中出现右附件肿块,血清CA125升高至4240IU/ml。她接受了包括网膜切除术的原发性细胞减灭术,腹膜活检,盆腔腹膜切除术和腹膜冲洗细胞学,子宫切除术和双侧输卵管卵巢切除术,腹膜后和盆腔淋巴结清扫术.手术性腹膜癌变指数(PCI)为5。最终的组织病理学显示,高级别浆液性腺癌累及右侧附件。她接受了六个周期的辅助化疗。在3个月的随访中,PET扫描显示发现胃底病变.调查显示卵巢浆液性癌有异时转移,经组织病理学评估证实。患者接受了转移灶的手术切除和全身化疗以实现疾病控制。对于患有胃肿块和卵巢癌病史的任何患者,应将卵巢癌的胃转移视为鉴别诊断。
    Metastasis of ovarian cancer to the stomach is extremely rare. The tumors most commonly metastasizing to the stomach include melanoma, breast, lung, and oesophageal carcinoma, while ovarian cancer comprises only 0.013-1.6% of all gastric metastatic tumors. The aim of this study was to present a rare case of an isolated metachronous gastric metastasis from an ovarian carcinoma, in a 59-year-old lady. A 59-year-old lady presented with a right adnexal mass on MRI imaging of the abdomen and pelvis and an elevated serum CA 125 of 4240 IU/ml. She underwent a primary cytoreductive surgery comprising of omentectomy, peritoneal biopsies, pelvic peritonectomy and peritoneal washing cytology, hysterectomy and bilateral salpingo-oophorectomy, and a retroperitoneal and pelvic nodal dissection. The surgical Peritoneal Carcinomatosis Index (PCI) was 5. The final histopathology showed a high-grade serous adenocarcinoma involving the right adnexa. She received six cycles of adjuvant chemotherapy. On a 3-monthly follow-up, the PET scan revealed that a gastric fundic lesion was noted. Investigations revealed a metachronous metastasis from the serous carcinoma of the ovary, confirmed by histopathological evaluation. The patient was treated with surgical resection of the metastasis and systemic chemotherapy to achieve disease control. Gastric metastasis from ovarian cancer should be considered a differential diagnosis in any patient presenting with a gastric mass and a history of ovarian cancer.
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  • 文章类型: Journal Article
    每周紫杉醇(WP)是治疗铂耐药卵巢癌患者的化疗基石。多次WP给药方案已在临床上使用并单独研究。然而,这些方案的正式比较无法为临床决策提供客观指导.这项研究的主要目的是比较使用80mg/m2/周的紫杉醇的累积剂量,使用3周的4(WP3)或4周的4(WP4)方案给药。次要目标是评估与两种方案相关的临床结局,包括疗效和毒性参数。我们的回顾性队列包括2012年1月至2023年1月在魁北克CHU治疗的149例铂耐药卵巢癌患者。WP3和WP4达到相似的累积剂量(1353.7vs.1404.2mg/m2;p=0.29)。在临床结果中没有观察到显著差异。WP4的剂量减少频率显着高于WP3(44.7%vs.4.9%;p<0.01),主要是由于毒性引起的治疗不耐受(34.0%vs.3.9%;p<0.01)。我们的数据表明,WP3方案提供了与WP4相似的累积剂量,因此在不影响疗效的情况下提供了更好的疗效。
    Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.
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  • 文章类型: Journal Article
    透明细胞卵巢癌(CCOC)是一种侵袭性恶性肿瘤,影响年轻女性。尽管卵巢癌亚型具有不同的分子和临床特征,晚期疾病的主要治疗方法仍然是细胞毒性化疗。晚期CCOC对常规化疗耐药,这意味着受影响的患者的预后欠佳。尽管详细的基因组,表观基因组,转录组,和蛋白质组学表征,CCOC的亚型特异性治疗进展甚微.定义CCOC的独特糖原积累表明代谢途径活性和依赖性改变。这项研究提出了卵巢癌亚型的第一个代谢组学景观,包括42个CCOC,20个高级别浆液性卵巢癌和21个子宫内膜样卵巢癌,包括三种最常见的卵巢癌亚型。与其他卵巢癌亚型相比,我们描述了CCOC的独特代谢组学景观,包括能量利用和半胱氨酸代谢的改变。此外,我们确定了代谢途径中的CCOC特异性改变,包括丝氨酸生物合成和ROS相关途径,这些改变可以作为潜在的治疗靶点.我们的研究提供了对卵巢癌代谢组的首次深入研究,并提供了丰富的资源来支持正在进行的研究工作,以确定可以改善这种破坏性恶性肿瘤患者的不良结局的亚型特异性治疗靶标。©2024作者(S)。由JohnWiley&SonsLtd代表英国和爱尔兰病理学会出版的病理学杂志。
