Molecular analysis of androgen receptor mutants

Treatment-induced mutations in the ligand binding domain of the androgen receptor (AR) are known to change antagonists into agonists. Recently, the F877L mutation has been described to convert Enzalutamide (Enza) into an agonist. This mutation was seen to co-occur in the endogenous AR allele of the LNCaP cells, next to the T878A mutation. Here, we studied the effects of Enza on the F877L and T878A mutants, as well as the double mutant AR (F877L/T878A). Molecular modeling revealed favorable structural changes in the double mutant AR that lead to a decrease in steric clashes for Enza. Ligand binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for Enza, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in co-regulator recruitment and chromatin interactions. Our data show that Enza is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double mutant AR.

from Cancer via ola Kala on Inoreader http://ift.tt/27udM0u
via IFTTT

Chromatin regulators for chemotherapy response

The limited capacity to predict a patient's response to distinct chemotherapeutic agents is a major hurdle in cancer management. The efficiency of a large fraction of current cancer therapeutics (radio- and chemotherapies) is influenced by chromatin structure. Reciprocally, alterations in chromatin organization may impact resistance mechanisms. Here, we explore how the mis-expression of chromatin regulators-factors involved in the establishment and maintenance of functional chromatin domains-can inform about the extent of docetaxel response. We exploit gene Affymetrix and NanoString gene expression data for a set of chromatin regulators generated from breast cancer patient-derived xenograft (PDX) models and patient samples treated with docetaxel. Random Forest classification reveals specific panels of chromatin regulators, including key components of the SWI/SNF chromatin remodeler, which readily distinguish docetaxel high-responders and poor-responders. Further exploration of SWI/SNF components in the comprehensive NCI-60 dataset reveals that the expression inversely correlates with docetaxel sensitivity. Finally, we show that loss of the SWI/SNF subunit BRG1 (SMARCA4) in a model cell line leads to enhanced docetaxel sensitivity. Altogether, our findings identify chromatin regulators as biomarkers for drug response as well as therapeutic targets to sensitize patients towards docetaxel and combat drug resistance.

from Cancer via ola Kala on Inoreader http://ift.tt/1ThpOko
via IFTTT

PIM inhibitors selectively kill hypoxic tumor cells

Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases is a pro-survival pathway that is upregulated in response to hypoxia, in a HIF-1-independent manner. We demonstrate that pharmacological or genetic inhibition of PIM kinases is significantly more toxic toward cancer cells in hypoxia as compared to normoxia. Xenograft studies confirm that PIM kinase inhibitors impede tumor growth and selectively kill hypoxic tumor cells in vivo. Experiments show that PIM kinases enhance the ability of tumor cells to adapt to hypoxia-induced oxidative stress by increasing the nuclear localization and activity of Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which functions to increase the expression of antioxidant genes. Small molecule PIM kinase inhibitors prevent Nrf2 from accumulating in the nucleus, reducing the transcrption of cytoprotective genes and leading to the build up of intracellular reactive oxygen species (ROS) to toxic levels in hypoxic tumor cells. This toxic effect of PIM inhibitors can be successfully blocked by ROS scavengers, including N-acetyl cystine and superoxide dismutase. Thus, inhibition of PIM kinases has the potential to oppose hypoxia-mediate therapeutic resistance and induce cell death in the hypoxic tumor microenvironment.

from Cancer via ola Kala on Inoreader http://ift.tt/27udCX4
via IFTTT

mTORC1/2 in ovarian cancer platinum resistance

There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K-AKT-mTOR pathway signaling, DNA damage and repair response (DDR) gene expression and translational control were all investigated. We show that platinum resistant OVCAR-3 ovarian cancer cells are re-sensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared to animals treated with carboplatin plus everolimus which inhibits only mTORC1. Reduced tumor growth, metastasis and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT activating phosphorylation and increased 4E-BP1 hypo-phosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses and translation, promoting improved survival in the background of platinum resistance.

from Cancer via ola Kala on Inoreader http://ift.tt/1ThpXUW
via IFTTT

Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan (Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.

from Cancer via ola Kala on Inoreader http://ift.tt/1TjIOlw
via IFTTT

Biomarkers for outcome of pembrolizumab-treated patients

Purpose: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) following pembrolizumab treatment in melanoma patients. Experimental design: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab. Kaplan-Meier analysis and Cox regression were applied for survival analysis. Results: Relative eosinophil count (REC) {greater than or equal to}1.5%, relative lymphocyte count (RLC) {greater than or equal to}17.5%, {less than or equal to}2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n=177) and the confirmation (n=182) cohort and had independent positive impact (all P<0.001). Their independent role was subsequently confirmed in the validation cohort (n=257; all P<0.01). The number of favorable factors was strongly associated with prognosis. One-year-OS probabilities of 83.9% vs 14.7% and response rates of 58.3% vs 3.3% were observed in patients with four out of four compared to those with none out of four favorable baseline factors present, respectively. Conclusions: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated.

from Cancer via ola Kala on Inoreader http://ift.tt/1OyTU61
via IFTTT

Full-field OCT in ovarian tissue

Purpose: Autotransplantation of ovarian tissue can be used to restore fertility in cancer patients following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor detection methods render the ovarian tissue unsuitable for transplantation. Full-field optical coherence tomography (FF-OCT) is an imaging modality that rapidly produces high-resolution histology-like images without the need to fix, freeze, or stain the tissue. In this proof-of-concept study, we investigated whether FF-OCT can be used to detect metastases in ovarian tissue, thereby increasing the safety of ovarian tissue autotransplantation. We also evaluated whether cortical ovarian tissue and follicles remain viable following FF-OCT imaging. Experimental Design: Formalin-fixed, paraffin-embedded tissue samples were obtained from seven normal ovaries and fourteen ovaries containing metastases and/or micrometastases. These samples were deparaffinized and imaged using FF-OCT. The FF-OCT images were then compared to corresponding hematoxylin-and-eosin-stained tissue sections. Finally, we examined the effect of FF-OCT imaging on the viability of ovarian tissues and follicles in fresh bovine ovarian tissue using a glucose uptake and neutral red staining, respectively. Results: FF-OCT illustrated both normal structures and metastases in ovarian tissue within minutes. Primordial follicles were readily identifiable. Finally, tissues and follicles remained viable following FF-OCT imaging for up to 180 and 60 minutes, respectively. Conclusions: FF-OCT imaging is a promising method for the non-invasive detection of metastases, including micrometastases, in ovarian tissue. Moreover, this method facilitates the selection of cortical ovarian tissue with the highest density of primordial follicles, potentially increasing the likelihood of restoring ovarian function following ovarian tissue autotransplantation.

from Cancer via ola Kala on Inoreader http://ift.tt/22enZKJ
via IFTTT

Molecular predictors of response to fulvetsrant

Purpose: Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor positive (ER+) breast cancer. With the exception of ER levels, there are no established predictive biomarkers of response to single agent fulvestrant. We attempted to identify a gene signature of response to fulvestrant in advanced breast cancer. Experimental Design: Primary tumor samples from 134 patients enrolled in the phase III CONFIRM study of patients with metastatic ER+ breast cancer comparing treatment with either 250mg or 500mg fulvestrant were collected for genome-wide transcriptomic analysis. Gene expression profiling was performed using Affymetrix microarrays. An exploratory analysis was performed to identify biological pathways and new signatures associated with response to fulvestrant. Results: Pathway analysis demonstrated that increased EGF pathway and FOXA1 transcriptional signaling is associated with decreased response to fulvestrant. Using a multivariate Cox model we identified a novel set of 37 genes whose expression is independently associated with progression free survival (PFS). TFAP2C, a known regulator of ER activity was ranked second in this gene set and high expression was associated with a decreased response to fulvestrant. The negative predictive value of TFAP2C expression at the protein level was confirmed by immunohistochemistry. Conclusions: We identified biological pathways and a novel gene signature in primary ER+ breast cancers that predicts for response to treatment in the CONFIRM study. These results suggest potential new therapeutic targets and warrant further validation as predictive biomarkers of fulvestrant treatment in metastatic breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/1OyTXPp
via IFTTT

