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Chemokine Profile Is Different in Normal Testis Compared to Seminoma - Especially in Tumor Infiltrating Lymphocytes. 正常睾丸与精原细胞瘤的趋化因子谱不同--尤其是肿瘤浸润淋巴细胞。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17321
Jonas M Händelin, Hanna-Riikka Teppo, Kirsi-Maria Haapasaari, Riina K Ollikainen, Janette Kemppainen, Hanne Kuitunen, Outi Kuittinen, Milla E L Kuusisto

Background/aim: Testicular cancers, particularly seminomas and non-seminomas, generally have a favorable prognosis, although a small subset of patients experience mortality. Current knowledge of clinical markers associated with relapse and poor prognosis in seminoma is limited. Chemokines, key proteins in the tumor microenvironment, are underexplored in seminoma prognosis. Additionally, tumor-infiltrating lymphocytes (TILs), which play a critical role in cancer prognosis, require further investigation in the context of seminoma.

Patients and methods: Samples from 25 seminoma patients and 24 control patients who underwent orchiectomy were immunohistochemically (IHC) stained for chemokines CXCR4, CXCR5, and their ligands CXCL12, CXCL13, and the proliferation marker Ki-67. The associations between IHC results and clinical presentations were examined.

Results: Chemokine profiles differed between seminoma and normal testis. The expression of chemokines in TILs in seminoma samples was especially over-expressed. The cytoplasmic expression of CXCL13 in TILs multiplied by the percentage of TILs in each sample, appeared to approach statistical significance concerning the likelihood of relapse.

Conclusion: The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.

背景/目的:睾丸癌,尤其是精原细胞瘤和非精原细胞瘤,一般预后良好,但也有一小部分患者会死亡。目前对与精原细胞瘤复发和预后不良相关的临床标志物的了解还很有限。趋化因子是肿瘤微环境中的关键蛋白,但对精原细胞瘤预后的研究还不够。此外,肿瘤浸润淋巴细胞(TILs)在癌症预后中起着关键作用,需要对精原细胞瘤进行进一步研究:对 25 例精索瘤患者和 24 例接受睾丸切除术的对照组患者的样本进行免疫组织化学(IHC)染色,检测趋化因子 CXCR4、CXCR5 及其配体 CXCL12、CXCL13 以及增殖标记物 Ki-67。研究了 IHC 结果与临床表现之间的关联:结果:精索瘤和正常睾丸的趋化因子谱不同。结果:精原细胞瘤和正常睾丸的趋化因子谱不同。TIL细胞质中CXCL13的表达量乘以每个样本中TIL的百分比,似乎与复发的可能性接近统计学意义:结论:TILs在精原细胞瘤生物学中的参与值得进一步研究,尤其是它们在肿瘤微环境和发病机制中的作用。TIL中的趋化因子和Ki-67表达可作为评估精原细胞瘤预后的潜在标志物。
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引用次数: 0
Interplay Between Western Diet and Mammary Cancer: Data from a Chemically-induced Model in Wistar Rats. 西方饮食与乳腺癌之间的相互作用:来自化学诱导的 Wistar 大鼠模型的数据。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17310
Jessica Silva, Tiago Azevedo, Inês Aires, Francisco Peixoto, Maria J Neuparth, Felisbina L Queiroga, Fernanda Seixas, Rita Ferreira, Ana I Faustino-Rocha, José Alberto Duarte, Paula A Oliveira

Background/aim: This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development.

Materials and methods: Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors.

Results: No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group.

Conclusion: WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated.

