MicroRNA-155 expression inversely correlates with pathologic stage of gastric cancer and it inhibits gastric cancer cell growth by targeting cyclin D1

Abstract

Purpose

MicroRNAs (miRs) have been frequently reported dysregulating in tumors and playing a crucial role in tumor development and progression. However, the expression of miR-155 and its role in gastric cancer (GC) are still obscure.

Methods

qRT-PCR was applied to detect miR-155 expression in 60 matched GC samples and four GC cell lines, and the relationship between miR-155 levels and clinicopathological features of GC was analyzed. Next, the effects of miR-155 on GC cell growth were evaluated by gain- and loss-of-function analysis. Finally, the target gene(s) of miR-155 in GC cells were explored.

Results

Our results revealed that miR-155 levels were significantly lower in both GC tissues and GC cell lines than in their normal controls, and its expression inversely correlated with tumor size and the pathologic stage. Moreover, our study showed that enforced expression of miR-155 impaired GC cell proliferation, promoted G1 phase arrest and induced apoptosis in vitro. In addition, we identified cyclin D1 as the direct target of miR-155, and knockdown of cyclin D1 partially phenocopied the role of miR-155 in GC cells.

Conclusions

Our findings suggest that miR-155 may act as a potential diagnostic marker for early-stage GC and may represent a novel therapeutic target for GC treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/1QKd8Bj
via IFTTT

Socioeconomic and Other Demographic Disparities Predicting Survival among Head and Neck Cancer Patients

Background

The Institute of Medicine (IOM) report, “Unequal Treatment,� which defines disparities as racially based, indicates that disparities in cancer diagnosis and treatment are less clear. While a number of studies have acknowledged cancer disparities, they have limitations of retrospective nature, small sample sizes, inability to control for covariates, and measurement errors.

Objective

The purpose of this study was to examine disparities as predictors of survival among newly diagnosed head and neck cancer patients recruited from 3 hospitals in Michigan, USA, while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality).

Methods

Longitudinal data were collected from newly diagnosed head and neck cancer patients (N = 634). The independent variables were median household income, education, race, age, sex, and marital status. The outcome variables were overall, cancer-specific, and disease-free survival censored at 5 years. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models were performed to examine demographic disparities in relation to survival.

Results

Five-year overall, cancer-specific, and disease-free survival were 65.4% (407/622), 76.4% (487/622), and 67.0% (427/622), respectively. Lower income (HR, 1.5; 95% CI, 1.1â€"2.0 for overall survival; HR, 1.4; 95% CI, 1.0â€"1.9 for cancer-specific survival), high school education or less (HR, 1.4; 95% CI, 1.1â€"1.9 for overall survival; HR, 1.4; 95% CI, 1.1â€"1.9 for cancer-specific survival), and older age in decades (HR, 1.4; 95% CI, 1.2â€"1.7 for overall survival; HR, 1.2; 95% CI, 1.1â€"1.4 for cancer-specific survival) decreased both overall and disease-free survival rates. A high school education or less (HR, 1.4; 95% CI, 1.0â€"2.1) and advanced age (HR, 1.3; 95% CI, 1.1â€"1.6) were significant independent predictors of poor cancer-specific survival.

Conclusion

Low income, low education, and advanced age predicted poor survival while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Recommendations from the Institute of Medicine’s Report to reduce disparities need to be implemented in treating head and neck cancer patients.

from Cancer via ola Kala on Inoreader http://ift.tt/24PiRz8
via IFTTT

Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p

from Cancer via ola Kala on Inoreader http://ift.tt/1p6gzuI
via IFTTT

Tumor Necrosis Factor Inhibition and Head and Neck Cancer Recurrence and Death in Rheumatoid Arthritis

The objective of this retrospective cohort study was to determine the effect of tumor necrosis factor inhibitor (TNFi) therapy on the risk of head and neck cancer (HNC) recurrence or HNC-attributable death in patients with rheumatoid arthritis (RA). RA patients with HNC were assembled from the US national Veterans’ Affairs (VA) administrative databases, and diagnoses confirmed and data collected by electronic medical record review. The cohort was divided into those treated with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) versus TNF inhibitors (TNFi) after a diagnosis of HNC. Likelihood of a composite endpoint of recurrence or HNC-attributable death was determined by Cox proportional hazards regression. Of 180 patients with RA and HNC, 31 were treated with TNFi and 149 with nbDMARDs after the diagnosis of HNC. Recurrence or HNC-attributable death occurred in 5/31 (16.1%) patients in the TNFi group and 44/149 (29.5%) patients in the nbDMARD group (p = 0.17); it occurred in 2/16 (13%) patients who received TNFi in the year prior to HNC diagnosis but not after. Overall stage at diagnosis (p = 0.03) and stage 4 HNC (HR 2.49 [CI 1.06â€"5.89]; p = 0.04) were risk factors for recurrence or HNC-attributable death; treatment with radiation or surgery was associated with a lower risk (HR 0.35 [CI 0.17â€"0.74]; p = 0.01 and HR 0.39 [CI 0.20â€"0.76]; p = 0.01 respectively). Treatment with TNFi was not a risk factor for recurrence or HNC-attributable death (HR 0.75; CI 0.31â€"1.85; p = 0.54). We conclude that treatment with TNFi may be safe in patients with RA and HNC, especially as the time interval between HNC treatment and non-recurrence increases. In this study, TNF inhibition was not associated with an increase in recurrence or HNC-attributable death.

from Cancer via ola Kala on Inoreader http://ift.tt/24PiPr8
via IFTTT

Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer

Head and neck squamous cell cancer (HNSCC) is the 7^th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.

