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https://www.readbyqxmd.com/read/28529925/targeting-lung-cancer-stem-cells-research-and-clinical-impacts
#1
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
https://www.readbyqxmd.com/read/28512410/rrx-001-priming-of-pd-1-inhibition-in-the-treatment-of-small-cell-carcinoma-of-the-vagina-a-rare-gynecological-tumor
#2
Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28511612/ngs-analysis-on-tumor-tissue-and-cfdna-for-genotype-directed-therapy-in-metastatic-nsclc-patients-between-hope-and-hype
#3
Alexander T Falk, Simon Heeke, Véronique Hofman, Virginie Lespinet, Camille Ribeyre, Olivier Bordone, Michel Poudenx, Josiane Otto, Georges Garnier, Olivier Castelnau, Joël Guigay, Sylvie Leroy, Charles-Hugo Marquette, Paul Hofman, Marius Ilié
The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called "personalized or precision" medicine in clinical routine practice for metastatic NSCLC...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28469773/crizotinib-synergizes-with-cisplatin-in-preclinical-models-of-ovarian-cancer
#4
Xiao-Xiu Huang, Feng-Feng Xie, Li-Jiao Hou, Xiu-Xiu Chen, Rong-Ying Ou, Jiang-Tao Yu, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Di-Wei Zheng, Yao Chen, Jia-Rong Huang, Kun Wang, Meng-Ning Wei, Wen-Feng Li, Zhi Shi, Xiao-Jian Yan
Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#5
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#6
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic CRC cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34 a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28363995/response-heterogeneity-of-egfr-and-her2-exon-20-insertions-to-covalent-egfr-and-her2-inhibitors
#7
Takayuki Kosaka, Junko Tanizaki, Raymond M Paranal, Hideki Endoh, Christine Lydon, Marzia Capelletti, Claire E Repellin, Jihyun Choi, Atsuko Ogino, Antonio Calles, Dalia Ercan, Amanda J Redig, Magda Bahcall, Geoffrey R Oxnard, Michael J Eck, Pasi A Jänne
Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28361078/targeting-the-seeds-of-small-cell-lung-cancer
#8
EDITORIAL
Sylvia Mahara, Ron Firestein
The concept of antibody drug conjugates (ADCs), which includes the delivery of cytotoxic drugs to antigen-expressing tumor cells by harnessing the antigen-selectivity of a monoclonal antibody, has the potential to redefine the landscape of translational medicine. With the advent of patient derived xenograft (PDX) models and sophisticated genomic technologies, the identification of a selective antigen can be accurately validated within the appropriate tumor milieu. However, a major biological hurdle in cancer translational medicine is the inherent tumoral heterogeneity, underscoring the importance of targeting the 'right' sub-population of cancer cells...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28245430/man2a1-fer-fusion-gene-is-expressed-by-human-liver-and-other-tumor-types-and-has-oncogenic-activity-in-mice
#9
Zhang-Hui Chen, Yan P Yu, Junyan Tao, Silvia Liu, George Tseng, Michael Nalesnik, Ronald Hamilton, Rohit Bhargava, Joel B Nelson, Arjun Pennathur, Satdarshan P Monga, James D Luketich, George K Michalopoulos, Jian-Hua Luo
BACKGROUND & AIMS: Human tumors and liver cancer cell lines express the product of a fusion between the first 13 exons in the mannosidase α class 2A member 1 gene (MAN2A1) and the last 6 exons in the FER tyrosine kinase gene (FER), called MAN2A1-FER. We investigated whether MAN2A1-FER is expressed by human liver tumors and its role in liver carcinogenesis. METHODS: We performed reverse transcription polymerase chain reaction analyses of 102 non-small cell lung tumors, 61 ovarian tumors, 70 liver tumors, 156 glioblastoma multiform samples, 27 esophageal adenocarcinomas, and 269 prostate cancer samples, as well as 10 nontumor liver tissues and 20 nontumor prostate tissues, collected at the University of Pittsburgh...