Prediction of pathological response for LARC using MRI

Purpose:To evaluate multi-parametric MRI features in predicting pathological response after preoperative chemo-radiation therapy (CRT) for locally advanced rectal cancer (LARC). Experimental Design: Forty-eight consecutive patients (01/2012-11/2014) receiving neoadjuvant CRT were enrolled. All underwent anatomical T1/T2, Diffusion-Weighted-MRI(DWI) and Dynamic-Contrast-Enhanced(DCE)-MRI before CRT. A total of 103 imaging features, analyzed using both volume-averaged and voxelized methods, were extracted for each patient. Univariate analyses were performed to evaluate the capability of each individual parameter in predicting pathological-complete-response (pCR) or good-response (GR) evaluated based on tumor regression grade (TRG). Artificial neural network (ANN) with 4-fold validation technique was further utilized to select the best predictor sets to classify different response groups and the predictive performance was calculated using receiver operating characteristic (ROC) curves. Results:The conventional volume-averaged analysis could provide an area under ROC curve (AUC) ranging from 0.54-0.73 in predicting pCR. While if the models were replaced by voxelized heterogeneity analysis, the prediction accuracy measured by AUC could be improved to 0.71-0.79. Similar results were found for GR prediction. In addition, each sub-category images could generate moderate power in predicting the response, which if combining all information together, the AUC could be further improved to 0.84 for pCR and 0.89 for GR prediction, respectively. Conclusions:Through a systematic analysis of multi-parametric MR imaging features, we are able to build models with improved predictive value over conventional imaging metrics. The results are encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailoring the treatment into the era of personalized medicine.

from Cancer via ola Kala on Inoreader http://ift.tt/22eo0OL
via IFTTT

MET, FOXM1 and DNA damage-induced senescence

Purpose: Deregulated signaling via the MET receptor tyrosine kinase is abundant in gastric tumors, with up to 80% of cases displaying aberrant MET expression. A growing body of evidence suggests MET as a potential target for tumor radiosensitization. Experimental Design: Cellular proliferation and DNA damage-induced senescence were studied in a panel of MET-overexpressing human gastric cancer cell lines as well as in xenograft models following MET inhibition and/or ionizing radiation. Pathways activation and protein expression were assessed by immunoblotting and immunohistochemistry. Tumor tissue microarrays (91 gastric cancer patients) were generated and copy number alteration (178 patients) and gene expression (373 patients) data available at The Cancer Genome Atlas were analyzed to assess co-alterations of MET and FOXM1. Results: MET targeting administered prior ionizing radiation instigates DNA damage-induced senescence (~80%, P<0.001) rather than cell death. MET inhibition-associated senescence is linked to blockade of the MAPK pathway, correlates with downregulation of FOXM1 and can be abrogated (11,8% vs. 95,3%, P<0.001) by ectopic expression of FOXM1 in the corresponding gastric tumor cells. Cells with ectopic FOXM1 expression demonstrate considerable (~20%, P<0.001) growth advantage despite MET targeting, suggesting a novel clinically-relevant resistance mechanism to MET inhibition as the co-presence of both MET and FOXM1 protein (33%) and mRNA (30%) overexpression as well as gene amplification (24,7%) is common in patients with gastric cancer. Conclusions: FOXM1, a negative regulator of senescence, has been identified as a key downstream effector and potential clinical biomarker that mediates MET signaling following infliction of DNA damage in gastric tumors.

from Cancer via ola Kala on Inoreader http://ift.tt/1OyU79x
via IFTTT

Intra-tumor heterogeneity in GEP test risk stratification

Purpose: To examine the effect of intra-tumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs), and the subsequent ability to predict prognostic risk. Experimental Design: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER) positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n=26), low/negative PR (n=13), or both (n=5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data. Results: Hierarchical clustering using all GEP genes showed that majority (61/71) of tumor samples clustered by patient, indicating greater inter-patient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r=0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18/71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate and high risk. Conclusions: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or over-estimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction.

from Cancer via ola Kala on Inoreader http://ift.tt/22enU9Z
via IFTTT

ACRIN6684: MRI and FMISO PET in newly diagnosed GBM

Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma (GBM). Experimental Design: Prior to start of chemoradiation, GBM patients underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression free and overall survival. Results: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pre-treatment 18F-FMISO SUVpeak (p=0.048), mean ktrans (p=0.024), and median ktrans (p=0.045) were significantly associated with shorter overall survival. Higher pre-treatment median ktrans (p=0.021), normalized RCBV (p=0.0096), and nCBF (p=0.038) were significantly associated with shorter progression free survival. SUVpeak (AUC = 0.75, 95%CI 0.59 to 0.91), nRCBV (AUC=0.72, 95% CI0.56-0.89) and nCBF (AUC = 0.72, 95%CI 0.56 to 0.89) were predictive of survival at 1 year. Conclusions: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed GBM patients and these important physiological markers can be measured safely and reliably using MRI and 18F-FMISO PET.

from Cancer via ola Kala on Inoreader http://ift.tt/1OyTOeB
via IFTTT

Use of Liquid Biopsies in Clinical Oncology

Purpose: There is growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer. Experimental Design: 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined. Results: Fifty-eight percent of patients (98/168) had {greater than or equal to}1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had {greater than or equal to} 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with {greater than or equal to} 1 alteration in common compared to 14.4 months (P=0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with {greater than or equal to} 1 alteration with ctDNA {greater than or equal to} 5% and shorter survival (median = 4.03 months versus not reached at median follow up of 6.1 months; P<0.001). Finally, five of the twelve evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease {greater than or equal to} 6 months/partial remission compared to two of 28 patients (7.1%) for the unmatched patients, P=0.02. Conclusions: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/22eo0yf
via IFTTT

Cross Talk between Cancer Cells and Neighboring Cells May Contribute to Tumor Growth

Pancreatic tumor cells and neighboring normal cells engage in a two-way molecular conversation that helps drive malignant behavior in the cancer cells, according to new study results.

Working in cell lines from mice, researchers showed that pancreatic cancer cells that have cancer-causing mutations in the KRAS gene can coerce nearby healthy cells to release growth signals. These signals then activate a chain of events in the tumor cells that enhance their ability to survive and multiply.

from Cancer via ola Kala on Inoreader http://ift.tt/1Tjz1fe
via IFTTT

Erratum

Volume 17, Issue 5, May 2016, pages 577-577<br/>10.1080/15384047.2016.1170468<br/>

from Cancer via ola Kala on Inoreader http://ift.tt/1OyEz5A
via IFTTT

Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/β-catenin signaling pathway downregulation

