Τρίτη 23 Ιανουαρίου 2018
Transfusion practices in traumatic brain injury
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Staff and family response to end-of-life care in the ICU
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Pediatric trauma transfusion and cognitive aids
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Spirituality at the end of life
http://ift.tt/2DCjSpP
American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway
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Age Does Not Affect Metoprolol’s Effect on Perioperative Outcomes (From the POISE Database)
http://ift.tt/2n7uUc3
The Effects of Agrin Isoforms on Diabetic Neuropathic Pain in a Rat Streptozotocin Model
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Electroencephalography and Brain Oxygenation Monitoring in the Perioperative Period
http://ift.tt/2BpodGR
Comparison of Intranasal Dexmedetomidine and Oral Pentobarbital Sedation for Transthoracic Echocardiography in Infants and Toddlers: A Prospective, Randomized, Double-Blind Trial
http://ift.tt/2Bqgjg7
NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy
Abstract
Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial–mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P=0.0167) and disease-free survival (P=0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P=0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy. This article is protected by copyright. All rights reserved.
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NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy
Abstract
Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial–mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P=0.0167) and disease-free survival (P=0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P=0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy. This article is protected by copyright. All rights reserved.
http://ift.tt/2DB1oGb
Celiac disease associated with aplastic anemia in a 6-year-old girl: a case report and review of the literature
Celiac disease may present with hematological abnormalities including long-standing anemia. Both aplastic anemia and celiac disease have a similar underlying autoimmune process but an association between the t...
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A review discussing fluciclovine (18F) PET/CT imaging in the detection of recurrent prostate cancer
Future Oncology, Ahead of Print.
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The prognostic analysis of different metastatic patterns in extensive-stage small-cell lung cancer patients: a large population-based study
Future Oncology, Ahead of Print.
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A review discussing fluciclovine (18F) PET/CT imaging in the detection of recurrent prostate cancer
Future Oncology, Ahead of Print.
http://ift.tt/2ruKEuA
The prognostic analysis of different metastatic patterns in extensive-stage small-cell lung cancer patients: a large population-based study
Future Oncology, Ahead of Print.
http://ift.tt/2Gbd2oJ
Changes in biodistribution on 68 Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression
Abstract
Background
To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients.
Methods
Twenty-one patients who underwent GaTate PET/CT before and after commencement of SSA therapy were reviewed. Maximum standardized uptake values (SUVmax) were measured in normal organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable disease were also compared. Serum chromogranin-A (CgA) levels were available for correlation between scans in 17/21 patients.
Results
Mean thyroid, spleen and liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9 to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p = < 0.0001 for all). Pituitary SUVmax increased from 10.2 to 11.0 (p = 0.004) whereas adrenal and salivary gland SUVmax did not change. Tumour SUVmax increased in 7 of 12 patients with stable disease; CgA was stable or decreasing in 5 of these patients. 30/49 (61%) metastatic lesions had an increase in SUVmax and lesion-to-liver uptake ratio increased in 40/49 (82%) following SSA therapy.
Conclusion
Long-acting SSA therapy decreases GaTate uptake in the thyroid, spleen and liver but in most cases increases intensity of uptake within metastases. This has significant implications for interpretation of GaTate PET/CT following commencement of therapy as increased intensity alone may not represent true progression. Our findings also suggest pre-dosing with SSA prior to PRRT may enable higher doses to be delivered to tumour whilst decreasing dose to normal tissues.
http://ift.tt/2n5unHH
Changes in biodistribution on 68 Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression
Abstract
Background
To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients.
Methods
Twenty-one patients who underwent GaTate PET/CT before and after commencement of SSA therapy were reviewed. Maximum standardized uptake values (SUVmax) were measured in normal organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable disease were also compared. Serum chromogranin-A (CgA) levels were available for correlation between scans in 17/21 patients.
Results
Mean thyroid, spleen and liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9 to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p = < 0.0001 for all). Pituitary SUVmax increased from 10.2 to 11.0 (p = 0.004) whereas adrenal and salivary gland SUVmax did not change. Tumour SUVmax increased in 7 of 12 patients with stable disease; CgA was stable or decreasing in 5 of these patients. 30/49 (61%) metastatic lesions had an increase in SUVmax and lesion-to-liver uptake ratio increased in 40/49 (82%) following SSA therapy.
Conclusion
Long-acting SSA therapy decreases GaTate uptake in the thyroid, spleen and liver but in most cases increases intensity of uptake within metastases. This has significant implications for interpretation of GaTate PET/CT following commencement of therapy as increased intensity alone may not represent true progression. Our findings also suggest pre-dosing with SSA prior to PRRT may enable higher doses to be delivered to tumour whilst decreasing dose to normal tissues.
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Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report
Abstract
Background
Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab.
Case presentation
A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor.
Conclusion
This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.
