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Thyroid Cancer With Autocrine Sialyl-fibronectin Depletion Has a Poor Prognosis due to EMT Progression. 甲状腺癌自分泌 Sialyl-纤连蛋白耗竭导致 EMT 进展,预后较差。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17285
Ryo Miyake, Hiroshi Takeyama, Yoshinobu Manome, Muneyuki Koyama, Isao Tabei, Hisashi Shioya, Takashi Kazama, Hiroko Nogi

Background/aim: Elevated blood fibronectin (FN) levels have been observed in various cancers; however, their significance remains controversial. Herein, we measured the levels of sialyl-fibronectin (S-FN), a type of FN secreted by tumor cells, and investigated whether blood S-FN secretion is associated with recurrent metastasis and epithelial-mesenchymal transition (EMT).

Patients and methods: An ELISA system recognizing S-FN was constructed, and the amount of S-FN in blood samples from 63 patients with thyroid carcinoma was measured. The relationship between S-FN secretion and clinical prognosis was also examined. Vimentin immunostaining was performed to identify the mesenchymal status of the cells during EMT.

Results: After 12 years of observation, 17/63 patients had recurrent metastases, including nine cases of lymph node recurrence (LNR) and eight cases of remote metastasis (RM). LNR occurred in 7/39 (17.9%) of S-FN-negative cases, where 4/7 (57.1%) had two or more repeat recurrences. In S-FN-positive cases, LNR was observed in 2/24 cases (8.3%), and no repeat recurrence was observed. For RM, 6/39 (15.4%) patients were S-FN-negative, of which 5/6 (83.3%) had progressive disease even during treatment at metastasis. Of the S-FN-positive cases, RM was observed in 2/24 (8.3%) patients; progressive disease was observed in 1/2 (50.0%) patients. In 9/11 S-FN-negative recurrent metastasis cases (81.8%) and 2/4 S-FN-positive cases (50.0%), many vimentin-positive, FN-secreting cells were found in the interstitial tissue around the tumor.

Conclusion: S-FN-negative thyroid cancer has a poor prognosis because of the progression of EMT associated with increased paracrine FN levels in the stroma.

背景/目的:在多种癌症中均观察到血液中纤维连接蛋白(FN)水平升高,但其意义仍存在争议。在此,我们测定了由肿瘤细胞分泌的一种纤连蛋白(S-FN)的水平,并研究了血液中 S-FN 的分泌是否与复发性转移和上皮-间质转化(EMT)有关:构建了识别S-FN的ELISA系统,并测定了63例甲状腺癌患者血液样本中S-FN的含量。同时还研究了S-FN分泌与临床预后之间的关系。此外,还进行了Vimentin免疫染色,以确定细胞在EMT过程中的间质状态:经过12年的观察,17/63例患者出现复发转移,其中9例淋巴结复发(LNR),8例远处转移(RM)。在S-FN阴性病例中,7/39(17.9%)患者出现淋巴结复发,其中4/7(57.1%)患者出现两次或两次以上的复发。在 S-FN 阳性病例中,有 2/24 例(8.3%)观察到 LNR,没有观察到重复复发。就 RM 而言,6/39(15.4%)例患者为 S-FN 阴性,其中 5/6(83.3%)例患者即使在转移灶治疗期间疾病仍在进展。在 S-FN 阳性病例中,2/24(8.3%)例患者观察到 RM;1/2(50.0%)例患者观察到疾病进展。在9/11例S-FN阴性复发转移病例(81.8%)和2/4例S-FN阳性病例(50.0%)中,肿瘤周围的间质组织中发现了许多波形蛋白阳性、分泌FN的细胞:结论:S-FN阴性甲状腺癌的预后较差,因为EMT的进展与基质中旁分泌型FN水平的升高有关。
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引用次数: 0
Tumor Dormancy Within the Lymphovascular Embolus Is Regulated by Multiple Metabolism-signaling Pathways. 淋巴管栓塞内的肿瘤休眠受多种代谢信号途径调控
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17247
Yin Ye, Justin Wang, Jordan Dillard, Sanford H Barsky

Background/aim: Recently, we demonstrated that cancer dormancy is initiated within the lymphovascular tumor embolus and consists of decreased proliferation and lower mammalian target of rapamycin (mTOR) activity. In the present study, we investigated other intersecting metabolism-signaling pathways that may ultimately determine whether the lymphovascular tumor embolus remains dormant or undergoes cell death.