Volume 17, Issue 5, May 2016, pages 558-565<br/>10.1080/15384047.2016.1177675<br/>Ning Wu

from Cancer via ola Kala on Inoreader http://ift.tt/1TTWwHW
via IFTTT

Abrus agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death

Abstract

Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenosine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells. Additionally, it observed that AGG induced autophagic cell death in Bax knock down (Bax-KD) and 5-FU resistant HeLa cells, confirming as an alternate cell killing pathway to apoptosis. At the molecular level, AGG induced ER stress in PERK dependent pathway and inhibition of ER stress by salubrinal, eIF2α phosphatase inhibitor as well as siPERK reduced autophagic death in the presence of AGG. Further, our in silico and colocalization study showed that AGG interacted with pleckstrin homology (PH) domain of Akt to suppress its phosphorylation and consequent downstream mTOR dephosphorylation in HeLa cells. We showed that Akt overexpression could not augment GRP78 expression and reduced autophagic cell death by AGG as compared to pcDNA control, indicating Akt modulation was the upstream signal during AGG's ER stress mediated autophagic cell death. In conclusion, we established that AGG stimulated cell death by autophagy might be used as an alternative tumor suppressor mechanism in human cervical cancer. This article is protected by copyright. All rights reserved

from Cancer via ola Kala on Inoreader http://ift.tt/1XgyThZ
via IFTTT

KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients

Abstract

Mutations in the KRAS and TP53 genes have been found frequently in lung tumors and specimens from individuals at high risk for lung cancer and have been suggested as predictive markers for lung cancer. In order to assess the prognostic value of these 2 genes' mutations in lung cancer recurrence, we analyzed mutations in codon 12 of the KRAS gene and in hotspot codons of the TP53 gene in 176 bronchial biopsies obtained from 77 former lung cancer patients. Forty-seven patients (61.0%) showed mutations, including 35/77 (45.5%) in the KRAS gene and 25/77 (32.5%) in the TP53 gene, among them 13/77 (16.9%) had mutations in both genes. When grouped according to past or current smoking status, a higher proportion of current smokers showed mutations, in particular those in the TP53 gene (p = 0.07), compared with ex-smokers. These mutations were found in both abnormal lesions (8/20 or 40%) and histologically normal tissues (70/156 or 44.9%) (p = 0.812). They consisted primarily of G to A transition and G to T transversion in both the KRAS (41/56 or 73.2%) and TP53 (24/34 or 70.6%) genes, consistent with mutations found in lung tumors of smoking lung cancer patients. Overall, recurrence free survival (RFS) among all subjects could be explained by age at diagnosis, tumor stage, tumor subtype, and smoking (p < 0.05, Cox proportional hazard). Therefore, KRAS and TP53 mutations were frequently detected in bronchial tissues of former lung cancer patients. However, the presence of mutation of bronchial biopsies was not significantly associated with a shorter RFS time. This article is protected by copyright. All rights reserved

from Cancer via ola Kala on Inoreader http://ift.tt/1qp0WPn
via IFTTT

Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16

Cancer Biotherapy & Radiopharmaceuticals May 2016, Vol. 31, No. 4: 125-132.


from Cancer via ola Kala on Inoreader http://ift.tt/1TFeRJ0
via IFTTT

Inhibition of Human Glioma Cell Proliferation Caused by Knockdown of Utrophin Using a Lentivirus-Mediated System

Cancer Biotherapy & Radiopharmaceuticals May 2016, Vol. 31, No. 4: 133-138.


from Cancer via ola Kala on Inoreader http://ift.tt/1OxBFOl
via IFTTT

A Freeze-Dried Kit for the Preparation of 188Re-HEDP for Bone Pain Palliation: Preparation and Preliminary Clinical Evaluation

Cancer Biotherapy & Radiopharmaceuticals May 2016, Vol. 31, No. 4: 139-144.


from Cancer via ola Kala on Inoreader http://ift.tt/1TFf1zO
via IFTTT

The Effect of G2 Adjuvant on Gene Expression and Delivery of NKG2D Receptor on NK Cells in Peripheral Blood

Cancer Biotherapy & Radiopharmaceuticals May 2016, Vol. 31, No. 4: 119-124.


from Cancer via ola Kala on Inoreader http://ift.tt/1OxBPFm
via IFTTT

Overexpression of Annexin II Receptor-Induced Autophagy Protects Against Apoptosis in Uveal Melanoma Cells

Cancer Biotherapy & Radiopharmaceuticals May 2016, Vol. 31, No. 4: 145-151.


from Cancer via ola Kala on Inoreader http://ift.tt/1TFeQVs
via IFTTT

Plutella xylostella granulovirus late gene promoter activity in the context of the Autographa californica multiple nucleopolyhedrovirus genome

Abstract

Within Baculoviridae, little is known about the molecular mechanisms of replication in betabaculoviruses, despite extensive studies in alphabaculoviruses. In this study, the promoters of nine late genes of the betabaculovirus Plutella xylostella granulovirus (PlxyGV) were cloned into a transient expression vector and the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) genome, and compared with homologous late gene promoters of AcMNPV in Sf9 cells. In transient expression assays, all PlxyGV late promoters were activated in cells transfected with the individual reporter plasmids together with an AcMNPV bacmid. In infected cells, reporter gene expression levels with the promoters of PlxyGV e18 and AcMNPV vp39 and gp41 were significantly higher than those of the corresponding AcMNPV or PlxyGV promoters, which had fewer late promoter motifs. Observed expression levels were lower for the PlxyGV p6.9, pk1, gran, p10a, and p10b promoters than for the corresponding AcMNPV promoters, despite equal numbers of late promoter motifs, indicating that species-specific elements contained in some late promoters were favored by the native viral RNA polymerases for optimal transcription. The 8-nt sequence TAAATAAG encompassing the ATAAG motif was conserved in the AcMNPV polh, p10, and pk1 promoters. The 5-nt sequence CAATT located 4 or 5 nt upstream of the T/ATAAG motif was conserved in the promoters of PlxyGV gran, p10c, and pk1. The results of this study demonstrated that PlxyGV late gene promoters could be effectively activated by the RNA polymerase from AcMNPV, implying that late gene expression systems are regulated by similar mechanisms in alphabaculoviruses and betabaculoviruses.

from Cancer via ola Kala on Inoreader http://ift.tt/1TiK4FB
via IFTTT

Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib

Abstract

Background

Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking.

Methods

We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used.

Results

We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival.

Conclusion

These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells.

from Cancer via ola Kala on Inoreader http://ift.tt/2572iBu
via IFTTT

Unusual Soft Tissue Uptake of F-18 Sodium Fluoride in Three Patients Undergoing F-18 NaF PET/CT Bone Scans for Prostate Cancer

Abstract

Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.

from Cancer via ola Kala on Inoreader http://ift.tt/1siYI5k
via IFTTT

Health-related quality of life before and after head and neck squamous cell carcinoma: Analysis of the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linkage

BACKGROUND

Understanding health-related quality of life (HRQOL) is crucial to providing high-quality survivorship care for patients with head and neck squamous cell carcinoma (HNSCC). Trends in and prognostic significance of HRQOL before and after HNSCC have not been well described.

METHODS

HRQOL for older individuals with HNSCC was examined using the linked Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey database. Surveys assessing HRQOL from 5 years prediagnosis to 10 years postdiagnosis were included. HRQOL over time was modeled using multilevel linear regression with restricted cubic splines and was reported as either total HRQOL or change in HRQOL (denoted Δ). The association of prediagnosis HRQOL with survival was examined.

RESULTS

In total, 1653 individuals were included; of these, 61% completed 1 survey, and 39% completed multiple surveys. Overall HRQOL decreased progressively until 13 months postdiagnosis, then recovered toward baseline between 2 and 5 years. However, after stratification by survival group, the postdiagnosis recovery was not observed. Individuals with shorter survival had lower HRQOL prediagnosis (<2-year survivors, 87.3; > 5-year survivors, 96.4; P = .004) with a steeper decline in HRQOL during diagnosis and treatment (<2-year survivors: Δ, −16.6; 95% confidence interval [CI], −23.8, −9.4; > 5-year survivors: Δ, −0.9; 95% CI, −1.8, 0.08). Radiotherapy and advanced stage were associated with greater declines in HRQOL during diagnosis and treatment (P < .001). Higher prediagnosis HRQOL was independently associated with improved overall survival (adjusted hazard ratio for 10-point increase, 0.91; 95% CI, 0.85-0.97).

