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1.
Melanoma central nervous system metastases: current approaches,challenges, and opportunities 下载免费PDF全文
Justine V. Cohen Hussain Tawbi Kim A. Margolin Ravi Amravadi Marcus Bosenberg Priscilla K. Brastianos Veronica L. Chiang John de Groot Isabella C. Glitza Meenhard Herlyn Sheri L. Holmen Lucia B. Jilaveanu Andrew Lassman Stergios Moschos Michael A. Postow Reena Thomas John A. Tsiouris Patrick Wen Richard M. White Timothy Turnham Michael A. Davies Harriet M. Kluger 《Pigment cell & melanoma research》2016,29(6):627-642
Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area. 相似文献
2.
Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases 下载免费PDF全文
Heike Seifert Eishu Hirata Martin Gore Komel Khabra Christina Messiou James Larkin Erik Sahai 《Pigment cell & melanoma research》2016,29(1):92-100
Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression. Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co‐administration of a PI‐3 kinase inhibitor. We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK‐ and PI3K‐activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS. 相似文献
3.
Linna Duan Eric M. Mukherjee Deepak Narayan 《The Yale journal of biology and medicine》2015,88(4):389-395
Oncology has been revolutionized by the ability to selectively inhibit the growth of cancerous cells while ostensibly avoiding the disruption of proteins and pathways necessary for normal cellular function. This paradigm has triggered an explosion of targeted therapies for cancer, creating a burgeoning billion-dollar industry of small molecules and monoclonal antibodies [1]. Largely due to these new treatments, spending on cancer pharmaceuticals has surpassed $100 billion worldwide [2]. In particular, the treatment of melanoma, a deadly and fast-spreading form of skin cancer, has been transformed by these new targeted therapies. In this mini-review, we summarize the progress made in the field of personalized treatment of melanoma, with an emphasis on targeted therapies. We then outline future directions for treatment, including novel cell-mediated therapies and new potential targets. 相似文献
4.
Glenn Merlino Meenhard Herlyn David E. Fisher Boris C. Bastian Keith T. Flaherty Michael A. Davies Jennifer A. Wargo Clara Curiel‐Lewandrowski Michael J. Weber Sancy A. Leachman Maria S. Soengas Martin McMahon J. William Harbour Susan M. Swetter Andrew E. Aplin Michael B. Atkins Marcus W. Bosenberg Reinhard Dummer Jeffrey E. Gershenwald Allan C. Halpern Dorothee Herlyn Giorgos C. Karakousis John M. Kirkwood Michael Krauthammer Roger S. Lo Georgina V. Long Grant McArthur Antoni Ribas Lynn Schuchter Jeffrey A. Sosman Keiran S. Smalley Patricia Steeg Nancy E. Thomas Hensin Tsao Thomas Tueting Ashani Weeraratna George Xu Randy Lomax Alison Martin Steve Silverstein Tim Turnham Ze'ev A. Ronai 《Pigment cell & melanoma research》2016,29(4):404-416
The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas – diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts as per the current status, challenges, and opportunities in the four respective areas. The current state and immediate and long‐term needs of the melanoma field, from basic research to clinical management, are presented in the following report. 相似文献
5.
Isabella C. Glitza Keiran S. M. Smalley Priscilla K. Brastianos Michael A. Davies Ian McCutcheon James K. C. Liu Kamran A. Ahmed John A. Arrington Brittany R. Evernden Inna Smalley Zeynep Eroglu Nikhil Khushalani Kim Margolin Harriet Kluger Michael B. Atkins Hussein Tawbi Adrienne Boire Peter Forsyth 《Pigment cell & melanoma research》2020,33(4):527-541
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease. 相似文献
6.
Ines Pires da Silva Isabella C. Glitza Lauren E. Haydu Romany Johnpulle Patricia D. Banks George D. Grass Simone M. A. Goldinger Jessica L. Smith Ashlyn S. Everett Peter Koelblinger Rachel Roberts‐Thomson Michael Millward Victoria G. Atkinson Alexander Guminski Rony Kapoor Robert M. Conry Matteo S. Carlino Wei Wang Mark J. Shackleton Zeynep Eroglu Serigne Lo Angela M. Hong Georgina V. Long Douglas B. Johnson Alexander M. Menzies 《Pigment cell & melanoma research》2019,32(4):553-563
7.
Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy 下载免费PDF全文
Martin Tio Xuan Wang Matteo S. Carlino Brindha Shivalingam Gerald B. Fogarty Alexander D. Guminski Serigne Lo Angela M. Hong Alexander M. Menzies Georgina V. Long 《Pigment cell & melanoma research》2018,31(4):509-515
Historically, the prognosis of patients with melanoma brain metastases is poor, with median overall survival (OS) of 4‐6 months. Little is known of OS in the era of modern systemic therapies and local therapy with stereotactic radiosurgery (SRS) or surgery. Patients diagnosed with melanoma brain metastases at Melanoma Institute Australia from January 2011 to December 2014 were included. OS and prognostic factors were analysed using Cox regression and Kaplan‐Meier survival analyses.355 patients were included. The median OS was 7.1 months (95% confidence interval [CI] 6.0‐8.1). Median OS differed by treatment modality: systemic therapy and SRS and/or surgery 14.9 months (95% CI 10.7‐19.0), SRS and/or surgery with or without whole brain radiotherapy (WBRT) 6.4 months (95% CI 5.4‐7.5), systemic therapy 5.4 months (95% CI 3.1‐7.7), systemic therapy and WBRT 5.2 months (95% CI 4.1‐6.4), WBRT 4.4 months (95% CI 2.4‐6.3), and best supportive care 1.8 months (95% CI 1.2‐2.3). OS for patients with melanoma brain metastases appears improved in the modern era, particularly for patients who are candidates for systemic therapy with SRS and/or surgery. 相似文献
8.
Karen A. Malkhasyan Yousef Zakharia Mohammed Milhem 《Pigment cell & melanoma research》2017,30(6):511-520
For patients with metastatic melanoma, the emergence of immune checkpoint inhibitors and targeted BRAF and MEK inhibitors has markedly enhanced clinical outcomes compared with chemotherapy. However, these novel agents are also associated with unique sets of adverse events, and increased overall survival can lead to prolonged exposure to some novel agents. Therefore, clinical evaluation of these therapies has now included the analysis of health‐related quality of life (HRQoL) in addition to more traditional efficacy and safety outcomes as a measure of patient perception of benefit. The current review focuses on HRQoL outcomes in clinical trials of immune checkpoint inhibitors and targeted therapies in patients with advanced and metastatic melanoma to inform healthcare providers about patient perception of HRQoL as a new perspective in treatment decision making. 相似文献
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Torres FE Recht MI Coyle JE Bruce RH Williams G 《Current opinion in structural biology》2010,20(5):598-605
Higher throughput thermodynamic measurements can provide value in structure-based drug discovery during fragment screening, hit validation, and lead optimization. Enthalpy can be used to detect and characterize ligand binding, and changes that affect the interaction of protein and ligand can sometimes be detected more readily from changes in the enthalpy of binding than from the corresponding free-energy changes or from protein-ligand structures. Newer, higher throughput calorimeters are being incorporated into the drug discovery process. Improvements in titration calorimeters come from extensions of a mature technology and face limitations in scaling. Conversely, array calorimetry, an emerging technology, shows promise for substantial improvements in throughput and material utilization, but improved sensitivity is needed. 相似文献
11.
Robert Mason Helen C. Dearden Bella Nguyen Jennifer A. Soon Jessica Louise Smith Manreet Randhawa Andrew Mant Lydai Warburton Serigne Lo Tarek Meniawy Alexander Guminski Phillip Parente Sayed Ali Andrew Haydon Georgina V. Long Matteo S. Carlino Michael Millward Victoria G. Atkinson Alexander M. Menzies 《Pigment cell & melanoma research》2020,33(2):358-365
The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response. 相似文献
12.