Materials and methods: The present study exploited a singular patient-derived xenograft (PDX) of inflammatory breast cancer (Mary-X) that spontaneously forms high density spheroids, the in vitro equivalent of emboli. The AMPK metabolic checkpoint pathway, the mTOR nutrient-responsive cell growth pathway, the P13K/Akt intracellular quiescence regulating pathway, and the calpain-mediated E-cadherin proteolytic pathway responsible for spontaneous spheroid-genesis were also investigated, to determine their relative contributions to dormancy.

Results: The levels of phosphorylated AMPK proteins (AMPKα and β subunits) decreased gradually with the formation of MARY-X spheroids in vitro. Rapamycin down-regulated mTOR activity, yet dormancy persisted. LY294002, a PI3K/Akt inhibitor, completely abolished mTOR and induced spheroid disadherence and apoptosis. Compound C (AMPK inhibitor) up-regulated mTOR and induced spheroid disadherence and apoptosis. Increasing cellular metabolism led to cell death, even in enriched medium, whereas growing the spheroids in serum-free media (starvation) did not result in further mTOR inhibition, and dormancy was maintained.

Conclusion: An increase in our understanding of dormancy from the standpoint of internal signaling pathways might ultimately provide clues to the external stimuli (starvation, hypoxia or other not yet understood phenomena) that act through these pathways to maintain or disrupt dormancy.

背景/目的:最近,我们证实癌症休眠始于淋巴管瘤栓,包括增殖减少和雷帕霉素哺乳动物靶标(mTOR)活性降低。在本研究中,我们调查了可能最终决定淋巴管瘤栓是保持休眠还是发生细胞死亡的其他交叉代谢信号通路:本研究利用了一种自发形成高密度球体(相当于体外栓子)的炎性乳腺癌(Mary-X)患者衍生异种移植物(PDX)。研究人员还调查了AMPK代谢检查点通路、mTOR营养响应型细胞生长通路、P13K/Akt细胞内静止调节通路以及钙蛋白酶介导的E-cadherin蛋白溶解通路,这些通路负责自发形成球形体,以确定它们对休眠的相对贡献:结果:磷酸化AMPK蛋白(AMPKα和β亚基)的水平随着体外MARY-X球体的形成而逐渐下降。雷帕霉素降低了 mTOR 的活性,但休眠仍然存在。PI3K/Akt抑制剂LY294002能完全抑制mTOR,并诱导球体失粘和凋亡。化合物 C(AMPK 抑制剂)上调了 mTOR,并诱导球体失粘和细胞凋亡。即使在富集培养基中,细胞新陈代谢的增加也会导致细胞死亡,而在无血清培养基(饥饿)中生长球体不会导致进一步的 mTOR 抑制,休眠得以维持:结论:我们从内部信号通路的角度加深对休眠的理解,最终可能会为通过这些通路维持或破坏休眠的外部刺激(饥饿、缺氧或其他尚不清楚的现象)提供线索。
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引用次数: 0
Systemic Inflammation Indexes and Risk of Immune-related Adverse Events in Patients With Metastatic Urothelial Carcinoma Treated With Immunotherapy. 接受免疫疗法的转移性尿路上皮癌患者的全身炎症指数与免疫相关不良事件的风险
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17267
Michele Dionese, Davide Bimbatti, Francesco Pierantoni, Eleonora Lai, Elisa Erbetta, Nicolò Cavasin, Salim Jubran, Umberto Basso, Marco Maruzzo

Background/aim: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic urothelial carcinoma (mUC). However, they could be associated with immune-related adverse events (irAEs), which may be clinically significant. Identifying clinical characteristics that may be associated with a higher risk of irAEs is of great importance.

