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Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation. β-受体阻滞剂辅助疗法作为一种前瞻性的抗转移疗法,具有心脏肿瘤学调节作用。
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2024-01-05 DOI: 10.1007/s10585-023-10258-y
Sachin G Nair, Sonu Benny, Wesley M Jose, Aneesh T P

The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.

癌症治疗中的主流治疗策略仍然面临着初步诊断后可能出现转移扩散的难题。要克服治疗失败的发生率,必须重点关注抗转移药物。肾上腺素能刺激是转移扩散的基础,这为β受体阻滞剂作为抗转移药物的重新用途突破铺平了道路。然而,目前的治疗方法未能充分利用这种药物在抑制可能的转移方面的多功能潜力。人们发现,β受体阻滞剂对患者的促转移和预后参数具有多种控制作用。免疫疗法、肿瘤高血压、手术引起的应激、诱导细胞凋亡和血管生成抑制等方面的新干预措施被用作证据,以解释我们讨论该药物在现有抗癌方案中的潜在辅助作用这一目标。作为化疗不可避免的副作用,合并高血压的发生率相对较高,因此需要一种抗高血压药物,我们尝试建议使用β-受体阻滞剂来填补这一空缺。然而,鉴于临床研究的匮乏,我们旨在回顾一下β受体阻滞剂在这一领域的现状,并说明该药物应如何作为每一位接受癌症治疗的患者的首选药物。
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引用次数: 0
Cutting-edge innovations in breast cancer diagnosis- the potential of HDMI biomarkers. 乳腺癌症诊断的前沿创新-HDMI生物标志物的潜力。
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-10-17 DOI: 10.1007/s10585-023-10238-2
Kainat Zahra, Hanzala Ahmed Farooqi
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引用次数: 0
Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance. 与间皮瘤相比,Occludin 在输卵管卵巢高级别浆液性癌中过度表达,是肿瘤进展和化疗耐药性的标志物。
IF 4.2 3区 医学 Q2 ONCOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-23 DOI: 10.1007/s10585-023-10251-5
Margarida Varela Dos Santos, Arild Holth, Katharina Bischof, Ben Davidson

The objective of this study was to analyze the expression and prognostic role of the tight junction protein occludin in high-grade serous carcinoma (HGSC). Occludin protein expression by immunohistochemistry was analyzed in 602 HGSC (417 effusions, 185 surgical specimens). Expression in mesothelioma (n = 87; 45 effusions, 42 surgical specimens) was studied for comparative purposes. Occludin protein expression was found in 587/602 (98%) HGSC vs. 40/87 (46%) mesotheliomas and was predominantly limited to < 5% of cells in the latter (p < 0.001). Occludin was additionally overexpressed in HGSC effusions compared to surgical specimens (p < 0.001) and was overexpressed in post-chemotherapy effusions compared to chemo-naive effusions tapped at diagnosis (p = 0.015). Occludin expression in HGSC surgical specimens was associated with poor chemoresponse (p < 0.001) and primary resistance (p = 0.001). Expression in effusions and surgical specimens was unrelated to survival (p > 0.05). In conclusion, occludin expression is higher in HGSC compared to mesothelioma, and this protein is overexpressed in HGSC effusions, possibly reflecting changes in adhesion related to anchorage-independent growth in this microenvironment. Overexpression in post-chemotherapy compared to chemo-naïve effusions suggest a role in disease progression. Occludin expression in surgical specimens may be related to chemoresistance.