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Shifting breast cancer surveillance from current hospital setting to a community based setting: a cost-effectiveness study
Abstract
Background
This study explores the effectiveness and cost-effectiveness of surveillance after breast cancer treatment provided in a hospital-setting versus surveillance embedded in the community-based National Breast Cancer Screening Program (NBCSP).
Methods
Using a decision tree, strategies were compared on effectiveness and costs from a healthcare perspective over a 5-year time horizon. Women aged 50–75 without distant metastases that underwent breast conserving surgery in 2003–2006 were selected from the Netherlands Cancer Registry (n = 14,093). Key input parameters were mammography sensitivity and specificity, risk of loco regional recurrence (LRR), and direct healthcare costs. Primary outcome measure was the proportion true test results (TTR), expressed as the positive and negative predictive value (PPV, NPV). The incremental cost-effectiveness ratio (ICER) is defined as incremental costs per TTR forgone.
Results
For the NBCSP-strategy, 13,534 TTR (8 positive; 13,526 negative), and 12,923 TTR (387 positive; 12,536 negative) were found for low and high risks respectively. For the hospital-based strategy, 26,663 TTR (13 positive; 26,650 negative) and 24,883 TTR (440 positive; 24,443 negative) were found for low and high risks respectively. For low risks, the PPV and NPV for the NBCSP-based strategy were 3.31% and 99.88%, and 2.74% and 99.95% for the hospital strategy respectively. For high risks, the PPV and NPV for the NBCSP-based strategy were 64.10% and 98.87%, and 50.98% and 99.71% for the hospital-based strategy respectively. Total expected costs of the NBCSP-based strategy were lower than for the hospital-based strategy (low risk: €1,271,666 NBCSP vs €2,698,302 hospital; high risk: €6,939,813 NBCSP vs €7,450,150 hospital), rendering ICERs that indicate cost savings of €109 (95%CI €95–€127) (low risk) and €43 (95%CI €39–€56) (high risk) per TTR forgone.
Conclusion
Despite expected cost-savings of over 50% in the NBCSP-based strategy, it is nearly 50% lower accurate than the hospital-based strategy, compromising the goal of early detection of LRR to an extent that is unlikely to be acceptable.
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Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report
Abstract
Background
Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab.
Case presentation
A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor.
Conclusion
This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.
http://ift.tt/2G9H4cp
Shifting breast cancer surveillance from current hospital setting to a community based setting: a cost-effectiveness study
Abstract
Background
This study explores the effectiveness and cost-effectiveness of surveillance after breast cancer treatment provided in a hospital-setting versus surveillance embedded in the community-based National Breast Cancer Screening Program (NBCSP).
Methods
Using a decision tree, strategies were compared on effectiveness and costs from a healthcare perspective over a 5-year time horizon. Women aged 50–75 without distant metastases that underwent breast conserving surgery in 2003–2006 were selected from the Netherlands Cancer Registry (n = 14,093). Key input parameters were mammography sensitivity and specificity, risk of loco regional recurrence (LRR), and direct healthcare costs. Primary outcome measure was the proportion true test results (TTR), expressed as the positive and negative predictive value (PPV, NPV). The incremental cost-effectiveness ratio (ICER) is defined as incremental costs per TTR forgone.
Results
For the NBCSP-strategy, 13,534 TTR (8 positive; 13,526 negative), and 12,923 TTR (387 positive; 12,536 negative) were found for low and high risks respectively. For the hospital-based strategy, 26,663 TTR (13 positive; 26,650 negative) and 24,883 TTR (440 positive; 24,443 negative) were found for low and high risks respectively. For low risks, the PPV and NPV for the NBCSP-based strategy were 3.31% and 99.88%, and 2.74% and 99.95% for the hospital strategy respectively. For high risks, the PPV and NPV for the NBCSP-based strategy were 64.10% and 98.87%, and 50.98% and 99.71% for the hospital-based strategy respectively. Total expected costs of the NBCSP-based strategy were lower than for the hospital-based strategy (low risk: €1,271,666 NBCSP vs €2,698,302 hospital; high risk: €6,939,813 NBCSP vs €7,450,150 hospital), rendering ICERs that indicate cost savings of €109 (95%CI €95–€127) (low risk) and €43 (95%CI €39–€56) (high risk) per TTR forgone.
Conclusion
Despite expected cost-savings of over 50% in the NBCSP-based strategy, it is nearly 50% lower accurate than the hospital-based strategy, compromising the goal of early detection of LRR to an extent that is unlikely to be acceptable.
http://ift.tt/2rEe35F
Fc-mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models
A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric and murine monoclonal antibodies against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development.
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Keratin 19 expression in hepatocellular carcinoma is regulated by fibroblast-derived HGF via a MET-ERK1/2-AP1 and SP1 axis
Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC), however regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of fibrous tumor stroma in KRT19-positive HCC, suggesting that crosstalk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an in vitro model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK-ERK1/2 pathway which upregulated KRT19 expression in HCC cells. Further, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (n=339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.