背景/目的:本研究旨在探讨西方饮食对 Wistar 雌性大鼠乳腺癌的影响,重点关注全身反应和肿瘤发生:28 只 Wistar 雌性大鼠经适应性训练后分为 4 个实验组(每组 7 只):西式饮食组(WD)、西式饮食加 N-甲基-N-亚硝基脲(MNU)给药组(WD+MNU)、标准饮食组(CTR)和标准饮食加 MNU 给药组(CTR+MNU)。动物在七周大时腹腔注射 50 毫克/千克的 MNU 以诱发乳腺癌。为期 20 周的实验包括监测动物体重、食物和水的摄入量。研究结束时,对大鼠实施安乐死,并采集血液样本和器官样本,用于血液学和血浆生化分析、氧化应激以及肿瘤的组织病理学和免疫生物学评估:结果:体重、成分或器官重量无明显差异,但WD组的食物和水摄入量减少,胆固醇水平降低。WD+MNU组的瘦素和脂联素水平较高,表明食欲调节发生了变化。组织病理学分析显示,MNU诱导的两组中都存在恶性肿瘤。然而,与CTR+MNU组相比,WD组的肿瘤数量较少:结论:WD 提高了饲料效率,增加了内脏脂肪组织,但降低了全身胆固醇和甘油三酯水平。虽然这种日粮降低了肿瘤发病率,但肿瘤的体积和重量却增加了。此外,WD还降低了ERα和孕酮受体的免疫表达,同时升高了Ki-67的免疫表达。
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引用次数: 0
Packing of the Gastroduodenal Artery Stump Using Falciform Ligament During Pancreaticoduodenectomy. 在胰十二指肠切除术中使用镰状韧带包装胃十二指肠动脉残端
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17339
Teruyuki Usuba, Ryota Iwase, Yuichi Nakaseko, Shinji Onda, Yoshihiro Shirai, Masashi Tsunematsu, Masaichi Ogawa, Toru Ikegami

Background/aim: Pseudoaneurysm formation is a potentially fatal complication after pancreaticoduodenectomy. We developed a packing method in which the gastroduodenal artery stump is packed inside a falciform ligament to reduce the post-pancreatectomy hemorrhage due to pseudoaneurysm formation. This study aimed to evaluate its efficacy.

Patients and methods: This study included 210 patients who underwent pancreaticoduodenectomies between January 2007 and December 2023. The study population was divided into two groups; the packing group (n=110) and the no-packing group (n=100), and the clinical variables were compared between the two groups.

Results: Pseudoaneurysms were observed in six (2.9%) patients, and post-pancreatectomy hemorrhage was observed in four (1.9%) patients. There was no significant difference in pseudoaneurysm formation between the packing and no-packing groups (p=0.477), and the mortality rates for both pseudoaneurysm and post-pancreatectomy hemorrhage were zero. Two patients in the no-packing group were found to have shock, whereas four patients in the packing group (n=4) did not. Additionally, we encountered a 6 cm unruptured pseudoaneurysm following packing.

Conclusion: The packing method did not reduce pseudoaneurysm formation after pancreaticoduodenectomy, but may prevent pseudoaneurysm rupture.

背景/目的:假性动脉瘤的形成是胰十二指肠切除术后潜在的致命并发症。我们开发了一种填塞方法,将胃十二指肠动脉残端填塞在镰状韧带内,以减少假性动脉瘤形成导致的胰腺切除术后出血。本研究旨在评估其疗效:本研究纳入了 2007 年 1 月至 2023 年 12 月间接受胰十二指肠切除术的 210 例患者。研究对象分为两组:填料组(n=110)和无填料组(n=100),并比较了两组的临床变量:6例(2.9%)患者出现假性动脉瘤,4例(1.9%)患者出现胰腺切除术后出血。包装组和未包装组在假性动脉瘤形成方面无明显差异(P=0.477),假性动脉瘤和胰腺切除术后出血的死亡率均为零。未包装组有两名患者出现休克,而包装组有四名患者(n=4)未出现休克。此外,我们还发现了一个包装后未破裂的 6 厘米假性动脉瘤:结论:填塞法并不能减少胰十二指肠切除术后假性动脉瘤的形成,但可以防止假性动脉瘤破裂。
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引用次数: 0
Clinical Significance of FAM83G in Breast Cancer: Association With Triple-negative Subtype and Prognosis. FAM83G 在乳腺癌中的临床意义:与三阴性亚型和预后的关系
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17313
Takako Ikeda, Chikako Kanno Honda, Sasagu Kurozumi, Takehiko Yokobori, Ayaka Katayama, Kei Masuda, Tetsunari Oyama, Kyoichi Kaira, Jun Horiguchi, Ken Shirabe, Takaaki Fujii

Background/aim: Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer.