本研究的目的是分析紧密连接蛋白Occludin在高级别浆液性癌(HGSC)中的表达和预后作用。通过免疫组化方法分析了602例高级别浆液性癌(417例渗出液,185例手术标本)中Occludin蛋白的表达情况。为了进行比较,还研究了间皮瘤(n = 87;45 个渗出液,42 个手术标本)中的表达情况。在 587/602 例(98%)HGSC 与 40/87 例(46%)间皮瘤中发现了 Occludin 蛋白表达,且主要限于 0.05)。总之,Occludin 在 HGSC 中的表达高于间皮瘤,而且这种蛋白在 HGSC 渗出液中过表达,这可能反映了在这种微环境中与锚定依赖性生长相关的粘附性变化。与化疗无效的渗出液相比,化疗后渗出液中这种蛋白的过表达表明它在疾病进展中起着一定的作用。手术标本中 Occludin 的表达可能与化疗耐药性有关。
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引用次数: 0
Comparison of Gamma Knife (GK) and Linear Accelerator (LINAC) radiosurgery of brain metastasis resection cavity: a systematic review and proportional meta-analysis. 伽玛刀(GK)和直线加速器(LINAC)脑转移切除腔放射外科的比较:一项系统综述和比例荟萃分析。
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-11-09 DOI: 10.1007/s10585-023-10240-8
Rajiv Dharnipragada, Kathryn Dusenbery, Yoichi Watanabe, Clara Ferreira, Clark C Chen

Purpose: Stereotactic radiosurgery (SRS) to the resection cavity is essential in the treatment of brain metastasis (BM) amenable to surgical resection. The two most common platforms for SRS delivery include Gamma Knife (GK) and LINAC. Here we collated the available peer-reviewed literature and performed a meta-analysis on clinical outcomes after GK or LINAC resection cavity SRS.

Methods: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include all studies evaluating each post-operative SRS modality. Local control, overall survival, radiation necrosis, and leptomeningeal disease were evaluated from the available data. A proportional meta-analysis was performed via R using the metafor package to pool the outcomes of studies and a moderator effect to assess the significance between groups.

Results: We identified 21 GK studies (n = 2009) and 28 LINAC studies (n = 2219). The radiosurgery doses employed were comparable between GK and LINAC studies. The pooled estimate of 1-year local control, 1-year overall survival, and risk of leptomeningeal disease were statistically comparable between GK and LINAC (81.7 v 85.8%; 61.4 v 62.7%; 10.6 v 12.5%, respectively). However, the risk of radiation necrosis (RN) was higher for LINAC resection cavity SRS (5.4% vs. 10%, p = 0.036). The volume of the resection cavity was a significant modifying factor for RN in both modalities (p = 0.007) with a 0.5% and 0.7% increase in RN risk with every 1 cm3 increase in tumor volume for GK and LINAC, respectively.

Conclusions: Our meta-analysis suggests that GK and LINAC SRS of resection cavity achieve comparable 1-year local control and survival. However, resection cavity treated with GK SRS was associated with lowered RN risk relative to those treated with LINAC SRS.

目的:切除腔的立体定向放射外科(SRS)在治疗可手术切除的脑转移瘤(BM)中至关重要。SRS交付的两个最常见的平台包括伽玛刀(GK)和LINAC。在这里,我们整理了现有的同行评审文献,并对GK或LINAC切除腔SRS后的临床结果进行了荟萃分析。方法:根据PRISMA指南,对PUBMED和MEDLINE进行了搜索,以包括评估每种术后SRS模式的所有研究。根据现有数据评估局部控制、总生存率、放射性坏死和软脑膜疾病。通过R进行比例荟萃分析,使用metafor软件包汇总研究结果,并使用调节效应评估组间的显著性。结果:我们确定了21项GK研究(n = 2009)和28项LINAC研究(n = 2219)。GK和LINAC研究中使用的放射外科剂量具有可比性。GK和LINAC对1年局部控制、1年总生存率和软脑膜疾病风险的汇总估计具有统计学可比性(分别为81.7对85.8%、61.4对62.7%、10.6对12.5%)。然而,LINAC切除腔SRS的放射坏死(RN)风险更高(5.4%vs.10%,p = 0.036)。在两种模式下,切除腔的体积是RN的一个显著修正因素(p = 0.007),GK和LINAC的肿瘤体积每增加1cm3,RN风险分别增加0.5%和0.7%。结论:我们的荟萃分析表明,切除腔的GK和LINAC SRS实现了相当的1年局部控制和生存率。然而,与LINAC SRS治疗相比,GK SRS治疗的切除腔与RN风险降低有关。
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引用次数: 0
Computational markers for personalized prediction of outcomes in non-small cell lung cancer patients with brain metastases. 用于个性化预测脑转移非小细胞肺癌患者预后的计算标记。
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-02-01 Epub Date: 2023-12-20 DOI: 10.1007/s10585-023-10245-3
Sébastien Benzekry, Pirmin Schlicke, Alice Mogenet, Laurent Greillier, Pascale Tomasini, Eléonore Simon