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Myeloma Cells are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex which Senses Lipopolysaccharide
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a non-canonical LPS receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other TLR ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180. Administration of LPS significantly increased the number of CD180/CD138 double-positive cells in a murine xenograft model when MM cells were inoculated with direct attachment to BMSC. Knockdown of CD180 canceled the LPS response in vitro and in vivo. Promoter analyses identified IKZF1 (Ikaros) as a pivotal transcriptional activator of the CD180 gene. Both cell adhesion and hypoxia activated transcription of the CD180 gene by increasing Ikaros expression and its binding to the promoter region. Pharmacological targeting of Ikaros by the immunomodulatry drug lenalidomide ameliorated the response of MM cells to LPS in a CD180-dependent manner in vitro and in vivo. Thus, the CD180/MD-1 pathway may represent a novel mechanism of growth regulation of MM cells in a BM milieu and may be a therapeutic target of preventing the regrowth of dormant MM cells.
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Downregulation of membrane trafficking proteins and lactate conditioning determine loss of dendritic cell function in lung cancer
Restoring antigen presentation for efficient and durable activation of tumor-specific CD8+ T cell responses is pivotal to immunotherapy, yet the mechanisms that cause subversion of dendritic cells (DC) functions are not entirely understood, limiting the development of targeted approaches. In this study, we show that bone fide DC resident in lung tumor tissues or DC exposed to factors derived from whole lung tumors become refractory to endosomal and cytosolic sensor stimulation and fail to secrete IL-12 and IFN-I. Tumor conditioned DC exhibited downregulation of the SNARE VAMP3, a regulator of endosomes trafficking we found to be required for cross-presentation of tumor antigens and DC-mediated tumor rejection. Dissection of cell-extrinsic suppressive pathways identified lactic acid in the tumor microenvironment as sufficient to inhibit type-I interferon downstream of TLR3 and STING. DC conditioning by lactate also impacted adaptive function, accelerating antigen degradation and impairing cross-presentation. Importantly, DC conditioned by lactate failed to prime anti-tumor responses in vivo. These findings provide a new mechanistic viewpoint to the concept of DC suppression and hold potential for future therapeutic approaches.
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Tumor-stroma IL-1{beta}-IRAK4 feedforward circuitry drives tumor fibrosis, chemoresistance, and poor prognosis in pancreatic cancer
Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) holds promise to augment the effect of chemotherapy, but success in the clinic has thus far been limited. Preclinical mouse models suggest that near-depletion of cancer-associated fibroblasts (CAF) carries a risk of accelerating PDAC progression, underscoring the need to concurrently target key signaling mechanisms that drive the malignant attributes of both CAF and PDAC cells. We previously reported that inhibition of interleukin-1 receptor associated kinase 4 (IRAK4) suppresses NF-κB activity and promotes response to chemotherapy in PDAC cells. In this study, we report that CAF in PDAC tumors robustly express activated IRAK4 and NF-κB. IRAK4 expression in CAF promoted NF-κB activity, drove tumor fibrosis, and supported PDAC cell proliferation, survival, and chemoresistance. Cytokine array analysis of CAF and microarray analysis of PDAC cells identified IL-1β as a key cytokine that activated IRAK4 in CAF. Targeting IRAK4 or IL-1β rendered PDAC tumors less fibrotic and more sensitive to gemcitabine. In clinical specimens of human PDAC, high stromal IL-1β expression associated strongly with poor overall survival. Together, our studies establish a tumor-stroma IL-1β-IRAK4 feedforward signal that can be therapeutically disrupted to increase chemotherapeutic efficacy in PDAC.
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Anti-estrogen therapy increases plasticity and cancer stemness of prolactin-induced ER{alpha}+ mammary carcinomas
Although anti-estrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25-40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSCs), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors. Like a subset of ERα+ patient cancers, the prolactin-induced adenocarcinomas contained two major tumor subpopulations that expressed markers of normal luminal and basal epithelial cells. CSC activity was distributed equally across these two tumor subpopulations. Treatment with the selective estrogen receptor downregulator (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive responses in CSC activity, increased markers of plasticity including target gene reporters of Wnt/Notch signaling and epithelial-mesenchymal transition, and increased double positive (K8/K5) cells. In primary tumorsphere cultures, ICI stimulated CSC self-renewal, and was able to overcome the dependence of self-renewal upon Wnt or Notch signaling individually, but not together. Our findings demonstrate that treatment of aggressive mixed lineage ERα+ breast cancers with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and regenerative CSC activity, predicting likely negative impacts on patient tumors with these characteristics.
