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Abeer A Nasir, Razan Salah, Abla Sayyed Ahmad, Samah Abu Hijleh, Sa'eed Abu Kattab, Alia Al Kurd, Rawan Al Sharif, Raed Amro, Ahmad Khatib, Hana' Mousa, Walaa Shamasnah, Khammisa Shqerat, Rita Giacaman
BACKGROUND: Hamm is an Arabic word that is used to express suffering. Idioms of distress are communicated differently in different contexts and cultures. Understanding idioms of distress and symptoms can help in diagnosis and lead to socioculturally sensitive health care. METHODS: In this qualitative study, we did semi-structured interviews with men and women of all age groups. Questions focused on the definition, causes, and consequences of Hamm. Responses were analysed by reading and re-reading interview transcripts until themes and subthemes emerged...
February 21, 2018: Lancet
JinYing Liu, Xiaokang Liu, Wei Ma, Wei Kou, CaiLi Li, Jin Zhao
PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Shweta Duggal, Noor Jailkhani, Mukul Kumar Midha, Kanury V S Rao, Ajay Kumar
The Rb protein is a tumor suppressor protein that regulates the key G1S checkpoint consequently blocking the progression of cell cycle into S-phase. Despite its pertinent role in cell cycle regulation, comprehensive information on its interacting partners across cell cycle progression is lacking. Here, we aim to submit a comprehensive set of Rb interactors as the cell progresses from G0 through G1 and S into G2 phase in HEK 293 cell line. Affinity purification of HA-tagged Rb protein along with its interactors was analyzed by mass spectrometry (AP-MS)...
April 2018: Data in Brief
Periklis G Foukas, Sotirios Tsiodras, Panagiota Economopoulou, Aris Spathis, Maria Mademli, Konstantinos Leventakos, Amanda Psyrri, Petros Karakitsos, Ioannis G Panayiotides
The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC); however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6) in a nivolumab treated patient with NSCLC...
2018: IDCases
Riccardo Marconcini, Francesco Spagnolo, Luigia Stefania Stucci, Simone Ribero, Elena Marra, Francesco De Rosa, Virginia Picasso, Lorenza Di Guardo, Carolina Cimminiello, Stefano Cavalieri, Laura Orgiano, Enrica Tanda, Laura Spano, Alfredo Falcone, Paola Queirolo
Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation...
February 23, 2018: Oncotarget
Erik H Middlebrooks, Brian C Westbrook, Robert M Conry
Immune checkpoint blockade (CPB) utilizing such agents as ipilimumab, nivolumab, or pembrolizumab has revolutionized melanoma therapy and has seen continued utilization in numerous other malignancies in recent years. However, these agents come at the price of inflammatory immune-related adverse events. Despite the increasing recognition of biochemical thyroid dysfunction associated with CPB, information regarding potential imaging findings is sparse. We describe the first 2 cases of acute thyroiditis following CPB presenting as diffuse thyromegaly documented by computed tomography, ultrasound, and iodine uptake imaging...
February 2018: Radiology Case Reports
Zilong Hu, Yue Ma, Zhiyang Shang, Shidong Hu, Kai Liang, Wentao Liang, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting...
April 2018: Oncology Letters
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Sarah Sertic, Antonio Mollica, Ilaria Campus, Stefania Roma, Emanuela Tumini, Andrés Aguilera, Marco Muzi-Falconi
UV-induced photoproducts are responsible for the pathological effects of sunlight. Mutations in nucleotide excision repair (NER) cause severe pathologies characterized by sunlight sensitivity, coupled to elevated predisposition to cancer and/or neurological dysfunctions. We have previously shown that in UV-irradiated non-cycling cells, only a particular subset of lesions activates the DNA damage response (DDR), and this requires NER and EXO1 activities. To define the molecular mechanism acting at these lesions, we demonstrate that Y family TLS polymerases are recruited at NER- and EXO1-positive lesion sites in non-S phase cells...
March 3, 2018: Molecular Cell
Simon David Brown, Olga Dorota Jarosinska, Alexander Lorenz
Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals, they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events...
March 17, 2018: Current Genetics
Graham Pawelec
Since the first immunomodulatory antibody was licensed by the FDA in 2011 for treating melanoma it has remained the case that only a certain proportion of cancer patients respond favourably to a particular therapy. Recent results from combining two or more different antibodies each targeting a different immune checkpoint indicate that the proportion of responding patients can be increased, but thus far there are no such therapies routinely yielding clinical benefit in 100% of patients in any cancer type. Therefore, predicting which patients will respond to a particular therapy remains of the utmost importance in order to maximise treatment efficacy and minimise side-effects and costs...