Intracranial progression after curative treatment of early-stage non-small cell lung cancer (NSCLC) occurs from 10 to 50% and is difficult to manage, given the heterogeneity of clinical presentations and the variability of treatments available. The objective of this study was to develop a mechanistic model of intracranial progression to predict survival following a first brain metastasis (BM) event occurring at a time [Formula: see text]. Data included early-stage NSCLC patients treated with a curative intent who had a BM as the first and single relapse site (N = 31). We propose a mechanistic mathematical model able to derive computational markers from primary tumor and BM data at [Formula: see text] and estimate the amount and sizes of (visible and invisible) BMs, as well as their future behavior. These two key computational markers are [Formula: see text], the proliferation rate of a single tumor cell; and [Formula: see text], the per day, per cell, probability to metastasize. The predictive value of these individual computational biomarkers was evaluated. The model was able to correctly describe the number and size of metastases at [Formula: see text] for 20 patients. Parameters [Formula: see text] and [Formula: see text] were significantly associated with overall survival (OS) (HR 1.65 (1.07-2.53) p = 0.0029 and HR 1.95 (1.31-2.91) p = 0.0109, respectively). Adding the computational markers to the clinical ones significantly improved the predictive value of OS (c-index increased from 0.585 (95% CI 0.569-0.602) to 0.713 (95% CI 0.700-0.726), p < 0.0001). We demonstrated that our model was applicable to brain oligoprogressive patients in NSCLC and that the resulting computational markers had predictive potential. This may help lung cancer physicians to guide and personalize the management of NSCLC patients with intracranial oligoprogression.

早期非小细胞肺癌(NSCLC)治愈性治疗后的颅内进展发生率为 10%至 50%,鉴于临床表现的异质性和现有治疗方法的差异性,这种进展很难控制。本研究的目的是建立一个颅内进展的机理模型,以预测首次发生脑转移(BM)事件后的生存期[公式:见正文]。数据包括以治愈为目的接受治疗的早期 NSCLC 患者,他们的首次和单一复发部位均为脑转移灶(N = 31)。我们提出了一个机理数学模型,能够从原发肿瘤和骨髓瘤数据中得出计算标记物[公式:见正文],并估算(可见和不可见)骨髓瘤的数量和大小及其未来行为。这两个关键的计算标记是:[公式:见正文],单个肿瘤细胞的增殖率;[公式:见正文],每个细胞每天发生转移的概率。对这些计算生物标志物的预测价值进行了评估。该模型能够正确描述 20 名患者在[公式:见正文]时的转移数量和大小。公式:见正文]和[公式:见正文]参数与总生存期(OS)显著相关(分别为 HR 1.65 (1.07-2.53) p = 0.0029 和 HR 1.95 (1.31-2.91) p = 0.0109)。在临床标记物中加入计算标记物可明显提高 OS 的预测价值(c 指数从 0.585(95% CI 0.569-0.602)提高到 0.713(95% CI 0.700-0.726),p = 0.0029)。
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引用次数: 0
Acetone compression improves lymph node yield and metastasis detection in colorectal cancer. 丙酮压迫可提高结直肠癌淋巴结检出率和转移检测率。
IF 4.2 3区 医学 Q2 ONCOLOGY Pub Date : 2024-02-01 Epub Date: 2024-01-04 DOI: 10.1007/s10585-023-10259-x
Christina Schnoz, Katrin Schmid, Guacimara Ortega Sanchez, Sabina Schacher-Kaufmann, Michel Adamina, Georgios Peros, Dieter Erdin, Peter Karl Bode