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Fc-mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models
A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric and murine monoclonal antibodies against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development.
http://ift.tt/2E2uYRN
Keratin 19 expression in hepatocellular carcinoma is regulated by fibroblast-derived HGF via a MET-ERK1/2-AP1 and SP1 axis
Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC), however regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of fibrous tumor stroma in KRT19-positive HCC, suggesting that crosstalk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an in vitro model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK-ERK1/2 pathway which upregulated KRT19 expression in HCC cells. Further, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (n=339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.
http://ift.tt/2DwgBE2
Myeloma Cells are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex which Senses Lipopolysaccharide
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a non-canonical LPS receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other TLR ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180. Administration of LPS significantly increased the number of CD180/CD138 double-positive cells in a murine xenograft model when MM cells were inoculated with direct attachment to BMSC. Knockdown of CD180 canceled the LPS response in vitro and in vivo. Promoter analyses identified IKZF1 (Ikaros) as a pivotal transcriptional activator of the CD180 gene. Both cell adhesion and hypoxia activated transcription of the CD180 gene by increasing Ikaros expression and its binding to the promoter region. Pharmacological targeting of Ikaros by the immunomodulatry drug lenalidomide ameliorated the response of MM cells to LPS in a CD180-dependent manner in vitro and in vivo. Thus, the CD180/MD-1 pathway may represent a novel mechanism of growth regulation of MM cells in a BM milieu and may be a therapeutic target of preventing the regrowth of dormant MM cells.
http://ift.tt/2E2jaPk
Downregulation of membrane trafficking proteins and lactate conditioning determine loss of dendritic cell function in lung cancer
Restoring antigen presentation for efficient and durable activation of tumor-specific CD8+ T cell responses is pivotal to immunotherapy, yet the mechanisms that cause subversion of dendritic cells (DC) functions are not entirely understood, limiting the development of targeted approaches. In this study, we show that bone fide DC resident in lung tumor tissues or DC exposed to factors derived from whole lung tumors become refractory to endosomal and cytosolic sensor stimulation and fail to secrete IL-12 and IFN-I. Tumor conditioned DC exhibited downregulation of the SNARE VAMP3, a regulator of endosomes trafficking we found to be required for cross-presentation of tumor antigens and DC-mediated tumor rejection. Dissection of cell-extrinsic suppressive pathways identified lactic acid in the tumor microenvironment as sufficient to inhibit type-I interferon downstream of TLR3 and STING. DC conditioning by lactate also impacted adaptive function, accelerating antigen degradation and impairing cross-presentation. Importantly, DC conditioned by lactate failed to prime anti-tumor responses in vivo. These findings provide a new mechanistic viewpoint to the concept of DC suppression and hold potential for future therapeutic approaches.
http://ift.tt/2Dty3Jn
Tumor-stroma IL-1{beta}-IRAK4 feedforward circuitry drives tumor fibrosis, chemoresistance, and poor prognosis in pancreatic cancer
Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) holds promise to augment the effect of chemotherapy, but success in the clinic has thus far been limited. Preclinical mouse models suggest that near-depletion of cancer-associated fibroblasts (CAF) carries a risk of accelerating PDAC progression, underscoring the need to concurrently target key signaling mechanisms that drive the malignant attributes of both CAF and PDAC cells. We previously reported that inhibition of interleukin-1 receptor associated kinase 4 (IRAK4) suppresses NF-κB activity and promotes response to chemotherapy in PDAC cells. In this study, we report that CAF in PDAC tumors robustly express activated IRAK4 and NF-κB. IRAK4 expression in CAF promoted NF-κB activity, drove tumor fibrosis, and supported PDAC cell proliferation, survival, and chemoresistance. Cytokine array analysis of CAF and microarray analysis of PDAC cells identified IL-1β as a key cytokine that activated IRAK4 in CAF. Targeting IRAK4 or IL-1β rendered PDAC tumors less fibrotic and more sensitive to gemcitabine. In clinical specimens of human PDAC, high stromal IL-1β expression associated strongly with poor overall survival. Together, our studies establish a tumor-stroma IL-1β-IRAK4 feedforward signal that can be therapeutically disrupted to increase chemotherapeutic efficacy in PDAC.
http://ift.tt/2E2uYkL
Anti-estrogen therapy increases plasticity and cancer stemness of prolactin-induced ER{alpha}+ mammary carcinomas
Although anti-estrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25-40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSCs), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors. Like a subset of ERα+ patient cancers, the prolactin-induced adenocarcinomas contained two major tumor subpopulations that expressed markers of normal luminal and basal epithelial cells. CSC activity was distributed equally across these two tumor subpopulations. Treatment with the selective estrogen receptor downregulator (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive responses in CSC activity, increased markers of plasticity including target gene reporters of Wnt/Notch signaling and epithelial-mesenchymal transition, and increased double positive (K8/K5) cells. In primary tumorsphere cultures, ICI stimulated CSC self-renewal, and was able to overcome the dependence of self-renewal upon Wnt or Notch signaling individually, but not together. Our findings demonstrate that treatment of aggressive mixed lineage ERα+ breast cancers with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and regenerative CSC activity, predicting likely negative impacts on patient tumors with these characteristics.
http://ift.tt/2DyaEGE
Opium Consumption and the Incidence of Cancer: Does Opium Account as an Emerging Risk Factor for Gastrointestinal Cancer?