CONCLUSIONS

HRQOL declines before and after HNSCC, whereas any observed posttreatment recovery is likely an artifact of shorter survival among individuals with the lowest HRQOL. The prognostic implication of prediagnosis HRQOL may inform patient counseling. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/256Phb0
via IFTTT

Outcomes of patients with chronic lymphocytic leukemia treated with first-line idelalisib plus rituximab after cessation of treatment for toxicity

BACKGROUND

More active therapies are needed for older and unfit patients with chronic lymphocytic leukemia (CLL) who are not eligible for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The phosphyotidylinositol-3-kinase δ inhibitor idelalisib is effective in patients with treatment-naive and relapsed/refractory CLL as monotherapy and in combination with rituximab, but it can be associated with treatment-limiting adverse events, particularly diarrhea/colitis. The outcomes for patients who cease treatment for adverse events have not been previously described.

METHODS

The authors analyzed long-term follow-up data from 40 treatment-naïve patients aged ≥65 years who received treatment at The University of Texas MD Anderson Cancer Center on a phase 2 study of idelalisib plus rituximab for CLL.

RESULTS

In patients who permanently ceased treatment because of toxicity, the time to subsequent disease progression was analyzed according to baseline characteristics. Fifteen patients permanently ceased therapy (PCT) because of toxicity (PCT_TOX), most commonly diarrhea/colitis (n = 7), at a median of 11 months after commencing treatment. PCT_TOX was associated with a higher risk of subsequent disease progression (hazard ratio, 6.61; 95% confidence interval, 1.77-16.15) relative to that observed in patients who remained on therapy. Ten patients subsequently progressed, and 7 required salvage therapy; 5 patients remained progression-free at a median of 23.3 months (range, 8.5-28.6 months). Patients who were positive for ζ-associated protein-70 had more rapid disease progression after treatment cessation (P = .048). There were no CLL-related deaths.

CONCLUSIONS

PCT_TOX is the major determinant of PFS in patients who receive first-line idelalisib-based treatment. However, a subgroup of patients with favorable biologic characteristics has prolonged PFS, even after PCT_TOX. The absence of CLL-related deaths indicates that salvage treatment is generally successful after PCT_TOX. Cancer 2016;000:000–000. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/256PivH
via IFTTT

Increased incidence but improved median overall survival for biliary tract cancers diagnosed in Ontario from 1994 through 2012: A population-based study

BACKGROUND

To the authors' knowledge, the incidence of biliary tract cancer (BTC) in Canada is unknown. In the current study, the authors sought to describe the epidemiology of BTC using a large population-based cancer database from Ontario, Canada.

METHODS

The current study was a population-based cohort study using the Ontario Cancer Registry. Patients with intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC) diagnosed between 1994 and 2012 were included. Age-standardized incidence and mortality rates were compared using incidence rate ratios (IRRs). Overall survival from the time of diagnosis was calculated for 3 eras: 1994 through 1999, 2000 through 2005, and 2006 through 2012. The number of patients receiving chemotherapy, radiotherapy, or surgery was determined using linked clinical data.

RESULTS

A total of 9039 cases (1569 IHCC cases, 4337 EHCC cases, and 3133 GBC cases) were identified. The rate of BTC increased by 1.6% per year (IRR, 1.016; 95% confidence interval [95% CI], 1.008-1.024 [P<.001]). The incidence increased by 7.0% per year among cases of IHCC (IRR, 1.070; 95% CI, 1.058-1.081 [P<.001]) and 1.8% per year in cases of EHCC (IRR, 1.018; 95% CI, 1.009-1.027 [P<.001]), whereas the incidence of GBC remained unchanged (IRR, 0.991; 95% CI, 0.982-1.001 [P = .086]). The median survival for the cohort was 8.3 months, with improvement noted over the study period (6.1 months for 1994-1999 vs 8.5 months for 2000-2005 vs 10.3 months for 2006-2012 [P<.001]). The median survival was the longest for EHCC (11.3 months), followed by GBC (6.4 months) and IHCC (6.2 months). The percentage of patients receiving chemotherapy and/or radiotherapy increased over the study (P<.001), whereas the percentage of patients receiving surgery decreased (P<.001).

CONCLUSIONS

An increased incidence of BTC during 1994 through 2012 was observed. Explanations for the observed temporal improvement in median survival require further exploration. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/256PiM4
via IFTTT

Influence of the treatment facility volume on the survival of patients with non-Hodgkin lymphoma

BACKGROUND

Prior studies have shown that a higher hospital volume or physician caseload is associated with better outcomes for complex and uncommon surgical procedures. Similar studies in the medical management of rare diseases such as hematologic cancers are limited. This retrospective, observational study using the US National Cancer Data Base determined the extent to which the number of new non-Hodgkin lymphoma (NHL) patients treated annually at a treatment facility affected overall survival (OS).

METHODS

There were 278,985 patients treated at 1151 facilities from 1998 to 2006. Treatment facilities were classified by quartiles based on the average number of new NHL patients seen annually: quartile 1 (Q1), 2 to 13 patients; quartile 2 (Q2), 14 to 20 patients; quartile 3 (Q3), 21 to 32 patients; and quartile 4 (Q4), 33 or more patients. The outcome of interest was OS according to facility volume.

RESULTS

The unadjusted median OS was 61.8 months for Q1, 65.9 months for Q2, 71.4 months for Q3, and 83.6 months for Q4. A multivariate analysis that was adjusted for demographic (sex, age, race, and ethnicity), socioeconomic (income and insurance type), geographic (area of residence), disease-specific (NHL subtype and stage), and facility-specific factors (type and location) showed that the facility volume was associated with OS. Compared with patients at Q4 facilities, patients at lower quartile facilities had higher mortality (hazard ratio for Q3, 1.05 [95% confidence interval, 1.04-1.06]; hazard ratio for Q2, 1.08 [95% confidence interval, 1.07-1.10]; hazard ratio for Q1, 1.14 [95% confidence interval, 1.11-1.17]).

CONCLUSIONS

NHL patients treated at higher volume facilities may survive longer than those treated at lower volume facilities. Further work is needed to understand the mechanisms of these differences and whether volume should be considered in the determination of referrals for NHL patients. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/1TSPpiP
via IFTTT

The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/256PgUs
via IFTTT

Past approaches and future directions for targeting tumor hypoxia in squamous cell carcinomas of the head and neck

Publication date: Available online 16 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Kelly K. Curtis, William W. Wong, Helen J. Ross
Recurrent squamous cell carcinoma of the head and neck (SCCHN) carries a poor prognosis. Tumor hypoxia (TH) has been implicated as one of many factors contributing to SCCHN recurrence. TH leads to radiation resistance by reversing radiation-induced DNA damage. Effective strategies to overcome TH may improve outcomes in patients with SCCHN. We searched the English literature on PubMed and reviewed the reference sections of key articles related to TH (publications spanning from the early 1900s to the present). We summarized the underlying theory of TH in SCCHN, methods for quantifying it, and the numerous therapies developed to modulate it. We included articles that set the foundation of TH as a theory and the most relevant articles published within the last 15 years related to TH quantification and therapeutic targeting. Despite extensive research, targeting TH in SCCHN has not become a part of routine clinical practice in North America, and we analyze the pitfalls in hypoxia research that have led to this failure. We propose that future studies should test a combined approach of targeting the immune system in addition to cellular pathways rendered aberrant in TH and should include development of novel surrogate markers of TH and/or TH imaging.



from Cancer via ola Kala on Inoreader http://ift.tt/1TSPC5F
via IFTTT

Serum anti-HSP27 antibody titers in patients with metabolic syndrome, with or without diabetes mellitus

