Chronic lymphocytic leukemia (CLL) cells multiply and become more resistant to immunochemotherapy in 'proliferation centers' within tissues, whereas apoptosis occurs in the periphery. Various models recapitulate these microenvironments in vitro, such as stimulation with CD154 and IL-4. Using this system, we observed a 30-40 fold induction of wild-type p53 protein in 50 distinct human CLL specimens tested, without the induction of either cell cycle arrest or apoptosis. In contrast, the mRNA levels for p53 did not increase, indicating that its elevation occurred posttranscriptionally. Mechanistic investigations revealed that under the conditions studied p53 was phosphorylated on residues associated with p53 activation and increased half-life. However, p53 protein induced in this manner could transcriptionally activate only a subset of target genes. The addition of a DNA damaging agent further upregulated p53 protein levels which led to apoptosis. p53 induction relied on the increase in intracellular reactive oxygen species (ROS) observed after CD154 and IL-4 stimulation. We propose that chronic oxidative stress is a characteristic of the microenvironment in B cell 'proliferation centers' in CLL which are capable of elevating the basal expression of p53, but to levels below the threshold needed to induce arrest or apoptosis. Our findings suggest that reactivation of the full transcriptional activities of p53 in proliferating CLL cells may offer a possible therapeutic strategy.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 7 Σεπτεμβρίου 2016
Role of ROS-induced p53 in CLL.
Role of CD166 in multiple myeloma progression
Multiple myeloma (MM) is incurable once osteocytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in MM cell lines and primary bone marrow (BM) cells from patients. CD166+ MM cells homed more efficiently than CD166- cells to the BM of engrafted immunodeficient NSG mice. CD166 silencing in MM cells enabled longer survival, a smaller tumor burden and less osteolytic lesions, as compared to mice bearing control cells. CD166 deficiency in MM cell lines or CD138+ BM cells from MM patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Further, CD166 deficiency in MM cells also reduced formation of osteolytic disease in vivo after intra-tibial engraftment. Mechanistic investigation revealed that CD166 expression in MM cells inhibited osteoblastogenesis of BM-derived osteoblast progenitors by suppressing RUNX2 gene expression. Conversely, CD166 expression in MM cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in MM cell homing to the BM and MM progression, rationalizing its further study as a candidate therapeutic target for MM treatment.
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NRBP2 promotes HCC cell chemosensitivity
Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy. Research data supported that cancer stem cells (CSCs) may be responsible for the chemoresistance, and strategies that suppress CSCs stemness could also inhibit the drug resistance. In this study, we found that NRBP2 expression was downregulated in the CD133+ HCC CSCs. Most adjacent non-cancerous liver tissue analyzed expressed higher level of NRBP2 compared with cancerous tissue in HCC patients, and high NRBP2 expression indicated a better prognosis. Realtime PCR results showed that NRBP2 negatively correlated with stemness-related genes, including Oct3/4, Nanog, Notch1, Ep300 and CD133 mRNA expression. High NRBP2 expression in HCC cells downregulated CK19 protein expression, inhibited tumorsphere formation and tumorigenesis ability, indicates that high NRBP2 expression restrains the HCC cell stemness. Overexpression of NRBP2 reduced the IC50 of sorafenib in HCC cells, and NRBP2 expression was negatively correlated with HCC cell resistance to the chemotherapy agents, including cisplatin and the Akt signaling inhibitor perifosine. Co-immunoprecipitation results showed that NRBP2 could bind with annexin A2 (ANXA2) and inhibit ANXA2 expression. Co-expression of ANXA2 restored the chemoresistant ability in NRBP2-overexpressing HCC cells. Further analysis showed that that NRBP2 downregulated Akt and its downstream signaling target Bad phosphorylation level. ANXA2 co-expression partially restored the Akt phosphorylation. Analysis of the expression of Bcl2 family proteins showed that NRBP2 may increase HCC cell chemosensitivity by regulating expression of survival proteins involved in the Akt and Bcl2 pathway. These results suggest that NRBP2 plays an important role in the tumor progression and chemotherapeutic resistance of HCC.