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

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m²) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p

from Cancer via ola Kala on Inoreader http://ift.tt/24PiOU8
via IFTTT

Tumor-Associated Endothelial Cells Promote Tumor Metastasis by Chaperoning Circulating Tumor Cells and Protecting Them from Anoikis

Tumor metastasis is a highly inefficient biological process as millions of tumor cells are released in circulation each day and only a few of them are able to successfully form distal metastatic nodules. This could be due to the fact that most of the epithelial origin cancer cells are anchorage-dependent and undergo rapid anoikis in harsh circulating conditions. A number of studies have shown that in addition to tumor cells, activated endothelial cells are also released into the blood circulation from the primary tumors. However, the precise role of these activated circulating endothelial cells (CECs) in tumor metastasis process is not known. Therefore, we performed a series of experiments to examine if CECs promoted tumor metastasis by chaperoning the tumor cells to distal sites. Our results demonstrate that blood samples from head and neck cancer patients contain significantly higher Bcl-2-positive CECs as compared to healthy volunteers. Technically, it is challenging to know the origin of CECs in patient blood samples, therefore we used an orthotopic SCID mouse model and co-implanted GFP-labeled endothelial cells along with tumor cells. Our results suggest that activated CECs (Bcl-2-positive) were released from primary tumors and they co-migrated with tumor cells to distal sites. Bcl-2 overexpression in endothelial cells (EC-Bcl-2) significantly enhanced adhesion molecule expression and tumor cell binding that was predominantly mediated by E-selectin. In addition, tumor cells bound to EC-Bcl-2 showed a significantly higher anoikis resistance via the activation of Src-FAK pathway. In our in vivo experiments, we observed significantly higher lung metastasis when tumor cells were co-injected with EC-Bcl-2 as compared to EC-VC. E-selectin knockdown in EC-Bcl-2 cells or FAK/FUT3 knockdown in tumor cells significantly reversed EC-Bcl-2-mediated tumor metastasis. Taken together, our results suggest a novel role for CECs in protecting the tumor cells in circulation and chaperoning them to distal sites.

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

Prospective, single-center cohort study analyzing the efficacy of complete laparoscopic resection on recurrent hepatocellular carcinoma

Abstract

Background

Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma (HCC). However, few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy. The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence.

Methods

We conducted a prospective study of 64 patients, all of whom had undergone open surgery once before, who were diagnosed with recurrent HCC between June 2014 and November 2014. The laparoscopic group (n = 31) underwent laparoscopic hepatectomy, and the control group (n = 33) underwent conventional open surgery. Operation time, intraoperative blood loss, surgical margins, postoperative pain scores, postoperative time until the patient could walk, anal exsufflation time, length of hospital stay, and inpatient costs were compared between the two groups. The patients were followed up for 1 year after surgery, and relapse-free survival was compared between the two groups.

Results

All surgeries were successfully completed. No conversion to open surgery occurred in the laparoscopic group, and no serious postoperative complications occurred in either group. No significant difference in inpatient costs was found between the laparoscopic group and the control group (P = 0.079), but significant differences between the two groups were observed for operation time (116.7 ± 37.5 vs. 148.2 ± 46.7 min, P = 0.031), intraoperative blood loss (117.5 ± 35.5 vs. 265.9 ± 70.3 mL, P = 0.012), postoperative time until the patient could walk (1.6 ± 0.6 vs. 2.2 ± 0.8 days, P < 0.05), anal exsufflation time (2.1 ± 0.3 vs. 2.8 ± 0.7 days, P = 0.041), visual analogue scale pain score (P < 0.05), postoperative hepatic function (P < 0.05), and length of hospital stay (4.5 ± 1.3 vs. 6.0 ± 1.2 days, P = 0.014). During the 1-year postoperative follow-up period, 6 patients in each group had recurrent HCC on the side of the initial operation, but no significant difference between groups was observed in the recurrence rate or relapse-free survival. In the laparoscopic group, operation time, postoperative time until the patient could walk, anal exsufflation time, and inpatient costs were not different (P > 0.05) between the patients with contralateral HCC recurrence (n = 18) and those with ipsilateral HCC recurrence (n = 13). However, intraoperative blood loss was significantly less (97.7 ± 14.0 vs. 186.3 ± 125.6 mL, P = 0.012) and the hospital stay was significantly shorter (4.2 ± 0.7 vs. 6.1 ± 1.7 days, P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence.

Conclusions

For the patients who previously underwent conventional open surgical resection of HCC, complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time, less intraoperative blood loss, and a faster postoperative recovery than conventional open surgery. Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.

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

Fever of Unknown Origin in Cancer Patients

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): A. Loizidou, M. Aoun, J. Klastersky
Fever of unknown origin (FUO) remains a challenging clinical problem, namely in patients with cancer. In cancer patients, FUO may be due to the cancer itself, as it is the case of hematological malignancies; digestive tumors (colon cancer, liver metastases) are significantly associated with FUO and infection can be demonstrated in some cases. Prevention with G-CSF and empirical antimicrobial therapy are essential approaches for the management of FUO in cancer patients. New diagnostic approaches, such as PET imaging, should be further evaluated in cancer patients with FUO.



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

PET-adapted omission of radiotherapy in early stage Hodgkin lymphoma − a systematic review and meta-analysis

Publication date: Available online 6 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Marie T. Sickinger, Bastian von Tresckow, Carsten Kobe, Peter Borchmann, Andreas Engert, Nicole Skoetz
BackgroundHodgkin lymphoma (HL) is one of the most common malignancies in young adults and one of the most curable cancers worldwide. With interim PET-scan, HL treatment is in the process of being modified: A negative or positive interim PET separates good and poor responders to initial therapy; therefore, deescalated or escalated additional treatment is currently being evaluated in clinical trials.MethodsThe Cochrane Library, MEDLINE and conference proceedings were searched until 05.2015 for randomized controlled trials (RCTs) comparing FDG-PET-adapted therapy to standard treatment in untreated early stage HL patients with a negative PET-scan. Two review authors independently screened search results and extracted relevant study data. Hazard ratios (HR) were used for time-to-event data and risk rations (RR) for dichotomous data, with 95% confidence intervals (CI). If trials were considered sufficiently clinically homogenous, fixed-effect model was used to pool data.ResultsThree RCTs involving a total of 1480 participants were included in the meta-analysis. Only one trial provided data for OS, without evidence for a difference between both arms (HR 0.51; 95% CI 0.15 to 1.68). All three trials assessed progression free survival, which was inferior in the PET-adapted arms (without radiotherapy) compared to the standard treatment arms (HR 2.40; 95% CI 1.63 to 3.53). Adverse events were reported in one study only, without evidence for a difference between both arms. There were no data on long-term adverse events, quality of life and treatment-related mortality availableConclusionTo date, no robust data on survival and adverse events are available. However, this systematic review found that PFS was significantly decreased in the PET-adapted treatment arm (without radiotherapy) in early stage HL patients.



