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Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds.

Ahmed K Farag, Ahmed H E Hassan, Byung Sun Ahn, Ki Duk Park, Eun Joo Roh,

Hybridization of reported weakly active antiproliferative hit 5-amino-4-pyrimidinol derivative with 2-anilino-4-phenoxypyrimidines suggests a series of 2,5-diamino-4-pyrimidinol derivatives as potential antiproliferative agents. Few compounds belonging to the proposed series were reported as CSF1R/DAPK1 inhibitors as anti-tauopathies. However, the correlation between CSF1R/DAPK1 signalling pathways and cancer progression provides motives to reprofile them ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2020, 35(1):311-324]

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Benzothiazole derivatives as anticancer agents.

Ali Irfan, Fozia Batool, Syeda Andleeb Zahra Naqvi, Amjad Islam, Sameh M Osman, Alessio Nocentini, Siham A Alissa, Claudiu T Supuran,

Benzothiazole (BTA) belongs to the heterocyclic class of bicyclic compounds. BTA derivatives possesses broad spectrum biological activities such as anticancer, antioxidant, anti-inflammatory, anti-tumour, antiviral, antibacterial, anti-proliferative, anti-diabetic, anti-convulsant, analgesic, anti-tubercular, antimalarial, anti-leishmanial, anti-histaminic and anti-fungal among others. The BTA scaffolds showed a crucial role in the inhibition of the metalloenzyme ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2020, 35(1):265-279]

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Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism.

Xin Zhou, Chenxi He, Jiangong Ren, Congxin Dai, Sharon R Stevens, Qianghu Wang, Daniel Zamler, Takashi Shingu, Liang Yuan, Chythra R Chandregowda, Yunfei Wang, Visweswaran Ravikumar, Arvind Uk Rao, Feng Zhou, Hongwu Zheng, Matthew N Rasband, Yiwen Chen, Fei Lan, Amy B Heimberger, Benjamin M Segal, Jian Hu,

Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature myelin is traditionally considered metabolically inert. Surprisingly, we discovered that mature myelin lipids undergo rapid turnover, and quaking (Qki) is a major regulator of myelin lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2020, :]

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Adenosine-to-inosine RNA editing in the immune system: friend or foe?

Taisuke Nakahama, Yukio Kawahara,

Our body expresses sensors to detect pathogens through the recognition of expressed molecules, including nucleic acids, lipids, and proteins, while immune tolerance prevents an overreaction with self and the development of autoimmune disease. Adenosine (A)-to-inosine (I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a post-transcriptional modification ... Read more >>

Cell. Mol. Life Sci. (Cellular and molecular life sciences : CMLS)
[2020, :]

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c-Met is expressed by highly autoreactive encephalitogenic CD8+ cells.

Mahdia Benkhoucha, Isis Senoner, Patrice H Lalive,

BACKGROUND:CD8+ T lymphocytes are critical mediators of neuroinflammatory diseases. Understanding the mechanisms that govern the function of this T cell population is crucial to better understanding central nervous system autoimmune disease pathology. We recently identified a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes and found that hepatocyte growth ... Read more >>

J Neuroinflammation (Journal of neuroinflammation)
[2020, 17(1):68]

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Supportive roles of brain macrophages in CNS metastases and assessment of new approaches targeting their functions.

Hua You, Szymon Baluszek, Bozena Kaminska,

Metastases to the central nervous system (CNS) occur frequently in adults and their frequency increases with the prolonged survival of cancer patients. Patients with CNS metastases have short survival, and modern therapeutics, while effective for extra-cranial cancers, do not reduce metastatic burden. Tumor cells attract and reprogram stromal cells, including ... Read more >>

Theranostics (Theranostics)
[2020, 10(7):2949-2964]

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Clinical Applications of Cerebrospinal Fluid Circulating Tumor DNA as a Liquid Biopsy for Central Nervous System Tumors.

Weiwei Yan, Tingting Xu, Hui Zhu, Jinming Yu,

Central nervous system (CNS) malignancies are associated with poor prognosis, as well as exceptional morbidity and mortality, likely as a result of low rates of early diagnosis and limited knowledge of the tumor growth and resistance mechanisms, dissemination, and evolution in the CNS. Monitoring patients with CNS malignancies for treatment ... Read more >>

Onco Targets Ther (OncoTargets and therapy)
[2020, 13:719-731]

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Management of immune checkpoint inhibitor-related adverse events: A review of case reports.