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Epigenetic Alterations in Unfavorable Neuroblastomas
The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor- and cell line–derived global histone modification analyses and epigenetic drug treatment in vitro. We found that DNA methylation patterns identify divergent patient subgroups with respect to survival and clinicobiologic variables, including amplified MYCN. Transcriptome integration and histone modification–based definition of enhancer elements revealed intragenic enhancer methylation as a mechanism for high-risk–associated transcriptional deregulation. Furthermore, in high-risk neuroblastomas, we obtained evidence for cooperation between PRC2 activity and DNA methylation in blocking tumor-suppressive differentiation programs. Notably, these programs could be re-activated by combination treatments, which targeted both PRC2 and DNA methylation. Overall, our results illuminate how epigenetic deregulation contributes to neuroblastoma pathogenesis, with novel implications for its diagnosis and therapy. Cancer Res; 76(18); 1–15. ©2016 AACR.
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Antimetastatic activity of novel ruthenium (III) pyridine complexes
Abstract
Ruthenium-based complexes have emerged as promising anticancer, especially antimetastatic agents. Among them, NAMI-A (trans-[Ru(III)Cl4 (DMSO)(Im)][ImH], Im = imidazole, DMSO = dimethyl sulfoxide) was well studied. In this study, we studied the antimetastatic activities of two novel NAMI-A derivatives containing pyridine, G26b and G94a, using cultured cells and tumor-bearing mice. Same to NAMI-A, these two complexes displayed little direct cytotoxicity to the cancer cells in vitro and in vivo, but they, especially G26b, significantly reduced the occurrence and development of lung metastases in mice bearing the 4T1 mammary carcinoma. In vitro, these two complexes displayed significant suppressive effect on invasion and migration of cells and tube formation of human umbilical vein endothelial cell, to the same extent of NAMI-A. The transcription of important molecules involved in metastasis, matrix metalloproteinase 2 and 9 (MMP-2 and -9), and vascular endothelial growth factor, was suppressed by the two complexes, as well as NAMI-A. Plasma atomic emission spectrometer showed G26b had a longer Ru-elimination time in lung, which may be a reason for better antimetastatic effect of G26b than NAMI-A. Our results have demonstrated that G26b is a more effective antimetastatic agent than NAMI-A.
The ruthenium (III)-pyridine complexes, G26b and G94a, which is derived from NAMI-A, could strongly reduce the occurrence and development of lung metastases in mice when kept a slower Ru elimination, which prolonged contact with the metastatic cells in the lungs. The ruthenium (III)-pyridine complexes had coped better than well-studied NAMI-A.
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A study on the value of computer-assisted assessment for SPECT/CT-scans in sentinel lymph node diagnostics of penile cancer as well as clinical reliability and morbidity of this procedure
Abstract
Background
Because of the increasing importance of computer-assisted post processing of image data in modern medical diagnostic we studied the value of an algorithm for assessment of single photon emission computed tomography/computed tomography (SPECT/CT)-data, which has been used for the first time for lymph node staging in penile cancer with non-palpable inguinal lymph nodes. In the guidelines of the relevant international expert societies, sentinel lymph node-biopsy (SLNB) is recommended as a diagnostic method of choice. The aim of this study is to evaluate the value of the afore-mentioned algorithm and in the clinical context the reliability and the associated morbidity of this procedure.
Methods
Between 2008 and 2015, 25 patients with invasive penile cancer and inconspicuous inguinal lymph node status underwent SLNB after application of the radiotracer Tc-99m labelled nanocolloid. We recorded in a prospective approach the reliability and the complication rate of the procedure. In addition, we evaluated the results of an algorithm for SPECT/CT-data assessment of these patients.
Results
SLNB was carried out in 44 groins of 25 patients. In three patients, inguinal lymph node metastases were detected via SLNB. In one patient, bilateral lymph node recurrence of the groins occurred after negative SLNB. There was a false-negative rate of 4 % in relation to the number of patients (1/25), resp. 4.5 % in relation to the number of groins (2/44). Morbidity was 4 % in relation to the number of patients (1/25), resp. 2.3 % in relation to the number of groins (1/44). The results of computer-assisted assessment of SPECT/CT data for sentinel lymph node (SLN)-diagnostics demonstrated high sensitivity of 88.8 % and specificity of 86.7 %.