Abstract
Purpose
Some epidemiological studies have shown an association between opium consumption and the incidence of gastrointestinal (GI) cancer. The present study was designed to investigate the effects of opium on the initiation of GI cancer in rats.
Methods
Forty-five rats were randomly divided into three groups; each received different treatment for 40 weeks. The rats in group 1 received purified water, while animals in group 2 were treated with 5 mg/kg diethylnitrosamine (DEN) orally for 8 weeks and continued with purified water by the end of the experiment. The third experimental group received 300 mg/kg opium for 16 weeks and then continued with 50 mg/kg phenobarbital by the end of the 40th week. The growth of tumors in the treated groups was assessed by histological changes and the up/down expression of p53, cdkn1, cdk2, e-cdh, and n-cdh genes in different parts of GI tract.
Results
Histological examinations revealed that DEN was able to induce the growth of tumor in GI tract as shown by active mitotic figure in different regions of GI system and hyperplasia of hepatocytes associated with infiltration of inflammatory cells, intestinal villous hypertrophy, and colorectal adenoma. There was also significant (p < 0.05) overexpression of p53, cdk2, and n-Cdh genes in different parts of digestive system in DEN-treated group. However, these pathological changes and the degradation of gene expression were not observed in the opium-treated group.
Conclusion
The results of this study suggest that the opium does not promote the initiation of cancer in GI tract.
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Opium Consumption and the Incidence of Cancer: Does Opium Account as an Emerging Risk Factor for Gastrointestinal Cancer?
Abstract
Purpose
Some epidemiological studies have shown an association between opium consumption and the incidence of gastrointestinal (GI) cancer. The present study was designed to investigate the effects of opium on the initiation of GI cancer in rats.
Methods
Forty-five rats were randomly divided into three groups; each received different treatment for 40 weeks. The rats in group 1 received purified water, while animals in group 2 were treated with 5 mg/kg diethylnitrosamine (DEN) orally for 8 weeks and continued with purified water by the end of the experiment. The third experimental group received 300 mg/kg opium for 16 weeks and then continued with 50 mg/kg phenobarbital by the end of the 40th week. The growth of tumors in the treated groups was assessed by histological changes and the up/down expression of p53, cdkn1, cdk2, e-cdh, and n-cdh genes in different parts of GI tract.
Results
Histological examinations revealed that DEN was able to induce the growth of tumor in GI tract as shown by active mitotic figure in different regions of GI system and hyperplasia of hepatocytes associated with infiltration of inflammatory cells, intestinal villous hypertrophy, and colorectal adenoma. There was also significant (p < 0.05) overexpression of p53, cdk2, and n-Cdh genes in different parts of digestive system in DEN-treated group. However, these pathological changes and the degradation of gene expression were not observed in the opium-treated group.
Conclusion
The results of this study suggest that the opium does not promote the initiation of cancer in GI tract.
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Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced cancers of the gastrointestinal tract or anus
Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal (GI) and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative. Experimental Design: Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with GI carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples. Results: Evidence of ctDNA was detected in 344/417 (82%) samples, and of these ≥1 one reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented. Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with GI carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and, with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced GI cancers as a complementary approach to tissue testing, and further investigation is warranted.
http://ift.tt/2DAFlzp
Nitric Oxide Production by Myeloid Derived Suppressor Cells Plays a Role in Impairing Fc Receptor-Mediated Natural Killer Cell Function.
Purpose: Monoclonal antibodies (mAb) are used to treat solid and hematological malignancies, and work in part through Fc receptors (FcR) on natural killer cells (NK). However, FcR mediated functions of NK cells from cancer patients are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy. Experimental Design: Co-cultures of autologous NK cells and MDSC from cancer patients were used to study the effect of MDSC on NK cell FcR mediated functions including antibody dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro. Mouse breast cancer models were utilized to study the effect of MDSC on antibody therapy in vivo and test the efficacy of combination therapies including a mAb and a MDSC targeting agent. Results: Cancer patient MDSC were found to significantly inhibit NK cell FcR mediated functions including ADCC, cytokine production, and signal transduction in a contact independent manner. In addition, adoptive transfer of MDSC abolished the efficacy of mAb therapy in a mouse model of pancreatic cancer. Inhibition of iNOS restored NK cell functions and signal transduction. Finally, non-specific elimination of MDSC or inhibition of iNOS in vivo significantly improved the efficacy of mAb therapy in a mouse model of breast cancer. Conclusions: MDSC antagonize NK cell FcR mediated function and signal transduction leading to impaired response to mAb therapy in part through nitric oxide production. Thus, elimination of MDSC or inhibition of nitric oxide production offers a strategy to improve mAb therapy.