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

Impact of Dermatologic adverse events induced by targeted therapies on quality of life

Publication date: Available online 5 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Cécile Charles, Catherine Bungener, Darius Razavi, Christine Mateus, Emilie Routier, Emilie Lanoy, Michèle Verschoore, Caroline Robert, Sarah Dauchy
BackgroundInvestigations about the impact of dermatologic adverse events on quality of life in the context of targeted therapies are quite recent and results vary in some dimensions. This article aims to summarize the existing data and to clarify needs in terms of clinical management and future research.MethodsA literature review was done with Pubmed, Medline, Scopus and PsycInfo databases and it combined the empirical studies published in English and in French over the past ten years.Results and conclusionsDermatologic adverse events globally have a low to moderate impact on quality of life, mainly in the physical and emotional domains. Reasons for inter-individual variations in adjustment and long-term impact are still not well known. Making quality of life assessments systematic, making early referrals of patients to dermatology consultations and giving more attention to individual experience were identified as measures that could help prevent deterioration in quality of life.



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

Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques

Publication date: Available online 5 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Giuseppe Rubini, Artor Niccoli-Asabella, Cristina Ferrari, Vito Racanelli, Nicola Maggialetti, Francesco Dammacco
Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient's quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and disadvantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra-medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two mentioned imaging procedures and is particularly useful not only for the detection of osteolytic lesions unrevealed by conventional X-ray, but also in the assessment of prognosis and therapeutic response.



from Cancer via ola Kala on Inoreader http://ift.tt/1p7MtHP
via IFTTT

Treatment that follows guidelines closely dramatically improves overall survival of patients with anal canal and margin cancers

Publication date: Available online 4 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Jean-Baptiste Delhorme, Delphine Antoni, Kimberley S. Mak, François Severac, Kelle C. Freel, Catherine Schumacher, Serge Rohr, Cécile Brigand, Georges Noel
BackgroundTo assess relevance of ESMO-ESSO-ESTRO treatment guidelines in a retrospective analysis of patients with anal canal or anal margin cancers.Material and methods155 patients were separated into standard treatment group (STG), treated according to or closely the guidelines, and an altered treatment group (ATG).ResultsThe median follow-up time was 50.7 months. In the STG, the 5- and 10-year LR-DFS rates were 75.2% and 72.7%; in the ATG, they were 66.8% and 61.2%, respectively. In the STG, the 5- and 10-year OS rates were 81.8% and 68%; in the ATG, they were 63.3% and 49.5%, respectively (p=0.037). In the multivariate analysis, favorable prognostic factors for OS included the standard treatment, age <60, tumor < T3, no HIV infection and a total radiation dose >50.4Gy.ConclusionThis study identifies the superiority of treatment according to standard guidelines compared to altered treatment. Our results corroborate the guidelines.



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

Paget Disease of the Vulva

Publication date: Available online 4 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): M. van der Linden, K.A.P. Meeuwis, J. Bulten, T. Bosse, M.I.E. van Poelgeest, J.A. de Hullu
In this review, we provide an overview of the clinical aspects, histopathology, molecular genetics, and treatment options for Vulvar Paget's Disease (VPD), a rare skin disease, most commonly found in postmenopausal Caucasian women. The underlying cause of VPD remains not well understood. VPD is rarely associated with an underlying urogenital, gastrointestinal or vulvar carcinoma. In approximately 25% of the cases, VPD is invasive; in these cases, the prognosis is worse than in non-invasive cases. Recurrence rates in invasive VPD are high: 33% in cases with clear margins, and even higher when surgical margins are not clear, regardless of invasion. Historically, surgical excision has been the treatment of choice. Recent studies show that imiquimod cream may be an effective and safe alternative.



from Cancer via ola Kala on Inoreader http://ift.tt/1QJVGN7
via IFTTT

Correlation between PD-L1 expression and outcome of NSCLC patients treated with anti-PD-1/PD-L1 agents: A meta-analysis

Publication date: Available online 6 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Omar Abdel-Rahman
BackgroundA meta analysis of the correlation between PD-L1 levels and outcomes of PD-1/PD-L1 inhibitors in advanced non small cell lung cancer (NSCLC) has been performed.MethodsEligible studies included those evaluating PD-1/PD-L1 inhibitors in advanced NSCLC and correlating the outcomes to PD-L1 levels.ResultsThe search strategy yielded 250 potentially relevant citations from searched databases. After preclusion of ineligible studies, 12 studies were included. Comparing PD-1/PD-L1 inhibitors to docetaxel in second line treatment, the pooled hazard ratio (HR) for progression free survival (PFS) and overall survival (OS) was 0.75 (95% CI 0.62–0.90; p=0.002) and 0.61 (95% CI 0.50-75; p=0.00001) respectively; while the pooled odds ratio (OR) for objective response rate (ORR) was 1.98 (95% CI 1.28–3.07; p=0.002) in the PD-L1>1% population. Moreover, for PD-L1>1% patients versus PD-L1<1% patients treated with PD-1/PD-L1 targeted agents, the OR of ORR was 2.18 (95% CI 1.45–3.29; p=0.0002); while for PD-L1>5% patients versus PD-L1<5% patients, it was 2.66 (95% CI 1.74–4.07; p<0.00001); and for PD-L1>10% versus PD-L1<10% patients, it was 3.38 (95% CI 2.23–5.13; p<0.00001); and for PD-L1>50% versus PD-L1<50% patients, it was 3.99 (95% CI 2.81–5.66; p<0.00001).ConclusionsThe current analysis of data indicates that the benefit from PD-1 inhibitors versus docetaxel in second line treatment of NSCLC is limited to the PD-L1>1% subpopulation. Moreover, a possible dose effect relationship between the intensity of PD-L1 staining and the potential benefit from PD-1/PD-L1 targeted agents does exist with higher intensity associated with higher ORR.



