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Cell Cycle Checkpoints p16 and p21-Strong Predictors of Clinicopathologic Outcomes in High-Grade Osteosarcoma. 细胞周期检查点 p16 和 p21--高级别骨肉瘤临床病理结果的有力预测因素
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-05-01 DOI: 10.1097/PPO.0000000000000714
Elham Nasri, Dianne E Torrence, Terrie Vasilopoulos, Jacquelyn A Knapik, Joanne P Lagmay, John D Reith, Charles Parker Gibbs

Purpose: In this study, we used a series of immunohistochemical measurements of 2 cell cycle regulators, p16 and p21, to evaluate their prognostic value, separately and in combination, for the disease outcomes.

Method: A total of 101 patients with high-grade osteosarcoma were included in this study. Clinicopathologic data were collected, and immunohistochemistry for p16 and p21 was performed and interpreted by 3 independent pathologists. Statistical analysis was performed to assess the strength of each of these markers relative to disease outcome.

Results: Our results indicate that more than 90% expression (high) of p16 by immunohistochemistry on the initial biopsy has a strong predictive value for good histologic response to chemotherapy. The patients are also more likely to survive the past 5 years and less likely to develop metastasis than patients with less than 90% p16 (low) expression. The results for p21, on the other hand, show a unique pattern of relationship to the clinicopathologic outcomes of the disease. Patients with less than 1% (low) or more than 50% (high) expression of p21 by immunohistochemistry show a higher chance of metastasis, poor necrotic response to chemotherapy, and an overall decreased survival rate when compared with p21 expression between 1% and 50% (moderate). Our results also showed that the expression of p16 and combined p16 and p21 demonstrates a stronger predictive relationship to 5-year survival than tumor histologic necrosis and p21 alone.

Discussion: The results of this study, once proven to be reproducible by a larger number of patients, will be valuable in the initial assessment and risk stratification of the patients for treatment and possibly the clinical trials.

目的:在这项研究中,我们对两种细胞周期调节因子p16和p21进行了一系列免疫组化测定,以评估它们单独或联合使用对疾病预后的影响:方法:本研究共纳入101例高级别骨肉瘤患者。收集临床病理数据,由 3 位独立病理学家对 p16 和 p21 进行免疫组化并做出解释。研究人员进行了统计分析,以评估这些标记物与疾病预后的相关性:结果:我们的研究结果表明,在初次活检中,免疫组化法检测的 p16 表达率超过 90%(高),对化疗的良好组织学反应具有很强的预测价值。与 p16 表达低于 90%(低表达)的患者相比,这些患者在过去 5 年中存活的可能性更大,发生转移的可能性更小。另一方面,p21 的结果显示出与疾病临床病理结果的独特关系模式。与 p21 表达在 1%-50%(中度)之间的患者相比,免疫组化结果显示 p21 表达低于 1%(低度)或高于 50%(高度)的患者发生转移的几率更高,对化疗的坏死反应更差,总体生存率更低。我们的结果还显示,与肿瘤组织学坏死和单独的p21相比,p16的表达以及p16和p21的联合表达对5年生存率的预测关系更强:这项研究的结果一旦被更多患者证实具有可重复性,将对患者治疗的初步评估和风险分层以及可能的临床试验具有重要价值。
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引用次数: 0
Molecular Imaging and Therapy of Differentiated Thyroid Carcinoma in Adults. 成人分化型甲状腺癌的分子成像与治疗
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-05-01 DOI: 10.1097/PPO.0000000000000713
Philipose Getachew Mulugeta, Anthony W Chi, Thomas Michael Anderson

Abstract: Differentiated thyroid carcinoma (DTC) has been increasing in incidence in the United States over the last several decades, although mortality rates have remained low. Radioactive iodine therapy (RAI-T) has been a mainstay of treatment for DTC since the 1940s. Imaging of DTC before and after RAI-T primarily focuses on molecular imaging of the sodium iodide symporter. The expanding understanding of the molecular profile of DTC has increased available treatment options. Incorporation of risk stratification to treatment approaches has led to deintensification of both surgical and nonsurgical treatments, leading to decreased morbidity without compromising disease control.

