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https://www.readbyqxmd.com/read/29474420/a-new-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-the-determination-of-paclitaxel-and-6%C3%AE-hydroxy-paclitaxel-in-human-plasma-development-validation-and-application-in-a-clinical-pharmacokinetic-study
#1
Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe Toffoli
Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found...
2018: PloS One
https://www.readbyqxmd.com/read/29455644/mir-19b-enhances-proliferation-and-apoptosis-resistance-via-the-egfr-signaling-pathway-by-targeting-pp2a-and-bim-in-non-small-cell-lung-cancer
#2
Ulrich Baumgartner, Fabienne Berger, Ali Hashemi Gheinani, Sabrina Sofia Burgener, Katia Monastyrskaya, Erik Vassella
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454912/anticancer-effect-of-petroleum-ether-extract-from-bidens-pilosa-l-and-its-constituent-s-analysis-by-gc-ms
#3
Yiwei Shen, Zhouliang Sun, Peiying Shi, Gang Wang, Youjia Wu, Shaoguang Li, Yanjie Zheng, Liying Huang, Liqing Lin, Xinhua Lin, Hong Yao
ETHNOPHARMACOLOGICAL RELEVANCE: Bidens pilosa L, belonging to the family of Acanthaceae, has been used as an anticancer medicine in folk in China. In our preliminary experiments, the petroleum ether extract from B. pilosa showed good cytotoxic activity to human lung cancer A549 cell. However, to date, it's lack of the further study on antitumor effect, mechanism and active substances composition of the petroleum ether extract of B. pilosa. AIM OF THE STUDY: The study aimed to evaluate the anti-lung cancer efficacy of the petroleum ether extract from B...
February 15, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29444468/a-major-component-of-vitamin-e-%C3%AE-tocopherol-inhibits-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-eml4-alk
#4
Yuki Uchihara, Takayuki Kidokoro, Kenji Tago, Tadahiko Mashino, Hiroomi Tamura, Megumi Funakoshi-Tago
Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. α-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29444439/differential-effector-engagement-by-oncogenic-kras
#5
Tina L Yuan, Arnaud Amzallag, Rachel Bagni, Ming Yi, Shervin Afghani, William Burgan, Nicole Fer, Leslie A Strathern, Katie Powell, Brian Smith, Andrew M Waters, David Drubin, Ty Thomson, Rosy Liao, Patricia Greninger, Giovanna T Stein, Ellen Murchie, Eliane Cortez, Regina K Egan, Lauren Procter, Matthew Bess, Kwong Tai Cheng, Chih-Shia Lee, Liam Changwoo Lee, Christof Fellmann, Robert Stephens, Ji Luo, Scott W Lowe, Cyril H Benes, Frank McCormick
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444297/draft-genomes-of-two-blister-beetles-genus-hycleus-harvested-for-the-potent-blistering-agent-cantharidin
#6
Yuan-Ming Wu, Jiang Li, Xiang-Sheng Chen
Background: Commonly known as blister beetles or Spanish fly, there are more than 1,500 species in the Meloidae family (Hexapoda: Coleoptera: Tenebrionoidea) that produce the potent defensive blistering agent cantharidin. Cantharidin and its derivatives have been used to treat cancers, such as liver, stomach, lung and esophageal cancers. Hycleus cichorii and Hycleus phaleratus are the most commercially important blister beetles in China due to their ability to biosynthesize this potent vesicant...
February 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29436155/design-of-cyclic-and-d-amino-acids-containing-peptidomimetics-for-inhibition-of-protein-protein-interactions-of-her2-her3
#7
Sandeep Pallerla, Himgauri Naik, Sitanshu Singh, Ted Gauthier, Rushikesh Sable, Seetharama D Jois
HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2-positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2-mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18) exhibited antiproliferative activity in HER2-overexpressing lung cancer cell lines with IC50 values in the nanomolar concentration range...