from Cancer via ola Kala on Inoreader http://ift.tt/1TqDT3t
via IFTTT

Diagnostic accuracy of serum biomarkers for head and neck cancer: A systematic review and meta-analysis

Publication date: Available online 4 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Eliete Neves Silva Guerra, Daniela Fortunato Rêgo, Silvia Taveira Elias, Ricardo D. Coletta, Luis André Mendonça Mezzomo, David Gozal, Graziela De Luca Canto
Serum biomarkers could be helpful to characterize head and neck squamous cell carcinoma (HNSCC). Thus, the purpose of this systematic review and meta-analysis was to determine the diagnostic capability of serum biomarkers in the assessment of HNSCC patients. Studies were gathered by searching LILACS, PubMed, Science Direct, Scopus and Web of Science up to April 10th, 2015. Studies that focused on serum biomarkers in the diagnosis of HNSCC compared with controls were considered. Sixty-five studies were identified, and the sample size included 9098 subjects. Combined biomarkers demonstrated improved accuracy than those tested individually. Therefore, 12.8% of single and 34.3% of combined indicated that serum biomarkers discriminate patients with HNSCC from controls. The combined biomarkers with better diagnostic capability included Epidermal growth factor receptor (EGFR)+Cyclin D1 and squamous cell cancer-associated antigen (SCCA)+EGFR+Cyclin D1. Beta2-microglobin may also be a promising single biomarker for future studies. Serum biomarkers can be potentially useful in the diagnosis of HNSCC. However, further research is required to validate these biomarkers.



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

Editorial Board

Publication date: March 2016
Source:Critical Reviews in Oncology/Hematology, Volume 99





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

BRAF mutations in non-small cell lung cancer: has finally Janus opened the door?

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Rafael Caparica, Gilberto de Castro, Ignacio Gil-Bazo, Christian Caglevic, Raffaele Calogero, Marco Giallombardo, Edgardo S. Santos, Luis E. Raez, Christian Rolfo
B-Raf mutations occur in about 1–2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warranted to validate these findings. Enrollment of these patients in clinical trials is an interesting strategy to offer a potentially more effective and less toxic targeted therapy.



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

Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: A meta-analysis of published trials

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Giandomenico Roviello, Sandra Sigala, Romano Danesi, Marzia del Re, Alberto Bonetta, Maria Rosa Cappelletti, Laura Zanotti, Alberto Bottini, Daniele Generali
Abiraterone acetate and orteronel are two CYP-17 inhibitors that have been studied in prostate cancer. They have shown relevant toxicities, including fluid retention/oedema, hypokalaemia, hypertension, liver function test abnormalities and cardiac events. The goal of this study was to determine the risk of special adverse events related to CYP- 17 inhibitor in patients with metastatic castration-resistant prostate cancer (CRCP). Summary data from four randomized phase III trials comparing CYP-17 inhibitors and prednisone versus placebo and prednisone in metastatic CRCP patients were meta-analysed. Pooled risk ratios (RRs) for the risk of all-grade and grade 3–4 adverse events of special interest were calculated. Data from 4916 patients (2849 in the AA experimental arm; 2067 in the control arm) were analysed. The incidence of grade 3 to 4 adverse events was never more than 10% of the patients. However, compared with placebo, the CYP-17 inhibitor significantly increased the all-grade events of hypertension (RR=1.53; 95% CI=1.3–1.8; p<0.00001), hypokalaemia (RR=1.56; 95% CI=1.29–1.89; p<0.00001), cardiac disorders (RR=1.47; 95% CI=1.27–1.7; p<0.00001) liver function test abnormalities (RR=1.93; 95% CI=1.15–3.24; p=0.01) grade ≥3 adverse events, hypokalaemia (RR=4.23; 95% CI=1.28–13.99; p=0.02) and cardiac disorders (RR=1.55; 95% CI=1.18–2.05; p=0.002). A lot of adverse events such as hypertension, hypokalaemia, cardiac disorders and liver function test abnormalities are increased during CYP-17 inhibitor based therapy. Strict monitoring of these side effects should be considered during CYP- 17 inhibitor therapy in prostate cancer patients.



from Cancer via ola Kala on Inoreader http://ift.tt/1TqDQo3
via IFTTT

The psychosocial outcomes of individuals with hematological cancers: Are we doing enough high quality research, and what is it telling us?

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Jamie Bryant, Elise Mansfield, Alix Hall, Amy Waller, Allison Boyes, Amanda Jayakody, Natalie Dodd, Rob Sanson-Fisher
This systematic review assessed the quantity and quality of research examining the psychosocial outcomes among hematological cancer patients. Studies were categorised as either measurement, descriptive or intervention. Intervention studies were further assessed according to Effective Practice and Organisation of Care (EPOC) methodological criteria. A total of 261 eligible papers were identified. The number of publications increased by 8.8% each year (95% CI=7.5–10.2%; p<0.0001). The majority of studies were descriptive (n=232; 89%), with few measurement (n=8; 3%) and intervention (n=21; 8%) studies identified. Ten intervention studies met EPOC design criteria, however only two interventions, one targeted at individuals with Hodgkin's or Non-Hodgkin's lymphoma and one targeted at individuals with leukaemia, lymphoma or myelomatosis were successful in improving patients' psychosocial outcomes. Despite an increasing volume of research examining psychosocial outcomes of hematological cancer patients, there is a need for robust measurement and methodologically rigorous intervention research in this area.