摘要:过去几十年来,分化型甲状腺癌(DTC)在美国的发病率不断上升,但死亡率一直很低。自 20 世纪 40 年代以来,放射性碘治疗(RAI-T)一直是治疗 DTC 的主要方法。RAI-T 治疗前后 DTC 的成像主要集中在碘化钠合剂的分子成像上。随着对 DTC 分子特征认识的不断深入,可供选择的治疗方案也越来越多。将风险分层纳入治疗方法后,手术和非手术治疗的强度都有所降低,从而在不影响疾病控制的情况下降低了发病率。
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引用次数: 0
PET Imaging for Monitoring Cellular and Immunotherapy of Cancer. 用于监测癌症细胞和免疫疗法的 PET 成像。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-05-01 DOI: 10.1097/PPO.0000000000000722
Benjamin M Larimer

Abstract: Cancer immunotherapy, including checkpoint blockade and cellular therapy, has become a cornerstone in cancer treatment. However, understanding the factors driving patient response or resistance to these therapies remains challenging. The dynamic interplay between the immune system and tumors requires new approaches for characterization. Biopsies and blood tests provide valuable information, but their limitations have led to increased interest in positron emission tomography (PET)/computed tomography imaging to complement these strategies. The noninvasive nature of PET imaging makes it ideal for monitoring the dynamic tumor immune microenvironment. This review discusses various PET imaging approaches, including immune cell lineage markers, immune functional markers, immune cell metabolism, direct cell labeling, and reporter genes, highlighting their potential in targeted immunotherapies and cell-based approaches. Although PET imaging has limitations, its integration into diagnostic strategies holds promise for improving patient outcomes and accelerating drug development in cancer immunotherapy.

摘要:癌症免疫疗法,包括检查点阻断和细胞疗法,已成为癌症治疗的基石。然而,了解患者对这些疗法的反应或耐药性的驱动因素仍具有挑战性。免疫系统与肿瘤之间的动态相互作用需要新的表征方法。活组织检查和血液化验可提供有价值的信息,但由于其局限性,人们对正电子发射断层扫描(PET)/计算机断层扫描成像的兴趣日益浓厚,以补充这些策略。PET 成像的无创特性使其成为监测动态肿瘤免疫微环境的理想选择。本综述讨论了各种 PET 成像方法,包括免疫细胞系标志物、免疫功能标志物、免疫细胞代谢、直接细胞标记和报告基因,强调了它们在靶向免疫疗法和基于细胞的方法中的潜力。尽管 PET 成像有其局限性,但将其纳入诊断策略有望改善患者预后,加快癌症免疫疗法的药物开发。
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引用次数: 0
Molecular Imaging of Steroid Receptors in Breast Cancer. 乳腺癌中类固醇受体的分子成像。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-05-01 DOI: 10.1097/PPO.0000000000000715
Quinton J Keigley, Amy M Fowler, Sophia R O'Brien, Farrokh Dehdashti

Abstract: Steroid receptors regulate gene expression for many important physiologic functions and pathologic processes. Receptors for estrogen, progesterone, and androgen have been extensively studied in breast cancer, and their expression provides prognostic information as well as targets for therapy. Noninvasive imaging utilizing positron emission tomography and radiolabeled ligands targeting these receptors can provide valuable insight into predicting treatment efficacy, staging whole-body disease burden, and identifying heterogeneity in receptor expression across different metastatic sites. This review provides an overview of steroid receptor imaging with a focus on breast cancer and radioligands for estrogen, progesterone, and androgen receptors.

摘要:类固醇受体调节许多重要生理功能和病理过程的基因表达。雌激素、孕激素和雄激素受体已在乳腺癌中得到广泛研究,它们的表达提供了预后信息和治疗目标。利用正电子发射断层扫描和针对这些受体的放射性标记配体进行无创成像,可为预测治疗效果、对全身疾病负担进行分期以及确定不同转移部位受体表达的异质性提供有价值的信息。本综述概述了类固醇受体成像,重点是乳腺癌和针对雌激素、孕激素和雄激素受体的放射性配体。
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引用次数: 0
A General Approach to Patients Presenting With Locally Advanced or Distant Metastatic Disease. 治疗局部晚期或远处转移性疾病患者的一般方法。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000704
James W Smithy, Paul B Chapman

Abstract: The widespread adoption of immune checkpoint inhibitors and small molecule inhibitors of the MAP kinase pathway has transformed the management of locally advanced and metastatic melanoma. Here, we provide a broad overview on the use of these agents in the first-line setting, incorporating a review of the clinical literature as well as the practice patterns of our respective melanoma groups. Throughout, we highlight areas of uncertainty that provide opportunities for future clinical investigation and additional improvement in outcomes for patients with melanoma.