In a previous paper we have presented a double ligand enzyme linked immunosorbent assay (ELISA) technique suitable for the detection of human antibodies to different brain antigens. In the present study, we have applied this technique to the analysis of 100 neurologically affected patients with regard to both a list of clinical parameters and the presence in their sera of nervous tissue specific antibodies, in an attempt to highlight the meaning of such antibodies in different neurologic disorder. We show that the presence of these antibodies cannot be used for elucidation of pathogenesis or for diagnostic purposes, but can be used as a prognostic index. 相似文献
13.
Ali Mohammadpour Maryam Derakhshan Hassan Darabi Pegah Hedayat Mohammad Momeni 《Journal of cellular physiology》2019,234(4):3307-3320
Melanoma is known as an aggressive tumor which shows an increasing incidence and poor prognosis in the metastatic phase. Hence, it seems that diagnosis and effective management (including early diagnosis, choosing of the effective therapeutic platform, caring, and training of patients for early detection) are major aspects of melanoma therapy. Early detection of melanoma is a key point for melanoma therapy. There are various diagnosis options such as assessing of biopsy, imaging techniques, and biomarkers (i.e., several proteins, polymorphism, and liquid biopsy). Among the various biomarkers, assessing circulating tumor cells, cell-free DNAs, cell-free RNAs, and microRNAs (miRNAs) have emerged as powerful diagnosis tools for melanoma patients. Deregulations of these molecules are associated with melanoma pathogenesis. After detection of melanoma, choosing of effective therapeutic regimen is a key step for recovery of melanoma patients. Several studies indicated that various therapeutic approaches including surgery, immunotherapy, systematic therapy, radiation therapy and antibodies therapy could be used as potential therapeutic candidates for melanoma therapy. Caring for melanoma patients is one of the important components of melanoma therapy. Caring and training for melanoma patients could contribute to better monitoring of patients in response to various therapeutic options. Here, we summarized various diagnosis approaches such as assessing biopsy, imaging techniques, and utilization of various biomarkers (i.e., proteins, CTCs, cfDNAs, and miRNAs) as a diagnostic biomarker for detection and monitoring patients with melanoma. Moreover, we highlighted various therapeutic options and caring aspects in patients with melanoma. 相似文献
14.
María Tereza Nieto-Coronel Allan David López-Vásquez Diana Marroquín-Flores Sandy Ruiz-Cruz Jorge Luis Martínez-Tláhuel Jaime De la Garza-Salazar 《Reports of Practical Oncology and Radiotherapy》2018,23(4):266-269
Osteosarcoma is the most common primary malignancy of bone in children and young adults, the highest incidence peak is during adolescence and doesn’t have any gender predominance. The main site of metastasis are the lungs and extrapulmonary cases are occasional. The incidence of metastasis in the Central Nervous System (CNS) is 2–6.5%, increase to 10–15% in patients with pulmonary metastases. Therefore, metastatic disease of the CNS is rare and the information on such patients is limited. Here, we describe a case of a 20-year old patient diagnosed with osteosarcoma in the left distal femur stage IIB, he developed pulmonary disease, during palliative chemotherapy experienced relapse to the brain classified as recursive partitioning analysis (RPA) class II, and was treated with external radiotherapy (30?Gy in 10 fractions) and later he had a poor evolution and died. 相似文献
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16.
Vladimir Parpura Gabriel A. Silva Peter A. Tass Kevin E. Bennet M. Meyyappan Jessica Koehne Kendall H. Lee Russell J. Andrews 《Journal of neurochemistry》2013,124(4):436-453
The brain operates through complex interactions in the flow of information and signal processing within neural networks. The ‘wiring’ of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromodulation are discussed. The use of water‐dispersible carbon nanotubes has been proven effective in the modulation of neurite outgrowth in culture and in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing ‘misfiring’ neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real‐time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. 相似文献
17.