    Clear cell ovarian carcinoma (CCOC) is an aggressive malignancy affecting younger women. Despite ovarian cancer subtypes having diverse molecular and clinical characteristics, the mainstay of treatment for advanced stage disease remains cytotoxic chemotherapy. Late stage CCOC is resistant to conventional chemotherapy, which means a suboptimal outcome for patients affected. Despite detailed genomic, epigenomic, transcriptomic, and proteomic characterisation, subtype-specific treatment for CCOC has shown little progress. The unique glycogen accumulation defining CCOC suggests altered metabolic pathway activity and dependency. This study presents the first metabolomic landscape of ovarian cancer subtypes, including 42 CCOC, 20 high-grade serous and 21 endometrioid ovarian carcinomas, together comprising the three most common ovarian carcinoma subtypes. We describe a distinct metabolomic landscape of CCOC compared with other ovarian cancer subtypes, including alterations in energy utilisation and cysteine metabolism. In addition, we identify CCOC-specific alterations in metabolic pathways including serine biosynthesis and ROS-associated pathways that could serve as potential therapeutic targets. Our study provides the first in-depth study into the metabolome of ovarian cancers and a rich resource to support ongoing research efforts to identify subtype-specific therapeutic targets that could improve the dismal outcome for patients with this devastating malignancy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    目的:不伴有浸润性癌的浆液性输卵管上皮内癌(STIC)偶尔被发现,并与随后腹膜癌的高风险相关。管理需要优化。这项研究探讨了专业人士对诊断的意见和临床实践,咨询,孤立的STIC的治疗和随访,以促进临床决策和优化未来研究的方向。次要目标是评估国际临床指南。
    方法:焦点小组研究。
    方法:四个在线会话。
    方法:国际妇科医生小组(n=12个国家),妇科肿瘤学家,病理学家和医学肿瘤学家(n=49)。
    方法:使用半结构化访谈指南。两名独立的研究人员通过开放和轴向编码分析了转录本。结果按领域进行组织。筛选了有关(国际)国家指南,以提供有关孤立STIC的建议。
    方法:专业人员关于孤立的STIC管理的意见和临床实践。
    结果:关于病理学,大多数专业人士将SEE-FIM协议确定为高危患者的护理标准,而一般人群输卵管的组织病理学检查存在差异。建议由专业病理学家确认STIC诊断。关于STIC诊断后的工作和随访,有多样性和不和谐。关于结果的数据有限。至于治疗,大多数人不推荐化疗和PARP抑制剂.11条准则提供了有限的建议。
    结论:我们确定了建议,并强调了孤立性STIC的诊断和管理方面的知识差距。此外,临床指南中的建议有限.商定有必要进行国际合作,以进行孤立的STIC的预期注册。
    OBJECTIVE: A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals\' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow-up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines.
    METHODS: Focus group study.
    METHODS: Four online sessions.
    METHODS: International panel (n = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists (n = 49).
    METHODS: A semi-structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC.
    METHODS: Professionals\' opinions and clinical practices regarding isolated STIC management.
    RESULTS: Regarding pathology, most professionals identified the SEE-FIM protocol as standard of care for high-risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work-up and follow-up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations.
    CONCLUSIONS: We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC.
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  • 文章类型: Journal Article
    卵巢癌(OC)是妇科癌症女性死亡的主要原因。它的诊断更有可能发生在高龄,在咨询中,老年人口最多。聚(ADP-核糖)抑制剂(PARPi)改变了OC的临床实践和发展,显示出巨大的效益。然而,在老年人群中缺乏PARPi可能影响治疗决策和安全性/有效性的证据.避免年龄作为PARPis处方的限制因素是必要的。我们对一线治疗晚期OC后维持PARPi的最相关的随机III期试验进行了综述。我们观察到缺乏考虑老年患者的单一标准,不同的试验。PARPis在不同人群中有益处。然而,PARPi对生活质量的影响没有报道,考虑到他们的脆弱性,这是非常相关的。需要采取措施使老年患者受益,以更好地适应PARPi治疗。
    Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.