from Cancer via ola Kala on Inoreader http://ift.tt/1QJVI7I
via IFTTT

Male breast cancer is not congruent with the female disease

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Ian S. Fentiman
It has become customary to extrapolate from the results of treatment trials for female breastcancer and apply them to males with the disease. In the absence of results from national and international randomised trials for male breast cancer (MBC) this appears superficially to be an appropriate response. Closer examination of available data reveals that aspects of the aetiology and treatment of MBC do not fit the simplistic model that men usually have endocrine sensitive tumours which behave like those in postmenopausal women. Most females and males with breast cancer have none of the recognised risk factors, indicating the gaps in our knowledge of the epidemiology of this disease. Several studies have compared epidemiological risk factors for MBC and female breast cancer (FBC) but many have been blighted by small numbers. In comparison with FBC there is a larger proportion of BRCA2 tumours, (occurring in 10% of MBC), and underrepresentation of BRCA1 tumours (found in only 1%), suggesting significant differences in the genetic aetiology of MBC and FBC.Genome-wide association studies in FBC reported single nucleotide polymorphisms (SNPs) in 12 novel independent loci were consistently associated with disease but for MBC 2 SNPs had a significantly increased risk. Molecular profiles of matched cancers in males and females showed a gender-associated modulation of major processes including energy metabolism, regulation of translation, matrix remodelling and immune recruitment. Immunohistochemistry for kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 indicate a significant difference in the immunostaining of tumours from male patients compared with females.MBC is almost always estrogen receptor positive (ER+ve) and so systemic treatment is usually endocrine. With evidence in FBC that aromatase inhibitors are more effective than tamoxifen in the postmenopausal it was seemingly logical that the same would be true for MBC. Results however suggest less efficacy with AIs and an increase in risk of mortality compared to tamoxifen. The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. These important biological differences point the way to the development of new therapies for MBC based on differences rather than similarities with FBC.



from Cancer via ola Kala on Inoreader http://ift.tt/1TqDQ7L
via IFTTT

Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response

Publication date: Available online 27 February 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Nicolas De Picciotto, Wulfran Cacheux, Arnaud Roth, Pierre O. Chappuis, S. Intidhar Labidi-Galy
Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that protects the genome from double-strand DNA damage. Recent studies revealed frequent somatic mutations of BRCA1/BRCA2 and hypermethylation of the promoter of BRCA1 in EOC, in addition to germline mutations. Comparison of DNA copy number changes in tumors with or without BRCA1/BRCA2 alterations, lead to the identification of several signatures that detect HR pathway defects, here named "HRness". These signatures predict platinum-sensitivity and survival in EOC, as it was previously shown for germline mutations of BRCA1/BRCA2. They are currently investigated in clinical trials as potential predictive biomarker for response to poly(ADP- ribose) polymerase inhibitors.



from Cancer via ola Kala on Inoreader http://ift.tt/1KV5VBm
via IFTTT

Association of methylenetetrahydrofolate reductase ( MTHFR ) gene C677T polymorphism with autism: evidence of genetic susceptibility

Abstract

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (OR_Tvs.C = 1.48; 95 % CI: 1.18–1.86; P = 0.0007; OR_{TT + CT vs. CC} = 1.70, 95 % CI = 0.96–2.9, p = 0.05; OR_{TT vs. CC} = 1.84, 95 % CI = 1.12–3.02, p = 0.02; OR_{CT vs.CC} = 1.60, 95 % CI = 1.2–2.1, p = 0.003; OR_{TT vs.CT+CC} = 1.5, 95 % CI = 1.02–2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (OR_Tvs.C = 1.43; 95 % CI = 1.1–1.87; p = 0.009) and Asian population (OR_Tvs.C = 1.68; 95 % CI = 1.02–2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.

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

Iris metastasis of gastric adenocarcinoma

Abstract

Background

Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis.

Case presentation

A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy.

Conclusions

Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.

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

Downregulation of selenium-binding protein 1 is associated with poor prognosis in lung squamous cell carcinoma

Abstract

Background

We found that selenium-binding protein 1 (SBP1) was progressively decreased in the human bronchial epithelial carcinogenic processes. Knockdown of SBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. However, the relationship between SBP1 expression and clinicopathological factors of patients has not been defined completely. The specific role of SBP1 in prognosis of lung squamous cell carcinoma (LSCC) is still unknown.

Methods

Tissue samples from 82 patients treated by pulmonary lobectomy for LSCC were used. Immunohistochemistry and western blotting were used to detect the expressions of SBP1 protein. The relationships between the expression level of SBP1 and the clinicopathological features of patients were analyzed. Cox proportional hazard regression analysis and Kaplan–Meier method were used to perform survival analysis.

Results

Expressions of SBP1 proteins were significantly lower in LSCC tissues than that in the corresponding normal bronchial epithelium (NBE) tissues (P = 0.000). In LSCC, The expression levels of SBP1 had not correlated with patients' age, gender, smoking state, primary tumor stages (T), TNM clinical stages, and distant metastasis (M) (P > 0.05). However, downregulation of SBP1 was significantly associated with higher lymph node metastasis and lower overall survival rate (P < 0.05). Cox regression analysis indicated low expressions of SBP1 can be an independent prognostic factor for poor overall survival in LSCC patients (P = 0.002).

Conclusions

Downregulation of SBP1 may play a key role in the tumorigenic process of LSCC. SBP1 may be a novel potential prognostic factor of LSCC.

from Cancer via ola Kala on Inoreader http://ift.tt/24OQ0Lk
via IFTTT

The ALPPS procedure as a novel “liver-first” approach in treating liver metastases of colon cancer: the first experience in Greek Cypriot area

Abstract

Background

Despite recent advances in multimodality and multidisciplinary treatment of colorectal liver metastases, many patients suffer from extensive bilobar disease, which prevents the performance of a single procedure due to an insufficient future liver remnant (FLR). We present a novel indication for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a "liver-first" approach when inadequate FLR was faced preoperatively, in a patient with extensive bilobar liver metastatic disease of colon cancer origin.