Abstract

Metabolic syndrome (MetS) is characterized by clustering of clinical, physiological, biochemical, and metabolic factors that are associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus. Immune response to heat shock protein 27 (Hsp27) has been suggested to be implicated in atherogenesis. We aimed to investigate the association between serum anti-Hsp27 antibody concentrations and type 2 diabetes in patients with MetS. This was a cross-sectional observational study on groups of MetS and healthy subjects. The population sample was derived from MASHAD STUDY, a national cross-sectional study conducted by the Ministry of Health and Medical Education in 2004. Pregnant and breastfeeding women and patients who had cardiovascular disease, myocardial infarction, stroke, or systemic disease were excluded from the 9600 subjects of the MASHAD STUDY population. A total of 933 subjects including 477 women and 456 men were classified as having MetS, diabetes mellitus, or neither. Data including age, gender, and smoking habit collected using a questionnaire. MetS was diagnosed based on the International Diabetes Federation (IDF) definition. The serum anti-HSP27 antibody titers were measured by ELISA. There was no difference in serum anti-HSP27 concentrations between subjects with and without MetS, or diabetes mellitus, nor was there a significant difference in anti-HSP27 levels between men and women. There was no significant difference in anti-HSP27 antibody between diabetic MetS patients, normal population, non-diabetic MetS, and diabetic non-MetS patients (p value >0.05). Serum anti-Hsp27 antibody concentrations did not differ between individuals with or without MetS or diabetes mellitus.

from Cancer via ola Kala on Inoreader http://ift.tt/1ZXQQRG
via IFTTT

Metachronous testicular seminoma after radiotherapy and chemotherapy: a case report

Abstract

Background

Bilateral testicular neoplasia is rare, with an incidence ranging from 1 to 5 %. Long-term survival has improved in recent years due to advanced diagnostic approaches and new therapeutic methods that are highly effective against germ cell tumors.

Case presentation

We present the case of a patient with a primary seminomatous testicular tumor, who developed a contralateral metastasis and a subsequent metachronous tumor following chemotherapy and consolidation radiotherapy treatment.

Conclusions

Strict follow-up, including physical examination and ultrasound examination of the contralateral testis, enabled early diagnosis of the second tumor, giving the patient a high likelihood of a definitive cure.

from Cancer via ola Kala on Inoreader http://ift.tt/1ZY0XWz
via IFTTT

Prognostic significance of K-ras mutations in pancreatic cancer: a meta-analysis

Abstract

Background

K-ras gene mutations are common in patients with pancreatic cancer (PC); however, their prognostic value for PC remains inconclusive. This meta-analysis was performed to quantitatively evaluate the association between K-ras mutations and survival in patients with pancreatic cancer.

Methods

We performed a comprehensive search of electronic sources including MEDLINE (via PubMed), Web of Science, and the Cochrane Library. The search covered a publication period from inception to November 2015.

Results

Seventeen studies with a total of 2249 patients with pancreatic cancer were included in the tissue detection of this study. The meta-analysis indicated a significant association between mutant K-ras genes and overall survival (OS) (HR = 1.51, 95 % CI 1.32–1.72, P < 0.001). Moreover, further subgroup analyses by ethnicity, publication year, therapy method, cancer resectability, and gene detection method all revealed that pancreatic cancer patients with the K-ras mutation had significantly poorer OS (P < 0.05). And results from four studies with 225 patients focused on plasma K-ras mutations enhanced such association (HR = 2.23, 95 % CI 1.69–2.95, P < 0.001).

Conclusions

As a prediction of poor prognosis, the detection of K-ras mutations may be a useful prognostic factor for pancreatic cancer patients.

from Cancer via ola Kala on Inoreader http://ift.tt/256v0Co
via IFTTT

Neutrophil/lymphocyte ratio has a prognostic value for patients with terminal cancer

Abstract

Background

Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex. In this study, we evaluated the feasibility of neutrophil/lymphocyte ratio (NLR) as an index to estimate survival in terminal cancer patients.

Methods

NLR was calculated retrospectively based on blood tests performed at 3 months, 2 months, 4 weeks, 3 weeks, 2 weeks, 1 week, and within 3 days before death in 160 cancer patients (82 men, 78 women; age range, 33–99 years; mean age, 69.8 years).

Results

NLR increased significantly with time (P < 0.0001). Mean NLR was significantly higher in patients who died within 4 weeks (29.82) than in those who lived more than 4 weeks (6.15). The NLR cutoff point was set at 9.21 according to receiver operating characteristic curve analysis (area under the curve, 0.82; 95 % confidence interval, 0.79–0.85). We inferred that life expectancy would be <4 weeks when NLR >9.21. The sensitivity, specificity, positive predictive value, and negative predictive value were 65.6, 84.1, 90.6, and 51.1 %, respectively. The positive and negative likelihood ratios were 4.125 and 0.409, respectively.

Conclusions

NLR appears to be a useful and simple parameter to predict the clinical outcomes of patients with terminal cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/1ZY19Ft
via IFTTT

Long-term soy consumption and tumor tissue MicroRNA and gene expression in triple-negative breast cancer

BACKGROUND

Soy food intake may have protective effects against the risk for breast cancer, including estrogen receptor (ER)–negative breast cancer. However, the underlying molecular mechanisms remain unclear.

METHODS

To evaluate the association of soy intake with the expression of microRNAs (miRNAs) and genes in the tumor tissue of patients with triple-negative breast cancer (TNBC; ie, breast cancer lacking expression of ER, progesterone receptor, and human epidermal growth factor receptor 2), the expression of 800 miRNAs and 302 genes were measured with NanoString nCounter assays in formalin-fixed, paraffin-embedded tumor tissue from 272 TNBC patients. Soy intake during the 1-year period before the cancer diagnosis was assessed with a validated food-frequency questionnaire. The association of soy intake with the expression of miRNAs and genes was evaluated via linear regression analysis with adjustments for patient age and TNM stage.

RESULTS

A total of 14 miRNAs and 24 genes were significantly associated with soy food intake (P < .05): Thirteen of the 14 miRNAs (92.9%) and 9 of the 24 genes (37.5%), including tumor suppressors miR-29a-3p and IGF1R, showed overexpression for those women with high soy intake, whereas the remaining miRNAs and genes, including oncogenes KRAS and FGFR4, showed underexpression. Furthermore, cell growth–related genes showed a predominantly underexpression pattern according to a comparison of tumor samples from women with high soy food intake and samples from women with lower soy food intake.

CONCLUSIONS

This study suggests that long-term prediagnosis soy intake may lead to increased expression of tumor suppressors and decreased expression of oncogenes, especially cell growth–related genes, in breast tumor tissues. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/1siuShv
via IFTTT

Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis

Abstract

Background

When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis.

Objective

To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis.

Materials and methods

Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight.

Results

Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm²; P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm²; P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index.

Conclusion

We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights – two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis.

from Cancer via ola Kala on Inoreader http://ift.tt/24UTdIt
via IFTTT

Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma—Results of the REchallenge with SUnitinib in MEtastatic RCC (RESUME) Study

Publication date: July 2016
Source:European Journal of Cancer, Volume 62
Author(s): Stéphane Oudard, Lionnel Geoffrois, Aline Guillot, Christine Chevreau, Jean-Laurent Deville, Sabrina Falkowski, Helen Boyle, Marjorie Baciuchka, Pierre Gimel, Brigitte Laguerre, Mathieu Laramas, Christian Pfister, Delphine Topart, Frédéric Rolland, Eric Legouffe, Gwénaël Denechere, Eric Yaovi Amela, Sophie Abadie-Lacourtoisie, Marine Gross-Goupil
AimTo assess the efficacy and tolerability of sunitinib rechallenge in the third-line or later setting in patients with metastatic renal cell carcinoma (mRCC).Patients and methodsThis observational study comprised 61 mRCC patients at 19 centres in France who received sunitinib rechallenge between January 2006 and May 2013. Patients received first-line sunitinib, ≥1 different targeted therapies, and then sunitinib rechallenge. Patient/disease characteristics, tolerability, treatment modalities, and outcomes of therapeutic lines were recorded. The primary end-point was progression-free survival (PFS) in sunitinib rechallenge.ResultsAnalyses included 52 patients; median age was 59 years, 75% were male, and 98% had clear-cell mRCC and prior nephrectomy. At sunitinib rechallenge versus first-line, patients had poorer performance (Karnofsky performance status 90–100: 30% versus 81%) and Memorial Sloan Kettering Cancer Centre prognostic risk (poor risk: 18% versus 3%). Overall, 20%, 65%, 12%, and 4% received sunitinib rechallenge as third-, fourth-, fifth-, and sixth-line therapy, respectively, at 14.6 months (median) after stopping initial treatment. With first-line sunitinib and rechallenge, median PFS was 18.4 and 7.9 months, respectively; objective response rate was 54% and 15%. Two of eight rechallenge responders had not achieved first-line response. Median overall survival was 55.9 months. The sunitinib rechallenge safety profile was as expected, with no new adverse events reported.ConclusionsSunitinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. Disease progression with first-line sunitinib may not be associated with complete or irreversible resistance to therapy.