Patients and methods: We retrospectively collected data from all patients who received anti-PD1 or anti-PD-L1 for metastatic UC at our Institution from January 2017 to December 2022. Patients were dichotomized according to baseline neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) values. We performed univariate and multivariate logistic regression to determine the association between baseline characteristics and the development of irAEs.

Results: A total of 119 patients were identified. At a median follow-up of 29.6 months, 96 patients progressed and 82 died. Forty-five patients developed irAEs of any grade, 8 patients developed grade 3 toxicities. In the univariate analysis PS of 0 (p<0.01), baseline NLR <3.52, baseline PLR <194 (p=0.04) and baseline SII <906 (p=0.01) were significantly associated with a higher risk of developing irAEs, whereas in the multivariate analysis only PS=0 (p<0.01) and NLR <3.52 (p=0.03) maintained their correlation. Median progression-free survival (mPFS) and overall survival (mOS) were significantly longer in patients with NLR <3 (mPFS 3.8 vs. 2.6 months, p=0.01; mOS 15.3 vs. 5.6 months, p=0.002) and PS=0 (mPFS 4.8 vs. 2.1 months, p<0.001; mOS 15.3 vs. 3.8 months, p<0.001).

Conclusion: Low baseline NLR, PLR, and SII and good PS are associated with a higher risk of developing irAEs in patients treated with ICIs for mUC.

背景/目的:免疫检查点抑制剂(ICIs)彻底改变了转移性尿路上皮癌(mUC)的治疗方法。然而,它们可能与免疫相关不良事件(irAEs)有关,而这些不良事件可能具有临床意义。识别可能与较高的irAEs风险相关的临床特征非常重要:我们回顾性地收集了2017年1月至2022年12月在本机构接受抗PD1或抗PD-L1治疗转移性UC的所有患者的数据。根据基线中性粒细胞与淋巴细胞比值(NLR)、全身免疫炎症指数(SII)和血小板与淋巴细胞比值(PLR)对患者进行二分。我们进行了单变量和多变量逻辑回归,以确定基线特征与虹膜急性呼吸衰竭发生之间的关系:结果:共发现 119 例患者。中位随访时间为 29.6 个月,96 名患者病情恶化,82 名患者死亡。45名患者出现了任何程度的虹膜AEs,8名患者出现了3级毒性反应。在单变量分析中,PS 为 0(pConclusion:基线 NLR、PLR 和 SII 值低以及 PS 值高与接受 ICIs 治疗的 mUC 患者发生 irAEs 的风险较高有关。
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引用次数: 0
The Dominant Component and Clinicopathological Characteristics of Combined Hepatocellular-cholangiocarcinoma After Radical Resection. 根治性切除术后合并肝细胞胆管癌的主要成分和临床病理特征
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17284
Keiso Matsubara, Tsuyoshi Kobayashi, Takeshi Tadokoro, Yosuke Namba, Sotaro Fukuhara, K O Oshita, Naruhiko Honmyo, Shintaro Kuroda, Koji Arihiro, Hideki Ohdan

Background/aim: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver carcinoma, characterized by the unequivocal presence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, its clinicopathological characteristics have not yet been thoroughly elucidated. In particular, cholangiolocellular carcinoma (CLC) was classified as a subtype of cHCC-CCA according to the 2010 World Health Organization (WHO) classification. However, according to the 2019 WHO classification, tumors displaying histological features consistent with CLC but lacking evidence of hepatocellular differentiation should be regarded as a distinct subtype of iCCA. Nevertheless, there may be notable differences in prognosis between CLC and iCCA, indicating the necessity for refining the classification when devising clinical treatment strategies. This study aimed to determine the clinicopathological features and prognostic factors of cHCC-CCAs following radical resection.