Case presentation

A 51-year-old lady was referred to our center due to a stage IV colon cancer with extensive bilobar liver disease and synchronous colon obstruction. During the multidisciplinary tumor board, it was recommended to proceed first in a palliative loop colostomy (at the level of transverse colon) operation and afterwards to offer her palliative chemotherapy. After seven cycles of chemotherapy, the patient was re-evaluated by CT scans that revealed an excellent response (>30 %), but the metastatic liver disease was still considered inoperable. Moreover, with the completion of 12 cycles, the indicated restaging process showed further response. Subsequent to a thorough review by the multidisciplinary team, it was decided to proceed to the ALPPS procedure as a feasible means to perform extensive or bilobar liver resections, combined with a decreased risk of tumor progression in the interim.

Conclusions

All in all, ALPPS can offer a feasible but surgically demanding liver-first approach with satisfactory short-term results in selected patients. Larger studies are mandatory to evaluate short- and long-term results of the procedure on survival, morbidity, and mortality.

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

Flap fixation reduces seroma in patients undergoing mastectomy: a significant implication for clinical practice

Abstract

Background

Seroma formation is a common complication following mastectomy for invasive breast cancer. Mastectomy flap fixation is achieved by reducing dead space volume using interrupted subcutaneous sutures.

Methods

All patients undergoing mastectomy due to invasive breast cancer or ductal carcinoma in situ (DCIS) were eligible for inclusion. From May 2012 to March 2013, all patients undergoing mastectomy in two hospitals were treated using flap fixation. The skin flaps were sutured on to the pectoral muscle using polyfilament absorbable sutures. The data was retrospectively analysed and compared to a historical control group that was not treated using flap fixation (May 2011 to March 2012).

Results

One hundred and eighty patients were included: 92 in the flap fixation group (FF) and 88 in the historical control group (HC). A total of 33/92 (35.9 %) patients developed seroma in the group that underwent flap fixation; 52/88 (59.1 %) patients developed seroma in the HC group (p = 0.002). Seroma aspiration was performed in 14/92 (15.2 %) patients in the FF group as opposed to 38/88 (43.2 %) patients in the HC group (p < 0.001).

Conclusions

Flap fixation is an effective surgical technique in reducing dead space and therefore seroma formation and seroma aspirations in patients undergoing mastectomy for invasive breast cancer or DCIS.

from Cancer via ola Kala on Inoreader http://ift.tt/24OQ0v0
via IFTTT

Neoadjuvant imatinib treatment and laparoscopic anus-preserving surgery for a large gastrointestinal stromal tumor of the rectum

Abstract

Background

Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST.

Case presentation

A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery.

Conclusions

Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.

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

Misdiagnosis of primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type, a case report

Abstract

Background

Extra-nodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue originating in the liver is less common.

Case presentation

We described the clinical presentation, immunohistochemistry, and immunophenotypes of this lymphoma, which was misdiagnosed with tiny hepatic carcinoma in a 44-year-old woman with hepatitis C; the patient underwent left lateral sectionectomy. The immunophenotype identified the most of the lymphoid cells as positive CD20, CD34, Ki67, CD3, CD4, CD79a, CD45RO, MUM-1, and CD5 and negative CD10, CD15, CD30, ACT, CK, CRO, DES, and HMB45. The diagnosis of primary hepatic mucosa-associated lymphoid tissue (MALT) was made by histology after surgery; the patient went through the excellent recovery with no chemotherapy and is disease free for 27 months.

Conclusions

Primary hepatic MALT is less common with incidental finding; local resection is beneficial due to its oncological indolence.

from Cancer via ola Kala on Inoreader http://ift.tt/24OQ1Pi
via IFTTT

Warburg effect(s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism

Abstract

Virtually everyone working in cancer research is familiar with the "Warburg effect", i.e., anaerobic glycolysis in the presence of oxygen in tumor cells. However, few people nowadays are aware of what lead Otto Warburg to the discovery of this observation and how his other scientific contributions are seminal to our present knowledge of metabolic and energetic processes in cells. Since science is a human endeavor, and a scientist is imbedded in a network of social and academic contacts, it is worth taking a glimpse into the biography of Otto Warburg to illustrate some of these influences and the historical landmarks in his life. His creative and innovative thinking and his experimental virtuosity set the framework for his scientific achievements, which were pioneering not only for cancer research. Here, I shall allude to the prestigious family background in imperial Germany; his relationships to Einstein, Meyerhof, Krebs, and other Nobel and notable scientists; his innovative technical developments and their applications in the advancement of biomedical sciences, including the manometer, tissue slicing, and cell cultivation. The latter were experimental prerequisites for the first metabolic measurements with tumor cells in the 1920s. In the 1930s–1940s, he improved spectrophotometry for chemical analysis and developed the optical tests for measuring activities of glycolytic enzymes. Warburg's reputation brought him invitations to the USA and contacts with the Rockefeller Foundation; he received the Nobel Prize in 1931. World politics and world wars heavily affected Warburg's scientific survival in Berlin. But, after his second postwar recovery, Warburg's drive for unraveling the energetic processes of life, both in plants and in tumor cells, continued until his death in 1970. The legacy of Otto Warburg is not only the Warburg effect, but also the identification of the "respiratory ferment" and hydrogen-transferring cofactors and the isolation of glycolytic enzymes. His hypothesis of respiratory damage being the cause of cancer remains to be a provocative scientific issue, along with its implications for cancer treatment and prevention. Warburg is therefore still stimulating our thinking, as documented in a soaring increase in publications citing his name in the context of tumor metabolism.