Materials and methods: Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients.

Results: FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases.

Conclusion: This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.

背景/目的:序列相似性家族 83 成员 G(FAM83G)在各类癌症的侵袭性和患者预后中发挥着重要作用。然而,FAM83G 蛋白在乳腺癌中的表达与临床病理因素、乳腺癌亚型和预后的关系还不十分明确。本研究旨在阐明乳腺癌中 FAM83G 蛋白表达的临床意义:采用免疫组织化学方法检测 75 例乳腺癌组织中 FAM83G 蛋白的表达,评估其作为乳腺癌患者生物标志物的潜力。用Kaplan-Meier绘图仪估计FAM83G mRNA表达与TNBC患者生存结果之间的相关性:结果:FAM83G蛋白主要定位于乳腺癌细胞的胞浆中,在整个肿瘤组织中均呈均匀表达。与非癌区相比,癌区的 FAM83G 表达明显较高。FAM83G 的高表达在三阴性乳腺癌(TNBC)病例中比在激素受体阳性病例中更为普遍。虽然在我们的队列中,FAM83G蛋白的高表达对预后没有明显影响,但一项大规模数据库分析显示,在TNBC病例中,FAM83G的高表达与预后不良有关:本研究表明,乳腺癌组织中 FAM83G 的高表达与 TNBC 存在关联。结论:本研究表明,FAM83G在乳腺癌组织中的高表达与TNBC存在关联,FAM83G可作为乳腺癌患者的一种有前景的生物标记物和治疗靶点。
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引用次数: 0
Routine Elastic Staining Helps Detection of Vascular Invasion in Colorectal Cancer: A Comprehensive Analysis of T3 or Higher Tumors Without Lymph Node Metastasis. 常规弹性染色有助于检测结直肠癌的血管侵犯:对无淋巴结转移的 T3 或以上肿瘤的全面分析
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17330
You-Na Sung, Yeseul Kim, Anna Therese Datuin, Inho Jang, Jongmin Sim

Background/aim: Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection.

Patients and methods: The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed.

Results: The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis.

Conclusion: VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.

背景/目的:结直肠癌(CRC)的血管侵犯(VI)是一个独立的预后特征,也是 II 期 CRC 辅助化疗的高风险指标。本研究评估了弹性染色对 VI 检测的影响:采用弹性染色法评估了154例CRC患者的VI。根据苏木精和伊红(H&E)染色,病例被分为三组:无(80 例)、模糊(23 例)和疑似(51 例)。使用弹性染色法对每个病例的两张切片进行 VI 评估,确认其中一张或两张切片上均存在 VI。最后,分析了VI与其他临床病理因素之间的相关性:结果:使用弹性染色法检测 VI 的总检出率为 67/154(51.4%)。在无VI组、模糊组和疑似组中,分别有17/80(21.3%)、3/23(13.0%)和47/51(92.2%)名患者检测到VI。有 28 例患者在弹性染色切片的两个切面中都检测到了 VI,有 38 例患者仅在一个切面中检测到了 VI。VI与神经周围侵犯、M期和同步转移有明显相关性:结论:仅使用 H&E 染色检测 VI 并不可靠,这强调了弹性染色在提高 VI 检测中的重要性。因此,我们建议将弹性染色纳入所有 pT3 和 pT4 CRC 病例的常规病理检查中。
{"title":"Routine Elastic Staining Helps Detection of Vascular Invasion in Colorectal Cancer: A Comprehensive Analysis of T3 or Higher Tumors Without Lymph Node Metastasis.","authors":"You-Na Sung, Yeseul Kim, Anna Therese Datuin, Inho Jang, Jongmin Sim","doi":"10.21873/anticanres.17330","DOIUrl":"https://doi.org/10.21873/anticanres.17330","url":null,"abstract":"<p><strong>Background/aim: </strong>Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection.</p><p><strong>Patients and methods: </strong>The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed.</p><p><strong>Results: </strong>The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis.</p><p><strong>Conclusion: </strong>VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding the Genomic Landscape of Glioblastoma: Opportunities for Targeted Therapies. 了解胶质母细胞瘤的基因组图谱:靶向治疗的机遇。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17295
Sabrina L Zeller, Eris Spirollari, Anisha M Chandy, Simon J Hanft, Chirag D Gandhi, Meena Jhanwar-Uniyal

Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival.