Patients and methods: Between January 2010 and September 2020, based on the 2010 WHO classification, we retrospectively studied the clinicopathological features and prognoses of patients with cHCC-CCAs in relation to the pathological dominant classification. The patients were classified according to the pathological dominant components of cHCC-CCA as HCC-dominant (HCC-D), iCCA-dominant (iCCA-D), or CLC-dominant (CLC-D).

Results: Data of 55 patients who underwent primary radical hepatectomy for cHCC-CCA were analyzed. The prevalences of each dominant classification were HCC-D, 21 (38.2%); iCCA-D, 11 (20.0%); and CLC-D, 23 (41.8%). Multivariate analysis showed that dominant classification was an independent risk factor for recurrence and cancer-specific survival (CSS).

Conclusion: The dominant classification of cHCC-CCA has the potential to predict recurrence and CSS.

背景/目的:合并肝细胞胆管癌(cHCC-CCA)是原发性肝癌的一种罕见亚型,其特点是同时明确存在肝细胞癌(HCC)和肝内胆管癌(iCCA)。然而,其临床病理特征尚未得到彻底阐明。特别是,根据 2010 年世界卫生组织(WHO)的分类,胆管细胞癌(CLC)被归类为 cHCC-CCA 的一个亚型。然而,根据 2019 年世界卫生组织的分类,显示与 CLC 一致的组织学特征但缺乏肝细胞分化证据的肿瘤应被视为 iCCA 的一个独特亚型。然而,CLC 和 iCCA 的预后可能存在显著差异,这表明在制定临床治疗策略时有必要完善分类。本研究旨在确定cHCC-CCAs根治性切除术后的临床病理特征和预后因素:2010年1月至2020年9月期间,根据2010年WHO分类,我们回顾性研究了cHCC-CCAs患者的临床病理特征和预后与病理优势分类的关系。根据 cHCC-CCA 的病理显性成分将患者分为 HCC-显性(HCC-D)、iCCA-显性(iCCA-D)或 CLC-显性(CLC-D):结果:分析了55例接受原发性根治性肝切除术治疗的cHCC-CCA患者的数据。各优势分类的发生率分别为:HCC-D,21 例(38.2%);iCCA-D,11 例(20.0%);CLC-D,23 例(41.8%)。多变量分析显示,显性分类是复发和癌症特异性生存率(CSS)的独立风险因素:结论:cHCC-CCA的优势分类有可能预测复发和CSS。
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引用次数: 0
Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer. 基质金属蛋白酶-8 基因型、吸烟、饮酒和幽门螺旋杆菌感染对胃癌的影响
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17253
Chun-Kai Fu, Wei-Ching Chien, Ying-Jing Chen, Mei-Due Yang, Jaw-Chyun Chen, Tao-Wei Ke, Chia-Wen Tsai, Wen-Shin Chang, Yi-Chih Hung, DA-Tian Bau

Background/aim: In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection.

Patients and methods: The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls.

Results: No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001).