February 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28225538/may-you-live-in-interesting-times
#10
(no author information available yet)
Whether or not the so-called curse, "May you live in interesting times" is apocryphal, we have to acknowledge that we do indeed live in interesting times. It has been only three months since the October 2016 issue of MEDICC Review, but the changes since-in many directions-have been head-spinning. For starters, scientists at Roswell Park Cancer Institute have launched a clinical trial of CIMAvax, the therapeutic lung cancer vaccine developed at Cuba's Molecular Immunology Center, surely a win-win for the citizens of both countries...
January 2017: MEDICC Review
https://www.readbyqxmd.com/read/28219640/identification-and-characterization-of-functional-antioxidant-response-elements-in-the-promoter-of-the-aldo-keto-reductase-akr1b10-gene
#11
Toru Nishinaka, Takeshi Miura, Kahori Shimizu, Tomoyuki Terada
AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the involvement of the transcription factor Nrf2 in AKR1B10 gene regulation. There are at least five potential Nrf2-responsive consensus sequences, so-called antioxidant response elements (AREs), and several ARE-like sequences in the 5'-flanking region up to -3282 bp of the AKR1B10 gene...
February 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28197929/epithelial-mesenchymal-transition-emt-and-non-small-cell-lung-cancer-nsclc-a-mutual-association-with-airway-disease
#12
Malik Quasir Mahmood, Chris Ward, Hans Konrad Muller, Sukhwinder Singh Sohal, Eugene Haydn Walters
NSCLC is a leading cause of morbidity and mortality worldwide. It includes adeno- and squamous cell carcinoma. In the background, COPD and smoking play a vital role in development of NSCLC. Local progression and metastasis of NSCLC has been associated with various mechanisms, but in particular by a process called epithelial mesenchymal transition (EMT), which is implicated in COPD pathogenesis. In this study, we have investigated whether expression of EGFR (activation marker) and S100A4, vimentin and N-cadherin (as EMT) is different both in central and leading edge of NSCLC and to what extent related to EMT activity of both small and large airways, stage and differentiation of NSCLC...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28151378/checkpoint-inhibition-new-treatment-options-in-urologic-cancer
#13
Daan Joost De Maeseneer, Brant Delafontaine, Sylvie Rottey
Both urothelial (UC) and renal cell cancer (RCC) are highly immunogenic tumours. Recent advances in cellular immunity understanding have resulted in a successful new class of therapeutic agents. Interaction between the programmed cell death 1 (PD1) on regulatory T-cells (Treg) and programmed cell death 1 ligand (PDL1) on cancer cells inhibits an effective immune response and is an important mechanism for cancer cells to evade the immune system. Monoclonal anti-PD1 and anti-PDL1 antibodies inhibit this interaction and are called checkpoint inhibitors...
February 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28122122/the-effect-of-radiation-dose-reduction-on-computer-aided-detection-cad-performance-in-a-low-dose-lung-cancer-screening-population
#14
Stefano Young, Pechin Lo, Grace Kim, Matthew Brown, John Hoffman, William Hsu, Wasil Wahi-Anwar, Carlos Flores, Grace Lee, Frederic Noo, Jonathan Goldin, Michael McNitt-Gray
PURPOSE: Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population...
