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https://www.readbyqxmd.com/read/28938699/change-from-lung-adenocarcinoma-to-small-cell-lung-cancer-as-a-mechanism-of-resistance-to-afatinib
#1
Paolo Manca, Marco Russano, Francesco Pantano, Giuseppe Tonini, Daniele Santini
We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938646/concordance-between-circulating-tumor-cells-and-clinical-status-during-follow-up-in-anaplastic-lymphoma-kinase-alk-non-small-cell-lung-cancer-patients
#2
Mariano Provencio, David Pérez-Callejo, María Torrente, Paloma Martin, Virginia Calvo, Lourdes Gutiérrez, Fernando Franco, Maria José Coronado, Juan Luis Cruz-Bermúdez, Asunción Martín Ruiz-Valdepeñas, Alberto Cruz-Bermúdez, Margarita Sánchez-Beato, Atocha Romero, Aránzazu García-Grande
BACKGROUND: The identification of anaplastic lymphoma kinase (ALK) rearrangements is found in approximately 5% of non-small-cell lung cancers (NSCLCs). However, the development of liquid biopsies as a diagnostic tool is less developed in these cases. This study investigates the use of CTCs during treatment, together with an extended follow-up to correlate with clinical evolution. PATIENTS AND METHODS: A total of 13 patients out of a cohort of 212 patients with lung adenocarcinoma, presented ALK rearrangements (6%) confirmed by tumor biopsy...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#3
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#4
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936924/expression-of-cross-tolerance-to-a-wide-range-of-conditions-in-a-human-lung-cancer-cell-line-after-adaptation-to-nitric-oxide
#5
Zane Deliu, Timothy Tamas, Juel Chowdhury, Madeeha Aqil, Maaly Bassiony, James A Radosevich
Previously, we have shown that A549, a human lung adenocarcinoma, can be adapted to nitric oxide (NO(●)). NO(●) is a nitrogen-based free radical that is synthesized by a family of enzymes known as nitric oxide synthases. NO(●) has been shown to be overexpressed in patient populations of different cancers. In addition, it has been observed that patients who express high levels of nitric oxide synthases tend to have poorer clinical outcomes than those with low levels of expression. The original cell line A549 (parent) and the adapted A549-HNO (high nitric oxide) cell line serve as a useful model system to investigate the role of NO(●) in tumor progression and prognosis...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28935493/update-on-egfr-mutational-testing-and-the-potential-of-noninvasive-liquid-biopsy-in-non-small-cell-lung-cancer
#6
REVIEW
Edward Kim, Rebecca Feldman, Ignacio I Wistuba
Mutations in the epidermal growth factor receptor (EGFR) are important drivers of non-small-cell lung cancer (NSCLC) and have led to the emergence of EGFR-targeted therapies as critical treatment options for NSCLC. Although these agents have shown clinical activity in NSCLC patients, acquired resistance to EGFR-targeted agents is inevitable. Therefore, the ability to conveniently biopsy patient tumors is of increasing importance as new mechanisms of resistance and agents to target these resistance mutations are identified...
August 12, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28934754/cntn-1-enhances-chemoresistance-in-human-lung-adenocarcinoma-through-induction-of-epithelial-mesenchymal-transition-by-targeting-the-pi3k-akt-pathway
#7
Ruijie Zhang, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, Wenxiang Tang, Yan Zhou, Jianping Xu, Pei Li
BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28933413/the-role-of-the-nrf2-are-antioxidant-system-in-preventing-cardiovascular-diseases
#8
REVIEW
Robert E Smith, Kevin Tran, Cynthia C Smith, Miranda McDonald, Pushkar Shejwalkar, Kenji Hara
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor...
November 11, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28933054/high-stmn1-expression-is-associated-with-cancer-progression-and-chemo-resistance-in-lung-squamous-cell-carcinoma
#9
Pinjie Bao, Takehiko Yokobori, Bolag Altan, Misaki Iijima, Youko Azuma, Ryoichi Onozato, Toshiki Yajima, Akira Watanabe, Akira Mogi, Kimihiro Shimizu, Toshiteru Nagashima, Yoichi Ohtaki, Kai Obayashi, Seshiru Nakazawa, Tuya Bai, Reika Kawabata-Iwakawa, Takayuki Asao, Kyoichi Kaira, Masahiko Nishiyama, Hiroyuki Kuwano
BACKGROUND: Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis. METHODS: Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity...
September 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28932850/amino-and-chloro-8-hydroxyquinolines-and-their-copper-complexes-as-proteasome-inhibitors-and-antiproliferative-agents
#10
Valentina Oliveri, Valeria Lanza, Danilo Milardi, Maurizio Viale, Irena Maric, Carmelo Sgarlata, Graziella Vecchio
Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents. The approval of the proteasome inhibitor drug bortezomib for the treatment of myeloma and lymphoma further highlights the need for UPS inhibitors...