Conclusions
SLNB is a very reliable method, associated with low morbidity. Computer-assisted assessment of SPECT/CT data of the SLN-diagnostics shows high sensitivity and specificity. While it cannot replace the assessment by medical experts, it can still provide substantial supplement and assistance.
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Promising novel therapeutic approaches in the management of gastrointestinal stromal tumors
Future Oncology Ahead of Print.
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Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications
Future Oncology Ahead of Print.
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Approach May Allow for Stem Cell Transplant without Radiation, Chemotherapy
In a proof-of-concept study in mice, researchers from the Stanford University School of Medicine successfully performed hematopoietic (blood) stem cell (HSC) transplants (also called bone marrow transplants) without first using radiation or chemotherapy.
Instead of these toxic conditioning regimens, which are normally used to clear existing stem cells in the bone marrow before transplantation, the researchers used two biological agents that selectively eliminated HSCs in the host mice but left other tissues and organs undamaged.
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Assessing Local Progression After Stereotactic Body Radiation Therapy For Unresectable Pancreatic Adenocarcinoma: CT versus PET
Publication date: Available online 7 September 2016
Source:Practical Radiation Oncology
Author(s): Diego A.S. Toesca, Erqi L. Pollom, Peter D. Poullos, Lesley Flynt, Yi Cui, Andrew Quon, Rie von Eyben, Albert C. Koong, Daniel T. Chang
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Attitudes of Radiation Oncologists Toward Palliative and Supportive Care in the United States: Report on National Membership Survey by the American Society for Radiation Oncology (ASTRO)
Publication date: Available online 7 September 2016
Source:Practical Radiation Oncology
Author(s): Randy L. Wei, Malcolm D. Mattes, James Yu, Adrienne Thrasher, Hui-kuo Shu, Harald Paganetti, Jennifer De Los Santos, Bridget Koontz, Christopher Abraham, Tracy Balboni
Background/PurposeRadiation oncologists are frequently involved in providing palliative and supportive care (PSC) for patients with advanced cancers through delivery of palliative radiation. Whether they are confident in their ability to assess and initiate treatments for pain, non-pain, and psychosocial distress is unknown. The American Society for Radiation Oncology (ASTRO) surveyed its practicing members in the United States on self-assessment of their primary PSC skills, and access to continuing medical education on PSC.MethodsWe electronically surveyed 4093 practicing radiation oncologists in the United States. The survey consisted of 16-questions in five sections: (1) demographics (2) PSC training (3) domains of PSC (4) perceived barriers as a radiation oncologist to initiate advanced care planning, and (5) discussion on prognosis.ResultsThe survey was emailed to 4093 ASTRO members and 649 responses were received (response rate 16%). The majority (91%) of radiation oncologists surveyed believe PSC is an important competency for radiation oncologists. Most radiation oncologists reported that they are moderately confident in their ability to assess and manage pain and GI symptoms but less confident in their ability to manage anorexia, anxiety, and depression. Despite areas of decreased confidence, a large number (42%) of radiation oncologists do not receive any additional PSC education beyond their residency training. Lastly, a perceived fear of upsetting referring medical oncologists and lack of clinic time are concerns for radiation oncologists who may want to initiate goals of care/advance care planning discussions with patients and their families.ConclusionRadiation oncologists are more confident in their ability to assess and manage pain than in their ability to manage depression, anxiety, anorexia, and fatigue. There is a need for increasing continuing medical educational efforts in PSC for practicing radiation oncologists, and strengthening PSC training in residency programs.