http://ift.tt/2n7oclt
Acquired resistance of ER- positive breast cancer to endocrine treatment confers an adaptive sensitivity to TRAIL through post-translational downregulation of c-FLIP
Purpose: One-third of ER-positive breast cancer patients who initially respond to endocrine therapy become resistant to treatment. Such treatment failure is associated with poor prognosis and remains an area of unmet clinical need. Here we identify a specific post-translational modification that occurs during endocrine resistance and which results in tumour susceptibility to the apoptosis inducer TNF-Related Apoptosis-Inducing Ligand (TRAIL). This potentially offers a novel stratified approach to targeting endocrine resistant breast cancer. Experimental Design: Cell line and primary-derived xenograft models of endocrine resistance were investigated for susceptibility to TRAIL. Tumour viability, cancer stem cell (CSC) viability (tumourspheres), tumour growth kinetics and metastatic burden were assessed. Western blots for the TRAIL-pathway inhibitor, c-FLIP, and upstream regulators were performed. Results were confirmed in primary culture of 26 endocrine-resistant and endocrine-naïve breast tumours. Results: Breast cancer cell lines with acquired resistance to tamoxifen-(TAMR) or faslodex were more sensitive to TRAIL than their endocrine-sensitive controls. Moreover, TRAIL eliminated CSC-like activity in TAMR cells, resulting in prolonged remission of xenografts in vivo. In primary culture, TRAIL significantly depleted CSCs in 85% endocrine-resistant, compared with 8% endocrine-naïve tumours, while systemic administration of TRAIL in endocrine-resistant patient-derived xenografts reduced tumour growth, CSC-like activity and metastases. Acquired TRAIL sensitivity correlated with a reduction in intra-cellular levels of c-FLIP, and an increase in Jnk-mediated phosphorylation of E3-ligase, ITCH, which degrades c-FLIP. Conclusions:These results identify a novel mechanism of acquired vulnerability to an extrinsic cell death stimulus, in endocrine resistant breast cancers, which has both therapeutic and prognostic potential.
http://ift.tt/2DyMnoi
Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced cancers of the gastrointestinal tract or anus
Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal (GI) and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative. Experimental Design: Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with GI carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples. Results: Evidence of ctDNA was detected in 344/417 (82%) samples, and of these ≥1 one reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented. Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with GI carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and, with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced GI cancers as a complementary approach to tissue testing, and further investigation is warranted.
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Nitric Oxide Production by Myeloid Derived Suppressor Cells Plays a Role in Impairing Fc Receptor-Mediated Natural Killer Cell Function.
Purpose: Monoclonal antibodies (mAb) are used to treat solid and hematological malignancies, and work in part through Fc receptors (FcR) on natural killer cells (NK). However, FcR mediated functions of NK cells from cancer patients are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy. Experimental Design: Co-cultures of autologous NK cells and MDSC from cancer patients were used to study the effect of MDSC on NK cell FcR mediated functions including antibody dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro. Mouse breast cancer models were utilized to study the effect of MDSC on antibody therapy in vivo and test the efficacy of combination therapies including a mAb and a MDSC targeting agent. Results: Cancer patient MDSC were found to significantly inhibit NK cell FcR mediated functions including ADCC, cytokine production, and signal transduction in a contact independent manner. In addition, adoptive transfer of MDSC abolished the efficacy of mAb therapy in a mouse model of pancreatic cancer. Inhibition of iNOS restored NK cell functions and signal transduction. Finally, non-specific elimination of MDSC or inhibition of iNOS in vivo significantly improved the efficacy of mAb therapy in a mouse model of breast cancer. Conclusions: MDSC antagonize NK cell FcR mediated function and signal transduction leading to impaired response to mAb therapy in part through nitric oxide production. Thus, elimination of MDSC or inhibition of nitric oxide production offers a strategy to improve mAb therapy.