Xiaoyan Si, Peng Song, Jun Ni, Mingyi Di, Chunxia He, Li Zhang, Xiaowei Liu, Yue Li, Hanping Wang, Xiaoxiao Guo, Jiaxin Zhou, Lian Duan, Xu Yang, Mengzhao Wang, Li Zhang,

Immune checkpoint inhibitors represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Management of irAEs is based on clinical experience because it is not easy to conduct prospective trials to evaluate the best treatment strategy. Using a ... Read more >>

Thorac Cancer (Thoracic cancer)
[2020, 11(3):498-504]

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A rare case of Blastomyces dermatitidis brain abscess in an immunocompetent host.

Magdalena Slomka, James Doub,

Here we present a case of a 41-year old immunocompetent female from central Maryland, who presented with new onset seizures. Magnetic resonance imaging of brain revealed a solitary ring-enhancing lesion. Stereotactic brain biopsy confirmed Blastomyces dermatitidis brain abscess. Patient's clinical course was complicated by voriconazole-induced pancytopenia that prompted surgical resection ... Read more >>

Med Mycol Case Rep (Medical mycology case reports)
[2020, 28:8-11]

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PD-L1, PD-1, LAG-3, and TIM-3 in Melanoma: Expression in Brain Metastases Compared to Corresponding Extracranial Tumors.

Jaeyun Jane Wang, Peter Burger, Janis Taube, Abha Soni, Kaisorn Chaichana, Mary Sheu, Zineb Belcaid, Christopher Jackson, Michael Lim,

Background Metastatic melanoma to the brain carries a particularly poor prognosis that may be associated with an attenuated antitumor response in the presence of central nervous system malignancies. Thus, the development of brain metastases could theoretically accelerate cancer progression both locally and systemically. Although dysregulation of checkpoint markers, such as ... Read more >>

Cureus (Cureus)
[2019, 11(12):e6352]

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TERT, a promoter of CNS malignancies.

Bhuvic Patel, Rukayat Taiwo, Albert H Kim, Gavin P Dunn,

AbstractAs cells replicate their DNA during mitosis, telomeres are shortened due to the inherent limitations of the DNA replication process. Maintenance of telomere length is critical for cancer cells to overcome cellular senescence induced by telomere shortening. Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, an RNA-dependent ... Read more >>

Neurooncol Adv (Neuro-oncology advances)
[2020, 2(1):]

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Therapeutic Role of Gamma Knife Stereotactic Radiosurgery in Neuro-Oncology.

Rupen Desai, Keith M Rich,

The Gamma Knife Center of St. Louis has established itself as a key facility offering stereotactic radiosurgery (SRS) for a variety of neuro-oncologic disorders. Since the Gamma Knife unit was first brought to Washington University in 1997, we have treated 5,696 patients. In this review, we discuss the effective role ... Read more >>

Mo Med (Missouri Medicine)
[2020, 117(1):33-38]

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The impact of systemic precision medicine and immunotherapy treatments on brain metastases.

Rowland H Han, Gavin P Dunn, Milan G Chheda, Albert H Kim,

Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell ... Read more >>

Oncotarget (Oncotarget)
[2019, 10(62):6739-6753]

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Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers.

Aaron C Tan, Malinda Itchins, Mustafa Khasraw,

The management of non-small cell lung cancer (NSCLC) has transformed with the discovery of therapeutically tractable oncogenic drivers. In addition to activating driver mutations, gene fusions or rearrangements form a unique sub-class, with anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) targeted agents approved as the standard of care ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2020, 21(4):]

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Comparative Study of Dermatological Diseases of the Elderly in Relation to the Rest Population.

Iordanis Papadopoulos,

Background:According to Eurostat, the geriatric population in Greece constitutes almost 21.8% of the total population, with an increasing tendency. Skin diseases of the elderly often originate from internal medicine diseases. The aim of this study was to identify different dermatological conditions among patients over 65 years of age compared to ... Read more >>

Clin Cosmet Investig Dermatol (Clinical, cosmetic and investigational dermatology)
[2020, 13:173-178]

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Skin cancer in children after organ transplantation.

Beata Imko-Walczuk, Magdalena Roskosz-Stożkowska, Katarzyna Szymańska, Damian Kadylak, Alicja Dębska-Ślizień,

Skin cancer is the second most common complication of organ transplantation in children. The frequency of skin cancer incidence after organ transplantation is different in paediatric and adult populations. The post-transplant lymphoproliferative disease is the most common group of malignancies after organ transplantation in paediatric population. The majority of researchers ... Read more >>

Postepy Dermatol Alergol (Postepy dermatologii i alergologii)
[2019, 36(6):649-654]

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The Brazilian TP53 mutation (R337H) and sarcomas.