摘要:免疫检查点抑制剂和MAP激酶通路小分子抑制剂的广泛应用改变了局部晚期和转移性黑色素瘤的治疗。在此,我们将结合临床文献综述以及我们各自黑色素瘤小组的实践模式,对这些药物在一线治疗中的使用情况进行广泛概述。我们还强调了存在不确定性的领域,这些领域为今后的临床研究和进一步改善黑色素瘤患者的预后提供了机会。
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引用次数: 0
Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care. 治疗标准疗法后病情进展的黑色素瘤患者的研究方法。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000702
Kylie A Fletcher, Douglas B Johnson

Abstract: The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.

摘要:有效的免疫疗法,特别是细胞毒性T淋巴细胞相关蛋白4和程序性细胞死亡1抑制剂,以及包括BRAF/MEK抑制剂在内的靶向疗法的出现,极大地改变了转移性黑色素瘤患者的预后。目前,多达50%的患者可获得长期生存。尽管黑色素瘤治疗取得了这些进展,但仍有许多患者病情恶化并最终死亡。因此,许多研究都旨在为这一人群提供新的治疗方案。目前正在研究的疗法包括但不限于新型免疫疗法、靶向疗法、肿瘤浸润淋巴细胞和其他细胞疗法、溶瘤病毒疗法和其他注射疗法以及粪便微生物群移植。在这篇综述中,我们将讨论在标准治疗方法基础上取得进展的转移性黑色素瘤患者的新治疗方案。
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引用次数: 0
How Far We've Come. 我们走了多远
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000710
Mario Sznol, Jeffrey S Weber
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引用次数: 0
Local and Systemic Management Options for Melanoma Brain Metastases. 黑色素瘤脑转移的局部和全身治疗方案。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000711
Afsaneh Amouzegar, Hussein A Tawbi

Abstract: Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and breakthrough systemic therapies including immunotherapy and targeted therapies have improved the outcomes of patients with metastatic melanoma, management of patients with melanoma brain metastases (MBMs) remains challenging. Notably, patients with MBMs have historically been excluded from clinical trials, limiting insights into their specific treatment responses. Encouragingly, a growing body of evidence shows the potential of systemic therapies to yield durable intracranial responses in these patients, highlighting the need for inclusion of patients with MBMs in future clinical trials. This is pivotal for expediting the advancement of novel therapies tailored to this distinct patient population. In this review, we will highlight the evolving landscape of MBM management, focusing on local and systemic treatment strategies.

摘要:脑转移是晚期黑色素瘤最严重的并发症之一,发病率和死亡率都很高。虽然立体定向放射外科手术等局部治疗方法以及免疫疗法和靶向疗法等突破性全身治疗方法的进步改善了转移性黑色素瘤患者的预后,但黑色素瘤脑转移(MBMs)患者的治疗仍然充满挑战。值得注意的是,脑转移瘤患者历来被排除在临床试验之外,这限制了对其特定治疗反应的了解。令人鼓舞的是,越来越多的证据显示,全身疗法有可能使这些患者产生持久的颅内反应,这突出表明有必要将脑转移瘤患者纳入未来的临床试验。这对于加快推进针对这一特殊患者群体的新型疗法至关重要。在这篇综述中,我们将重点介绍颅内间皮瘤治疗的演变情况,重点关注局部和全身治疗策略。
{"title":"Local and Systemic Management Options for Melanoma Brain Metastases.","authors":"Afsaneh Amouzegar, Hussein A Tawbi","doi":"10.1097/PPO.0000000000000711","DOIUrl":"10.1097/PPO.0000000000000711","url":null,"abstract":"<p><strong>Abstract: </strong>Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and breakthrough systemic therapies including immunotherapy and targeted therapies have improved the outcomes of patients with metastatic melanoma, management of patients with melanoma brain metastases (MBMs) remains challenging. Notably, patients with MBMs have historically been excluded from clinical trials, limiting insights into their specific treatment responses. Encouragingly, a growing body of evidence shows the potential of systemic therapies to yield durable intracranial responses in these patients, highlighting the need for inclusion of patients with MBMs in future clinical trials. This is pivotal for expediting the advancement of novel therapies tailored to this distinct patient population. In this review, we will highlight the evolving landscape of MBM management, focusing on local and systemic treatment strategies.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287053","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
Metastatic Melanoma Treatment in Special Populations. 特殊人群的转移性黑色素瘤治疗。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000701
Madeline Miceli, Christina Boatwright, Janice M Mehnert