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In vivo dosimetry with optically-stimulated luminescent dosimeters for conformal and intensity-modulated radiation therapy: A two year multi-center cohort study
Publication date: Available online 7 September 2016
Source:Practical Radiation Oncology
Author(s): Adam C. Riegel, Yu Chen, Ajay Kapur, Laura Apicello, Abraham Kuruvilla, Anthony J. Rea, Abolghassem Jamshidi, Louis Potters
PurposeOptically-stimulated luminescent dosimeters (OSLDs) are utilized for in vivo dosimetry (IVD) of modern radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Dosimetric precision achieved with conventional techniques may not be attainable. In this work, we measured accuracy and precision for a large sample of clinical OSLD-based IVD measurements.Methods and MaterialsWeekly IVD measurements were collected from 4 linear accelerators for 2years and were expressed as percent differences from planned doses. After outlier analysis, 10,224 measurements were grouped thusly: Overall, modality (photons, electrons), treatment technique (3D conformal, field-in-field [FIF] intensity modulation, inverse-planned IMRT, VMAT), placement location (gantry angle, cardinality, and central axis positioning), and anatomical site (prostate, breast, head-and-neck, pelvis, lung, rectum and anus, brain, abdominal, esophagus, and bladder). Distributions were modeled using a Gaussian function. Fitting was performed with least squares and goodness-of-fit was assessed with the coefficient of determination. Model means (μ) and standard deviations (σ) were calculated. Sample means and variances were compared for statistical significance using ANOVA and Levene's tests (α=0.05).ResultsOverall, μ±σ was 0.3±10.3%. Precision for electron measurements (6.9%) was significantly better than photons (10.5%). Precision varied significantly among treatment techniques (p<0.0001) with FIF lowest (σ=7.2%) and IMRT and VMAT highest (σ=11.9% and 13.4%). Treatment site models with goodness-of-fit greater than 0.90 (6 of 10) yielded accuracy within ±3% except for head-and-neck (μ=−3.7%). Precision varied with treatment site (7.3–13.0%) with breast and head-and-neck yielding the best and worst precision respectively. Placement on the central axis of cardinal gantry angles yielded more precise results (σ=8.5%) compared to other locations (10.5–11.4%).ConclusionsAccuracy of ±3% was achievable. Precision ranged from 6.9% to 13.4% depending on modality, technique, and treatment site. Simple, standardized locations may improve IVD precision. These findings may aid development of patient-specific tolerances for OSLD-based IVD.
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Impact of Treatment Year on Survival and Adverse Effects in Cervical Cancer Patients with Para-Aortic Lymph Node Metastases Treated with Definitive Extended-Field Radiation Therapy
Publication date: Available online 7 September 2016
Source:Practical Radiation Oncology
Author(s): Eleanor M. Osborne, Ann H. Klopp, Anuja Jhingran, Larissa A. Meyer, Patricia J. Eifel
PurposeTreatment for locoregionally advanced cervical cancer has changed dramatically since 2000. In that year, delivery of radiation therapy (RT) with concurrent chemotherapy became standard, and in the early 2000s, use of intensity-modulated RT (IMRT) and positron emission tomography (PET) became more prevalent. We sought to determine the impact of these changes on disease-specific survival (DSS) and treatment-related adverse effects in cervical cancer patients with para-aortic lymph node (PAN) metastases treated with definitive extended-field RT.Methods and MaterialsWe reviewed the medical records of 103 cervical cancer patients with PAN metastases treated with curative intent at our institution during 2000–2013. DSS, disease control in PANs, and treatment-associated adverse effects were compared between patient groups defined by treatment year.ResultsThe 5-year DSS rate was 23% (95% CI, 9%–38%) for the 34 patients treated during 2000–2004 and 47% (95% CI, 36%–59%) for the 69 patients treated during 2005–2013 (P=.005). Factors associated with improved DSS included concurrent chemoradiation (P=.001), baseline PET imaging (P=.01), and treatment of PANs with IMRT (P=.02). Only 3 patients (4%) treated during 2005–2013 versus 6 patients (18%) treated during 2000–2004 had recurrence in PANs (P=.03). Most recurrences in patients treated during 2005–2013 were at distant sites. The crude rate of grade 3 or higher late treatment-related adverse effects was 17%; of the 18 patients who developed serious adverse effects, 8 were being treated for recurrent disease at the time. Adverse effects most frequently involved the gastrointestinal and genitourinary systems.ConclusionsOutcomes for cervical cancer patients with PAN metastases have improved concurrently with advances in treatment including PET and IMRT. Future studies should focus on ways to improve systemic treatments and reduce late adverse effects without compromising local control.