September 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28931539/detachment-induced-e-cadherin-expression-promotes-3d-tumor-spheroid-formation-but-inhibits-tumor-formation-and-metastasis-of-lung-cancer-cells
#11
Phattrakorn Powan, Sudjit Luanpitpong, Xiaoqing He, Yon Rojanasakul, Pithi Chanvorachote
The interconversion between epithelial and mesenchymal is proposed to be a key machinery responsible for metastasis-related deaths. Likewise, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the linkage between the two events and their control mechanisms are unclear. We used a 3D tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial to mesenchymal transition in lung cancer cells...
September 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28931104/-molecular-diagnostics-of-alk-positive-lung-cancer
#12
József Tímár, Gábor Lotz, Erzsébet Rásó, Judit Moldvay
ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH)...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28930979/analysis-of-18fdg-pet-ct-imaging-as-a-tool-for-studying-mycobacterium-tuberculosis-infection-and-treatment-in-non-human-primates
#13
Alexander G White, Pauline Maiello, M Teresa Coleman, Jaime A Tomko, L James Frye, Charles A Scanga, Philana Ling Lin, JoAnne L Flynn
Mycobacterium tuberculosis remains the number one infectious agent in the world today. With the emergence of antibiotic resistant strains, new clinically relevant methods are needed that evaluate the disease process and screen for potential antibiotic and vaccine treatments. Positron Emission Tomography/Computed Tomography (PET/CT) has been established as a valuable tool for studying a number of afflictions such as cancer, Alzheimer's disease, and inflammation/infection. Outlined here are a number of strategies that have been employed to evaluate PET/CT images in cynomolgus macaques that are infected intrabronchially with low doses of M...
September 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930681/parkin-independent-mitophagy-controls-chemotherapeutic-response-in-cancer-cells
#14
Elodie Villa, Emma Proïcs, Camila Rubio-Patiño, Sandrine Obba, Barbara Zunino, Jozef P Bossowski, Romain M Rozier, Johanna Chiche, Laura Mondragón, Joel S Riley, Sandrine Marchetti, Els Verhoeyen, Stephen W G Tait, Jean-Ehrland Ricci
Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28927521/when-the-guardian-sleeps-reactivation-of-the-p53-pathway-in-cancer
#15
REVIEW
Olaf Merkel, Ninon Taylor, Nicole Prutsch, Philipp B Staber, Richard Moriggl, Suzanne D Turner, Lukas Kenner
The p53 tumor suppressor is inactivated in most cancers, thus suggesting that loss of p53 is a prerequisite for tumor growth. Therefore, its reintroduction through different means bears great clinical potential. After a brief introduction to current knowledge of p53 and its regulation by the ubiquitin-ligases MDM2/MDMX and post-translational modifications, we will discuss small molecules that are able to reactivate specific, frequently observed mutant forms of p53 and their applicability for clinical purposes...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28927133/benefit-of-rebiopsy-for-deciding-treatment-strategy-in-rectal-cancer-a-case-report
#16
Kenta Kawasaki, Yasuo Hamamoto, Takeshi Suzuki, Kenro Hirata, Yasutaka Sukawa, Akiyoshi Kasuga, Yuichiro Hayashi, Hiromasa Takaishi, Kaori Kameyama, Takanori Kanai
Rebiopsy is considered an option for specific types of cancer, such as breast, non-small cell lung, and prostate cancer, in clinical trials and in practice. The benefit of rebiopsy comes from the selection of a new treatment strategy based on the genetic profile of the cells, which may reflect the development of drug resistance or hormonal changes. For colorectal cancer, the presence of different genomic mutations between the primary tumor and its metastases is rare, and rebiopsy is therefore not generally performed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#17
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#18
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925877/4-aryl-heteroaryl-4h-fused-pyrans-as-anti-proliferative-agents-design-synthesis-and-biological-evaluation
#19
Dinesh Kumar, Gurpreet Singh, Pooja Sharma, Arem Quayum, Girish Mahajan, M J Mintoo, Shashank Kumar Singh, Dilip Manikrao Mondhe, Pms Bedi, Subheet K Jain, Girish Kumar Gupta
The current study is focused on the design and synthesis of 4-aryl/heteroaryl-4H-fused pyrans as anti-proliferative agents. All the synthesized molecules were screened against a panel of human carcinoma cell lines. Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with IC50 value of 0...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28924948/magnetic-nanoparticles-for-the-delivery-of-dapagliflozin-to-hypoxic-tumors-physicochemical-characterization-and-cell-studies
#20
Athina Angelopoulou, Efstathia Voulgari, Argiris Kolokithas-Ntoukas, Aristides Bakandritsos, Konstantinos Avgoustakis
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors...
September 18, 2017: AAPS PharmSciTech
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