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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/28548889/therapy-of-advanced-non-small-cell-lung-cancer-with-an-sn-38-anti-trop-2-drug-conjugate-sacituzumab-govitecan
#1
Rebecca Suk Heist, Michael J Guarino, Gregory Masters, W Thomas Purcell, Alexander N Starodub, Leora Horn, Ronald J Scheff, Aditya Bardia, Wells A Messersmith, Jordan Berlin, Allyson J Ocean, Serengulam V Govindan, Pius Maliakal, Boyd Mudenda, William A Wegener, Robert M Sharkey, David M Goldenberg, D Ross Camidge
Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points...
May 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28547860/inhibition-of-melanoma-metastasis-by-dual-peptide-plga-nps
#2
Denise Costa Arruda, Thaís Dolzany de Oliveira, Patrícia Harume Fukuda Cursino, Vera Susana Carneiro Maia, Rodrigo Berzaghi, Luiz R Travassos, Dayane Batista Tada
Despite the positive results observed in vitro and in vivo, clinical trials with bioactive peptides are generally hampered by their fast degradation in the biological system. Two bioactive peptides, P20 (CSSRTMHHC) and the combined peptide C (CVNHPAFACGYGHTMYYHHYQHHL) have been identified as anticancer therapeutics. Combined peptide C consists of peptide C (CVNHPAFAC), a tumor-homing peptide, conjugated to the antiangiogenic peptide HTMYYHHYQHHL with a GYG. In this work, PLGA NPs with peptide C were applied as a dual-peptide carrier for application in cancer therapy...
May 25, 2017: Biopolymers
https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#3
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28541775/cellular-response-to-exponentially-increasing-and-decreasing-dose-rates-implications-for-treatment-planning-in-targeted-radionuclide-therapy
#4
Jay H Solanki, Thomas Tritt, Jordan B Pasternack, Julia J Kim, Calvin N Leung, Jason D Domogauer, Nicholas W Colangelo, Venkat R Narra, Roger W Howell
The treatment of cancer using targeted radionuclide therapy is of interest to nuclear medicine and radiation oncology because of its potential for killing tumor cells while minimizing dose-limiting toxicities to normal tissue. The ionizing radiations emitted by radiopharmaceuticals deliver radiation absorbed doses over protracted periods of time with continuously varying dose rates. As targeted radionuclide therapy becomes a more prominent part of cancer therapy, accurate models for estimating the biologically effective dose (BED) or equieffective dose given in 2 fractions (EQD2α/β) will become essential for treatment planning...
May 25, 2017: Radiation Research
https://www.readbyqxmd.com/read/28538431/immunotherapy-for-lung-cancer-targeting-the-pd-1-pathway
#5
Sam Vafadar
Lung cancer is the third most common cancer in the United States and the top cause of cancer-related mortality in men and women. Despite advances in chemotherapy, molecular therapies, and CT screening, overall survival remains dismal. Additional options and a new treatment paradigm are needed. This article focuses on immunotherapy, a promising new approach targeted at the PD-1 inhibition pathway.
June 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28538184/taxane-platin-resistant-lung-cancers-co-develop-hypersensitivity-to-jumonjic-demethylase-inhibitors
#6
Maithili P Dalvi, Lei Wang, Rui Zhong, Rahul K Kollipara, Hyunsil Park, Juan Bayo, Paul Yenerall, Yunyun Zhou, Brenda C Timmons, Jaime Rodriguez-Canales, Carmen Behrens, Barbara Mino, Pamela Villalobos, Edwin R Parra, Milind Suraokar, Apar Pataer, Stephen G Swisher, Neda Kalhor, Natarajan V Bhanu, Benjamin A Garcia, John V Heymach, Kevin Coombes, Yang Xie, Luc Girard, Adi F Gazdar, Ralf Kittler, Ignacio I Wistuba, John D Minna, Elisabeth D Martinez
Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#7
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537761/correlation-analysis-of-18-f-fluorodeoxyglucose-and-18-f-fluoroazomycin-arabinoside-uptake-distributions-in-lung-tumours-during-radiation-therapy
#8
Dario Di Perri, John A Lee, Anne Bol, François-Xavier Hanin, Guillaume Janssens, Daniel Labar, Annie Robert, Edmond Sterpin, Xavier Geets
BACKGROUND: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [(18)F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [(18)F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours. MATERIAL AND METHODS: Fourteen patients with unresectable lung cancer underwent FDG and FAZA 4D-PET/CT on consecutive days at three time-points: prior to RT (pre), and during the second (w2), and the third (w3) weeks of RT...
May 24, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#9
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international phase 3 studies and national postmarketing surveillance of nivolumab in Japan...
May 24, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28536993/stereotactic-radiosurgery-for-focal-leptomeningeal-disease-in-patients-with-brain-metastases
#10
Amparo Wolf, Bernadine Donahue, Joshua S Silverman, Abraham Chachoua, Jean K Lee, Douglas Kondziolka
Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015...
