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https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#1
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#2
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28724926/enhanced-anti-metastatic-and-anti-tumorigenic-efficacy-of-berbamine-loaded-lipid-nanoparticles-in-vivo
#3
Priyambada Parhi, Sujit Suklabaidya, Sanjeeb Kumar Sahoo
Research on metastasis is gaining momentum for effective cancer management. Berbamine (BBM) has the potency to act as a therapeutic in multiple cancers and cancer metastasis. However, the major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life. Here, our major objective involved development of lipid based nanoparticles (NPs) loaded with BBM with an aim to circumvent the above problem. Moreover its, therapeutic potentiality was evaluated through various in vitro cellular studies and in vivo melanoma primary and experimental lung metastatic tumor model in C57BL/6 mice...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723670/quaking-5-suppresses-aggressiveness-of-lung-cancer-cells-through-inhibiting-%C3%AE-catenin-signaling-pathway
#4
Xuexia Zhou, Xuebing Li, Cuiyun Sun, Cuijuan Shi, Dan Hua, Lin Yu, Yanjun Wen, Feng Hua, Qian Wang, Qinghua Zhou, Shizhu Yu
Quaking-5 (QKI-5) belongs to the STAR (signal transduction and activation of RNA) family of RNA binding proteins and functions as a tumor suppressor in several human malignancies. In this study, we attempt to elucidate the role of QKI-5 in the pro-metastasis processes of lung cancer (LC) cells and the underlying mechanisms. We confirmed that QKI-5 was decreased in human LC tissues and cell lines, especially in high-metastatic cells. Moreover, QKI expression was positively correlated with LC patients' survival...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723623/daurinol-blocks-breast-and-lung-cancer-metastasis-and-development-by-inhibition-of-focal-adhesion-kinase-fak
#5
Jong K Woo, Hyun J Jung, Ji-Youn Park, Ju-Hee Kang, Byung I Lee, DongYun Shin, Chu W Nho, Soo-Young Cho, Je K Seong, Seung H Oh
FAK overexpression has been reported in diverse primary and metastatic tumor tissues, supporting its pro-tumorigenic and pro-metastatic roles. Therefore, we have developed a neo-treatment strategy using daurinol to effectively treat cancer metastasis. Daurinol blocked cancer cell migration and invasion in vitro and exhibited anti-metastatic activity in an experimental metastasis model of breast and lung cancer. Daurinol selectively inhibited phosphorylation of FAK at Tyr925, Tyr576/577, and Tyr397 sites in a dose- and time-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722353/auramine-o-an-incense-smoke-ingredient-promotes-lung-cancer-malignancy
#6
Jia-Chen Tung, Wei-Chien Huang, Juan-Cheng Yang, Guan-Yu Chen, Chi-Chen Fan, Yu-Chuan Chien, Pei-Shan Lin, Shih-Chun Candice Lung, Wei-Chao Chang
Burning incense to worship deities is a popular religious ritual in large parts of Asia, and is a popular custom affecting more than 1.5 billion adherents. Due to incomplete combustion, burning incense has been well recognized to generate airborne hazards to human health. However, the correlation between burning incense and lung cancer in epidemiological studies remains controversy. Therefore, we speculated that some unknown materials in incense smoke are involved in the initiation or progression of lung cancer...
July 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28722004/oral-gingival-metastasis-a-diagnostic-dilemma
#7
Nalini Aswath, Chandrakanth Balakrishnan, Vidyarani Shyamsundar, Sarumathi Thirrugnanamurthy
Oral cavity is a rare target for metastasis with an incidence of 1% among all oral cancers. In 24% of such cases, oral metastasis is the first indication of an undiagnosed primary. Metastatic oral malignancies have been reported in the mandible, tongue, and gingiva. Although gingival metastasis has been reported from lung, prostate, rectal carcinoma in men and carcinoma of breast, adrenal glands, and genitalia in females, gingival metastasis from carcinoma of the penis has not been reported. Herein, a case of metastatic gingival carcinoma that developed after extraction of teeth from primary carcinoma of the penis is presented...
May 2017: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
https://www.readbyqxmd.com/read/28721896/prognostic-importance-of-the-site-of-recurrence-in-patients-with-metastatic-recurrent-cervical-cancer
#8
Tae Hun Kim, Moon-Hong Kim, Beob-Jong Kim, Sang-Il Park, Sang-Young Ryu, Chul-Koo Cho
PURPOSE: The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. METHODS AND MATERIALS: Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28720841/novel-immunohistochemistry-based-signatures-to-predict-metastatic-site-of-triple-negative-breast-cancers
#9
Sergey Klimov, Padmashree Cg Rida, Mohammed A Aleskandarany, Andrew R Green, Ian O Ellis, Emiel Am Janssen, Emad A Rakha, Ritu Aneja
BACKGROUND: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most common underlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis. Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiple variables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis...