from Cancer via ola Kala on Inoreader http://ift.tt/2n7oclt
via IFTTT
Acquired resistance of ER- positive breast cancer to endocrine treatment confers an adaptive sensitivity to TRAIL through post-translational downregulation of c-FLIP
Purpose: One-third of ER-positive breast cancer patients who initially respond to endocrine therapy become resistant to treatment. Such treatment failure is associated with poor prognosis and remains an area of unmet clinical need. Here we identify a specific post-translational modification that occurs during endocrine resistance and which results in tumour susceptibility to the apoptosis inducer TNF-Related Apoptosis-Inducing Ligand (TRAIL). This potentially offers a novel stratified approach to targeting endocrine resistant breast cancer. Experimental Design: Cell line and primary-derived xenograft models of endocrine resistance were investigated for susceptibility to TRAIL. Tumour viability, cancer stem cell (CSC) viability (tumourspheres), tumour growth kinetics and metastatic burden were assessed. Western blots for the TRAIL-pathway inhibitor, c-FLIP, and upstream regulators were performed. Results were confirmed in primary culture of 26 endocrine-resistant and endocrine-naïve breast tumours. Results: Breast cancer cell lines with acquired resistance to tamoxifen-(TAMR) or faslodex were more sensitive to TRAIL than their endocrine-sensitive controls. Moreover, TRAIL eliminated CSC-like activity in TAMR cells, resulting in prolonged remission of xenografts in vivo. In primary culture, TRAIL significantly depleted CSCs in 85% endocrine-resistant, compared with 8% endocrine-naïve tumours, while systemic administration of TRAIL in endocrine-resistant patient-derived xenografts reduced tumour growth, CSC-like activity and metastases. Acquired TRAIL sensitivity correlated with a reduction in intra-cellular levels of c-FLIP, and an increase in Jnk-mediated phosphorylation of E3-ligase, ITCH, which degrades c-FLIP. Conclusions:These results identify a novel mechanism of acquired vulnerability to an extrinsic cell death stimulus, in endocrine resistant breast cancers, which has both therapeutic and prognostic potential.
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What is it about a cancer diagnosis that would worry people? A population-based survey of adults in England
Abstract
Background
Surveys indicate quite high prevalence of cancer worry in the general population, but little is known about what it is about cancer that worries people. A better understanding of the origins of cancer worry may help elucidate previously found inconsistencies in its behavioural effect on cancer prevention, screening uptake, and help-seeking for symptoms. In this study, we explore the prevalence and population distribution of general cancer worry and worries about specific aspects of cancer previously identified.
Methods
A population-based survey of 2048 English adults (18–70 years, April–May 2016), using face-to-face interviews to assess demographic characteristics, general cancer worry and twelve sources of cancer worry (adapted from an existing scale), including the emotional, physical, and social consequences of a diagnosis.
Results
In general, a third of respondents (37%) never worried about cancer, 57% worried occasionally/sometimes, and 6% often/very often. In terms of specific worries, two thirds would be 'quite a bit' or 'extremely' worried about the threat to life and emotional upset a diagnosis would cause. Half would worry about surgery, radiotherapy, chemotherapy, and loss of control over life. Worries about the social consequences were less commonly anticipated: just under half would worry about financial problems or their social roles, and a quarter would be worried about effects on identity, important relationships, gender role, and sexuality. Women and younger people reported more frequent worry about getting cancer, and would be more worried about the emotional, physical, and social consequences of a cancer diagnosis (p < .001). Those from ethnic minority backgrounds reported less frequent worry about getting cancer than their white counterparts, but would be equally worried about the emotional and physical impact of a cancer diagnosis, and worried more about the social consequences of a cancer diagnosis (p < .05).
Conclusions
The majority of English adults worry at least occasionally about getting cancer, and would be most worried about the emotional and physical impact of a cancer diagnosis. Distinguishing between the various worries that cancer can evoke may help inform efforts to allay undue worries in those who are deterred by them from engaging with cancer prevention and early detection.
http://ift.tt/2n6REcb
What is it about a cancer diagnosis that would worry people? A population-based survey of adults in England
Abstract
Background
Surveys indicate quite high prevalence of cancer worry in the general population, but little is known about what it is about cancer that worries people. A better understanding of the origins of cancer worry may help elucidate previously found inconsistencies in its behavioural effect on cancer prevention, screening uptake, and help-seeking for symptoms. In this study, we explore the prevalence and population distribution of general cancer worry and worries about specific aspects of cancer previously identified.
Methods
A population-based survey of 2048 English adults (18–70 years, April–May 2016), using face-to-face interviews to assess demographic characteristics, general cancer worry and twelve sources of cancer worry (adapted from an existing scale), including the emotional, physical, and social consequences of a diagnosis.
Results
In general, a third of respondents (37%) never worried about cancer, 57% worried occasionally/sometimes, and 6% often/very often. In terms of specific worries, two thirds would be 'quite a bit' or 'extremely' worried about the threat to life and emotional upset a diagnosis would cause. Half would worry about surgery, radiotherapy, chemotherapy, and loss of control over life. Worries about the social consequences were less commonly anticipated: just under half would worry about financial problems or their social roles, and a quarter would be worried about effects on identity, important relationships, gender role, and sexuality. Women and younger people reported more frequent worry about getting cancer, and would be more worried about the emotional, physical, and social consequences of a cancer diagnosis (p < .001). Those from ethnic minority backgrounds reported less frequent worry about getting cancer than their white counterparts, but would be equally worried about the emotional and physical impact of a cancer diagnosis, and worried more about the social consequences of a cancer diagnosis (p < .05).