May 23, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28536426/toll-like-receptor-4-mediates-lewis-lung-carcinoma-induced-muscle-wasting-via-coordinate-activation-of-protein-degradation-pathways
#11
Guohua Zhang, Zhelong Liu, Hui Ding, Hongyu Miao, Jose M Garcia, Yi-Ping Li
Cancer-induced cachexia, characterized by muscle wasting, is a lethal metabolic syndrome with undefined etiology. Current consensus is that multiple factors contribute to cancer-induced muscle wasting, and therefore therapy requires combinational strategies. Here, we show that Toll-like receptor 4 (TLR4) mediates cancer-induced muscle wasting by directly activating muscle catabolism as well as stimulating an innate immune response in mice bearing Lewis lung carcinoma (LLC), and targeting TLR4 alone effectively abrogate muscle wasting...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535533/malat1-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-through-downregulation-of-mir-145
#12
Yin Xiang, Yachen Zhang, Yong Tang, Qianhui Li
BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534823/preparation-and-in-vitro-photodynamic-activity-of-glucosylated-zinc-ii-phthalocyanines-as-underlying-targeting-photosensitizers
#13
Jian-Yong Liu, Chen Wang, Chun-Hui Zhu, Zhi-Hong Zhang, Jin-Ping Xue
Two novel glucosylated zinc(ІІ) phthalocyanines 7a-7b, as well as the acetyl-protected counterparts 6a-6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a-7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake...
May 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#14
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534101/evaluation-of-alk-gene-rearrangement-in-central-nervous-system-metastases-of-non-small-cell-lung-cancer-using-two-step-rt-pcr-technique
#15
M Nicoś, P Krawczyk, K Wojas-Krawczyk, A Bożyk, B Jarosz, M Sawicki, T Trojanowski, J Milanowski
PURPOSE: RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. MATERIALS: We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status...
May 22, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28533646/image-findings-of-rare-case-of-peritoneal-carcinomatosis-from-non-small-cell-lung-cancer-and-response-to-erlotinib-in-f-18-fdg-positron-emission-tomography-computed-tomography
#16
Koramadai Karuppusamy Kamaleshwaran, Jephy Joseph, Radha Krishnan Kalarikal, Ajit Sugunan Shinto
Lung cancer is currently one of the most common malignancies in the world. Metastatic disease is observed in ~ 40% of patients with lung cancer, with the most common sites of metastasis being the bone, liver, brain and adrenal glands. Peritoneal carcinomatosis (PC) is defined as the progression of the primary cancer to the peritoneum. PC is a rare clinical event in lung cancer. Tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), such as erlotinib are used for the treatment of patients with advanced non-small cell lung cancer (NSCLC)...
April 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28532508/is-it-possible-for-knowledge-based-planning-to-improve-intensity-modulated-radiation-therapy-plan-quality-for-planners-with-different-planning-experiences-in-left-sided-breast-cancer-patients
#17
Juanqi Wang, Weigang Hu, Zhaozhi Yang, Xiaohui Chen, Zhiqiang Wu, Xiaoli Yu, Xiaomao Guo, Saiquan Lu, Kaixuan Li, Gongyi Yu
BACKGROUND: Knowledge-based planning (KBP) is a promising technique that can improve plan quality and increase planning efficiency. However, no attempts have been made to extend the domain of KBP for planners with different planning experiences so far. The purpose of this study was to quantify the potential gains for planners with different planning experiences after implementing KBP in intensity modulated radiation therapy (IMRT) plans for left-sided breast cancer patients. METHODS: The model libraries were populated with 80 expert clinical plans from treated patients who previously received left-sided breast-conserving surgery and IMRT with simultaneously integrated boost...
May 22, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#18
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28530067/-stereotactic-ablative-body-radiation-sabr-a-new-therapeutic-option-for-treatment-of-stage-i-lung-cancer
#19
REVIEW
Sarit Appel, Zvi Symon
Stereotactic ablative radiotherapy (SABR) also known as stereotactic body radiation therapy (SBRT) offers a new therapeutic option for stage 1 lung cancer that cannot undergo surgery due to co-morbidities or patient refusal. This treatment evolved in the last decade thanks to technologic advancement of radiation therapy planning and delivery that allow real time imaging of the tumor and real time position correction before every treatment. Ultra high doses of radiation cause ablation of the target with very low collateral scatter dose to surrounding tissue...
November 2016: Harefuah
https://www.readbyqxmd.com/read/28529925/targeting-lung-cancer-stem-cells-research-and-clinical-impacts
#20
REVIEW
Norashikin Zakaria, Nazilah Abdul Satar, Noor Hanis Abu Halim, Siti Hawa Ngalim, Narazah Mohd Yusoff, Juntang Lin, Badrul Hisham Yahaya
Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC), which is one of two types of lung cancer, accounts for 85-90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs) because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells...
2017: Frontiers in Oncology
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