February 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29435111/impact-of-dlk1-dio3-imprinted-cluster-hypomethylation-in-smoker-patients-with-lung-cancer
#8
Sonia Molina-Pinelo, Ana Salinas, Nicolás Moreno-Mata, Irene Ferrer, Rocío Suarez, Eduardo Andrés-León, Manuel Rodríguez-Paredes, Julian Gutekunst, Eloisa Jantus-Lewintre, Carlos Camps, Amancio Carnero, Luis Paz-Ares
DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse pathological processes. The purpose of this study was to assess the methylation patterns of the DLK1-DIO3 cluster in patients with lung cancer to study its relevance in the pathogenesis of this disease. We found a characteristic methylation pattern of this cluster in smoking associated lung cancer, as compared to normal lung tissue...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435024/expression-of-ezh2-is-associated-with-poor-outcome-in-colorectal-cancer
#9
Zhuanpeng Chen, Ping Yang, Wanglin Li, Feng He, Jianchang Wei, Tong Zhang, Junbin Zhong, Huacui Chen, Jie Cao
Enhancer of zeste homolog 2 (EZH2), the critical component of polycomb group protein family, has been demonstrated to be overexpressed in various types of human cancer, including hepatocellular carcinoma, breast, bladder and lung cancer. The mechanism of how EZH2 promotes oncogenesis has also been well studied. However, little is known about the role of EZH2 in colorectal cancer (CRC). The main purpose of the present study was to analyze the association between EZH2 expression and the clinicopathological features of CRC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29435007/dexamethasone-induced-apoptosis-of-a549-cells-via-the-tgf-%C3%AE-1-smad2-pathway
#10
Xiao-Ling Feng, Hui-Zhi Fei, Ling Hu
Lung cancers are the most commonly diagnosed malignant tumors, and are one of the leading causes of morbidity and mortality worldwide. Dexamethasone (DEX) serves an important function in the regulation of lung cancer cell proliferation; however, the mechanisms involved still remain unknown. In the present study, the effects of DEX on A549 cell proliferation and apoptosis were examined, in addition to the potential downstream regulatory mechanisms underlying these effects. A549 cells were treated with different concentrations of DEX at 12, 24 and 48 h time points, followed by the addition of SB431542, an inhibitor of the TGF-β1 receptor, to block the TGF-β1 signaling pathway...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434997/function-of-axl-receptor-tyrosine-kinase-in-non-small-cell-lung-cancer
#11
Guoan Zhang, Meng Wang, Hongli Zhao, Wen Cui
Axl receptor tyrosine kinase (hereafter Axl) is a member of the tyrosine-protein kinase receptor Tyro3, Axl and proto-oncogene tyrosine-protein kinase Mer family of receptor tyrosine kinases, possessing multiple different functions in normal cells. Axl is overexpressed and activated in numerous different human cancer types, triggering several signaling pathways and enhancing tumor progression. The present review assesses previous studies on the function of Axl in non-small cell lung cancer (NSCLC). Axl is overexpressed in the tumor tissues of a number of patients with NSCLC and is associated with poorer clinical outcomes; it promotes NSCLC tumor growth, invasion/metastasis, drug resistance and the epithelial-mesenchymal transition, thus providing a survival advantage to tumor cells...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434924/enhanced-expression-of-kif4a-in-colorectal-cancer-is-associated-with-lymph-node-metastasis
#12
Yoshiko Matsumoto, Motonobu Saito, Katsuharu Saito, Yasuyuki Kanke, Yohei Watanabe, Hisashi Onozawa, Suguru Hayase, Wataru Sakamoto, Teruhide Ishigame, Tomoyuki Momma, Kensuke Kumamoto, Shinji Ohki, Seiichi Takenoshita
Kinesin family member 4A (KIF4A) is a member of the kinesin 4 subfamily of kinesin-related proteins and serves an important role in cell division. The expression levels of KIF4A have been investigated in numerous types of cancer, including cervical, lung, oral, and breast cancer, and are established to be associated with poor patient prognosis. However, the role of KIF4A, as well as its expression in colorectal cancer (CRC), remains to be elucidated. Therefore, the current study investigated KIF4A expression levels in patients with CRC and demonstrated that its levels were increased in tumor tissues compared with non-tumor tissues...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434849/family-with-sequence-similarity-83-member-b-is-a-predictor-of-poor-prognosis-and-a-potential-therapeutic-target-for-lung-adenocarcinoma-expressing-wild-type-epidermal-growth-factor-receptor
#13
Takumi Yamaura, Junji Ezaki, Naoyuki Okabe, Hironori Takagi, Yuki Ozaki, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Mika Hoshino, Jun Osugi, Yutaka Shio, Satoshi Waguri, Hirosumi Tamura, Jun-Ichi Imai, Emi Ito, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Hiroyuki Suzuki
Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor (EGFR) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B (FAM83B) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434606/macrophage-recognition-of-crystals-and-nanoparticles
#14
REVIEW
Masafumi Nakayama
Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433983/common-co-activation-of-axl-and-cdcp1-in-egfr-mutation-positive-non-smallcell-lung-cancer-associated-with-poor-prognosis
#15
Niki Karachaliou, Imane Chaib, Andres Felipe Cardona, Jordi Berenguer, Jillian Wilhelmina Paulina Bracht, Jie Yang, Xueting Cai, Zhigang Wang, Chunping Hu, Ana Drozdowskyj, Carles Codony Servat, Jordi Codony Servat, Masaoki Ito, Ilaria Attili, Erika Aldeguer, Ana Gimenez Capitan, July Rodriguez, Leonardo Rojas, Santiago Viteri, Miguel Angel Molina-Vila, Sai-Hong Ignatius Ou, Morihito Okada, Tony S Mok, Trever G Bivona, Mayumi Ono, Jean Cui, Santiago Ramón Y Cajal, Peng Cao, Rafael Rosell
Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo...
