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https://www.readbyqxmd.com/read/28302961/getting-to-the-heart-of-the-matter-in-cancer-novel-approaches-to-targeting-cancer-stem-cells
#1
Hugh Colvin, Masaki Mori
Cancer is one of the leading causes of deaths worldwide. While cancers may initially show good response to chemotherapy or radiotherapy, it is not uncommon for them to recur at a later date. This phenomenon may be explained by the existence of a small population of cancer stem cells, which are inherently resistant to anti-cancer treatment as well as being capable of self-renewal. Therefore, while most of the tumour bulk consisting of cells that are not cancer stem cells respond to treatment, the cancer stem cells remain, leading to disease recurrence...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28302659/clear-cell-adenocarcinoma-of-cervix-in-1-year-old-girl-without-in-utero-exposure-to-diethylstilbestrol-an-uncommon-tumour-at-an-uncommon-age-and-site
#2
Aditi Arora, Anurag Rastogi, Azfar Neyaz, Nuzhat Husain
Adenocarcinoma of cervix constitutes about 10-15% cases of carcinoma cervix. Clear cell variant is even a rarer variant of adenocarcinoma. It rarely occurs in the paediatric age group and a known risk factor is in utero exposure to diethylstilbestrol (DES). We report here a case of primary cervical tumour in a 1-year-old girl, which was initially suspected to be an embryonal rhabdomyosarcoma botryoides. Histopathology with immunohistochemical analysis revealed clear cell adenocarcinoma. There was no maternal history of DES intake during pregnancy...
March 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28301871/a-unified-model-of-the-hierarchical-and-stochastic-theories-of-gastric-cancer
#3
REVIEW
Yanjing Song, Yao Wang, Chuan Tong, Hongqing Xi, Xudong Zhao, Yi Wang, Lin Chen
Gastric cancer (GC) is a life-threatening disease worldwide. Despite remarkable advances in treatments for GC, it is still fatal to many patients due to cancer progression, recurrence and metastasis. Regarding the development of novel therapeutic techniques, many studies have focused on the biological mechanisms that initiate tumours and cause treatment resistance. Tumours have traditionally been considered to result from somatic mutations, either via clonal evolution or through a stochastic model. However, emerging evidence has characterised tumours using a hierarchical organisational structure, with cancer stem cells (CSCs) at the apex...
March 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28300057/combined-toll-like-receptor-3-7-9-deficiency-on-host-cells-results-in-t-cell-dependent-control-of-tumour-growth
#4
Johanna C Klein, Katrin Moses, Gennadiy Zelinskyy, Simon Sody, Jan Buer, Stephan Lang, Iris Helfrich, Ulf Dittmer, Carsten J Kirschning, Sven Brandau
Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293705/idh-mutation-is-paradoxically-associated-with-higher-18-f-fdopa-pet-uptake-in-diffuse-grade-ii-and-grade-iii-gliomas
#5
A Verger, Ph Metellus, Q Sala, C Colin, E Bialecki, D Taieb, O Chinot, D Figarella-Branger, E Guedj
PURPOSE: The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and (18)F-FDOPA uptake on PET in newly diagnosed gliomas...
March 14, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28291774/brca2-secondary-mutation-mediated-resistance-to-platinum-and-parp-inhibitor-based-therapy-in-pancreatic-cancer
#6
Michael J Pishvaian, Andrew V Biankin, Peter Bailey, David K Chang, Daniel Laheru, Christopher L Wolfgang, Jonathan R Brody
BACKGROUND: Pancreatic cancer has become the third leading cause of cancer death with minimal improvements in outcome for over 40 years. Recent trials of therapies that target-defective DNA maintenance using poly (ADP-ribose) polymerase (PARP) inhibitors are showing promising results, yet invariably patients recur and succumb to disease. Mechanisms of resistance to platinum-based and PARP inhibitor therapy in other cancer types include secondary mutations, which restore the integrity of DNA repair through an increasing number of different mechanisms...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28287107/dying-cells-actively-regulate-adaptive-immune-responses
#7
REVIEW
Nader Yatim, Sean Cullen, Matthew L Albert
Dying cells have an important role in the initiation of CD8(+) T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8(+) T cell cross-priming...