Heparanase mechanisms of melanoma metastasis to the brain: Development and use of a brain slice model 总被引:2,自引:0,他引:2
Murry BP Blust BE Singh A Foster TP Marchetti D 《Journal of cellular biochemistry》2006,97(2):217-225
Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) chains of proteoglycans (HSPG), and its expression has been associated with increased cell growth, invasion, and angiogenesis of tumors as well as with embryogenesis and tissue development. Since metastatic cancer cells express HPSE-1, we have developed an orthotopic brain slice model to study HPSE-1 involvement in brain-metastatic melanoma. This model allows for the characterization of tumor cell invasion at both quantitative and qualitative levels. Brain-metastatic melanoma cells (B16B15b) showed augmenting levels of HPSE-1 protein expression in a time-dependent manner. Secondly, B16B15b cells pre-treated with HPSE-1 showed a significant increase in the number of cells that invaded into the brain tissue. Finally, HPSE-1 exposure-augmented invasion depth in brain sections by brain-metastatic melanoma cells. We concluded that applying this brain slice model can be beneficial to investigate HPSE-1- related in vivo modalities in brain-metastatic melanoma and brain invasion in general. These results also further emphasize the potential relevance of using this model to design therapies for controlling this type of cancer by blocking HPSE-1 functionality. 相似文献
18.
《生物化学与生物物理学报:癌评论》2022,1877(3):188734
The Ubiquitin-Protease system (UPS) is a major destruction system responsible for eliminating dysfunctional/misfolded proteins, thus acting as a pivotal regulator of protein homeostasis in eukaryotic cells. In this review, the UPS system and its various functions in the cell and their detailed impact such as cell cycle control, DNA damage response, apoptosis, and cellular stress regulations have been elucidated with a focus on the central nervous system. Since the Ubiquitin-Protease pathway(UPP) plays a prominent role in the sculpting of the CNS cells and their maintenance, it is naturally deeply involved in many malignancies that develop due to dysregulation of the UPS. Understanding the major disruptive players of the UPS in the development of these malignancies, for example, insoluble protein aggregates or inclusion bodies deposits due to malfunctioning of the UPS has paved the pathway for the development of new therapeutics. Here, the de-regulation of the UPS at various checkpoints in CNS malignancies has been detailed, thus facilitating an easy comprehension of the different targets that remain to be explored yet. The present therapeutic advancements in the field of CNS malignancies management through UPS targeting have also been included thus broadening the scope of drug development. Thus, this review while shedding sufficient light on the details of the UPS system and its connection to CNS malignancies, also opens new avenues for therapeutic advancements in the form of novel targetable UPP proteins and their interactions. 相似文献
19.
Cancer cells must regulate plasticity and invasion to survive and metastasize. However, the identification of targetable mechanisms to inhibit metastasis has been slow. Signaling programs that drive stem and progenitor cells during normal development offer an inroad to discover mechanisms common to metastasis. Using a chick embryo transplant model, we have compared molecular signaling programs of melanoma and their embryonic progenitors, the neural crest. We report that malignant melanoma cells hijack portions of the embryonic neural crest invasion program. Genes associated with neural crest induction, delamination, and migration are dynamically regulated by melanoma cells exposed to an embryonic neural crest microenvironment. Specifically, we demonstrate that metastatic melanoma cells exploit neural crest-related receptor tyrosine kinases to increase plasticity and facilitate invasion while primary melanocytes may actively suppress these responses under the same microenvironmental conditions. We conclude that aberrant regulation of neural crest developmental genes promotes plasticity and invasiveness in malignant melanoma. 相似文献
20.
Rebecca Senetta Giulia Stella Ernesto Pozzi Niccolo Sturli Daniela Massi Paola Cassoni 《Journal of cellular and molecular medicine》2013,17(3):325-336
Caveolae are non‐clathrin invaginations of the plasma membrane in most cell types; they are involved in signalling functions and molecule trafficking, thus modulating several biological functions, including cell growth, apoptosis and angiogenesis. The major structural protein in caveolae is caveolin‐1, which is known to act as a key regulator in cancer onset and progression through its role as a tumour suppressor. Caveolin‐1 can also promote cell proliferation, survival and metastasis as well as chemo‐ and radioresistance. Here, we discuss recent findings and novel concepts that support a role for caveolin‐1 in cancer development and its distant spreading. We also address the potential application of caveolin‐1 in tumour therapy and diagnosis. 相似文献