July 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28720577/lysyl-oxidase-like-protein-loxl2-promotes-lung-metastasis-of-breast-cancer
#10
Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vazquez-Naharro, Patricia G Santamaría, Saleta Morales, Pierre Dubus, Laura Muinelo-Romay, Rafael López López, Jason C Tung, Valerie M Weaver, Francisco Portillo, Amparo Cano
The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28717395/brain-imaging-before-primary-lung-cancer-resection-a-controversial-topic
#11
Zoe Hudson, Eveline Internullo, Anthony Edey, Isabel Laurence, Davide Bianchi, Alfredo Addeo
OBJECTIVE: International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in EnglandClin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#12
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL-6, IL-1 and IL-12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors, and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716069/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#13
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716020/long-non-coding-rna-casc2-suppresses-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells-through-casc2-mir-367-fbxw7-axis
#14
Yufeng Wang, Zhikui Liu, Bowen Yao, Qing Li, Liang Wang, Cong Wang, Changwei Dou, Meng Xu, Qingguang Liu, Kangsheng Tu
BACKGROUND: Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear. METHODS: The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28713917/stim1-silencing-inhibits-the-migration-and-invasion-of-a549-cells
#15
Yadong Wang, Haiyu Wang, Teng Pan, Li Li, Jiangmin Li, Haiyan Yang
The present study aimed to explore the effects of stromal interaction molecule 1 (STIM1) knockdown on the migration, invasion and metastasis of A549 cells in vitro and in vivo. Western blotting and immunohistochemistry were used to detect protein expression levels. Wound healing and Transwell invasion assays were used to assess the migratory and invasive abilities of A549 cells transfected with STIM1‑specific short hairpin (sh)RNA (shSTIM1). In addition, a tail vein metastatic assay was performed. The results demonstrated that the frequency of STIM1 high‑expression was significantly increased in metastatic lung cancer tissues (72...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713152/metastatic-anaplastic-lymphoma-kinase-1-alk-1-rearranged-inflammatory-myofibroblastic-sarcoma-to-the-brain-with-leptomeningeal-involvement-favorable-response-to-serial-alk-inhibitors-a-case-report
#16
Cai Yuan, Muchou J Ma, John V Parker, Tarek M Mekhail
BACKGROUND ALK gene rearrangements as oncogenic drivers have been described in many cancers, including inflammatory myofibroblastic sarcoma (IMS). The first-generation ALK inhibitor was limited in its ability to cross the blood-brain-barrier to treat brain metastasis. Drug-resistance invariably develops over time in ALK-rearranged tumors, which leads to disease progression. The newer generations of ALK inhibitors are designed to have higher potency in ALK inhibition and improved CNS penetration. CASE REPORT We report a rare case of pulmonary IMS with ALK-1 gene rearrangement and multiple brain metastases as initial presentation...
July 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28712972/arenobufagin-inhibits-prostate-cancer-epithelial-mesenchymal-transition-and-metastasis-by-down-regulating-%C3%AE-catenin
#17
Liping Chen, Weiqian Mai, Minfeng Chen, Jianyang Hu, Zhenjian Zhuo, Xueping Lei, Lijuan Deng, Junshan Liu, Nan Yao, Maohua Huang, Yinghui Peng, Wencai Ye, Dongmei Zhang
Epithelial-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis; thus, developing EMT inhibitors may be a feasible treatment for metastatic PCa. Here, we discovered that arenobufagin and four other bufadienolides suppressed PC3 cell EMT. These compounds modulated EMT marker expression with elevating E-cadherin and reducing ZEB1, vimentin and slug expression, and attenuated the migration and invasion of PC3 cells. Among these five compounds, arenobufagin exhibited the most potent activity...
July 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28712929/exosomes-from-osteosarcoma-and-normal-osteoblast-differ-in-proteomic-cargo-and-immunomodulatory-effects-on-t-cells
#18
Ryan M Troyer, Carl E Ruby, Cheri P Goodall, Liping Yang, Claudia S Maier, Hassan A Albarqi, Jacqueline V Brady, Kallan Bathke, Oleh Taratula, Dan Mourich, Shay Bracha
BACKGROUND: Canine osteosarcoma (OSA) is the most common cancer of the appendicular skeleton and is associated with high metastatic rate to the lungs and poor prognosis. Recent studies have shown the impact of malignant-derived exosomes on immune cells and the facilitation of immune evasion. In the current study, we have characterized the proteomic profile of exosomes derived from healthy osteoblasts and osteosarcoma cell lines. We investigated the direct impact of these exosomes on healthy T cells...
July 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28712427/depression-inflammation-and-epidermal-growth-factor-receptor-egfr-status-in-metastatic-non-small-cell-lung-cancer-a-pilot-study
#19
Jamie M Jacobs, Lara Traeger, Justin Eusebio, Naomi M Simon, Lecia V Sequist, Joseph A Greer, Jennifer S Temel, William F Pirl
OBJECTIVE: Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28711941/combination-of-cadherin-17-and-satb-homeobox-2-serves-as-potential-optimal-makers-for-the-differential-diagnosis-of-pulmonary-enteric-adenocarcinoma-and-metastatic-colorectal-adenocarcinoma
#20
Tingting Bian, Jinli Zhao, Jia Feng, Qing Zhang, Li Qian, Jian Liu, Daishan Jiang, Yifei Liu, Jianguo Zhang
BACKGROUND: Pulmonary enteric adenocarcinoma (PEAC), a rare type of non-small cell lung cancer, has similar histological and immunohistochemical morphology to colorectal adenocarcinoma. Cadherin-17 (CDH17) and SATB homeobox 2 (SATB2) immunoexpression have recently been demonstrated in colorectal adenocarcinoma. In this study, we evaluated the value of CDH17 and SATB2 in the diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma. METHODS: A total of 13 PEAC cases and 27 metastatic colorectal adenocarcinoma cases were enrolled in our cohort study...
June 28, 2017: Oncotarget
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