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Immediate referral to colposcopy vs. cytological surveillance for low-grade cervical cytological abnormalities in the absence of HPV test: A systematic review and a meta-analysis of the literature
Abstract
We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intra-epithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis:32% vs.21%, RR:1.49, 95%CI=1.17-1.90); CIN1:21% vs.8%, RR:2.58, 95%CI=1.69-3.94). Although immediate colposcopy detected CIN2, CIN2+ and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+:10.3 vs.11.9%, RR:1.02, 95%CI=0.53-1.97), with significant inters-study heterogeneity (p<0.001,I2=93%). Default risk was significantly higher for repeat cytology (6months: 6.3 vs.13.3%, RR:3.85, 95%CI=1.27-11.63; 12months: 6.3 vs.14.8%, RR:6.39, 95%CI=1.24-32.95; 24 months: 0.9 vs.16.1%, RR:19.1,95%CI=9.02-40.4). Detection of CIN2+ for cytological surveillance over two years is similar to that of immediate colposcopy, although patients may default. Colposcopy may be first choice when good compliance is not assured, but may increase detection of insignificant lesions. This emphasizes the need for a reflex triage test to distinguish women who need diagnostic work-up from those who can return to routine recall. This article is protected by copyright. All rights reserved.
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Chemical Exposures and Risk of Acute Myeloid Leukemia and Myelodysplastic Syndromes in a Population-Based Study
Abstract
Benzene exposure is one of the few well-established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for AML and MDS using population-based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self-report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases, and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR=1.77, 95% CI 1.19, 2.63 and OR=2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR=2.05, 95% CI 1.15, 3.63 and OR=2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions, and coal dust were associated with AML (range ORs=2.68-4.03), while no association was seen between these exposures and MDS (range ORs=0.57-1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population-based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases. This article is protected by copyright. All rights reserved.
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MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells
MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells
British Journal of Cancer 115, 741 (06 September 2016). doi:10.1038/bjc.2016.234
Authors: Karthik Subramanian Chandrasekaran, Anusha Sathyanarayanan & Devarajan Karunagaran
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The utility of urine-circulating miRNAs for detection of prostate cancer
The utility of urine-circulating miRNAs for detection of prostate cancer
British Journal of Cancer 115, 707 (06 September 2016). doi:10.1038/bjc.2016.233
Authors: Kristina Stuopelyte, Kristina Daniunaite, Arnas Bakavicius, Juozas R Lazutka, Feliksas Jankevicius & Sonata Jarmalaite
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Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating
Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating
British Journal of Cancer 115, 635 (06 September 2016). doi:10.1038/bjc.2016.256
Authors: Evdokia Michalopoulou, Vinay Bulusu & Jurre J Kamphorst
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Acute tumour response to a bispecific Ang-2-VEGF-A antibody: insights from multiparametric MRI and gene expression profiling
Acute tumour response to a bispecific Ang-2-VEGF-A antibody: insights from multiparametric MRI and gene expression profiling
British Journal of Cancer 115, 691 (06 September 2016). doi:10.1038/bjc.2016.236
Authors: Lauren CJ Baker, Jessica KR Boult, Markus Thomas, Astrid Koehler, Tapan Nayak, Jean Tessier, Chia-Huey Ooi, Fabian Birzele, Anton Belousov, Magdalena Zajac, Carsten Horn, Clare LeFave & Simon P Robinson
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Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer
Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer
British Journal of Cancer 115, 641 (06 September 2016). doi:10.1038/bjc.2016.254
Authors: Robert Fruscio, Lorenzo Ceppi, Silvia Corso, Francesca Galli, Tiziana Dell'Anna, Federica Dell'Orto, Daniela Giuliani, Annalisa Garbi, Stefania Chiari, Costantino Mangioni, Rodolfo Milani, Irene Floriani, Nicoletta Colombo & Cristina Maria Bonazzi
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HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia
HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia
British Journal of Cancer 115, 725 (06 September 2016). doi:10.1038/bjc.2016.247
Authors: Anne Ørbo, Marit Arnes, Lena Myreng Lyså, Christer Borgfelt & Bjørn Straume
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FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience
FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience
British Journal of Cancer 115, 649 (06 September 2016). doi:10.1038/bjc.2016.222
Authors: Muralidharan K Chllamma, Natalie Cook, Neesha C Dhani, Kazim Giby, Anna Dodd, Lisa Wang, David W Hedley, Malcolm J Moore & Jennifer J Knox
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Do matrix metalloproteinases represent reliable circulating biomarkers in colorectal cancer?
