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https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#1
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28218040/comprehensive-profiling-and-quantitation-of-oncogenic-mutations-in-non-small-cell-lung-carcinoma-using-single-molecule-amplification-and-re-sequencing-technology
#2
Jian Shi, Meng Yuan, Zhan-Dong Wang, Xiao-Li Xu, Lei Hong, Shenglin Sun
The carcinogenesis of non-small cell lung carcinoma has been found to associate with activating and resistant mutations in the tyrosine kinase domain of specific oncogenes. Here, we assessed the type, frequency, and abundance of epithelial growth factor receptor, KRAS, BRAF, and ALK mutations in 154 non-small cell lung carcinoma specimens using single-molecule amplification and re-sequencing technology. We found that epithelial growth factor receptor mutations were the most prevalent (44.2%), followed by KRAS (18...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#3
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#4
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#5
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28194229/circulating-and-tissue-biomarkers-in-early-stage-non-small-cell-lung-cancer
#6
Caterina Fumagalli, Fabrizio Bianchi, Paola Rafaniello Raviele, Davide Vacirca, Giovanni Bertalot, Cristiano Rampinelli, Matteo Lazzeroni, Bernardo Bonanni, Giulia Veronesi, Nicola Fusco, Massimo Barberis, Elena Guerini-Rocco
OBJECTIVE: We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). MATERIALS AND METHODS: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test)...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#7
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28187448/impact-of-country-of-birth-on-genetic-testing-of-metastatic-lung-adenocarcinomas-in-france-african-women-exhibit-a-mutational-spectrum-more-similar-to-asians-than-to-caucasians
#8
Raphael Saffroy, Jean-François Morère, Nelly Bosselut, Pasquale F Innominato, Jocelyne Hamelin, Jean Trédaniel, Sophie Masse, Véronique Dussaule-Duchatelle, André Balaton, Pierre Validire, Catherine Guettier, Mohamed Bouchahda, Antoinette Lemoine
BACKGROUND: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans. AIM: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform. PATIENTS AND METHODS: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#9
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#10
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28158294/deep-proteome-mapping-of-wm-266-4-human-metastatic-melanoma-cells-from-oncogenic-addiction-to-druggable-targets
#11
Eumorphia G Konstantakou, Athanassios D Velentzas, Athanasios K Anagnostopoulos, Zoi I Litou, Ourania A Konstandi, Aikaterini F Giannopoulou, Ema Anastasiadou, Gerassimos E Voutsinas, George Th Tsangaris, Dimitrios J Stravopodis
Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma's heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28152690/molecular-testing-for-colorectal-and-lung-cancer-at-an-academic-cancer-center-satellite-site-opportunities-for-improvement
#12
Lawrence N Shulman, Joseph O Jacobson, Andrew David Norden
: 229 Background: Given their prevalence, colorectal and lung cancer are treated in both academic and community settings. Appropriate use of targeted therapies in these diseases is challenging given the need for biomarker testing prior to use. Rapidly changing practice standards, limited resources, and barriers to tissue processing make this particularly challenging in the community. We examined the use of biomarker testing and targeted therapies in colorectal and lung cancer at one of the Dana-Farber Cancer Institute satellite sites...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28150468/ciliated-muconodular-papillary-tumor-of-the-lung-harboring-alk-gene-rearrangement-case-report-and-review-of-the-literature
#13
Yan Jin, Xuxia Shen, Lei Shen, Yihua Sun, Haiquan Chen, Yuan Li
Ciliated muconodular papillary tumor (CMPT) of the lung is an extremely rare peripheral tumor of the lung. The pathogenesis of CMPT is still unknown, and its nature as a benign tumor or reactive process is still open to discussion. Recent studies have identified BRAF, EGFR and AKT1 mutations in CMPT, which would support a true neoplastic process. Here for the first time, we report a case of morphologically typical CMPT harboring ALK gene rearrangement to further provide convincing evidence that CMPT is a neoplastic process rather than a reactive lesion...
February 2, 2017: Pathology International
https://www.readbyqxmd.com/read/28145866/keap1-loss-modulates-sensitivity-to-kinase-targeted-therapy-in-lung-cancer
#14
Elsa B Krall, Belinda Wang, Diana M Munoz, Nina Ilic, Srivatsan Raghavan, Matthew J Niederst, Kristine Yu, David A Ruddy, Andrew J Aguirre, Jong Wook Kim, Amanda J Redig, Justin F Gainor, Juliet A Williams, John M Asara, John G Doench, Pasi A Janne, Alice T Shaw, Robert E McDonald Iii, Jeffrey A Engelman, Frank Stegmeier, Michael R Schlabach, William C Hahn
Inhibitors that target the receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) pathway have led to clinical responses in lung and other cancers, but some patients fail to respond and in those that do resistance inevitably occurs (Balak et al., 2006; Kosaka et al., 2006; Rudin et al., 2013; Wagle et al., 2011). To understand intrinsic and acquired resistance to inhibition of MAPK signaling, we performed CRISPR-Cas9 gene deletion screens in the setting of BRAF, MEK, EGFR, and ALK inhibition...