from Cancer via ola Kala on Inoreader http://ift.tt/1OvVd0k
via IFTTT

Decreased expression of hyaluronan synthase 1 and 2 associates with poor prognosis in cutaneous melanoma

Abstract

Background

Hyaluronan is a large extracellular matrix molecule involved in several biological processes such as proliferation, migration and invasion. In many cancers, hyaluronan synthesis is altered, which implicates disease progression and metastatic potential. We have previously shown that synthesis of hyaluronan and expression of its synthases 1–2 (HAS1-2) decrease in cutaneous melanoma, compared to benign melanocytic lesions.

Methods

In the present study, we compared immunohistological staining results of HAS1 and HAS2 with clinical and histopathological parameters to investigate whether HAS1 or HAS2 has prognostic value in cutaneous melanoma. The specimens consisted of 129 tissue samples including superficial (Breslow ≤ 1 mm) and deep (Breslow > 4 mm) melanomas and lymph node metastases. The differences in immunostainings were analysed with non-parametric Mann–Whitney U test. Associations between immunohistological staining results and clinical parameters were determined with the χ² test. Survival between patient groups was compared by the Kaplan-Meier method using log rank test and Cox's regression model was used for multivariate analyses.

Results

The expression of HAS1 and HAS2 was decreased in deep melanomas and metastases compared to superficial melanomas. Decreased immunostaining of HAS2 in melanoma cells was significantly associated with several known unfavourable histopathologic prognostic markers like increased mitotic count, absence of tumor infiltrating lymphocytes and the nodular subtype. Furthermore, reduced HAS1 and HAS2 immunostaining in the melanoma cells was associated with increased recurrence of melanoma (p = 0.041 and p = 0.006, respectively) and shortened disease- specific survival (p = 0.013 and p = 0.001, respectively).

Conclusions

This study indicates that reduced expression of HAS1 and HAS2 is associated with melanoma progression and suggests that HAS1 and HAS2 have a prognostic significance in cutaneous melanoma.

from Cancer via ola Kala on Inoreader http://ift.tt/1ZXiWMU
via IFTTT

Cystatin C Based Equation Accurately Estimates Glomerular Filtration Rate in Children With Solid and Central Nervous System Tumours: Enough Evidence to Change Practice?

Background

Assessing the glomerular filtration rate (GFR) of paediatric patients receiving nephrotoxic chemotherapy is a vital element of clinical practice. Isotopically measured GFR is the gold standard in terms of accuracy but requires injection of tracer followed by several hours of blood tests. Estimation of GFR using creatinine is widely used but inaccurate, and there is increasing concern regarding its usage for paediatric oncology patients. Cystatin C (CysC) based equations are increasingly used in other paediatric specialities to estimate GFR, and their usefulness in paediatric oncology practice is becoming evident.

Methods

We assessed the renal function of children with solid tumours and CNS tumours receiving nephrotoxic chemotherapy over a 1-year period using paired CysC and isotopic GFR.

Results

Fifty-six sets of measurements were reviewed with estimated GFR predicted using CysC-based and creatinine-based equations. The best performing equation was the 'new CKiD' equation, which estimated GFR within 30% of the measured GFR on 86% of occasions, outperforming the Schwartz equation. If estimated GFR using this equation was >100 ml/min/1.73 m², all values of measured GFR were normal at >90 ml/min/1.73 m², a category containing two-thirds of all measurements.

Conclusions

The new CKiD equation predicts GFR in paediatric oncology patients with more accuracy than creatinine-based equations. When the estimated GFR is >100 ml/min/1.73 m², isotopic GFR can be safely omitted.

from Cancer via ola Kala on Inoreader http://ift.tt/1TVh59F
via IFTTT

Home-Based Exercise Training Improves Left Ventricle Diastolic Function in Survivors of Childhood ALL: A Tissue Doppler and Velocity Vector Imaging Study

Background

Advanced echocardiographic methods may reveal signs of late anthracycline cardiac toxicity (ACT) even in asymptomatic patients. We studied echocardiographic tissue Doppler imaging (TDI) and velocity vector imaging (VVI) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) before and after an exercise intervention.

Methods

Twenty-one asymptomatic, anthracycline-treated, long-term childhood ALL survivors with matched controls were studied at baseline. Seventeen of the survivors participated in a 3-month home-based exercise program. Echocardiography with TDI and VVI was performed.

Results

At baseline, ejection fraction (60.7 ± 4.7% vs. 62.3 ± 3.7%, P = 0.22) and fractional shortening (32.6 ± 3.1% vs. 34.0 ± 2.8%, P = 0.13) were similar in survivors and controls. Lateral early diastolic mitral annulus velocity E′ (32.81 ± 5.71 cm/sec vs. 38.03 ± 6.21 cm/sec, P = 0.01), E′/A′ (1.60 ± 0.48 vs. 2.07 ± 0.63, P = 0.01), and E/E′ (2.78 ± 0.35 vs. 2.42 ± 0.62, P = 0.04) were impaired compared to controls. Peak circumferential strain and strain rate were attenuated at apex (–24.50 ± 3.46% vs. –28.06 ± 4.39%, P = 0.01 and –1.47 ± 0.22 sec^–1 vs. –1.68 ± 0.33 sec^–1, P = 0.02) compared to controls. After the intervention, early diastolic mitral inflow velocity E (87.76 ± 12.54 cm/s vs. 95.28 ± 10.48 cm/s, P = 0.04) and E′ increased (31.78 ± 5.50 cm/s vs. 34.96 ± 5.41 cm/s, P < 0.01). Peak circumferential systolic and diastolic strain rates at mid-level (–1.22 ± 0.21 sec^–1 vs. –1.35 ± 0.24 sec^–1, P = 0.04 and 1.25 ± 0.25 sec^–1 vs. 1.48 ± 0.35 sec^–1, P < 0.01) improved after the exercise program.

Conclusions

A simple home-based exercise program improved cardiac function in asymptomatic childhood ALL survivors. Adding TDI in routine echocardiographic examination may improve the recognition of early signs of ACT, and VVI may bring additional information. The improvements in cardiac function after the exercise program emphasize the importance of physical activity in this population.

from Cancer via ola Kala on Inoreader http://ift.tt/1rOKKIG
via IFTTT

Central Line Associated Blood Stream Infections in Pediatric Hematology/Oncology Patients With Different Types of Central Lines

Background

Central line associated bloodstream infections (CLABSIs) are a significant cause of morbidity and mortality in pediatric hematology/oncology (PHO) patients. Understanding the differences in CLABSI rates by central line (CL) type is important to inform clinical decisions.

Procedure

CLABSI, using similar definitions, noted with three commonly used CL types (totally implanted catheter [port], tunneled externalized catheter [TEC], peripherally inserted central catheter [PICC]) and CL-specific line days were prospectively tracked across 15 US PHO centers from May 2012 until April 2015 and CLABSI rates (CLABSI per 1,000 CL-specific line days) were calculated. Host and organism characterstics associated with the CLABSI events were analyzed.

