Cancer by Sfakianakis Alexandros: 04/14/18

Σάββατο 14 Απριλίου 2018

Combined effects of rat Schwann cells and 17β-estradiol in a spinal cord injury model

Abstract

Spinal cord injury (SCI) is a devastating traumatic event which burdens the affected individuals and the health system. Schwann cell (SC) transplantation is a promising repair strategy after SCI. However, a large number of SCs do not survive following transplantation. Previous studies demonstrated that 17β-estradiol (E2) protects different cell types and reduces tissue damage in SCI experimental animal model. In the current study, we evaluated the protective potential of E2 on SCs in vitro and investigated whether the combination of hormonal and SC therapeutic strategy has a better effect on the outcome after SCI. Primary SC cultures were incubated with E2 for 72 h. In a subsequent experiment, thoracic contusion SCI was induced in male rats followed by sustained administration of E2 or vehicle. Eight days after SCI, DiI-labeled SCs were transplanted into the injury epicenter in vehicle and E2-treated animals. The combinatory regimen decreased neurological and behavioral deficits and protected neurons and oligodendrocytes in comparison to vehicle rats. Moreover, E2 and SC significantly decreased the number of Iba-1+ (microglia) and GFAP⁺ cells (astrocyte) in the SCI group. In addition, we found a significant reduction of mitochondrial fission-markers (Fis1) and an increase of fusion-markers (Mfn1 and Mfn2) in the injured spinal cord after E2 and SC treatment. These data demonstrated that E2 protects SCs against hypoxia-induced SCI and improves the survival of transplanted SCs.

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Combined effects of rat Schwann cells and 17β-estradiol in a spinal cord injury model

Abstract

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CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients.

CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients.

Cancer Biol Ther. 2018 Apr 13;:1-22

Authors: Nicolaides NC, Schweizer C, Somers EB, Wang W, Fernando S, Ross EN, Grasso L, Hassan R, Kline JB

Abstract
The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care. To determine if CA125 has immunosuppressive effects on amatuximab ADCC and associated clinical outcomes, post hoc subgroup analysis of patients from a Phase 2 study with primary diagnosed stage 3/4 unresectable mesothelioma treated with amatuximab plus cisplatin and pemetrexed were conducted. Analysis found patients with baseline CA125 levels no greater than 57 U/m ( ∼3X the upper limit of normal) had a 2 month improvement in progression free survival (HR = 0.43, p = 0.0062) and a 7 month improvement in overall survival (HR = 0.40, p = 0.0022) as compared to those with CA125 above 57 U/mL. In vitro studies found that CA125 was able to bind amatuximab and perturb ADCC activity via decreased Fc-γ-receptor engagement. These data suggest that clinical trial designs of antibody-based drugs in cancers producing CA125, including mesothelioma, should consider stratifying patients on baseline CA125 levels for mAbs that are experimentally determined to be bound by CA125.

PMID: 29652548 [PubMed - as supplied by publisher]

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Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc.

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Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc.

Cancer Biol Ther. 2018 Apr 09;:1-8

Authors: Li S, Hu T, Yuan T, Cheng D, Yang Q

Abstract
Osteosarcoma (OS) is one of the most common primary bone tumors and has a high disablity rate and case-fatality rate. The protracted stagnancy of the chemotherapy program and surgical technology for OS treatment prompted us to focus on the mechanisms of cancer carcinogenesis progression in OS. Nucleoside diphosphate kinase B (NME2) is a type of nucleoside diphosphate kinase that plays an important role in cellular processes. In this study, we report overexpression of NME2 in OS cell lines and correlate this overexpression with the clinicopathologic features of osteosarcoma. We used si-NME2 to downregulate expression of NME2 in OS cell lines. The results of the CCK8 and clone forming assays show that NME2 promotes OS cell line proliferation. Western blot assays show that deregulation of NME2 results in enhanced the expression of c-Myc, which promotes OS proliferation.

PMID: 29630434 [PubMed - as supplied by publisher]

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CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients.

CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients.

Cancer Biol Ther. 2018 Apr 13;:1-22

Authors: Nicolaides NC, Schweizer C, Somers EB, Wang W, Fernando S, Ross EN, Grasso L, Hassan R, Kline JB

PMID: 29652548 [PubMed - as supplied by publisher]

https://ift.tt/2H1k9js

Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc.

Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc.

Cancer Biol Ther. 2018 Apr 09;:1-8

Authors: Li S, Hu T, Yuan T, Cheng D, Yang Q

PMID: 29630434 [PubMed - as supplied by publisher]

https://ift.tt/2GLDjOp

Integration of Structural and Functional Genomic Studies Advances Precision Oncology: An Example of Collaborative Science in Office of Cancer Genomics Programs

A collaborative study conducted by two OCG initiatives highlights the importance of integrating structural and functional genomics programs to improve cancer therapies, and more specifically, contribute to precision oncology treatments for children.