胶质母细胞瘤(GBM)被世界卫生组织(WHO)归类为四级胶质瘤,是中枢神经系统的一种致命性肿瘤。随着特定基因异常的发现,胶质母细胞瘤的分类已多次修改,以提供更好的诊断和预后准确性。尽管目前的治疗方法包括手术切除、辅助化疗和放射治疗,但生存率仍然很低,只能短暂控制肿瘤的发展。胶质母细胞瘤仍然具有侵袭性,其复发的主要原因是存在一批独特的无法治疗的胶质母细胞瘤干细胞(GSC)。高突变率和失调转录景观的存在增加了 GSC 对常规化疗和放疗的耐药性,导致 GBM 患者的预后不佳。因此,GSC 已成为新的 GBM 治疗范例的关注目标。因此,了解它们的独特特性非常重要,例如 GSC 与缺氧微环境的相互作用会促进它们的生长。信号通路的表观基因组调控因子和基本分子成分是 GBM 治疗的潜在靶点。在这篇综述中,我们旨在描述 GBM 分类的演变,并重点介绍目前针对 GBM 的治疗方法,包括基因和免疫疗法以及哺乳动物雷帕霉素靶点(mTOR)抑制剂。此外,我们还探讨了GSCs的分子途径、正在进行的循环肿瘤细胞(CTC)研究以及精准治疗,这些研究旨在为GBM提供新的发现和有效的治疗方法,从而提高患者的生存率。
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引用次数: 0
Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction. 福斯塔替尼通过诱导凋亡抑制卵巢癌细胞增殖
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17315
Hye Min Lee, Hee Jin Cho, Yul Min Lee, Hyun Jung Kim, Kyun Heo

Background/aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer.

Materials and methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes.

Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction.

Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.

背景/目的:卵巢癌死亡率高、预后差,尤其是在晚期,因此仍是一项重大挑战。尽管治疗取得了进展,但耐药性和复发问题依然存在,这凸显了对新的有效疗法的迫切需求。本研究旨在评估福斯塔替尼(一种口服脾脏酪氨酸激酶抑制剂,最初开发用于自身免疫性疾病)作为卵巢癌潜在治疗方法的可能性:采用WST-1细胞增殖试验评估福斯塔替尼对卵巢癌细胞株的影响。通过TUNEL检测、DNA片段分析和流式细胞术评估细胞凋亡。Western印迹分析用于检测凋亡蛋白(包括caspase-3和PARP)的裂解情况,流式细胞术分析细胞周期的变化:结果:福司他替尼治疗可导致卵巢癌细胞生长的剂量和时间依赖性降低,并诱导细胞凋亡,表现为TUNEL阳性细胞增加、DNA片段化以及早期和晚期细胞凋亡的增加。Western 印迹分析显示,凋亡蛋白的裂解增加,包括 caspase-3 和 PARP。流式细胞术还显示细胞周期的亚 G1 期增加,进一步证实了凋亡诱导作用:结论:福司他替尼可抑制细胞增殖并诱导细胞凋亡,有望成为卵巢癌的再治疗药物,为改善患者预后提供了一种新方法。
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引用次数: 0
Differential Effects of Punicic Acid on Cytotoxicity and Peroxiredoxin Expression in MCF-7 Breast Cancer and MCF-10A Normal Cells. 布尼克酸对 MCF-7 乳腺癌细胞和 MCF-10A 正常细胞中细胞毒性和过氧化物酶表达的不同影响
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17301
Braden Quitmeyer, Chiemelie Emelife, Hannah Klausner, Oluwafemi Gbayisomore, Shelley Phelan

Background/aim: The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line.