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  • 文章类型: Journal Article
    犬卵巢上皮性肿瘤(OET)目前分为卵巢腺瘤和癌,进一步不一致地分为乳头状或囊性,而在人类医学中,OET被细分为几个亚型。这项研究旨在建立清晰的形态学特征,从而在良性OET和卵巢癌(OvCas)之间进行更一致的区分,并定义犬OvCas的不同组织病理学模式。分析显示,有丝分裂计数阈值>2是区分OvCas与良性OET的潜在标准。除了卵巢腺瘤,在良性OET中,卵巢交界性肿瘤被引入为一个独特的类别。OvCas表现出五种不同的组织病理学模式,即乳头状,实性与管状分化,微乳头状,囊性和肉瘤。由于某些OvCas在形态上可以与其他卵巢肿瘤重叠,细胞角蛋白7的表达,一种在卵巢上皮中表达的细胞角蛋白,被评估并证明是有帮助的,尽管并非在所有情况下都有表达。此外,我们研究了14-3-3σ和环氧合酶2(COX-2)的表达。根据14-3-3σ的频繁表达式,该标记似乎在犬OET中起作用,因为它在正常犬卵巢中不表达。COX-2的不常见表达表明,它是犬OvCas中潜在治疗靶标的不良候选物。
    Canine ovarian epithelial tumours (OETs) are currently divided into ovarian adenomas and carcinomas, which are further inconsistently subclassified as papillary or cystic, whereas in human medicine, OETs are subdivided into several subtypes. This study aimed to establish clear morphological features enabling more consistent distinction between benign OETs and ovarian carcinomas (OvCas) as well as defining different histopathological patterns of canine OvCas. Analysis revealed a mitotic count threshold of >2 as a potential criterion for differentiating OvCas from benign OETs. Alongside ovarian adenomas, ovarian borderline tumours were introduced as a distinct category among benign OETs. OvCas exhibited five different histopathological patterns, namely papillary, solid with tubular differentiation, micropapillary, cystic and sarcomatous. Since some OvCas can morphologically overlap with other ovarian tumours, the expression of cytokeratin 7, a cytokeratin expressed in ovarian epithelium, was assessed and proved helpful, although it was not expressed in all cases. Furthermore, we investigated the expression of 14-3-3σ and cyclooxygenase 2 (COX-2). Based on the frequent expression of 14-3-3σ, this marker appears to have a role in canine OETs since it is not expressed in normal canine ovaries. The infrequent expression of COX-2 suggests that it is a poor candidate as a potential therapeutic target in canine OvCas.
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  • 文章类型: Journal Article
    背景:非浆液性子宫内膜和卵巢肿瘤通常作为两个独立的原发性肿瘤进行临床治疗,但几乎所有人都表现出基因组关系的证据。
    方法:本研究使用全外显子组测序调查了相关性的程度,这项研究是对27例并发肿瘤患者的配对非浆液性子宫内膜癌和卵巢癌进行的,该队列具有详细的临床病理注释。四个全外显子组测序衍生参数(突变,突变负担,突变特征和突变等位基因肿瘤异质性评分)用于开发一种新颖的无监督模型,用于评估基因组相似性,以推断配对肿瘤的基因组相关性。
    结果:这个新模型证明了所有肿瘤对的所有四个参数的基因组相关性。PTEN突变,ARID1A,CTNNB1,KMT2D和PIK3CA发生频率最高,27个肿瘤对中的24个(89%)在这些基因中的至少一个中共享相同的突变。所有配对都在许多其他基因中共享突变。卵巢子宫内膜异位症,CTNNB1外显子3突变,疾病进展和死亡在相似性排名中存在。错配修复缺陷与基因组相似的配对较少有关。
    结论:尽管整个队列存在多样性,在所有配对的肿瘤中,基因组相似性的存在支持以下假设:非浆液性子宫内膜癌和卵巢癌并发发生是基因组相关的,并且可能源于共同的起源.
    BACKGROUND: Concurrent non-serous endometrial and ovarian tumours are often managed clinically as two separate primary tumours, but almost all exhibit evidence of a genomic relationship.
    METHODS: This study investigates the extent of relatedness using whole exome sequencing, which was performed on paired non-serous endometrial and ovarian carcinomas from 27 patients with concurrent tumours in a cohort with detailed clinicopathological annotation. Four whole exome sequencing-derived parameters (mutation, mutational burden, mutational signatures and mutant allele tumour heterogeneity scores) were used to develop a novel unsupervised model for the assessment of genomic similarity to infer genomic relatedness of paired tumours.
    RESULTS: This novel model demonstrated genomic relatedness across all four parameters in all tumour pairs. Mutations in PTEN, ARID1A, CTNNB1, KMT2D and PIK3CA occurred most frequently and 24 of 27 (89 %) tumour pairs shared identical mutations in at least one of these genes, with all pairs sharing mutations in a number of other genes. Ovarian endometriosis, CTNNB1 exon 3 mutation, and progression and death from disease were present across the similarity ranking. Mismatch repair deficiency was associated with less genomically similar pairs.
    CONCLUSIONS: Although there was diversity across the cohort, the presence of genomic similarity in all paired tumours supports the hypothesis that concurrent non-serous endometrial and ovarian carcinomas are genomically related and may have arisen from a common origin.