Do matrix metalloproteinases represent reliable circulating biomarkers in colorectal cancer?
British Journal of Cancer 115, 633 (06 September 2016). doi:10.1038/bjc.2016.241
Authors: D Ligi & F Mannello
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Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer
Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer
British Journal of Cancer 115, 655 (06 September 2016). doi:10.1038/bjc.2016.252
Authors: Patricia Martin-Romano, Jose J Sola, Juan A Diaz-Gonzalez, Ana Chopitea, Yohana Iragorri, Fernando Martínez-Regueira, Mariano Ponz-Sarvise, Leire Arbea, Jose C Subtil, David Cano, Lucia Ceniceros, Jairo Legaspi, Jose Luis Hernandez & Javier Rodríguez
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Levels of matrix metalloproteinases differ in plasma and serum – aspects regarding analysis of biological markers in cancer
Levels of matrix metalloproteinases differ in plasma and serum – aspects regarding analysis of biological markers in cancer
British Journal of Cancer 115, 703 (06 September 2016). doi:10.1038/bjc.2016.127
Authors: Andreas Jonsson, Claes Hjalmarsson, Peter Falk & Marie-Lois Ivarsson
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Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case–control study
Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case–control study
British Journal of Cancer 115, 664 (06 September 2016). doi:10.1038/bjc.2016.237
Authors: Pierre-Antoine Dugué, Maree T Brinkman, Roger L Milne, Ee Ming Wong, Liesel M FitzGerald, Julie K Bassett, Jihoon E Joo, Chol-Hee Jung, Enes Makalic, Daniel F Schmidt, Daniel J Park, Jessica Chung, Anthony D Ta, Damien M Bolton, Andrew Lonie, Anthony Longano, John L Hopper, Gianluca Severi, Richard Saffery, Dallas R English, Melissa C Southey & Graham G Giles
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L1CAM expression in endometrial carcinomas: an ENITEC collaboration study
L1CAM expression in endometrial carcinomas: an ENITEC collaboration study
British Journal of Cancer 115, 716 (06 September 2016). doi:10.1038/bjc.2016.235
Authors: Louis JM van der Putten, Nicole CM Visser, Koen van de Vijver, Maria Santacana, Peter Bronsert, Johan Bulten, Marc Hirschfeld, Eva Colas, Antonio Gil-Moreno, Angel Garcia, Gemma Mancebo, Fransesc Alameda, Jone Trovik, Reidun K Kopperud, Jutta Huvila, Stefanie Schrauwen, Martin Koskas, Francine Walker, Vit Weinberger, Lubos Minar, Eva Jandakova, Marc PLM Snijders, Saskia van den Berg-van Erp, Xavier Matias-Guiu, Helga B Salvesen, Frederic Amant, Leon FAG Massuger & Johanna MA Pijnenborg
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Loss of SLCO1B3 drives taxane resistance in prostate cancer
Loss of SLCO1B3 drives taxane resistance in prostate cancer
British Journal of Cancer 115, 674 (06 September 2016). doi:10.1038/bjc.2016.251
Authors: Ellen S de Morrée, René Böttcher, Robert J van Soest, Ashraf Aghai, Corrina M de Ridder, Alice A Gibson, Ron HJ Mathijssen, Herman Burger, Erik AC Wiemer, Alex Sparreboom, Ronald de Wit & Wytske M van Weerden
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miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells
miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells
British Journal of Cancer 115, 731 (06 September 2016). doi:10.1038/bjc.2016.244
Authors: Zhen Yang, Xiang-ling Wang, Ru Bai, Wei-ying Liu, Xin Li, Min Liu & Hua Tang
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Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer
Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer
British Journal of Cancer 115, 682 (06 September 2016). doi:10.1038/bjc.2016.238
Authors: Gary Beale, Emma J Haagensen, Huw D Thomas, Lan-Zhen Wang, Charlotte H Revill, Sara L Payne, Bernard T Golding, Ian R Hardcastle, David R Newell, Roger J Griffin & Celine Cano