Abstract: This review outlines the most up-to-date metastatic melanoma treatment recommendations and relevant risks for patients with solid organ transplants, patients with renal dysfunction, and patients with preexisting autoimmune conditions. These specific treatment populations were excluded from the original clinical trials, which studied immune checkpoint inhibitors and BRAF/MEK inhibitors in the advanced melanoma setting. We have synthesized the current body of literature, mainly case series and retrospective analyses, to reflect the evidence for the treatment of these special patient populations at present.

摘要:本综述概述了最新的转移性黑色素瘤治疗建议,以及实体器官移植患者、肾功能不全患者和原有自身免疫性疾病患者的相关风险。最初的临床试验研究了晚期黑色素瘤环境中的免疫检查点抑制剂和BRAF/MEK抑制剂,但这些特定治疗人群被排除在外。我们综合了目前的文献,主要是病例系列和回顾性分析,以反映目前治疗这些特殊患者群体的证据。
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引用次数: 0
Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma. 治疗转移性黑色素瘤的肿瘤浸润淋巴细胞及其他细胞疗法。
IF 2.2 4区 医学 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1097/PPO.0000000000000705
Christy Los, Sebastian Klobuch, John B A G Haanen

Abstract: Major progress in prolonging survival of patients with advanced melanoma has been made in the past decade because of the development and approval of immune checkpoint inhibitor and targeted therapies. However, for nonresponding or relapsing patients, their prognosis is still dismal. Based on clinical trial data, treatment with adoptive cell therapies holds great promise. In patients with metastatic melanoma progressing on or nonresponsive to single-agent anti-programmed cell death 1, infusion of tumor-infiltrating lymphocytes can produce responses in up to half of patients, with durable complete responses in up to 20%. Genetic modification of peripheral blood T cells with T-cell receptors derived from tumor-specific T cells, or with chimeric antigen receptors, has the potential to further improve treatment outcomes in this refractory population. In this review, we will discuss the historical development, current status, and future perspectives of adoptive T-cell therapies in melanoma.

摘要:过去十年中,由于免疫检查点抑制剂和靶向疗法的开发和批准,在延长晚期黑色素瘤患者生存期方面取得了重大进展。然而,对于无应答或复发的患者来说,他们的预后仍然不容乐观。根据临床试验数据,采用细胞疗法进行治疗大有可为。对于单药抗程序性细胞死亡 1 进展或无反应的转移性黑色素瘤患者,输注肿瘤浸润淋巴细胞可使多达一半的患者产生反应,其中多达 20% 的患者可产生持久的完全反应。对外周血 T 细胞进行基因修饰,使其具有来自肿瘤特异性 T 细胞的 T 细胞受体或嵌合抗原受体,有可能进一步改善这类难治性人群的治疗效果。在这篇综述中,我们将讨论黑色素瘤采用T细胞疗法的历史发展、现状和未来展望。
{"title":"Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma.","authors":"Christy Los, Sebastian Klobuch, John B A G Haanen","doi":"10.1097/PPO.0000000000000705","DOIUrl":"10.1097/PPO.0000000000000705","url":null,"abstract":"<p><strong>Abstract: </strong>Major progress in prolonging survival of patients with advanced melanoma has been made in the past decade because of the development and approval of immune checkpoint inhibitor and targeted therapies. However, for nonresponding or relapsing patients, their prognosis is still dismal. Based on clinical trial data, treatment with adoptive cell therapies holds great promise. In patients with metastatic melanoma progressing on or nonresponsive to single-agent anti-programmed cell death 1, infusion of tumor-infiltrating lymphocytes can produce responses in up to half of patients, with durable complete responses in up to 20%. Genetic modification of peripheral blood T cells with T-cell receptors derived from tumor-specific T cells, or with chimeric antigen receptors, has the potential to further improve treatment outcomes in this refractory population. In this review, we will discuss the historical development, current status, and future perspectives of adoptive T-cell therapies in melanoma.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287057","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
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