Conclusions
The majority of English adults worry at least occasionally about getting cancer, and would be most worried about the emotional and physical impact of a cancer diagnosis. Distinguishing between the various worries that cancer can evoke may help inform efforts to allay undue worries in those who are deterred by them from engaging with cancer prevention and early detection.
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Loss in working years after a breast cancer diagnosis
Loss in working years after a breast cancer diagnosis
Loss in working years after a breast cancer diagnosis, Published online: 23 January 2018; doi:10.1038/bjc.2017.456
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Back from the dead: TIL apoptosis in cancer immune evasion
Back from the dead: TIL apoptosis in cancer immune evasion
Back from the dead: TIL apoptosis in cancer immune evasion, Published online: 23 January 2018; doi:10.1038/bjc.2017.483
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Comment on ‘Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer’
Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer'
Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer', Published online: 23 January 2018; doi:10.1038/bjc.2017.416
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Development and validation of a plasma-based melanoma biomarker suitable for clinical use
Development and validation of a plasma-based melanoma biomarker suitable for clinical use
Development and validation of a plasma-based melanoma biomarker suitable for clinical use, Published online: 23 January 2018; doi:10.1038/bjc.2017.477
Development and validation of a plasma-based melanoma biomarker suitable for clinical usefrom Cancer via ola Kala on Inoreader http://ift.tt/2rtoZCO
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Reply to ‘Comment on ‘Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer”
Reply to 'Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer"
Reply to 'Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer", Published online: 23 January 2018; doi:10.1038/bjc.2017.464
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Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota
Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota
Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota, Published online: 23 January 2018; doi:10.1038/bjc.2017.435
Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiotafrom Cancer via ola Kala on Inoreader http://ift.tt/2E493tA
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Loss in working years after a breast cancer diagnosis
Loss in working years after a breast cancer diagnosis
Loss in working years after a breast cancer diagnosis, Published online: 23 January 2018; doi:10.1038/bjc.2017.456
Loss in working years after a breast cancer diagnosishttp://ift.tt/2G90XAx
Back from the dead: TIL apoptosis in cancer immune evasion
Back from the dead: TIL apoptosis in cancer immune evasion
Back from the dead: TIL apoptosis in cancer immune evasion, Published online: 23 January 2018; doi:10.1038/bjc.2017.483
Back from the dead: TIL apoptosis in cancer immune evasionhttp://ift.tt/2Gc1iT1
A core matrisome gene signature predicts cancer outcome
A core matrisome gene signature predicts cancer outcome
A core matrisome gene signature predicts cancer outcome, Published online: 23 January 2018; doi:10.1038/bjc.2017.458
A core matrisome gene signature predicts cancer outcomehttp://ift.tt/2rtp6ye
Development and validation of a plasma-based melanoma biomarker suitable for clinical use
Development and validation of a plasma-based melanoma biomarker suitable for clinical use
Development and validation of a plasma-based melanoma biomarker suitable for clinical use, Published online: 23 January 2018; doi:10.1038/bjc.2017.477
Development and validation of a plasma-based melanoma biomarker suitable for clinical usehttp://ift.tt/2rtoZCO
Reply to ‘Comment on ‘Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer”
Reply to 'Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer"
Reply to 'Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer", Published online: 23 January 2018; doi:10.1038/bjc.2017.464
Reply to 'Comment on 'Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer"http://ift.tt/2DwAhYu
Hypofractionated Versus Standard Fractionated Proton-beam Therapy for Low-risk Prostate Cancer: Interim Results of a Randomized Trial PCG GU 002
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The Birth of the Illegitimate Linear No-Threshold Model: An Invalid Paradigm for Estimating Risk Following Low-dose Radiation Exposure
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Total Lifetime and Cancer-related Costs for Elderly Patients Diagnosed With Anal Cancer in the United States
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To What Extent Does Radiotherapy Improve the Quality of Life of Patients With Bone Metastasis?: A Prospective, Single-Institutional Study
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A Phase II Study of Biweekly Cisplatin, Fixed-Dose-Rate Gemcitabine and Infusional 5-Fluorouracil in Patients With Metastatic Pancreatic and Biliary Cancers
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The Evolving Role of Tumor Treating Fields in Managing Glioblastoma: Guide for Oncologists
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Clinical Outcomes of Patients With Gastrointestinal Malignancies Participating in Phase I Clinical Trials
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Does Delaying Surgical Resection After Neoadjuvant Chemoradiation Impact Clinical Outcomes in Locally Advanced Rectal Adenocarcinoma?: A Single-Institution Experience
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Patterns of Care and Outcomes of Hypofractionated Chemoradiation Versus Conventionally Fractionated Chemoradiation for Glioblastoma in the Elderly Population
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A Review of Treatment for Breast Cancer-Related Lymphedema: Paradigms for Clinical Practice
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