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https://www.readbyqxmd.com/read/28431340/first-macrocyclic-3-rd-generation-alk-inhibitor-for-treatment-of-alk-ros1-cancer-clinical-and-designing-strategy-update-of-lorlatinib
#1
REVIEW
Sulman Basit, Zaman Ashraf, Kwangho Lee, Muhammad Latif
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2(nd)-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3(rd)-generation macrocyclic ALK-TKI that demonstrates many advantages over 2(nd)-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28429775/fucoxanthin-provides-neuroprotection-in-models-of-traumatic-brain-injury-via-the-nrf2-are-and-nrf2-autophagy-pathways
#2
Li Zhang, Handong Wang, Youwu Fan, Yongyue Gao, Xiang Li, Zhigang Hu, Ke Ding, Yujie Wang, Xiaoliang Wang
Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429473/surgery-for-limited-stage-small-cell-lung-cancer
#3
REVIEW
Hayley Barnes, Katharine See, Stephen Barnett, Renée Manser
BACKGROUND: Current treatment guidelines for limited-stage small-cell lung cancer (SCLC) recommend concomitant platinum-based chemo-radiotherapy plus prophylactic cranial irradiation, based on the premise that SCLC disseminates early, and is chemosensitive. However, although there is usually a favourable initial response, relapse is common and the cure rate for limited-stage SCLC remains relatively poor. Some recent clinical practice guidelines have recommended surgery for stage 1 (limited) SCLC followed by adjuvant chemotherapy, but this recommendation is largely based on the findings of observational studies...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#4
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28428190/in-vivo-detection-of-egfrviii-in-glioblastoma-via-perfusion-magnetic-resonance-imaging-signature-consistent-with-deep-peritumoral-infiltration-the-%C3%AF-index
#5
Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M O'Rourke, Christos Davatzikos
<br />The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma non-invasively, using routine clinically-acquired imaging...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28428107/clinicopathologic-factors-associated-with-survival-in-patients-with-breast-cancer-brain-metastasis
#6
Rong Li, Kui Zhang, Gene P Siegal, Shi Wei
Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathologic factors associated with early onset of brain metastasis and survival outcomes after development of them...
April 17, 2017: Human Pathology
https://www.readbyqxmd.com/read/28427672/current-status-and-future-perspectives-of-sonodynamic-therapy-in-glioma-treatment
#7
REVIEW
Xiaobing Wang, Yali Jia, Pan Wang, Quanhon Liu, Hairong Zheng
Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28427213/clinical-benefit-of-continuing-crizotinib-therapy-after-initial-disease-progression-in-chinese-patients-with-advanced-alk-rearranged-non-small-cell-lung-cancer
#8
Xiangchan Hong, Qi Chen, Lingyu Ding, Ying Liang, Ningning Zhou, Wenfeng Fang, Xinru Chen, Haiying Wu
PURPOSE: Although most patients with ALK-positive non‒small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). MATERIALS AND METHODS: Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427196/breast-cancer-subtypes-predict-the-preferential-site-of-distant-metastases-a-seer-based-study
#9
Qi Wu, Juanjuan Li, Shan Zhu, Juan Wu, Chuang Chen, Qian Liu, Wen Wei, Yimin Zhang, Shengrong Sun
BACKGROUND AND AIMS: This study aimed to access possible relationships between breast cancer subtypes and sites of distant metastasis in breast cancer. RESULTS: A total of 243,896 patients, including 226,451 cases in control groups were identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases. Patients with all subtypes were most prone to bone metastases, the incidence of bone metastasis in HR+/HER2+ subtype was up to 5...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427190/pygopus2-inhibits-the-efficacy-of-paclitaxel-induced-apoptosis-and-induces-multidrug-resistance-in-human-glioma-cells
#10
Cefan Zhou, Hongxia Cheng, Wenying Qin, Yi Zhang, Hui Xiong, Jing Yang, Huang Huang, Yefu Wang, Xing-Zhen Chen, Jingfeng Tang
Anti-microtubule drugs, such as paclitaxel (PTX), are extensively used for the treatment of numerous cancers. However, growing evidence has shown that PTX resistance, either intrinsic or acquired, frequently occurs in patients and results in the failure of treatment, contributing to the high cancer mortality rate. Therefore, it is necessary to identify the genes or pathways involved in anti-microtubule drug resistance for future successful treatment of cancers. Pygopus2 (Pygo2), which contains a Zn-coordinated plant homeodomain (PHD) finger domain, is critical for β-catenin-dependent transcriptional switches in normal and malignant tissues and is over-expressed in various cancers, including human brain glioma...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#11
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
March 30, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28426839/medical-history-in-the-hellenic-journal-of-nuclear-medicine
#12
EDITORIAL
Andreas Otte, Byeong Cheol Ahn
The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th anniversary end of 2017. On board of the editorial team since 2003, this journal has influenced me like a good friend over the many past years. From time to time, the journal has published interesting and valuable historical notes. They show that nuclear medicine has a history and that medicine is its basis. They also teach us today, and some of the ancient perspectives and approaches are still valid. The reader of HJNM may be interested in these historical contributions, as they are timeless...