Conclusion: The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

背景/目的:与健康组织相比,胃癌(GCa)组织中基质金属蛋白酶-8(MMP-8)的 mRNA 表达明显减少。此外,血清中 MMP-8 水平的异常降低或升高与不良预后有关。MMP-8 基因型对 GCa 易感性的影响仍未得到充分探讨。我们的目的是评估 MMP-8 基因型对 GCa 易感性的影响及其与吸烟、饮酒和幽门螺旋杆菌(H. pylori)感染的潜在相互作用:研究利用基于聚合酶链式反应的限制性片段长度多态性(PCR-RFLP)分析了161名GCa患者和483名对照者的MMP-8 rs11225395、rs34009635和rs35866072基因型:MMP-8 rs11225395的基因型频率(趋势p=0.3635)和等位基因频率(p=0.1954)的分布无统计学差异。在显性模型下,CT+TT 组合基因型与 GCa 风险没有关联[几率比(OR)=0.77,95% 置信区间(95%CI)=0.54-1.10,p=0.1852]。同样,也没有观察到 MMP-8 rs34009635 或 rs35866072 的相关性。重要的是,当暴露于吸烟(OR=4.04,95%CI=2.28-7.16,p=0.0001)、饮酒(OR=2.83,95%CI=1.64-4.89,p=0.0002)和幽门螺杆菌感染(OR=3.53,95%CI=2.12-5.90,p=0.0001)时,MMP-8 rs11225395 CC 基因型个体的 GCa 风险显著增加:研究结果表明,携带 MMP-8 rs11225395 CC 基因型的个体对 GCa 的易感性增加,尤其是与吸烟、饮酒和幽门螺杆菌感染等危险因素结合时。这些结果表明,基于 MMP-8 基因型的预防策略,包括改变生活方式和有针对性的感染治疗,可能对减轻 GCa 的发展很有价值。
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引用次数: 0
MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma. MiR-140-3p 通过抑制肺腺癌中 PD-L1/ABCG2/MVP 的表达提高多西他赛的敏感性
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17258
Minji Kwon, Dayeon Lim, Jayeon Park, World Gil, Jiwoo Jung, Suyeon Jung, Chaeeon Kim, Minjeong Go, Ye Hwang Cheong, Hee Sun Park, Yong-Bin Eom, Sin-Aye Park

Background/aim: Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC.

Materials and methods: Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed.

Results: The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone.

Conclusion: These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.

背景/目的:肺腺癌(LUAD)或肺鳞癌(LUSC)占非小细胞肺癌(NSCLC)的大多数,已知这些细胞中程序性死亡配体1(PD-L1)的过度表达可诱导肿瘤免疫逃避或耐药性。然而,要确定减少PD-L1表达的微RNA(miRNA)是否能抑制NSCLC的耐药性,还需要进行详细的研究:采用 Kaplan Meier plotter 和 Receiver Operating Characteristic plotter 来确定特定 miRNA 对 NSCLC 患者生存和化疗反应的影响。此外,还进行了细胞活力、集落形成和侵袭测定以及 qPCR 分析:结果:与正常组相比,miRNA-140-3p(miR-140-3p)在LUAD患者中的表达量较低。miR-140-3p模拟物抑制了LUAD细胞的增殖、集落形成和侵袭。有趣的是,在对多西他赛无反应的LUAD患者组中,miR-140-3p的表达明显较低。在 LUAD 细胞中,miR-140-3p 和多西他赛联合治疗与单独使用其中一种治疗方法相比,能显著降低细胞活力以及与耐药性相关的基因 ABCG2 和 MVP 的表达。此外,与单独使用多西他赛相比,联合注射 miR-140-3p mimic 和多西他赛可明显抑制肿瘤生长:这些结果表明,miR-140-3p 在 LUAD 中的高表达与患者的良好预后相关,可能有助于 LUAD 的治疗,尤其是通过增加对多西他赛的反应性。
{"title":"MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma.","authors":"Minji Kwon, Dayeon Lim, Jayeon Park, World Gil, Jiwoo Jung, Suyeon Jung, Chaeeon Kim, Minjeong Go, Ye Hwang Cheong, Hee Sun Park, Yong-Bin Eom, Sin-Aye Park","doi":"10.21873/anticanres.17258","DOIUrl":"https://doi.org/10.21873/anticanres.17258","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC.</p><p><strong>Materials and methods: </strong>Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed.</p><p><strong>Results: </strong>The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone.</p><p><strong>Conclusion: </strong>These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4283-4299"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339890","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
Nondysplastic Colon Crypts Intercalated in Tubular Adenomas Support Field Cancerization. 管状腺瘤中夹杂的非增生性结肠隐窝支持现场癌化。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17266
Carlos A Rubio, Michael Vieth, Corinna Lang-Schwarz

Background/aim: Tubular adenomas of the colon (TA) are neoplastic polyps composed of dysplastic tube-like crypts. Nondysplastic crypts, mostly in asymmetric branching have been previously reported, both beneath and bordering TA. In the present article, intercalated nondysplastic crypts (INDC) amidst dysplastic crypts in TA are showcased.