February 1, 2017: ELife
https://www.readbyqxmd.com/read/28135039/clinicopathologic-characteristics-and-outcomes-of-chinese-patients-with-non-small-cell-lung-cancer-and-braf-mutation
#15
Xi Ding, Zengli Zhang, Tao Jiang, Xuefei Li, Chao Zhao, Bo Su, Caicun Zhou
BRAF mutation is one of the important driver oncogene in non-small-cell lung cancer (NSCLC). Data on Chinese patients with BRAF-mutant NSCLC are inadequate. Hence, we conducted this study to investigate the clinicopathologic features and outcomes of Chinese patients with NSCLC and BRAF mutations. We identified patients with BRAF-mutant NSCLC between January 2012 and April 2016. Patient characteristics and treatment outcomes were analyzed. In total, 1680 patients were included. Twenty-eight (1.7%) patients harbored BRAF mutations...
January 30, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28133304/-a-case-of-metastatic-colorectal-cancer-with-her2-overexpression-amplification
#16
Akio Matsumoto, Yoshifumi Shimada, Ryoma Yagi, Kohei Miura, Yosuke Tajima, Takuma Okamura, Masato Nakano, Hitoshi Kameyama, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Hiroshi Ichikawa, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
We report a case of panitumumab-resistant rectal cancer with HER2 gene amplification detected by CancerPlex®. A 51- year-old man was diagnosed with an obstructive rectal cancer having lung and adrenal metastases. He underwent the Hartmann 's operation, and KRAS mutations were not detected. After the surgery, 3 courses of CapeOx plus bevacizumab were administered as first-line chemotherapy; however, the lung and adrenal metastases progressed. Subsequently, 24 courses of IRIS/panitumumab was administered as second-line chemotherapy, and the metastases slowly progressed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133295/-a-systematic-analysis-of-oncogene-and-tumor-suppressor-genes-for-panitumumab-resistant-rectal-cancer-with-wild-ras-gene-a-case-report
#17
Yosuke Tajima, Yoshifumi Shimada, Ryoma Yagi, Takuma Okamura, Masato Nakano, Hitoshi Kameyama, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Kohei Miura, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
A 58-year-old man was admitted with the complaint of bloody stools. Colonoscopy and computed tomography revealed a rectal cancer with a liver metastasis and multiple lung metastases. After administering a regimen comprising 3 courses of XELOX plus bevacizumab chemotherapy, the sizes of the primary and metastatic lesions decreased remarkably. Abdominoperineal resection was performed for local control of the cancer; the specimen from the initial tumor was found to be KRAS wild type. After 14 courses of XELOX chemotherapy, brain metastases were detected...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133136/-a-case-of-metastatic-colon-cancer-dramatically-affected-by-anti-egfr-antibody-therapy
#18
Ryoma Yagi, Yoshifumi Shimada, Kohei Miura, Yosuke Tajima, Takuma Okamura, Masato Nakano, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii
RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer. CancerPlex®is a nextgeneration sequencer for 413 cancer genes...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28115307/fast-isolation-and-ex-vivo-culture-of-circulating-tumor-cells-from-the-peripheral-blood-of-lung-cancer-patients
#19
Wu Wenjun, Wang Zhihua, Wang Zhuo, Deng Yuliang, Shi Qihui
Circulating tumor cells (CTCs) are free tumor cells shed from tumor site and enter into blood circulation. CTCs represent a reliable source of tumor cells for the molecular characteristics of the original tumor. However, the extraordinary rarity of CTCs makes the subsequent molecular and functional analysis technically challenging. Here, we describe a one-step microfludics-based immunomagnetic isolation method to isolate CTCs directly from the whole blood of lung adenocarcinoma patients. This method avoids harsh sample preparation and enrichment steps, and therefore preserves the viability (>90%) of CTCs during the in vitro isolation...
January 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28108303/braf-v600e-mutation-is-not-always-present-as-expected-a-case-report-of-lung-and-thyroid-carcinomas
#20
Nicolas Piton, Mathieu Salaün, Florian Guisier, Florent Marguet, Emmanuel K Touré, Pierre Gémival, Luc Thiberville, Jean-Christophe Sabourin
No abstract text is available yet for this article.
January 17, 2017: Journal of Thoracic Oncology
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