Materials and methods: We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression.

Results: We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5.

Conclusion: Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.

背景/目的:石榴果实具有抗氧化和抗炎特性,对人体健康有多种益处。石榴酸(PA)是一种欧米伽-5 长链多不饱和脂肪酸,约占石榴籽油的 65-80%,已被发现在多种癌症类型中具有抗癌活性。为了更好地了解其细胞特异性,我们研究了石榴酸对 MCF-7 人类乳腺癌细胞系和 MCF-10A 非癌症乳腺上皮细胞系的影响:我们用不同浓度的布尼克酸处理这两种类型的细胞,并测量了存活细胞密度、细胞毒性、细胞凋亡以及过氧化物酶(Prdx)抗氧化剂的表达:结果:我们发现布尼克酸对两种细胞系都有细胞毒性,但 MCF-10A 细胞的细胞毒性水平更高,对低浓度的布尼克酸更敏感。我们进一步证实,两种细胞系的细胞毒性都与细胞凋亡有关。利用实时 PCR 技术,我们证实了 MCF-7 细胞中所有六种 Prdx mRNA 的诱导作用,从 2 μg/ml 时的 1.4 倍到 10 μg/ml 时的 5 倍以上不等。与此形成鲜明对比的是,MCF-10A 细胞在 10 μg/ml 浓度下对所有六种 Prdx mRNA 的诱导程度更高,对 Prdx1、Prdx2 和 Prdx5 的诱导程度超过 30 倍:我们的数据首次证明了布匿酸在这两种细胞系中不同的细胞毒性和 Prdx 调节作用。这些结果可能为了解布尼克酸在乳腺癌中的细胞特异性机制提供了重要信息。
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引用次数: 0
Lymphocyte Antigen 6 Family Member D (LY6D) Affects Stem Cell Phenotype and Progression of Pancreatic Adenocarcinoma. 淋巴细胞抗原 6 家族成员 D (LY6D) 影响干细胞表型和胰腺癌的进展
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17300
Shumpei Okimura, Naohiro Nishida, Hidekazu Takahashi, Yuhki Yokoyama, Hiroyuki Yamamoto, Atsushi Hamabe, Takayuki Ogino, Norikatsu Miyoshi, Hidenori Takahashi, Mamoru Uemura, Shogo Kobayashi, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto

Background/aim: The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC.

Materials and methods: We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC.

Results: In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC.

Conclusion: Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.

背景/目的:据报道,膜结合蛋白淋巴细胞抗原6家族成员D(LY6D)是早期B细胞系的标志物,在多种人类恶性肿瘤中均有表达,并与癌症干性有关。然而,它在胰腺导管腺癌(PDAC)中的表达及其在癌症干性中的作用在很大程度上仍未得到探讨。本研究旨在阐明 LY6D 在 PDAC 中的作用:我们对 LY6D 进行了功能分析,以评估其对体外 PDAC 细胞恶性特征的影响。利用我们自主开发的干细胞分离技术(该技术可分离出蛋白酶体活性低的细胞和癌症干细胞的CD44 v9细胞表面标志物),我们通过敲除LY6D的表达,在小鼠体内进行了球形成和化疗敏感性试验以及肿瘤形成试验。我们还进行了免疫组织病理学分析,以揭示 LY6D 在 PDAC 中的临床意义:结果:体外功能测试表明,LY6D在促进癌症恶性表型方面起着关键作用,包括增强侵袭能力、耐药性、迁移能力和癌症干性。免疫组织病理学分析表明,LY6D的高表达水平与PDAC的高复发率和较差的预后有关:我们的研究表明,LY6D是一种新的预后指标,在PDAC的癌症干性调控中发挥着关键作用。
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引用次数: 0
Potential Transcriptomic Biomarkers for Predicting Platinum-based Chemotherapy Resistance in Patients With High-grade Serous Ovarian Cancer. 预测高级别浆液性卵巢癌患者铂类化疗耐药性的潜在转录组生物标记物
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.21873/anticanres.17296
Sara Cocchi, Joanna Lopacinska-Jørgensen, Estrid V Høgdall

Background/aim: Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy.