March 15, 2018: Current Opinion in Immunology
L C Hewitt, I Z Inam, Y Saito, T Yoshikawa, A Quaas, A Hoelscher, E Bollschweiler, G E Fazzi, V Melotte, R E Langley, M Nankivell, D Cunningham, W Allum, G G Hutchins, H I Grabsch
BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status...
March 15, 2018: European Journal of Cancer
Stephane Ederhy, Jennifer Cautela, Yann Ancedy, Marion Escudier, Franck Thuny, Ariel Cohen
No abstract text is available yet for this article.
March 9, 2018: JACC. Cardiovascular Imaging
Matthew J Bott, Jonathan Cools-Lartigue, Kay See Tan, Joseph Dycoco, Manjit S Bains, Robert J Downey, James Huang, James M Isbell, Daniela Molena, Bernard J Park, Valerie W Rusch, Smita Sihag, David R Jones, Prasad S Adusumilli
BACKGROUND: Surgeons are increasingly asked to operate on patients with residual disease after immunotherapy. The safety and utility of lung resection in this setting are unknown. METHODS: We performed a retrospective review of patients who underwent lung resection within 6 months of treatment with checkpoint blockade agents for metastatic or unresectable cancer. Survival was estimated from first resection using the Kaplan-Meier approach. RESULTS: Database query identified 19 patients who underwent 22 resections for suspected residual disease with therapeutic intent following immunotherapy between 2012 and 2016...
March 14, 2018: Annals of Thoracic Surgery
Taylor T Chrisikos, Yifan Zhou, Natalie Slone, Rachel Babcock, Stephanie S Watowich, Haiyan S Li
Dendritic cells (DCs) are the principal antigen-presenting cells of the immune system and play key roles in controlling immune tolerance and activation. As such, DCs are chief mediators of tumor immunity. DCs can regulate tolerogenic immune responses that facilitate unchecked tumor growth. Importantly, however, DCs also mediate immune-stimulatory activity that restrains tumor progression. For instance, emerging evidence indicates the cDC1 subset has important functions in delivering tumor antigens to lymph nodes and inducing antigen-specific lymphocyte responses to tumors...
March 14, 2018: Molecular Immunology
Sara Villa-Hernández, Rodrigo Bermejo
Proliferating cells need to accurately duplicate and pass their genetic material on to daughter cells. Problems during replication and partition challenge the structural and numerical integrity of chromosomes. Diverse mechanisms, as the DNA replication checkpoint, survey the correct progression of replication and couple it with other cell cycle events to preserve genome integrity. The structural maintenance of chromosomes (SMC) cohesin complex primarily contributes to chromosome duplication by mediating the tethering of newly replicated sister chromatids, thus assisting their equal segregation in mitosis...
March 16, 2018: Current Genetics
Francesco Soria, Andrea I Beleni, David D'Andrea, Irene Resch, Kilian M Gust, Paolo Gontero, Shahrokh F Shariat
OBJECTIVES: A small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression (HP). Their prevalence in urothelial (UC) and renal cancer (RCC) remains, to date, mostly uninvestigated. Therefore, we aimed to provide a summary of the current knowledge about PP and HP during immune checkpoint inhibitor therapy in UC and RCC patients. METHODS AND MATERIALS: A systematic medline/pubmed© literature search was performed...
March 16, 2018: World Journal of Urology
Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver Waidmann, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven Becker, Klaus Strebhardt
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities...
March 16, 2018: Nature Communications
Pedro Berraondo, Inaki Etxeberria, Mariano Ponz-Sarvise, Ignacio Melero
Interleukin-12  antitumor activities are mediated by the activation of T and NK lymphocytes to produce IFN gamma. Systemically, recombinant interleukin-12 has a narrow therapeutic window that favors local delivery, i.e., by gene therapy approaches. Interleukin-12 is a powerful partner in immunotherapy combinations with checkpoint inhibitors and adoptive T-cell transfer.
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shinya Sakata, Yuichiro Matsuoka, Kenta Kawahara, Yosuke Kakiuchi, Akira Takaki, Akiyuki Hirosue, Ryoji Yoshida, Sho Saeki, Kazuhiko Fujii, Hideki Nakayama
A 70-year-old Japanese man with recurrent squamous cell carcinoma of the head and neck presented with severe interstitial pneumonia associated with nivolumab, after talc slurry pleurodesis. Following the development of malignant pleural effusion, he underwent chest drainage and was administered intrathoracic talc as a pleurodesis. Two weeks later, we administered nivolumab (3mg/kg) to be repeated every 2 weeks. However, on day 12, chest computed tomography scan demonstrated diffuse non-segmental ground-glass opacity and mild bronchiectasis...
March 2018: Respiratory Investigation
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