Results

Over the course of 2.8 million line days, 1,113 CLABSI events (397 in inpatients and 716 in ambulatory patients) were noted. The inpatient CLABSI rate was higher than the ambulatory CLABSI rate for each of the CL types: 1.48 versus 0.16 for ports, 3.51 versus 1.38 for TECs, and 3.07 versus 1.16 for PICCs, respectively. TECs and PICCs were associated with higher CLABSI rates than ports, inpatient and ambulatory.

Conclusions

We found that CLABSI rates were significantly higher for inpatients compared to ambulatory PHO patients for all CL types. Among ambulatory patients, TECs had the highest CLABSI rate and ports the lowest. Among inpatients, TECs and PICCs had higher CLABSI rates than ports but were not statistically different from one another. Cognizant that host and underlying disease attributes may contribute to these differences, these results can still inform CL choice in clinical practice.

from Cancer via ola Kala on Inoreader http://ift.tt/1TVh8SQ
via IFTTT

Can Preconsent Eliminate Some Barriers to Clinical Trial Enrollment of Children With Sickle Cell Disease in Crisis?

from Cancer via ola Kala on Inoreader http://ift.tt/1rOKEkh
via IFTTT

Late Toxicities of Intensity-Modulated Radiation Therapy for Head and Neck Rhabdomyosarcoma

Purpose/objectives

To examine the late effects of intensity-modulated radiation therapy (IMRT) in pediatric patients with rhabdomyosarcoma of the head and neck.

Materials/methods

All 1-year survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT at a single institution from 1999 to 2014 were assessed for long-term complications. Late toxicities were graded according to CTCAE version 4.03.

Results

Among 30 patients, median age at IMRT was 7.4 (1.5–20.8) years, median follow-up was 7.7 (1.2–14.4) years, and median IMRT dose was 50.4 (36–50.4) Gy. Tumor subsites included parameningeal (80%), orbit (13%), and other (7%). Common late toxicities were facial disfigurement (n = 23, 77%), growth hormone deficiency (n = 11, 37%), cataract (n = 10, 34%), and dental problems (n = 10, 33%). Twenty-two patients (73%) had ≥2 late toxicities and 14 patients (47%) had ≥3 late toxicities. Seventeen patients (57%) experienced grade 2 toxicity and 10 patients (33%) had grade 3 toxicity. Grade 3 toxicities included visual disturbance, cataract, facial disfigurement, chronic sinusitis/otitis, and hearing loss. Severe facial deformity was noted in nine patients (30%), and three patients underwent cosmetic surgery. Patients with severe facial deformity were treated at younger ages (median 6.0 years vs. 8.1 years for patients with no/nonsevere facial deformity) and more likely to have infratemporal fossa tumors. There were no secondary solid malignancies.

Conclusions

Late radiation toxicities are common in survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT. While the majority of late effects are mild–moderate, they can significantly impact quality of life, particularly facial disfigurement.

from Cancer via ola Kala on Inoreader http://ift.tt/1TVhbxS
via IFTTT

Is Extended Sedation Necessary for Young Children Receiving High-Dose 131I-MIBG Therapy?

from Cancer via ola Kala on Inoreader http://ift.tt/1TVh6KP
via IFTTT

Coombs Positive Thrombotic Thrombocytopenic Purpura in a Male Pediatric Patient: An Urgent Diagnostic Challenge

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy often caused by deficiency of von Willebrand (vW) factor cleaving protease, ADAMTS-13, leading to large vW multimers and intravascular platelet aggregation. Hemolysis in TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. We report a case of an adolescent with thrombocytopenia and Coombs positive anemia, diagnosed with Evans syndrome, but ultimately found to have TTP. TTP should be considered in children with thrombocytopenia and Coombs positive anemia who are refractory to steroids or develop signs of microangiopathy.  Recognition of this presentation can lead to life-saving treatment with plasma exchange.

from Cancer via ola Kala on Inoreader http://ift.tt/1rOKLw7
via IFTTT

Higher Gemcitabine Dose Was Associated With Better Outcome of Osteosarcoma Patients Receiving Gemcitabine-Docetaxel Chemotherapy

ABSTRACT

Background

Efficacy of gemcitabine and docetaxel (GEM + DOC) chemotherapy in patients with recurrent or refractory osteosarcoma was evaluated.

Methods

Data of 53 patients from 9 institutions, who received GEM (675 or 900 mg/m² on days 1 and 8) and DOC (100 mg/m² on day 8), were retrospectively reviewed.

Results

GEM + DOC was administered as adjuvant (n = 25) or palliative chemotherapy (n = 28). Patients received a median 3 courses (range, 1−10 courses). Objective response rate (CR + PR, where CR is complete response and PR is partial response) and disease control rate (CR+ PR + SD, where SD is stable disease) were 14.3% and 28.6%, respectively. Disease control rate was higher in patients receiving 900 mg/m² GEM than in patients receiving 675 mg/m² (50.0% vs. 12.5%, P = 0.03). Higher GEM dose was associated with better survival, both in adjuvant (1-year overall survival, 90.9 ± 8.7% vs. 38.5 ± 13.5%, P = 0.002) and palliative settings (50.0 ± 14.4% vs. 31.3 ± 11.6%, P = 0.04).

Conclusions

Further studies are necessary to investigate the efficacy of more aggressive and higher doses of GEM + DOC chemotherapy in osteosarcoma.

from Cancer via ola Kala on Inoreader http://ift.tt/1TVh9Gi
via IFTTT

Price and affordability of direct-acting antiviral regimens for hepatitis C virus in the United States

Abstract

Hepatitis C virus is a serious infection causing cirrhosis, liver cancer, and death. The recent development of direct-acting antivirals has dramatically improved tolerability of treatment and rates of cure. However, the high price of these medications has often limited access to care and resulted in rationing of medications in the United States to those with advanced liver disease, access to specialist care, and without active substance use. This review assesses the way pharmaceutical prices are established and how pricing of directly acting antiviral regimens in the United States has impacted access to treatment for hepatitis C virus.

from Cancer via ola Kala on Inoreader http://ift.tt/1WAdnGJ
via IFTTT

Cellular immune response to hepatitis-C-virus in subjects without viremia or seroconversion: is it important?

Abstract

Hepatitis C Virus (HCV) causes chronic infection and represents a global health burden. To date, there is no licensed vaccine for HCV. The high viral replication rate and the existence of several HCV genotypes and quasispecies hamper the development of an effective universal vaccine. In this regard, the current HCV vaccine candidates show genotype-specific protection or narrow cross reactivity against other genotypes. Importantly, HCV spontaneous clearance occurs in 15–50 % of infected subjects, indicating that natural resistance to chronic infection exists. This phenomenon was demonstrated among humans and chimpanzees and continues to motivate researchers attempting to develop an effective HCV vaccine. However, what constitutes a protective immune response or correlate of protection against HCV infection is still vague. Additionally, the mechanisms behind successful HCV clearance suggest the coordination of several arms of the immune system, with cell-mediated immunity (CMI) playing a crucial role in this process. By contrast, although neutralizing antibodies have been identified, they are isolate-specific and poorly correlate with viral clearance. Antigen-specific CD4 T cells, instead, correlate with transient decline in HCV viremia and long-lasting control of the infection. Unfortunately, HCV has been very successful in evading host immune mechanisms, leading to complications such as liver fibrosis, cirrhosis and hepatocellular carcinoma. Interestingly, CMI to HCV antigens were shown among exposed individuals without viremia or seroconversion, suggesting the clearance of prior HCV infection(s). These individuals include family members living with HCV-infected subjects, healthcare workers, IV drug users, and sexual contacts. The correlates of protection could be closely monitored among these individuals. This review provides a summary of HCV-specific immune responses in general and of CMI in particular in these cohorts. The importance of these CMI responses are discussed.

from Cancer via ola Kala on Inoreader http://ift.tt/1shvT9p
via IFTTT

Intimacy after prostate cancer: A brief couples' workshop is associated with improvements in relationship satisfaction

Abstract

Objective

Prostate cancer (PCa) treatments often leave men with erectile dysfunction (ED). Even when ED treatments are effective in restoring men's ability to have an erection sufficient for intercourse, couples continue to struggle sexually. Effective treatments to help couples recover sexually are needed.