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

Clinical significance of [ 18 F]-fluoro-deoxy-glucose positron emission tomography/computed tomography in patients with primary malignant melanoma of the esophagus: report of three cases

Abstract

Primary malignant melanoma of the esophagus (PMME) is a rare disease with poor prognosis. [¹⁸F]-Fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been used extensively for initial tumor staging, therapeutic monitoring, and follow-up evaluation in various malignant tumors, but the significance of FDG-PET in PMME is currently unknown. Herein, we report 3 cases of PMME. In all 3 cases, histological and immunohistochemical examination of the biopsy specimens led to diagnoses of malignant melanoma. FDG-PET/computed tomography was performed in all cases, and was useful for the detection of distant metastases. However, the identification of lymph node metastases at initial diagnosis was difficult. Esophagectomy was performed in one case, while systemic chemotherapy was administered in 2 cases. All 3 patients had a poor prognosis; the mean survival time was 13.3 months. In conclusion, PET/computed tomography is useful for the detection of distant metastasis at initial diagnosis as well as the therapeutic monitoring of PMME.

from Cancer via ola Kala on Inoreader http://ift.tt/1Swmpl7
via IFTTT

Three Authors Reply

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4qga
via IFTTT

Re: "Estimating Causal Associations of Fine Particles With Daily Deaths in Boston"

from Cancer via ola Kala on Inoreader http://ift.tt/1THXY5B
via IFTTT

Re: "A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer"

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4rAE
via IFTTT

Contents Page

from Cancer via ola Kala on Inoreader http://ift.tt/1THXY5x
via IFTTT

Comparison of Self-Reported Sleep Duration With Actigraphy: Results From the Hispanic Community Health Study/Study of Latinos Sueno Ancillary Study

Most studies of sleep and health outcomes rely on self-reported sleep duration, although correlation with objective measures is poor. In this study, we defined sociodemographic and sleep characteristics associated with misreporting and assessed whether accounting for these factors better explains variation in objective sleep duration among 2,086 participants in the Hispanic Community Health Study/Study of Latinos who completed more than 5 nights of wrist actigraphy and reported habitual bed/wake times from 2010 to 2013. Using linear regression, we examined self-report as a predictor of actigraphy-assessed sleep duration. Mean amount of time spent asleep was 7.85 (standard deviation, 1.12) hours by self-report and 6.74 (standard deviation, 1.02) hours by actigraphy; correlation between them was 0.43. For each additional hour of self-reported sleep, actigraphy time spent asleep increased by 20 minutes (95% confidence interval: 19, 22). Correlations between self-reported and actigraphy-assessed time spent asleep were lower with male sex, younger age, sleep efficiency <85%, and night-to-night variability in sleep duration ≥1.5 hours. Adding sociodemographic and sleep factors to self-reports increased the proportion of variance explained in actigraphy-assessed sleep slightly (18%–32%). In this large validation study including Hispanics/Latinos, we demonstrated a moderate correlation between self-reported and actigraphy-assessed time spent asleep. The performance of self-reports varied by demographic and sleep measures but not by Hispanic subgroup.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4pZx
via IFTTT

Announcement

from Cancer via ola Kala on Inoreader http://ift.tt/1THXVH6
via IFTTT

Sex-Based Differences in Rates, Causes, and Predictors of Death Among Injection Drug Users in Vancouver, Canada

In the present study, we sought to identify rates, causes, and predictors of death among male and female injection drug users (IDUs) in Vancouver, British Columbia, Canada, during a period of expanded public health interventions. Data from prospective cohorts of IDUs in Vancouver were linked to the provincial database of vital statistics to ascertain rates and causes of death between 1996 and 2011. Mortality rates were analyzed using Poisson regression and indirect standardization. Predictors of mortality were identified using multivariable Cox regression models stratified by sex. Among the 2,317 participants, 794 (34.3%) of whom were women, there were 483 deaths during follow-up, with a rate of 32.1 (95% confidence interval (CI): 29.3, 35.0) deaths per 1,000 person-years. Standardized mortality ratios were 7.28 (95% CI: 6.50, 8.14) for men and 15.56 (95% CI: 13.31, 18.07) for women. During the study period, mortality rates related to infection with human immunodeficiency virus (HIV) declined among men but remained stable among women. In multivariable analyses, HIV seropositivity was independently associated with mortality in both sexes (all P < 0.05). The excess mortality burden among IDUs in our cohorts was primarily attributable to HIV infection; compared with men, women remained at higher risk of HIV-related mortality, indicating a need for sex-specific interventions to reduce mortality among female IDUs in this setting.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4rk5
via IFTTT

Editorial: Gun Violence--Risk, Consequences, and Prevention

from Cancer via ola Kala on Inoreader http://ift.tt/1THXXP3
via IFTTT

Hierarchical Distributed-Lag Models: Exploring Varying Geographic Scale and Magnitude in Associations Between the Built Environment and Health

It is well known that associations between features of the built environment and health depend on the geographic scale used to construct environmental attributes. In the built environment literature, it has long been argued that geographic scales may vary across study locations. However, this hypothesized variation has not been systematically examined due to a lack of available statistical methods. We propose a hierarchical distributed-lag model (HDLM) for estimating the underlying overall shape of food environment–health associations as a function of distance from locations of interest. This method enables indirect assessment of relevant geographic scales and captures area-level heterogeneity in the magnitudes of associations, along with relevant distances within areas. The proposed model was used to systematically examine area-level variation in the association between availability of convenience stores around schools and children's weights. For this case study, body mass index (weight kg)/height (m)²) z scores (BMIz) for 7th grade children collected via California's 2001–2009 FitnessGram testing program were linked to a commercial database that contained locations of food outlets statewide. Findings suggested that convenience store availability may influence BMIz only in some places and at varying distances from schools. Future research should examine localized environmental or policy differences that may explain the heterogeneity in convenience store–BMIz associations.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4pIR
via IFTTT

A Note From the Editors

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

Basu et al. Respond to "Interdisciplinary Approach for Policy Evaluation"

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4r3C
via IFTTT

Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study

The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease.