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An investigation of the association of genetic susceptibility risk with somatic mutation burden in breast cancer
An investigation of the association of genetic susceptibility risk with somatic mutation burden in breast cancer
British Journal of Cancer 115, 752 (06 September 2016). doi:10.1038/bjc.2016.223
Authors: Bin Zhu, Anwesha Mukherjee, Mitchell J Machiela, Lei Song, Xing Hua, Jianxin Shi, Montserrat Garcia-Closas, Stephen J Chanock & Nilanjan Chatterjee
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Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism
Abstract
Introduction
The immune colloidal gold (ICG) method of measuring thyroid-stimulating hormone (TSH) is a rapid and easy-to-perform test, allowing off-site measurements. This study compared the clinical utility of the first ICG-based qualitative and quantitative TSH test methods in China with the third-generation serum TSH assay used worldwide.
Methods
Fingertip and venous blood was collected within 30 min from 283 patients initially suspected of hypothyroidism. TSH was measured in fingertip blood using ICG-based qualitative quantitative tests. Serum TSH in venous blood was tested using the third-generation serum TSH assay. Correlations between systems were tested by kappa or Spearman correlation coefficients.
Results
Compared with the third-generation serum TSH assay, the ICG-qualitative TSH test kit had a kappa coefficient of 0.86, a sensitivity of 85.00%, and a specificity of 99.38% in screening for hypothyroidism. The percentages of false negatives and false positives among all subjects were 6.38% and 0.35% respectively; the total consistency rate of the two methods was 93.26%. When compared with the third-generation serum TSH assay, the ICG-quantitative TSH analysis system had a Spearman correlation coefficient of 0.91, a sensitivity of 88.43%, and a specificity of 98.77%. The percentages of false negatives and false positives among all subjects were 4.95% and 0.71%, respectively; the total consistency rate of the two methods was 94.35%.
Conclusion
Both ICG-based assays are easier and faster to perform than the third-generation, laboratory-based serum TSH assay method. The ICG-based methods showed acceptable performance in the simplified screening for hypothyroidism.
Trial registration
ClinicalTrials.gov identifier, NCT01921452.
Funding
Merck Serono Co., Ltd.
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Tunicamycin enhances human colon cancer cells to TRAIL-induced apoptosis by JNK-CHOP-mediated DR5 upregulation and the inhibition of the EGFR pathway.
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Chlorogenic acid induces reactive oxygen species generation and inhibits the viability of human colon cancer cells.
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Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth
Increased exposure to multitargeted kinase inhibitor sunitinib is associated with improved outcome, emphasizing the importance of maintaining adequate dosing and drug levels. The currently approved schedule (5...
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Prospective assessment of the quality of life before, during and after image guided intensity modulated radiotherapy for prostate cancer
Radiotherapy (RT) in combination with androgen deprivation therapy (ADT) for prostate cancer (PCa) carries a risk of gastrointestinal (GI) and genitourinary toxicity, which might affect the quality of life (Qo...
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IMRT delivers lower radiation doses to dental structures than 3DRT in head and neck cancer patients
Radiotherapy (RT) is frequently used in the treatment of head and neck cancer, but different side-effects are frequently reported, including a higher frequency of radiation-related caries, what may be conseque...
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