April 2017: Medical Physics
https://www.readbyqxmd.com/read/28101034/a-case-of-poorly-differentiated-large-cell-neuroendocrine-carcinoma-of-the-cecum-a-rare-malignancy-with-review-of-the-literature
#15
Andrew T Mertz, Michelle A Ojemuyiwa
Poorly differentiated neuroendocrine carcinomas (NECs) are rare tumors that can arise anywhere along the gastrointestinal tract. They often present in advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. Characterization of these tumors is best accomplished with tissue biopsy, as peripheral tumor markers commonly used in NECs are of little utility. Therapeutic strategies often involve chemotherapeutic regimens that have been used to treat small-cell lung cancer. Recent studies have shown that programmed death-ligand 1 (PD-L1) expression within poorly differentiated NECs is a poor prognostic indicator...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28048635/su-f-t-184-3d-range-modulator-for-scanned-particle-therapy-development-monte-carlo-simulations-and-measurements
#16
Y Simeonov, P Penchev, T Printz Ringbaek, S Brons, U Weber, K Zink
PURPOSE: Active raster scanning in particle therapy results in highly conformal dose distributions. Treatment time, however, is relatively high due to the large number of different iso-energy layers used. By using only one energy and the so called 3D range-modulator irradiation times of a few seconds only can be achieved, thus making delivery of homogeneous dose to moving targets (e.g. lung cancer) more reliable. METHODS: A 3D range-modulator consisting of many pins with base area of 2...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048525/we-ab-207a-11-respiratory-motion-guided-4dcbct-a-step-towards-controlling-4dcbct-image-quality
#17
R O'Brien, U Stankovic, P Keall, J Sonke
PURPOSE: We have developed a method, called respiratory motion guided 4DCBCT (RMG-4DCBCT), in which the gantry speed and projection frequency are varied in response to the patient's real-time respiratory signal to eliminate streaking artifacts and to suppress duplicate projections in 4DCBCT images. In 2015, we realized RMG-4DCBCT on an Elekta Synergy linear accelerator with a mechanical relay to suppress projections and a potentiometer to adjust the gantry speed in response to the patient's real-time respiratory signal...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046421/su-c-bra-02-a-lung-tumor-autocontouring-algorithm-based-on-particle-filter-for-dynamic-magnetic-resonance
#18
A Bourque, S Bedwani, E Filion, J Carrier
PURPOSE: This study proposes a novel autocontouring algorithm for lung tumors based on particle filter. It is developed in the context of MR-linac treatments and is validated on in-vivo dynamic magnetic resonance images. METHODS: A sequential Monte Carlo method called particle filter is combined with Otsu's thresholding technique to contour lung tumors on dynamic MR images. Four non-small cell lung cancer (NSCLC) patients were imaged with a 1.5 T MR (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) for one minute at a rate of 4 images per second...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28008898/-argon-laser-ablation-is-a-new-method-of-airways-recanalization-for-tumoral-stenosis
#19
A A Rusanov, N V Kazakov, A V Gerasin, M G Kovalev, A L Akopov
AIM: To develop the new method of laser recanalization of airways for tumoral stenosis. MATERIAL AND METHODS: It is proposed to conduct laser effect in the gas environment that does not support combustion (argon). Also the device for these AIM: is suggested. The method is called argon-laser ablation (ALA). A comparison of ALA and conventional high-energy laser exposure (LPD) was performed. RESULTS: ALA and LPD were used in 46 patients and 17 patients with non-small cell lung cancer...
2016: Khirurgiia
https://www.readbyqxmd.com/read/27987588/report-of-two-cases-of-pseudoprogression-in-patients-with-non-small-cell-lung-cancer-treated-with-nivolumab-including-histological-analysis-of-one-case-after-tumor-regression
#20
Junko Tanizaki, Hidetoshi Hayashi, Masatomo Kimura, Kaoru Tanaka, Masayuki Takeda, Shigeki Shimizu, Akihiko Ito, Kazuhiko Nakagawa
The recent approval of nivolumab and other immune-checkpoint inhibitors for the treatment of certain solid tumors including non-small cell lung cancer (NSCLC) has transformed cancer therapy. However, it will be important to characterize effects of such agents not seen with classical cytotoxic drugs or other targeted therapeutics. We here report two cases of NSCLC showing so-called pseudoprogression during nivolumab treatment. In both cases, imaging assessment revealed that liver metastatic lesions initially progressed but subsequently shrank during continuous nivolumab administration, with treatment also resulting in a decline in serum levels of carcinoembryonic antigen...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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