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https://www.readbyqxmd.com/read/29453963/significance-of-spread-through-air-spaces-in-resected-pathological-stage-i-lung-adenocarcinoma
#1
Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer, which spreads within air spaces beyond the edge of the main tumor. In the current study, we investigated the significance of STAS in patients with pathological stage I adenocarcinoma. METHODS: STAS was assessed in a total of 276 patients with resected pathological stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens...
February 14, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29450544/hla-class-i-antigen-expression-in-conjunctival-melanoma-is-not-associated-with-pd-l1-pd-1-status
#2
Jinfeng Cao, Niels J Brouwer, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd G van Duinen, Nadine E de Waard, Bruce R Ksander, Arend Mulder, Frans H J Claas, Mirjam H M Heemskerk, Martine J Jager
Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29448845/a-systematic-review-of-economic-evaluations-of-tyrosine-kinase-inhibitors-of-vascular-endothelial-growth-factor-receptors-mammalian-target-of-rapamycin-inhibitors-and-programmed-death-1-inhibitors-in-metastatic-renal-cell-cancer
#3
Panagiotis Petrou
The therapeutic categories of Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors, mammalian target of rapamycin inhibitors and Programmed Death-1 inhibitors have transformed the treatment of metastatic renal cell cancer. Nevertheless, this comes at an increased cost, in tandem with similar fiscal pressures in the broader oncology sector, which may jeopardize the sustainability of health systems. Areas covered To this direction, the economic evaluation of these agents is essential for rational and efficient resource allocation...
February 16, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29446615/leveraging-engineering-of-cells-for-drug-delivery
#4
Zhaowei Chen, Quanyin Hu, Zhen Gu
Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns...
February 15, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29444918/immunotherapy-a-new-standard-of-care-in-thoracic-malignancies-a-summary-of-the-european-respiratory-society-research-seminar-of-the-thoracic-oncology-assembly
#5
Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S Tsao, Frances A Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G J V Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29444087/safety-and-efficacy-of-anti-pd-l1-therapy-in-the-woodchuck-model-of-hbv-infection
#6
Scott Balsitis, Volodymyr Gali, Pamela J Mason, Susan Chaniewski, Steven M Levine, Michael J Wichroski, Michael Feulner, Yunling Song, Karen Granaldi, James K Loy, Chris M Thompson, Jacob A Lesniak, Catherine Brockus, Narendra Kishnani, Stephan Menne, Mark I Cockett, Renuka Iyer, Stephen W Mason, Daniel J Tenney
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters...
2018: PloS One
https://www.readbyqxmd.com/read/29440172/a-distinct-oncogenerative-multinucleated-cancer-cell-serves-as-a-source-of-stemness-and-tumor-heterogeneity
#7
David Diaz-Carballo, Sahitya Saka, Jacqueline Klein, Tobias Rennkamp, Ali Haydar Acikelli, Sascha Malak, Holger Jastrow, Gunther Wennemuth, Clemens B Tempfer, Inge Schmitz, Andrea Tannapfel, Dirk Strumberg
The effects of anticancer treatments on cell heterogeneity and their proliferative potential play an important role in tumor persistence and metastasis. However, little is known about de-polyploidization, cell fate, and physiological stemness of the resulting cell populations. Here we describe a distinctive cell type termed "pregnant" P1 cells found within chemotherapy refractory ovarian tumors, which generate and gestate daughter generation Gn-cells intracytoplasmically. Release of Gn-cells occurred by ejection through crevices in P1 cell membrane by body contractions or using a funiculus-like structure...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439008/pd-1-and-pd-l1-expression-in-thymic-epithelial-tumours-and-non-neoplastic-thymus
#8
Emine Kilic Bagir, Arbil Acikalin, Alper Avci, Derya Gumurdulu, Semra Paydas
AIMS: We explored the relationships between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression and the pathological and clinical features of thymic epithelial tumours and thymic hyperplasia. METHODS: We evaluated PD-1 and PDL-1 expressions within epithelial and microenvironmental components in thymic epithelial tumours (n=44) and thymic hyperplasias (n=8), immunohistochemically. We compared the results with demographic, clinical and histopathological features of the cases...
February 8, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29438695/eradication-of-triple-negative-breast-cancer-cells-by-targeting-glycosylated-pd-l1
#9
Chia-Wei Li, Seung-Oe Lim, Ezra M Chung, Yong-Soo Kim, Andrew H Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P Perillo, Andrew K Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A Sahin, Gabriel N Hortobagyi, Stephen S Yoo, Mien-Chie Hung
Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438316/regulation-of-programmed-death-ligand-1-pd-l1-expression-in-breast-cancer-cell-lines-in-vitro-and-in-immunodeficient-and-humanized-tumor-mice
#10
Eva-Maria Rom-Jurek, Nicole Kirchhammer, Peter Ugocsai, Olaf Ortmann, Anja K Wege, Gero Brockhoff
Programmed death ligand 1 (PD-L1) expression is an efficient strategy of tumor cells to escape immunological eradiation. However, only little is known about the factors that affect the cellular expression levels. Here we assessed the PD-L1 expression on different breast cancer cell lines under standard in vitro culture conditions and as a function of Epirubicin or Paclitaxel treatment. Moreover, we evaluated the expression in immunodeficient tumor mice as well as in humanized tumor mice (i.e., in the presence of a human immune system)...