Method

PCa patients and partners (N = 59 couples) attending a one-time couples' intimacy workshop, participated in an evaluation. The workshop, offered eight times over a 2-year period, emphasized a couples-based approach to treatment that enhances direct communication about sexuality and implementation of sexual recovery strategies that are consistent with the couple's values. Couples completed pre and post questionnaires (at baseline and 2 months later) assessing the primary outcome of relationship adjustment (Revised Dyadic Adjustment Scale) and secondary outcome of sexual function (Sexual Function Questionnaire). T-tests were employed to examine pre-post changes in scores. A small qualitative sub-study was conducted on the use of a Commitment to Change goal-setting exercise, completed during the workshop.

Results

Results provide insight into the specific nature of improvements. Patients and partners showed improvements in relationship satisfaction. Improvements with small-to-medium effect sizes were observed for patients and partners sexual function; however, after adjusting for multiple comparisons, these changes were no longer statistically significant. The specific goals set by couples, and their achievement status, are presented.

Conclusions

The workshop offers a comprehensive, one-session intervention to help couples implement a treatment plan to promote sexual recovery after PCa treatment. Given the observed improvements, progression to a randomized control trial is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/1TjcspR
via IFTTT

Assessing depression in a geriatric cancer population

Abstract

Objective

To examine the ability of three popular self-report measures of depression to assess depression in a geriatric cancer setting.

Method

Cancer patients 70 years or older and on active treatment completed the Geriatric Depression Scale-Short Form, the Hospital Anxiety and Depression Scale, and the Center for Epidemiological Studies Depression Scale—Revised, and were interviewed using the depression module of the Structured Clinical Interview for DSM disorders (SCID) as the 'gold standard.' Analyses included calculating internal consistency, ROC curves, and the sensitivity and specificity to detect major depression (MDD) or minor depression (i.e. subthreshold depression).

Results

In a sample of 201 cancer patients (85% White; 64% completed college degree or higher), all three of the self-report measures produced adequate internal consistency and predicted depression greater than chance. However, the published cutoff scores for detecting MDD produced inadequate sensitivity, suggesting these scores will miss as many as 33%–83% of geriatric cancer patients who are depressed. Revised cutoff scores were lower than published cutoff scores.

Conclusion

Although these measures produced good internal consistency and were better than chance at predicting depression in a geriatric cancer sample, the published cutoff scores for these measures did not perform well in predicting MDD nor minor depression. Of the three measures, the CES-D appeared to have the most utility. This data suggests that these popular screening measures may be inadequate for reliably identifying depression in a geriatric cancer population. Researchers and clinicians, therefore, should use caution when selecting depression measures for geriatric cancer patients and consider using the lower cut-off scores presented here. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ov9xeT
via IFTTT

Spiritual well-being and spiritual distress predict adjustment in adolescent and young adult cancer survivors

Abstract

Objective

Spirituality is related to many aspects of cancer survivors' physical and psychological adjustment. Given their unique developmental issues, spiritual issues may be especially important to adolescent and young adult (AYA) survivors, yet little research has been conducted on spirituality with AYA survivors. The present study examines how two aspects of spirituality, spiritual well-being (comprising faith and meaning/peace), and spiritual struggle relate to later post-cancer adjustment.

Methods

At Time 1 (T1), 120 AYA survivors completed questionnaires on spirituality and adjustment (fear of recurrence, post-traumatic stress symptoms, perceived post-traumatic growth, psychological distress, and health-related quality of life). Eighty-three of these participants also completed these questionnaires at Time 2 (T2), one year later.

Results

Our sample reported fairly low spiritual well-being (meaning/peace, faith) and spiritual struggle. As expected, T1 spiritual well-being was positively correlated with some aspects of psychological adjustment at T2, whereas T1 spiritual struggle was inversely correlated with T2 psychological adjustment. Both dimensions of T1 spiritual well-being, but not struggle, were positively associated with perceived T2 posttraumatic growth. In general, T1 spiritual well-being and struggle correlated with T2 psychological adjustment even when demographics and cancer-related variables were controlled.

Conclusions

These results suggest that while spirituality is not important to all AYA survivors, both spiritual well-being and struggle have important associations with adjustment and may warrant clinical attention. Future research is needed to more fully understand the role of spirituality in AYA survivors' adjustment in more depth. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/1TjcrSY
via IFTTT

Coping and resiliency enhancement program (CARE): a pilot study for interpreters in cancer care

Abstract

Objective

There is a growing demand for interpreters in the cancer setting. Interpreters, the link to quality care for limited English proficiency patients, face many psychosocial stressors in their work. This project assessed interpreters' experiences of stress and piloted a resiliency program to help interpreters cope with stressors.

Methods

From 2013 to 2014, we pilot tested a targeted resiliency program with interpreters from three Boston-based hospitals. In Phase 1, we conducted five focus groups (n = 31) to identify interpreters' psychosocial needs. In Phase 2, we developed and tested a 4-h group program with 29 interpreters (response rate = 90%; 69% female, 54% Hispanic, 85% born outside of the U.S.).

Results

Phase 1. Stressors were patient-based (seeing young patients decline), interactions with medical team (unsure of role), and systems-based (appointment unpredictability). Phase 2. At baseline interpreters reported low abilities to cope with stress (measured by the Measure of Current Status (MOCS-A)). At 4-week follow-up we found improvements in job satisfaction (p = .02; Cohen's d = .41) and declines in sick days (p = .08; Cohen's d = .38). Stress reactivity (MOCS-A) improved; specifically participants reported feeling more assertive about their needs (p = .10; Cohen's d = .30) and more able to relax at will (p = .10; Cohen's d = .35)—important mechanisms to lower distress.

Conclusions

We piloted a resiliency program for medical interpreters in cancer care. We found that interpreters experience distress and have low coping skills. This program resulted in improved work factors and stress reactivity. Future research should include further implementation and testing in a larger, randomized trial. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ov9AqY
via IFTTT

Oncology and medical education—past, present and future

from Cancer via ola Kala on Inoreader http://ift.tt/1shoI0R
via IFTTT

Long-term Follow-up Data from Pivotal Studies of Adjuvant Trastuzumab in Early Breast Cancer

Abstract

The addition of adjuvant trastuzumab therapy for 1 year to standard chemotherapy significantly improved disease-free survival and overall survival versus chemotherapy alone in a number of pivotal early breast cancer studies. Here we review long-term follow-up data on the efficacy, cardiac safety, and general safety of trastuzumab in these pivotal studies. We also evaluate ongoing phase II/III adjuvant trials with newer HER2-targeted agents and the efficacy and safety of the recently developed subcutaneous (SC) formulation of trastuzumab in early breast cancer. Long-term follow-up data confirm the significant survival benefit afforded by the addition of trastuzumab to chemotherapy in patients with HER2-positive disease, with an acceptable safety profile. Long-term cardiac safety data suggest that the incidence of cardiac adverse events is maintained at a relatively low level with continued follow-up. At this present time, 1 year of trastuzumab treatment remains the standard of care in HER2-positive early breast cancer. Future adjuvant trastuzumab treatment strategies should focus on reducing cardiotoxicity, particularly in elderly patients, by identifying potential predictive biomarkers of cardiac dysfunction. Clinicians must also decide whether to omit trastuzumab in women who would achieve little benefit from treatment to avoid cardiotoxicity.

from Cancer via ola Kala on Inoreader http://ift.tt/1Th4EGy
via IFTTT