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  • 文章类型: Journal Article
    用胃肠酶酶水解叶蛋白浓缩物获得的菠萝蜜叶蛋白水解产物具有良好的技术功能特性和较高的抗氧化能力。然而,分子量,抗增殖活性,细胞毒性和减少活性氧(ROS)的能力仍然未知。因此,本研究旨在评估通过胃蛋白酶和胰酶酶酶水解获得的菠萝蜜叶蛋白水解产物在不同水解时间(30-240分钟)对分子量的影响,细胞毒性,癌细胞的抗增殖,以及H2O2诱导的HaCaT细胞中活性氧的减少。电泳图谱表明H-Pep含有分子量在25-20kDa之间的肽。同时,H-Pan由分子量在25-20kDa和<20kDa之间的产物组成。H-Pan和H-Pep(125-500µg/mL)对HaCaT(人角质形成细胞)和J774A.1(鼠巨噬细胞)未显示出明显的细胞毒性。在人宫颈中实现了抗增殖活性,卵巢,和肝癌细胞。H-Pan-240分钟(1000µg/mL)将宫颈癌细胞的细胞活力降低了23%,而H-Pan-60分钟则显着降低了卵巢癌和肝癌细胞的细胞活力14.5(500µg/mL)和17%(1000µg/mL),分别为(P<0.05)。H-Pep-60min对H2O2胁迫的HaCaT细胞具有抗氧化应激的保护作用,在250µg/mL时减少25%的ROS(P<0.05)。研究结果表明,绿色生物质可安全用作植物蛋白水解产物的来源。
    Jackfruit leaf protein hydrolysates obtained from the enzymatic hydrolysis of leaf protein concentrate with gastrointestinal enzymes have shown good techno-functional properties and high antioxidant capacity. However, molecular weight, antiproliferative activity, cytotoxicity and the ability to reduce reactive oxygen species (ROS) are still unknown. Therefore, this study aimed to evaluate the effect of jackfruit leaf protein hydrolysates obtained by enzymatic hydrolysis with pepsin and pancreatin at different hydrolysis times (30-240 min) on molecular weights, cytotoxicity, antiproliferation of cancer cells, and the reduction of reactive oxygen species in H2O2-induced HaCaT cells. The electrophoretic profile indicated that H-Pep contains peptides with molecular weights between 25 - 20 kDa. Meanwhile, H-Pan is composed of molecular weight products between 25 - 20 kDa and < 20 kDa. H-Pan and H-Pep (125-500 µg/mL) did not show significant cytotoxicity on HaCaT (human keratinocytes) and J774A.1 (murine macrophage cells). Antiproliferative activity was achieved in human cervical, ovarian, and liver cancer cells. H-Pan-240 min (1000 µg/mL) reduced the cell viability of cervical cancer cells by 23% while H-Pan-60 min significantly reduced cell viability of ovarian and liver cancer cells by 14.5 (500 µg/mL) and 17% (1000 µg/mL), respectively (P < 0.05). The protective effect against oxidative stress on H2O2-stressed HaCaT cells was obtained with H-Pep-60 min, which reduced 25% of ROS at 250 µg/mL (P < 0.05). The findings demonstrate the safe use of green biomass as a source of plant protein hydrolysates.
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  • 文章类型: Journal Article
    CD8+T细胞在对抗细胞内病原体和消除癌症中的恶性细胞中起关键作用。然而,CD8+T细胞在卵巢癌中的预后作用没有得到充分的利用.在这里,通过单变量Cox回归以及最小绝对收缩和选择算子(LASSO)回归分析,我们基于通过单细胞测序(scRNA-seq)分析鉴定的CD8+T细胞标志物,开发了一种新的预后模型.通过中位风险评分对患者进行分组显示,该模型在训练和验证队列中均具有出色的预后功效。值得注意的是,被归类为低危组的患者预后显著改善.此外,在风险评分较低的患者中,免疫相关通路的富集水平较高,多种免疫细胞的浸润水平增加.重要的是,低危患者对免疫疗法的应答率也较高.总之,该开发的CD8+T细胞相关预后模型可作为临床结局的优秀预测因子,并有助于指导卵巢癌患者的治疗策略选择.
    CD8+ T cells play pivotal roles in combating intracellular pathogens and eliminating malignant cells in cancer. However, the prognostic role of CD8+ T cells in ovarian carcinoma is insufficiently exploited. Herein, through univariate Cox regression along with least absolute shrinkage and selection operator (LASSO) regression analyses, we developed a novel prognostic model based on CD8+ T cell markers identified by single-cell sequencing (scRNA-seq) analyses. Patient grouping by the median risk score reveals an excellent prognostic efficacy of this model in both training and validation cohorts. Of note, patients classified as low-risk group exhibit a dramatically improved prognosis. In addition, higher enrichment level of immune-related pathways and increased infiltration level of multiple immune cells are found in patients with lower risk score. Importantly, low-risk patients also exhibited higher response rate to immunotherapies. Summarily, this developed CD8+ T cell-associated prognostic model serves as an excellent predictor for clinical outcomes and aids in guiding therapeutic strategy choices for ovarian cancer patients.
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