February 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#11
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435162/prognostic-value-of-pd-l1-expression-in-patients-with-primary-solid-tumors
#12
Xiao Xiang, Peng-Cheng Yu, Di Long, Xiao-Li Liao, Sen Zhang, Xue-Mei You, Jian-Hong Zhong, Le-Qun Li
Programmed death-ligand 1 (PD-L1) is thought to play a critical role in immune escape by cancer, but whether PD-L1 expression can influence prognosis of patients with solid tumors is controversial. Therefore, we meta-analyzed available data on whether PD-L1 expression correlates with overall survival (OS) in such patients. PubMed, EMBASE and other databases were systematically searched for cohort or case-control studies examining the possible correlation between PD-L1 expression and OS of patients with solid tumors...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435131/pd-l1-confers-resistance-to-egfr-mutation-independent-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-via-upregulation-of-yap1-expression
#13
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435038/high-expression-of-carcinoembryonic-antigen-and-telomerase-reverse-transcriptase-in-circulating-tumor-cells-is-associated-with-poor-clinical-response-to-the-immune-checkpoint-inhibitor-nivolumab
#14
Halin Bao, Tuya Bai, Koji Takata, Takehiko Yokobori, Takashi Ohnaga, Takeshi Hisada, Toshitaka Maeno, Pinjie Bao, Tomonori Yoshida, Yuji Kumakura, Hiroaki Honjo, Makoto Sakai, Makoto Sohda, Minoru Fukuchi, Bolag Altan, Tadashi Handa, Munenori Ide, Tatsuya Miyazaki, Kyoichi Ogata, Tetsunari Oyama, Kimihiro Shimizu, Akira Mogi, Takayuki Asao, Ken Shirabe, Hiroyuki Kuwano, Kyoichi Kaira
The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen ( CEA ), human Telomerase Reverse Transcriptase ( hTERT ), cytokeratin19 ( CK19 ), and programmed death ligand-1 ( PD-L1 ) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434915/immunohistochemical-cd73-expression-status-in-gastrointestinal-neuroendocrine-neoplasms-a-retrospective-study-of-136-patients
#15
Kohei Ono, Eisuke Shiozawa, Nobuyuki Ohike, Tomonori Fujii, Hideki Shibata, Tetsuya Kitajima, Koichiro Fujimasa, Naoko Okamoto, Yukiko Kawaguchi, Tasuku Nagumo, Sakiko Tazawa, Mayumi Homma, Toshiko Yamochi-Onizuka, Tomoko Norose, Hitoshi Yoshida, Masahiko Murakami, Gensyu Tate, Masafumi Takimoto
The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433902/safety-and-efficacy-of-pd-1-pd-l1-inhibitors-in-treatment-naive-and-chemotherapy-refractory-patients-with-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#16
Monica Khunger, Prantesh Jain, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors...
January 10, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#17
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
February 8, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29431467/correlation-between-programmed-death-receptor-1-expression-in-tumor-infiltrating-lymphocytes-and-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinoma
#18
Paloma Del C Monroig-Bosque, Brandon Driver, Joel A Morales-Rosado, Michael Deavers, David Tacha, Eric Bernicker, Philip T Cagle, Ross A Miller
CONTEXT: - The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non-small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease. OBJECTIVE: - To investigate the correlation of PD-1 and PD-L1 in non-small cell lung carcinoma tumor samples, with emphasis on stage I disease...
February 12, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29428415/genome-scale-signatures-of-gene-interaction-from-compound-screens-predict-clinical-efficacy-of-targeted-cancer-therapies
#19
Peng Jiang, Winston Lee, Xujuan Li, Carl Johnson, Jun S Liu, Myles Brown, Jon Christopher Aster, X Shirley Liu
Identifying reliable drug response biomarkers is a significant challenge in cancer research. We present computational analysis of resistance (CARE), a computational method focused on targeted therapies, to infer genome-wide transcriptomic signatures of drug efficacy from cell line compound screens. CARE outputs genome-scale scores to measure how the drug target gene interacts with other genes to affect the inhibitor efficacy in the compound screens. Such statistical interactions between drug targets and other genes were not considered in previous studies but are critical in identifying predictive biomarkers...
February 6, 2018: Cell Systems
https://www.readbyqxmd.com/read/29427150/programmed-death-ligand-1-expression-and-tumor-infiltrating-lymphocytes-in-neurofibromatosis-type-1-and-2-associated-tumors
#20
Shiyang Wang, Benjamin Liechty, Seema Patel, Jeffrey S Weber, Travis J Hollmann, Matija Snuderl, Matthias A Karajannis
Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD-L1 expression on tumor cells, as well as the presence of tumor infiltrating lymphocytes (TILs). It is currently unknown whether tumors associated with neurofibromatosis types 1 and 2 (NF1 and NF2) express PD-L1. We performed immunohistochemistry for PD-L1 (clones SP142 and E1L3N), CD3, CD20, CD8, and CD68 in NF1-related tumors (ten dermal and six plexiform neurofibromas) and NF2-related tumors (ten meningiomas and ten schwannomas) using archival formalin-fixed paraffin-embedded tissues...
February 9, 2018: Journal of Neuro-oncology
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