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

Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC-Potsdam Study

Higher levels of insulin-like growth factor–binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study. We included a randomly selected subcohort of persons without T2DM at the time of blood sampling (n = 2,269) and 776 individuals with incident T2DM identified between 1994 and 2005. For the highest quartile versus lowest, the multivariable-adjusted hazard rate ratios were 0.91 (95% confidence interval (CI): 0.68, 1.23; P for trend = 0.31) for IGF-1, 1.33 (95% CI: 1.00, 1.76; P for trend = 0.04) for IGFBP-3, and 0.77 (95% CI: 0.57, 1.03; P for trend = 0.03) for IGF-1:IGFBP-3 ratio. IGFBP-3 level remained positively associated with T2DM incidence—and the ratio of IGF-1 to IGFBP-3 was inversely related with T2DM incidence—in models that included adjustment for IGF-1 concentrations (P for trend < 0.05). Therefore, our findings do not confirm an association between total IGF-1 concentrations and risk of T2DM in the general study population, although higher IGFBP-3 levels might raise T2DM risk independent of IGF-1 levels.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4pst
via IFTTT

Editorial Board

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

Incorporating Transmission Into Causal Models of Infectious Diseases for Improved Understanding of the Effect and Impact of Risk Factors

Conventional measures of causality (which compare risks between exposed and unexposed individuals) do not factor in the population-scale dynamics of infectious disease transmission. We used mathematical models of 2 childhood infections (respiratory syncytial virus and rotavirus) to illustrate this problem. These models incorporated 3 causal pathways whereby malnutrition could act to increase the incidence of severe infection: increasing the proportion of infected children who develop severe infection, increasing the children's susceptibility to infection, and increasing infectiousness. For risk factors that increased the proportion of infected children who developed severe infection, the population attributable fraction (PAF) calculated conventionally was the same as the PAF calculated directly from the models. However, for risk factors that increased transmission (by either increasing susceptibility to infection or increasing infectiousness), the PAF calculated directly from the models was much larger than that predicted by the conventional PAF calculation. The models also showed that even when conventional studies find no association between a risk factor and an outcome, risk factors that increase transmission can still have a large impact on disease burden. For a complete picture of infectious disease causality, transmission effects must be incorporated into causal models.

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4psp
via IFTTT

Subscription Page

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

Re: "Estimating Causal Associations of Fine Particles With Daily Deaths in Boston"

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4qN0
via IFTTT

Health Behaviors, Mental Health, and Health Care Utilization Among Single Mothers After Welfare Reforms in the 1990s

We studied the health of low-income US women affected by the largest social policy change in recent US history: the 1996 welfare reforms. Using the Behavioral Risk Factor Surveillance System (1993–2012), we performed 2 types of analysis. First, we used difference-in-difference-in-differences analyses to estimate associations between welfare reforms and health outcomes among the most affected women (single mothers aged 18–64 years in 1997; n = 219,469) compared with less affected women (married mothers, single nonmothers, and married nonmothers of the same age range in 1997; n = 2,422,265). We also used a synthetic control approach in which we constructed a more ideal control group for single mothers by weighting outcomes among the less affected groups to match pre-reform outcomes among single mothers. In both specifications, the group most affected by welfare reforms (single mothers) experienced worse health outcomes than comparison groups less affected by the reforms. For example, the reforms were associated with at least a 4.0-percentage-point increase in binge drinking (95% confidence interval: 0.9, 7.0) and a 2.4-percentage-point decrease in the probability of being able to afford medical care (95% confidence interval: 0.1, 4.8) after controlling for age, educational level, and health care insurance status. Although the reforms were applauded for reducing welfare dependency, they may have adversely affected health.

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

Cover Page

from Cancer via ola Kala on Inoreader http://ift.tt/1Ys4pc5
via IFTTT

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing

Molecular Therapy 24, 422 (March 2016). doi:10.1038/mt.2016.21

Authors: Michael T Certo & Richard A Morgan

from Cancer via ola Kala on Inoreader http://ift.tt/1QI3Dm7
via IFTTT

A New Induction to the Gene and Cell Therapy Hall Of Fame: Genome Editing

A New Induction to the Gene and Cell Therapy Hall Of Fame: Genome Editing

Molecular Therapy 24, 407 (March 2016). doi:10.1038/mt.2016.25

Author: Michel Sadelain

from Cancer via ola Kala on Inoreader http://ift.tt/1TovD3Q
via IFTTT

Genome-editing Technologies for Gene and Cell Therapy

Genome-editing Technologies for Gene and Cell Therapy

Molecular Therapy 24, 430 (March 2016). doi:10.1038/mt.2016.10

Authors: Morgan L Maeder & Charles A Gersbach

from Cancer via ola Kala on Inoreader http://ift.tt/1QI3Dm3
via IFTTT

CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape

CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape

Molecular Therapy 24, 522 (March 2016). doi:10.1038/mt.2016.24

Authors: Gang Wang, Na Zhao, Ben Berkhout & Atze T Das

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

Engineered Viruses as Genome Editing Devices

Engineered Viruses as Genome Editing Devices

Molecular Therapy 24, 447 (March 2016). doi:10.1038/mt.2015.164

Authors: Xiaoyu Chen & Manuel A F V Gonçalves

from Cancer via ola Kala on Inoreader http://ift.tt/1QI3EGK
via IFTTT

Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation

Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation

Molecular Therapy 24, 536 (March 2016). doi:10.1038/mt.2015.226

Authors: Christian Huisman, Monique G P van der Wijst, Matthijs Schokker, Pilar Blancafort, Martijn M Terpstra, Klaas Kok, Ate G J van der Zee, Ed Schuuring, G Bea A Wisman & Marianne G Rots

from Cancer via ola Kala on Inoreader http://ift.tt/1pv7KLB
via IFTTT

Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications

Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications

Molecular Therapy 24, 458 (March 2016). doi:10.1038/mt.2015.151

Authors: Thomas Gaj, Benjamin E Epstein & David V Schaffer

from Cancer via ola Kala on Inoreader http://ift.tt/1QI3BL3
via IFTTT