Patients and methods: The occurrence of INDC was recorded in 139 TA.

Results: Out of the 139 TA, 31% exhibited INDC; of these, 58% were in asymmetric branching (INDCAB), 35% were single intercalated crypts without branching (INDSNB), and 7% were in symmetric branching (INDCSB). Luminal dysplasia occurred in 53% out of the 43 TA: in 37% TA with INDCAB, in 16% TA with INDSNB, but in none of the TA with INDCSB. Thus, INDCAB predominated.

Conclusion: The finding of INDC in TA domain contrasts with the infrequency of INDCSB and with the absence of INDCAB in the normal colorectal mucosa. Hence, INDC emerge as integral components in TA. Since only 1 or 2 sections were available per TA, the total number of INDC in the entire TA is likely higher. INDC in TA may be remnants of acquired nondysplastic mucosal cores of abnormal cryptogenesis that were subsequently replaced by top-down growing dysplastic epithelium. The present and previous findings support the concept of field cancerization in the human colorectum.

背景/目的:结肠管状腺瘤(TA)是由发育不良的管状隐窝组成的肿瘤性息肉。非增生性隐窝以前也有报道,大多呈不对称分支,既位于结肠管状腺瘤下方,也与结肠管状腺瘤相邻。本文展示了TA中发育不良的隐窝中夹杂的非增生性隐窝(INDC):患者和方法:记录了139例TA中INDC的发生情况:结果:在139例TA中,31%出现INDC;其中58%为非对称分支(INDCAB),35%为无分支的单个闰隐窝(INDSNB),7%为对称分支(INDCSB)。在43个TA中,53%出现管腔发育不良:37%的TA为INDCAB,16%的TA为INDSNB,但没有一个TA为INDCSB。因此,INDCAB占主导地位:结论:在 TA 中发现 INDC 与 INDCSB 不常见以及正常结直肠粘膜中不存在 INDCAB 形成鲜明对比。因此,INDC 是 TA 不可或缺的组成部分。由于每个 TA 只有 1 或 2 个切片,因此整个 TA 中 INDC 的总数可能更高。TA 中的 INDC 可能是后天非增生异常隐窝粘膜核心的残留物,随后被自上而下生长的增生异常上皮所取代。目前和以前的研究结果都支持人类结直肠中的野癌化概念。
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引用次数: 0
Therapy Intensity Outweighs the Prognostic Importance of the Timing of Chemoradiotherapy in Newly Diagnosed Glioblastoma Patients. 对新诊断的胶质母细胞瘤患者来说,化放疗时机的预后意义大于治疗强度。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17269
Jan Leppert, Claudia Ditz, Maximilian Grohmann, Christian Ziemann, Christina Hillbricht, Larysa Liubich, Maria Vittoria Matone, Dirk Rades, Jan Gliemroth, Anastassia Löser

Background/aim: To investigate the significance of the timing of chemoradiotherapy together with clinical and laboratory features in newly diagnosed glioblastoma.

Patients and methods: Clinical and laboratory parameters of 209 patients with glioblastoma potentially influencing overall (OS) and progression-free (PFS) survival were analyzed in univariable and multivariable models.

Results: On univariable analyses, Karnofsky performance status (p<0.001), recursive partitioning analysis (RPA) class (p<0.001), O6-methylguanine-DNA methyltransferase (MGMT)-status (p<0.001), extent of resection (p<0.001), radiotherapy dose (p=0.01), and the number of adjuvant temozolomide (TMZ) cycles (p<0.001) were significantly associated with OS. Additionally, MGMT-status (p<0.001), extent of resection (p=0.03), surgical site infections (p=0.02), and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with PFS. Multivariable analysis identified radiotherapy dose as the only independent predictor (p=0.049) of OS. MGMT-status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were independent predictors of PFS.