January 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#13
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28426725/dynamic-regulation-of-pin1-expression-and-function-during-zebrafish-development
#14
Maria Solange Ibarra, Carla Borini Etichetti, Carolina Di Benedetto, Germán L Rosano, Ezequiel Margarit, Giannino Del Sal, Marina Mione, Javier Girardini
The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed phosphorylation signaling by inducing local conformational changes in phosphorylated protein substrates. Extensive studies showed different roles for Pin1 in physiological processes and pathological conditions such as cancer and neurodegenerative diseases. However, there are still several unanswered questions regarding its biological role. Notably, despite evidences from cultured cells showing that Pin1 expression and activity may be regulated by different mechanisms, little is known on their relevance in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#15
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28426099/improving-brain-penetration-of-kinase-inhibitors-in-lung-cancer-patients-with-oncogene-dependency
#16
J Remon, J C Soria
No abstract text is available yet for this article.
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425014/clinicopathological-and-prognostic-significance-of-ki-67-immunohistochemical-expression-of-distant-metastatic-lesions-in-patients-with-metastatic-breast-cancer
#17
Hitoshi Inari, Nobuyasu Suganuma, Kae Kawachi, Tatsuya Yoshida, Takashi Yamanaka, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Hirotaka Nakayama, Katsuhiko Masudo, Takashi Oshima, Tomoyuki Yokose, Yasushi Rino, Satoru Shimizu, Yohei Miyagi, Munetaka Masuda
BACKGROUND: Surgical biopsy of metastatic lesions followed by pathological confirmation for the investigation of biomarkers is occasionally proposed as an effective strategy in the treatment of metastatic breast cancer. However, few reports have examined Ki-67 immunohistochemical expression in distant metastatic lesions of breast cancer patients. This study aimed to investigate the clinicopathological significance of subtypes and Ki-67 immunohistochemical expression in metastatic breast cancer lesions...
April 19, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28424757/the-emerging-role-of-targeted-therapy-and-immunotherapy-in-the-management-of-brain-metastases-in-non-small-cell-lung-cancer
#18
REVIEW
Annick Wong
Lung cancer is the worldwide leading cause of cancer-related mortality in men and second leading in women. Brain metastases (BM) account for 10% of non-small cell lung cancer (NSCLC) patients at initial presentation, with another 25-40% developing BM during the course of their disease. In the last decade, the field of precision oncology has led to the discovery of a multitude of heterogenous molecular abnormalities within NSCLC as well as the development of tyrosine kinase inhibitors that target them. In this review, the focus will be on targeted therapy and immunotherapy that show efficacy in BM rather than conventional treatment for multiple BM (such as surgical resection, WBRT, or stereotactic radiosurgery)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28424515/structure-and-allosteric-inhibition-of-excitatory-amino-acid-transporter-1
#19
Juan C Canul-Tec, Reda Assal, Erica Cirri, Pierre Legrand, Sébastien Brier, Julia Chamot-Rooke, Nicolas Reyes
Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound. The structures reveal architectural features of the human transporters, such as intra- and extracellular domains that have potential roles in transport function, regulation by lipids and post-translational modifications...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424427/nos2-expression-in-glioma-cell-lines-and-glioma-primary-cell-cultures-correlation-with-neurosphere-generation-and-sox-2-expression
#20
Paola Palumbo, Gianfranca Miconi, Benedetta Cinque, Francesca Lombardi, Cristina La Torre, Soheila Raysi Dehcordi, Renato Galzio, Annamaria Cimini, Antonio Giordano, Maria Grazia Cifone
Nitric oxide has been implicated in biology and progression of glioblastoma (GBM) being able to influence the cellular signal depending on the concentration and duration of cell exposure. NOS2 (inducible nitric oxide synthase) have been proposed as a component of molecular profile of several tumors, including glioma, one of the most aggressive primary brain tumor featuring local cancer stem cells responsible for enhanced resistance to therapies and for tumor recurrence. Here, we investigated the NOS2 mRNA expression by reverse transcription-PCR in human glioma primary cultures at several grade of malignancy and glioma stem cell (GSC) derived neurospheres...
March 10, 2017: Oncotarget
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