Lymph node status is one of the most important prognostic factors in colorectal cancer, and accurate pathological nodal staging and detection of lymph node metastases is crucial for determination of post-operative management. Current guidelines, including the TNM staging system and European Society for Medical Oncology (ESMO) guidelines, recommend examination of at least 12 lymph nodes. However, identification of an adequate number of lymph nodes can be challenging, especially in the setting of neoadjuvant treatment, which may reduce nodal size. In this study, we investigated 384 colorectal cancer resections that were processed at our department of pathology between January 2012 and December 2022, in which the number of detected lymph nodes was less than 12 subsequent to conventional preparation of mesocolic fat tissue. By means of acetone compression, lymph node harvest increased significantly (p < 0.0001), and the intended number of ≥ 12 lymph nodes was achieved in 98% of resection specimens. The number of nodal positive cases increased significantly from n = 95 (24.7%) before versus n = 131 (34.1%) after acetone compression due to additionally identified lymph node metastases (p < 0.001). In 36 patients (9.4%) initially considered as nodal negative, acetone compression led to a staging adjustment to a nodal positive category and thereby drove a recommendation to offer post-operative therapy. In conclusion, acetone compression is a reliable and useful method implementable in routine surgical pathology for the retrieval of lymph nodes in colorectal cancer specimen, allowing for an adequate lymph node sampling and an increase in nodal staging reliability.

淋巴结状态是结直肠癌最重要的预后因素之一,准确的病理结节分期和淋巴结转移检测对于确定术后治疗至关重要。目前的指南,包括 TNM 分期系统和欧洲肿瘤内科学会(ESMO)指南,都建议至少检查 12 个淋巴结。然而,确定足够数量的淋巴结可能具有挑战性,尤其是在新辅助治疗的情况下,因为新辅助治疗可能会缩小淋巴结的大小。在这项研究中,我们调查了病理科在 2012 年 1 月至 2022 年 12 月期间处理的 384 例结直肠癌切除术,在这些切除术中,常规制备中结肠脂肪组织后检测到的淋巴结数量少于 12 个。通过丙酮压缩,淋巴结收获量明显增加(p
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引用次数: 0
Mapping the single cell spatial immune landscapes of the melanoma microenvironment 绘制黑色素瘤微环境的单细胞空间免疫图谱
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-01-13 DOI: 10.1007/s10585-023-10252-4
Jamie Magrill, Dan Moldoveanu, Jiayao Gu, Mathieu Lajoie, Ian R Watson

Melanoma is a highly immunogenic malignancy with an elevated mutational burden, diffuse lymphocytic infiltration, and one of the highest response rates to immune checkpoint inhibitors (ICIs). However, over half of all late-stage patients treated with ICIs will either not respond or develop progressive disease. Spatial imaging technologies are being increasingly used to study the melanoma tumor microenvironment (TME). The goal of such studies is to understand the complex interplay between the stroma, melanoma cells, and immune cell-types as well as their association with treatment response. Investigators seeking a better understanding of the role of cell location within the TME and the importance of spatial expression of biomarkers are increasingly turning to highly multiplexed imaging approaches to more accurately measure immune infiltration as well as to quantify receptor-ligand interactions (such as PD-1 and PD-L1) and cell-cell contacts. CyTOF-IMC (Cytometry by Time of Flight - Imaging Mass Cytometry) has enabled high-dimensional profiling of melanomas, allowing researchers to identify complex cellular subpopulations and immune cell interactions with unprecedented resolution. Other spatial imaging technologies, such as multiplexed immunofluorescence and spatial transcriptomics, have revealed distinct patterns of immune cell infiltration, highlighting the importance of spatial relationships, and their impact in modulating immunotherapy responses. Overall, spatial imaging technologies are just beginning to transform our understanding of melanoma biology, providing new avenues for biomarker discovery and therapeutic development. These technologies hold great promise for advancing personalized medicine to improve patient outcomes in melanoma and other solid malignancies.