Materials and methods: We conducted a three-step search process on PubMed to systematically review English-language articles published between 2020 and 2024. From the 123 articles retrieved, we included 11 articles that investigated transcriptomic signatures by RNA sequencing in tissues from chemo-sensitive and -resistant HGSOC patients.

Results: We report the clinicopathological data of 727 patients in the experimental cohorts, transcriptomic signatures, and technical aspects. Finally, the review lists 15 publicly available datasets used in the included studies. Furthermore, we investigated the overlap of 167 differentially expressed genes retrieved across the various articles.

Conclusion: We believe this review might offer valuable insights for further studies focusing on predicting platinum resistance and personalized treatments. In addition to discussing the latest findings and potential candidates, we highlight the challenges of validating biomarkers across studies and publicly available datasets. Transcriptomic signatures represent a potential tool for patient stratification, prognosis, and the potential adoption of long-term therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPis).

背景/目的:由于缺乏筛查方案,高级别浆液性卵巢癌(HGSOC)患者往往在晚期才被确诊,这大大降低了患者的生存率。此外,约 70% 的高分化浆液性卵巢癌患者在初治后会复发。预测对初治化疗的耐药性仍是一项挑战。在研究环境中,转录组分析已成为预测哪些 HGSOC 患者可能从初治中获益的有力工具。本综述旨在研究证明转录组特征作为生物标志物评估铂类化疗耐药风险的潜力的文献:我们在PubMed上进行了三步检索,系统地回顾了2020年至2024年间发表的英文文章。在检索到的 123 篇文章中,我们纳入了 11 篇通过 RNA 测序研究化疗敏感和耐药 HGSOC 患者组织转录组特征的文章:我们报告了实验队列中 727 例患者的临床病理数据、转录组特征和技术方面的情况。最后,综述列出了纳入研究中使用的 15 个公开可用的数据集。此外,我们还调查了不同文章中检索到的 167 个差异表达基因的重叠情况:我们相信,这篇综述可能会为进一步研究铂金耐药性预测和个性化治疗提供有价值的见解。除了讨论最新发现和潜在候选者外,我们还强调了在不同研究和公开数据集之间验证生物标志物所面临的挑战。转录组特征是一种潜在的工具,可用于患者分层、预后判断以及长期疗法的潜在采用,如多(ADP-核糖)聚合酶抑制剂(PARPis)。
{"title":"Potential Transcriptomic Biomarkers for Predicting Platinum-based Chemotherapy Resistance in Patients With High-grade Serous Ovarian Cancer.","authors":"Sara Cocchi, Joanna Lopacinska-Jørgensen, Estrid V Høgdall","doi":"10.21873/anticanres.17296","DOIUrl":"https://doi.org/10.21873/anticanres.17296","url":null,"abstract":"<p><strong>Background/aim: </strong>Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy.</p><p><strong>Materials and methods: </strong>We conducted a three-step search process on PubMed to systematically review English-language articles published between 2020 and 2024. From the 123 articles retrieved, we included 11 articles that investigated transcriptomic signatures by RNA sequencing in tissues from chemo-sensitive and -resistant HGSOC patients.</p><p><strong>Results: </strong>We report the clinicopathological data of 727 patients in the experimental cohorts, transcriptomic signatures, and technical aspects. Finally, the review lists 15 publicly available datasets used in the included studies. Furthermore, we investigated the overlap of 167 differentially expressed genes retrieved across the various articles.</p><p><strong>Conclusion: </strong>We believe this review might offer valuable insights for further studies focusing on predicting platinum resistance and personalized treatments. In addition to discussing the latest findings and potential candidates, we highlight the challenges of validating biomarkers across studies and publicly available datasets. Transcriptomic signatures represent a potential tool for patient stratification, prognosis, and the potential adoption of long-term therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPis).</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Anticancer research
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