Sahlua Miguel Volc, Cíntia Regina Niederauer Ramos, Henrique de Campos Reis Galvão, Paula Silva Felicio, Aline Silva Coelho, Gustavo Noriz Berardineli, Natalia Campacci, Cristina da Silva Sabato, Lucas Faria Abrahao-Machado, Iara Viana Vidigal Santana, Nathalia Campanella, André van Helvoort Lengert, Daniel Onofre Vidal, Rui Manuel Reis, Caio F Dantas, Robson C Coelho, Erica Boldrini, Sergio Vicente Serrano, Edenir Inêz Palmero,

Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations ... Read more >>

PLoS ONE (PloS one)
[2020, 15(1):e0227260]

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Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis.

Yi Yang, Gang Jin, Yao Pang, Yijie Huang, Wenhao Wang, Hongyi Zhang, Guangxin Tuo, Peng Wu, Zequan Wang, Zijiang Zhu,

Background:Combination therapy with immune checkpoint inhibitors (ICIs) has been applied in the clinic to achieve synergistic effects and to improve clinical efficacy. Compared with monotherapy, combination therapy has promising efficacy against various advanced cancers. To further verify the effectiveness of combination therapy, we conducted a meta-analysis of the efficacy and ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2020, 11:40]

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Primary central nervous system marginal zone B-cell lymphoma arising from the dural meninges: A case report and review of literature.

Nerea Lopetegui-Lia, Lukas Delasos, Syed Daniyal Asad, Manish Kumar, Jonathan S Harrison,

Primary central nervous system (CNS) marginal zone B-cell lymphoma (MZBCL) arising from the dural meninges is a rare but indolent disease. This malignancy can present in various ways, hence making it difficult to diagnose. Biopsy results dictate an appropriate treatment plan, which commonly consists of a combination of surgical resection, ... Read more >>

Clin Case Rep (Clinical Case Reports)
[2020, 8(3):491-497]

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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing.

Isidro Cortés-Ciriano, Jake June-Koo Lee, Ruibin Xi, Dhawal Jain, Youngsook L Jung, Lixing Yang, Dmitry Gordenin, Leszek J Klimczak, Cheng-Zhong Zhang, David S Pellman, , Peter J Park, ,

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) ... Read more >>

Nat. Genet. (Nature genetics)
[2020, 52(3):331-341]

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Adoptive Cell Therapy: A Novel and Potential Immunotherapy for Glioblastoma.

Jingyu Wang, Fang Shen, Ying Yao, Lin-Lin Wang, Yongjian Zhu, Jue Hu,

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with very poor prognosis and few advances in its treatment. Recently, fast-growing cancer immunotherapy provides a glimmer of hope for GBM treatment. Adoptive cell therapy (ACT) aims at infusing immune cells with direct anti-tumor activity, including tumor-infiltrating lymphocyte ... Read more >>

Front Oncol (Frontiers in oncology)
[2020, 10:59]

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Differences in cancer survival by area-level socio-economic disadvantage: A population-based study using cancer registry data.

Nina Afshar, Dallas R English, Tony Blakely, Vicky Thursfield, Helen Farrugia, Graham G Giles, Roger L Milne,

Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age ... Read more >>

PLoS ONE (PloS one)
[2020, 15(1):e0228551]

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Primary CNS lymphoma commonly expresses immune response biomarkers.

Alexander Ou, Ashley Sumrall, Surasak Phuphanich, David Spetzler, Zoran Gatalica, Joanne Xiu, Sharon Michelhaugh, Andrew Brenner, Manjari Pandey, Santosh Kesari, W Michael Korn, Sandeep Mittal, Jason Westin, Amy B Heimberger,

Background:Primary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors. Materials and Methods:To genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from ... Read more >>

Neurooncol Adv (Neuro-oncology advances)
[2020, 2(1):vdaa018]

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B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury.

Takehiro Sugaya, Haruo Kanno, Michiharu Matsuda, Kyoichi Handa, Satoshi Tateda, Taishi Murakami, Hiroshi Ozawa, Eiji Itoi,

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, ... Read more >>

Cells (Cells)
[2019, 8(12):]

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Challenges of targeting BRAF V600E mutations in adult primary brain tumor patients: a report of two cases.

Matthew Smith-Cohn, Christian Davidson, Howard Colman, Adam L Cohen,

Aim: Therapeutic targeting of BRAF alterations in primary brain tumor patients has demonstrated clinical activity in case reports and early trials; however, there is limited high-level evidence of the efficacy. Patients & results: Targeting BRAF V600E mutations with concurrent dabrafenib and trametinib in anaplastic pleomorphic xanthoastrocytoma resulted in a transient ... Read more >>

CNS Oncol (CNS oncology)
[2019, 8(4):CNS48]

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