March 13, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28285964/survivin-and-gynaecological-tumours
#8
REVIEW
Dušan Braný, Dana Dvorská, Pavol Slávik, Richard Školka, Marián Adamkov
Survivin is the smallest member of the inhibitors of apoptosis (IAP) family. However, participation in inhibition of apoptosis is not the only function of this molecule. Survivin can also affect the proper process of mitosis and even promoting of angiogenesis or DNA repair. High levels of survivin expression are connected with foetal tissues during intrauterine development. In the overwhelming majority of healthy, differentiated adult tissues, amounts of survivin are markedly reduced. On the other hand, survivin is also often abundantly expressed in cases of various types of cancer...
February 24, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28284200/detection-in-blood-of-autoantibodies-to-tumour-antigens-as-a-case-finding-method-in-lung-cancer-using-the-earlycdt%C3%A2-lung-test-ecls-study-protocol-for-a-randomized-controlled-trial
#9
F M Sullivan, Eoghan Farmer, Frances S Mair, Shaun Treweek, Denise Kendrick, Cathy Jackson, Chris Robertson, Andrew Briggs, Colin McCowan, Laura Bedford, Ben Young, Kavita Vedhara, Stephanie Gallant, Roberta Littleford, John Robertson, Herb Sewell, Alistair Dorward, Joseph Sarvesvaran, Stuart Schembri
BACKGROUND: Lung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis. The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice? METHODS: A randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation...
March 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28284009/pituitary-carcinoma-in-a-patient-with-an-sdhb-mutation
#10
Nicola Tufton, Federico Roncaroli, Irene Hadjidemetriou, Mary N Dang, Judit Dénes, Leonardo Guasti, Maria Thom, Michael Powell, Stephanie E Baldeweg, Naomi Fersht, Márta Korbonits
We present the first case of pituitary carcinoma occurring in a patient with a succinate dehydrogenase subunit B (SDHB) mutation and history of paraganglioma. She was initially treated for a glomus tumour with external beam radiotherapy. Twenty-five years later, she was diagnosed with a non-functioning pituitary adenoma, having developed bitemporal hemianopia. Recurrence of the pituitary lesion (Ki-67 10% and p53 overexpressed) occurred 5 years after her transsphenoidal surgery, for which she underwent two further operations followed by radiotherapy...
March 10, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28276425/the-shc1-adaptor-simultaneously-balances-stat1-and-stat3-activity-to-promote-breast-cancer-immune-suppression
#11
Ryuhjin Ahn, Valérie Sabourin, Alicia M Bolt, Steven Hébert, Stephanie Totten, Nicolas De Jay, Maria Carolina Festa, Yoon Kow Young, Young Kyuen Im, Tony Pawson, Antonis E Koromilas, William J Muller, Koren K Mann, Claudia L Kleinman, Josie Ursini-Siegel
Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#12
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28273972/role-of-cd10-immunoexpression-in-grading-phyllodes-tumour-of-the-breast
#13
Maithili Mandar Kulkarni, Siddhi Gaurish Sinai Khandeparkar, Avinash R Joshi, Vishakha Kothikar, Anuja Nasare, Sukhada Patil, Supriya Niraspatil, Bhagyashree Dhande
INTRODUCTION: Fibroepithelial tumours are a heterogeneous group of biphasic neoplasms consisting of a proliferation of both epithelial and stromal components. Fibroadenoma (FA) and Phyllodes Tumour (PT) constitute the major entities. It is crucial to distinguish benign from borderline PT (low grade malignant PT), because the former do not metastasize, have a lesser risk of local recurrence and initial local recurrences are histologically benign in almost all instances. Multiple Immunohistochemical (IHC) markers are being studied to find their utility in grading the PT accurately for planning proper treatment...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28270683/max-inactivation-is-an-early-event-in-gist-development-that-regulates-p16-and-cell-proliferation
#14
Inga-Marie Schaefer, Yuexiang Wang, Cher-Wei Liang, Nacef Bahri, Anna Quattrone, Leona Doyle, Adrian Mariño-Enríquez, Alexandra Lauria, Meijun Zhu, Maria Debiec-Rychter, Susanne Grunewald, Jaclyn F Hechtman, Armelle Dufresne, Cristina R Antonescu, Carol Beadling, Ewa T Sicinska, Matt van de Rijn, George D Demetri, Marc Ladanyi, Christopher L Corless, Michael C Heinrich, Chandrajit P Raut, Sebastian Bauer, Jonathan A Fletcher
KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28270078/a-preliminary-study-of-the-action-of-virtosomes-from-non-dividing-cells-on-tumour-cell-replication-in-vitro-and-in-vivo