February 5, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29430849/mage-a-gene-expression-in-peripheral-blood-serves-as-a-poor-prognostic-marker-for-patients-with-lung-cancer
#16
Lina Gu, Meixiang Sang, Danjing Yin, Fei Liu, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
BACKGROUND: MAGE-A genes belong to the cancer/testis antigens family. The prognostic significance of MAGE-A expression in the peripheral blood of patients with lung cancer is unknown. Therefore, this study evaluated the expression and possible prognostic significance of MAGE-A in the peripheral blood of patients with lung cancer. METHODS: In this study, we detected MAGE-A gene expression in the peripheral blood of 150 patients with lung cancer and 30 healthy donors using multiplex semi-nested PCR and analyzed their correlation with clinicopathological risk factors...
February 12, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29427923/hg30-a-tetrahydroanthraquinone-compound-isolated-from-the-roots-of-prismatomeris-connate-induces-apoptosis-in-human-non-small-cell-lung-cancer-cells
#17
Shixiu Feng, Zhenzhen Wang, Min Zhang, Xiaohui Zhu, Zhanjun Ren
HG30, a tetrahydroanthraquinone compound isolated from the roots of Prismatomeris connate, was previously shown to inhibit the proliferation of A549 cells. The aim of this study was to evaluate the antitumor activity of HG30 in two non-small cell lung cancer cell lines, A549 and H1299, and to explore potential underlying mechanisms. In cell viability and colony formation assays, HG30 treatment suppressed the proliferation and number of colonies formed by A549 and H1299 cells. Western blot analysis further demonstrated that induction of apoptosis by HG30 in A549 and H1299 cells involves both caspase-dependent apoptosis pathways, including mitochondria- and death receptor-mediated pathways, and an apoptosis-inducing factor (AIF) -associated caspase-independent apoptosis pathway...
February 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29427669/high-kif2a-expression-promotes-proliferation-migration-and-predicts-poor-prognosis-in-lung-adenocarcinoma
#18
Tian Xie, Xingyu Li, Fei Ye, Chenxi Lu, Haitao Huang, Fei Wang, Xiaolei Cao, Chongjun Zhong
The Kinesin family member 2a (KIF2A), that belongs to the Kinesin-13 microtubule depolymerases, plays an important role in cancer cell proliferation, migration and apoptosis in various types of cancer such as gastric cancer, breast cancer, and squamous cell carcinoma of the oral tongue, but, its role and mechanism in lung adenocarcinoma (LUAD) is largely unknown. The present study reported that KIF2A was overexpressed in LUAD tissues as compared with adjacent normal tissues. KIF2A was closely correlated with TNM stage and lymph node metastasis (P < 0...
February 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29423112/ophiopogonin-b-sensitizes-trail-induced-apoptosis-through-activation-of-autophagy-flux-and-downregulates-cellular-flice-like-inhibitory-protein
#19
Uddin Md Nazim, Jae-Kyo Jeong, Sang-Youel Park
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein, belongs to the TNF superfamily. Compared to other family members, TRAIL is a promising anti-cancer agent that can selectively induce apoptosis of various types of transformed cells and xenografts, with negligible cytotoxicity against normal tissues. Ophiopogonin B is a bioactive ingredient of Radix Ophiopogon japonicus , which is frequently used in traditional Chinese medicine to treat cancer. In this study, we report that Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is the key determinant mediating TRAIL resistance in A549 cells and Ophiopogonin B downregulates c-FLIP and enhances TRAIL-induced apoptosis by activating autophagy flux...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422965/upregulation-of-bcl2-in-nsclc-with-acquired-resistance-to-egfr-tki
#20
Hio Teng Cheong, Fei Xu, Chi Tung Choy, Connie Wun Chun Hui, Tony Shu Kam Mok, Chi Hang Wong
Lung cancer has the highest incidence and mortality rate worldwide among all malignancy-associated mortalities, of which non-small cell lung cancer accounts for 80% of all cases. Resistance against epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) develops following 8-12 months of disease progression, and is a critical issue. HCC827 cell lines with resistance to EGFR-TKIs were successfully screened. The half maximal inhibitory concentration values were 1,000-fold higher than the values for the parental HCC827 cell line, thereby demonstrating cross-resistance against the same family of TKIs...
January 2018: Oncology Letters
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