Conclusion: The timing of chemoradiotherapy did not play a prognostic role. For OS, the radiotherapy dose, and for PFS, MGMT-status and the number of adjuvant TMZ cycles were identified as independent prognostic factors.

背景/目的:研究化放疗时机与新诊断胶质母细胞瘤的临床和实验室特征之间的关系:在单变量和多变量模型中分析了209例胶质母细胞瘤患者中可能影响总生存期(OS)和无进展生存期(PFS)的临床和实验室参数:结果:在单变量分析中,Karnofsky表现状态(p6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)-状态(pConclusion:化放疗的时机对预后没有影响。就OS而言,放疗剂量是独立的预后因素;就PFS而言,MGMT状态和TMZ辅助周期数是独立的预后因素。
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引用次数: 0
Corrigenda. 更正。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17293
{"title":"Corrigenda.","authors":"","doi":"10.21873/anticanres.17293","DOIUrl":"https://doi.org/10.21873/anticanres.17293","url":null,"abstract":"","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4663"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339876","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
TMPRSS2:ERG Gene Fusion Might Predict Resistance to PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer. TMPRSS2:ERG基因融合可预测转移性阉割抗性前列腺癌对PARP抑制剂的耐药性
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17250
Tim Svenstrup Poulsen, Anders Nygaard Lørup, Per Kongsted, Rikke Løvendahl Eefsen, Martin Højgaard, Estrid Vilma Høgdall

Background/aim: The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi). A frequent characteristic feature of prostate cancer (PC) is the occurrence of genomic rearrangement that affects the transmembrane protease serine 2 (TMPRSS2) and E26 transformation-specific (ETS)- transcription factor-related gene (ERG).

Materials and methods: In this study, a total of 114 patients with mCRPC had their RNA and DNA sequenced using next-generation sequencing.

Results: Based on their genetic profile of deleterious gene alterations of BRCA1/2 or ATM, six patients were selected for PARPi. Patients with TMPRSS2:ERG gene fusion and homozygous alteration in ATM or BRCA2 (n=2) or heterozygous alterations (BRCA1 or BRCA2) and lack of TMPRSS2:ERG gene fusion (n=2) did not show clinical benefit from PARPi (treatment duration <16 weeks). In contrast, patients (n=2) without TMPRSS2:ERG gene fusion and homozygous deleterious alterations in ATM or BRCA2 all had clinical benefit from PARPi (treatment duration ≥16 weeks).

Conclusion: The TMPRSS2:ERG transcript product might be used as a PARPi resistance biomarker.

背景/目的:分子靶向治疗药物(MTTD)中出现的新型DNA损伤修复(DDR)通路在治疗转移性耐阉割前列腺癌(mCRPC)患者方面取得了可喜的成果。约 25% 的 mCRPC 患者的 DDR 基因存在可操作的有害畸变,主要是在同源重组 (HR) 途径中。然而,当接受基于聚 ADP 核糖聚合酶(PARP)抑制剂的治疗(PARPi)时,BRCA1/2 或 HRR 相关基因突变患者的应答率仅为 45%-55%。前列腺癌(PC)的一个常见特征是发生影响跨膜丝氨酸蛋白酶2(TMPRSS2)和E26转化特异性(ETS)转录因子相关基因(ERG)的基因组重排:本研究共对114名mCRPC患者的RNA和DNA进行了新一代测序:结果:根据BRCA1/2或ATM有害基因改变的遗传特征,6名患者被选中接受PARPi治疗。TMPRSS2:ERG转录产物可用作PARPi耐药性生物标志物。
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Anticancer research
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