#15
Mariano Garcia-Arranz, Damian Garcia-Olmo, Luz Vega-Clemente, Maurice Stroun
BACKGROUND: A DNA-RNA-lipoprotein complex, termed a virtosome, is released spontaneously from healthy human, other mammalian, avian, amphibian and plant cells in a regulated and energy-dependent manner. Studies on human and mouse lymphocytes, hepatocytes, NIH 3T3 cells and mouse tumour cell lines have shown that virtosomes may be acting as inter-cellular messengers. In particular, virtosomes from non-dividing cells blocked 3H-thymidine incorporation into DNA in tumour cell lines. OBJECTIVE: Study of the effect of virtosomes on tumors "in vivo" and "in vitro" Methods and Results...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28266569/ogg1-dna-interactions-facilitate-nf-%C3%AE%C2%BAb-binding-to-dna-targets
#16
Lang Pan, Wenjing Hao, Xu Zheng, Xianlu Zeng, Adeel Ahmed Abbasi, Istvan Boldogh, Xueqing Ba
DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5' or 3' guanine in runs of guanines to mimic oxidative effects...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261513/primary-clear-cell-microcystic-adenoma-of-the-sinonasal-cavity-pathological-or-fortuitous-association
#17
Rosalin Cooper, Hannah Markham, Jeffery Theaker, Adrian Bateman, David Bunyan, Matthew Sommerlad, Gillian Crawford, Diana Eccles
Primary clear cell microcystic adenoma of the sinonasal cavity is rare. It has previously been described only as a VHL-associated tumour. Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome characterised by an elevated risk of neoplasia including clear cell renal cell carcinoma (ccRCC), haemangioblastoma, and phaeochromocytoma. We describe the second reported case of a primary clear cell microcystic adenoma of the sinonasal cavity. The 39-year-old patient with VHL syndrome had previously undergone resection and ablation of ccRCC...
2017: Case Reports in Pathology
https://www.readbyqxmd.com/read/28255482/sinonasal-melanoma-a-case-report-and-literature-review
#18
I S S Alves, L G S Berriel, R T Alves, M B Pinto, C F P Oliveira, A C Cazzotto, W V Moura
Purpose. Sinonasal malignant mucosal melanoma is a rare, aggressive tumour. Nasal obstruction and epistaxis are the most commonly reported symptoms, although symptomatology may develop late and be nonspecific, which tends to delay diagnosis, resulting in a poorer prognosis. Case Report. This report describes a 64-year-old male patient with nasal obstruction and epistaxis. Computed tomography of the facial sinuses revealed a large lesion in the right nasal cavity, with infiltration into the left cavity, ethmoidal cells, and erosion of the cribriform plate...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28255418/28-year-late-spermatic-cord-relapse-of-a-testicular-non-seminomatous-germ-cell-tumour-managed-robotically
#19
James R Hayes, Michael A S Jewett, Robert J Hamilton
We present a patient who relapsed symptomatically 28 years post-orchiectomy, initially followed by active surveillance for clinical stage I non-seminomatous germ cell tumour (CSI NSGCT). His relapse was localized to the pelvis, managed with robotic surgery, and achieved a complete resection with tumour markers normalized. We highlight the current Princess Margaret guidelines for followup of CSI NSGCT and discuss the trade-off between lifelong radiographic surveillance to detect the very small risk of late relapse...
July 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28255411/structured-assessment-and-followup-for-patients-with-hereditary-kidney-tumour-syndromes
#20
Jean-Baptiste Lattouf, Stephen E Pautler, M Neil Reaume, Raymond H Kim, Melanie Care, Jane Green, Alan So, Philippe D Violette, Issam Saliba, Philippe Major, Shane Silver, Richard Leicht, Joan Basiuk, Simon Tanguay, Michael A S Jewett, Darrel Drachenberg
INTRODUCTION: Optimal clinical assessment and subsequent followup of patients with or suspected of having a hereditary renal cell carcinoma syndrome (hRCC) is not standardized and practice varies widely. We propose protocols to optimize these processes in patients with hRCC to encourage a more uniform approach to management that can then be evaluated. METHODS: A review of the literature, including existing guidelines, was carried out for the years 1985-2015. Expert consensus was used to define recommendations for initial assessment and followup...
July 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
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