黑色素瘤是一种高免疫原性恶性肿瘤,具有突变负荷高、弥漫性淋巴细胞浸润等特点,是对免疫检查点抑制剂(ICIs)反应率最高的恶性肿瘤之一。然而,在所有接受 ICIs 治疗的晚期患者中,有一半以上的患者要么没有反应,要么病情进展。空间成像技术正越来越多地被用于研究黑色素瘤的肿瘤微环境(TME)。此类研究的目的是了解基质、黑色素瘤细胞和免疫细胞类型之间复杂的相互作用及其与治疗反应的关系。为了更好地了解细胞在TME中的位置作用以及生物标记物空间表达的重要性,研究人员越来越多地转向高度复用的成像方法,以更准确地测量免疫浸润以及量化受体配体相互作用(如PD-1和PD-L1)和细胞-细胞接触。CyTOF-IMC(飞行时间-成像质量细胞计数法)实现了对黑色素瘤的高维分析,使研究人员能够以前所未有的分辨率识别复杂的细胞亚群和免疫细胞的相互作用。其他空间成像技术,如多重免疫荧光和空间转录组学,揭示了免疫细胞浸润的独特模式,突出了空间关系的重要性及其对调节免疫疗法反应的影响。总之,空间成像技术刚刚开始改变我们对黑色素瘤生物学的认识,为生物标记物的发现和治疗方法的开发提供了新的途径。这些技术有望推动个性化医疗的发展,改善黑色素瘤和其他实体恶性肿瘤患者的预后。
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引用次数: 0
Axillary nodal staging in breast cancer: what have we learned? 乳腺癌腋窝结节分期:我们学到了什么?
IF 4 3区 医学 Q1 Medicine Pub Date : 2024-01-13 DOI: 10.1007/s10585-023-10262-2
Theresa L Schwartz

Axillary management in patients with breast cancer is in a constant state of evolution. To provide appropriate treatment recommendations, we must understand the historical implications and the current indications for nodal staging as well as the clinical implications of nodal metastases. As we move away from maximal axillary surgical intervention that was previously the mainstay of breast cancer management, future research efforts will focus on targeted therapies based on tumor biology and identifying oncologically safe methods to de-escalate our management strategies.

乳腺癌患者的腋窝治疗一直在不断发展变化。为了提供适当的治疗建议,我们必须了解结节分期的历史意义和当前适应症,以及结节转移的临床意义。随着我们逐渐放弃以前作为乳腺癌治疗主流的最大腋窝手术干预,未来的研究工作将侧重于基于肿瘤生物学的靶向治疗,以及确定肿瘤学上安全的方法来降低我们的治疗策略。
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引用次数: 0
Topography and probability diagram of cervical and intra-parotid lymph node metastasis in parotid gland cancer 腮腺癌颈淋巴结和腮腺内淋巴结转移的地形图和概率图
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-11 DOI: 10.1007/s10585-023-10244-4
Nayeon Choi, Yung Jee Kang, Junhun Cho, Dongryul Oh, Jaewoo Jeong, Han-Sin Jeong

In parotid gland cancer (PGC), cervical lymph node metastasis (LNM) and intra-parotid LNM are known as significant indicators of poor prognosis. However, the topography of LNM in the affected parotid gland and the lymphatic progression of PGC has never been explored in detail. This was a retrospective analysis of data from 423 patients with previously untreated primary PGC (2005 to 2020), excluding patients with squamous cell carcinoma, lymphoma or metastatic disease in the parotid gland. The pattern of LNM was analyzed by neck sub-level and parotid sub-site. Using the conditional probability of neck level involvement, a probability diagram was plotted on several thresholds to visualize the sequential progression of LNM in PGC. The pattern of LNM progression was found to be similar between low- and high-grade pathology, but the incidence differed significantly (8.0% vs. 45.4%). Intra-parotid LNs and level IIa LNs were the most common sites (57.3% and 61.0%) of LNM in PGC, followed by level III (31.7%), Ib (25.6%), IV (22.0%), IIb (20.7%) and Va (20.7%) LNM. In intra-parotid LNs, the incidence of LNM in the deep parotid LNs was relatively low (9.4%); most intra-parotid LNMs were observed in the superficial parotid (90.6%) and peri-tumoral (in contact with the tumor) (31.3%) LNs. LNM to levels Ia, Vb and contra-lateral LNM occurred only in the very late stage. Our results provide detailed information about LNM progression in PGC at the sub-level and can help clinicians decide the treatment extent, including surgery or radiation.

众所周知,在腮腺癌(PGC)中,颈淋巴结转移(LNM)和腮腺内淋巴结转移是预后不良的重要指标。然而,有关受影响腮腺内淋巴结转移的地形图以及 PGC 的淋巴发展过程的研究却从未详细探讨过。这是一项回顾性分析,研究对象是423名既往未接受过治疗的原发性PGC患者(2005年至2020年),排除了腮腺鳞状细胞癌、淋巴瘤或转移性疾病患者。按颈部亚层和腮腺亚部位分析了LNM的模式。利用颈部受累的条件概率,在几个阈值上绘制了概率图,以直观显示PGC中LNM的顺序进展。结果发现,低级别和高级别病理的 LNM 进展模式相似,但发生率却有显著差异(8.0% 对 45.4%)。腮腺内LNM和IIa级LNM是PGC中最常见的LNM部位(57.3%和61.0%),其次是III级(31.7%)、Ib级(25.6%)、IV级(22.0%)、IIb级(20.7%)和Va级(20.7%)LNM。在腮腺内LNM中,腮腺深层LNM的发生率相对较低(9.4%);大多数腮腺内LNM发生在腮腺浅层(90.6%)和瘤周(与肿瘤接触)LN(31.3%)。Ⅰa、Ⅴb级和对侧LNM仅发生在晚期。我们的研究结果提供了 PGC 亚层 LNM 进展的详细信息,有助于临床医生决定治疗范围,包括手术或放射治疗。
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引用次数: 0
Ketogenic diet does not promote triple-negative and luminal mammary tumor growth and metastasis in experimental mice 生酮饮食不会促进实验小鼠体内三阴性和腔隙性乳腺肿瘤的生长和转移
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-09 DOI: 10.1007/s10585-023-10249-z
Meret Grube, Arno Dimmler, Anja Schmaus, Rafael Saup, Tabea Wagner, Boyan K. Garvalov, Jonathan P. Sleeman, Wilko Thiele

Ketogenic diets (KDs) can improve the well-being and quality of life of breast cancer patients. However, data on the effects of KDs on mammary tumors are inconclusive, and the influence of KDs on metastasis in general remains to be investigated. We therefore assessed the impact of a KD on growth and metastasis of triple negative murine 4T1 mammary tumors, and on the progression of luminal breast tumors in an autochthonous MMTV-PyMT mouse model. We found that KD did not influence the metastasis of 4T1 and MMTV-PyMT mammary tumors, but impaired 4T1 tumor cell proliferation in vivo, and also temporarily reduced 4T1 primary tumor growth. Notably, the ketogenic ratio (the mass of dietary fat in relation to the mass of dietary carbohydrates and protein) that is needed to induce robust ketosis was twice as high in mice as compared to humans. Surprisingly, only female but not male mice responded to KD with a sustained increase in blood β-hydroxybutyrate levels. Together, our data show that ketosis does not foster primary tumor growth and metastasis, suggesting that KDs can be safely applied in the context of luminal breast cancer, and may even be advantageous for patients with triple negative tumors. Furthermore, our data indicate that when performing experiments with KDs in mice, the ketogenic ratio needed to induce ketosis must be verified, and the sex of the mice should also be taken into account.

生酮饮食(KDs)可以改善乳腺癌患者的健康和生活质量。然而,有关生酮饮食对乳腺肿瘤影响的数据尚无定论,生酮饮食对转移的总体影响仍有待研究。因此,我们评估了KD对三阴性小鼠4T1乳腺肿瘤生长和转移的影响,以及对自体MMTV-PyMT小鼠模型中腔隙性乳腺肿瘤进展的影响。我们发现,生酮比率并不影响4T1和MMTV-PyMT乳腺肿瘤的转移,但会损害4T1肿瘤细胞在体内的增殖,并暂时降低4T1原发性肿瘤的生长。值得注意的是,小鼠诱导强效酮病所需的生酮比率(膳食脂肪与膳食碳水化合物和蛋白质的质量比)是人类的两倍。令人惊讶的是,只有雌性小鼠而非雄性小鼠对酮病有反应,血液中的β-羟丁酸水平持续上升。总之,我们的数据表明酮病不会促进原发性肿瘤的生长和转移,这表明酮病可以安全地应用于腔隙性乳腺癌,甚至可能对三阴性乳腺癌患者有利。此外,我们的数据还表明,在小鼠体内进行酮病实验时,必须验证诱导酮病所需的生酮比例,同时还应考虑小鼠的性别。
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