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Pseudoprogression manifesting as recurrent ascites with anti-PD-1 immunotherapy in urothelial bladder cancer

Abstract

Background

Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed.

Case Presentation

In this case, we highlight a patient who developed recurrent, large-volume ascites, while simultaneously having a 49% reduction in peritoneal tumor lesion size by RECIST criteria. Sampling of the fluid revealed high levels of IL-6 and IL-15. Cytology revealed no malignant cells on 4 separate paracenteses over a period of 6 weeks. Cell counts revealed that 45% of cells were lymphocytes, and further analysis was performed by fluorescence-activated cell sorting (FACS). The majority of lymphocytes were CD8⁺, of which 78% were PD-1⁺ and 43% were HLA-DR⁺ indicating an activated phenotype.

Conclusions

In summary, treatment with anti-PD-1 therapy may result in pseudoprogression manifested by ascitic fluid accumulation due to the influx of activated T cells. Since worsening of ascites is typically associated with disease progression, it is important to consider the possibility of pesudoprogression in such patients undergoing therapy with immune checkpoint inhibitors.

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Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in classical Hodgkin lymphoma and promotes survival and migration

Abstract

Background

Phosphatase of regenerating liver-3 (PRL-3) is implicated in oncogenesis of hematological and solid cancers. PRL-3 expression increases metastatic potential, invasiveness and is associated with poor prognosis. With this study, we aimed to show a possible oncogenic role of PRL-3 in classical Hodgkin lymphoma (cHL).

Methods

PRL-3 expression was measured in 25 cHL patients by immunohistochemistry and gene expression was analyzed from microdissected malignant cells. We knocked down PRL-3 in the cHL cell lines L1236 and HDLM2 and used small molecular inhibitors against PRL-3 to investigate proliferation, migration and cytokine production.

Results

PRL-3 protein was expressed in 16% of patient samples. In three different gene expression datasets, PRL-3 was significantly overexpressed compared to normal controls. PRL-3 knockdown reduced proliferation, viability and Mcl-1 expression in L1236, but not in HDLM2 cells. Thienopyridone, a small molecule inhibitor of PRL-3, reduced proliferation of both L1236 and HDLM2. PRL-3 affected IL-13 secretion and enhanced STAT6 signaling. IL-13 stimulation partially rescued proliferation in L1236 cells after knockdown of PRL-3. PRL-3 knockdown reduced migration in both L1236 and HDLM2 cells.

Conclusion

PRL-3 was overexpressed in a subset of cHL patients. Inhibition of PRL-3 increased IL-13 cytokine production and reduced migration, proliferation and viability. The effects could be mediated through regulation of the anti-apoptotic molecule Mcl-1 and a feedback loop of IL-13 mediated activation of STAT6. This point to a role for PRL-3 in the pathogenesis of Hodgkin lymphoma, and PRL-3 could be a possible new drug target.

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Cancer mortality in Serbia, 1991–2015: an age-period-cohort and joinpoint regression analysis

Abstract

Background

As the result of dramatic political changes, civil wars, and a long-term refugee crisis from the end of the last to beginning of this century, the population of Serbia has experienced significant health problems. The aim of this study was to assess cancer mortality trends in Serbia.

Methods

This nationwide study was carried out to analyze cancer mortality in Serbia during 1991–2015 using official data. The age-standardized mortality rates (per 100,000) were calculated by direct standardization, using the world standard population by Segi. The average annual percent change (AAPC) and corresponding 95% confidence interval (CI) were computed using joinpoint regression analysis. Age-period-cohort analysis was performed to address the possible underlying reasons for the observed temporal trends.

Results

Over the 25-year study period, there were 466,075 cancer deaths (266,043 males and 200,032 females) in Serbia. Overall cancer mortality increased between 1991 and 2009 in both males (by + 0.9% per year) and females (by + 0.8% per year) and has been decreasing since then, by − 0.9% annually in both sexes. For almost all major cancers except stomach cancer, cancer mortality in Serbia demonstrated upward trends during the study period. The largest increases were noted in lung cancer among females (AAPC = + 3.7, 95% CI 3.5–3.9) and prostate cancer in males (AAPC = + 1.9, 95% CI 1.4–2.3).

Conclusions

After two decades of increase, cancer mortality rates are finally declining in Serbia. Despite this, these rates place Serbia among the countries with the highest cancer mortality in the world.

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EUS-Guided Biliary Drainage for Unresectable Malignant Biliary Obstruction: 10-Year Experience of 99 Cases at a Single Center

Abstract

Purpose

To evaluate clinical outcomes of endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) for unresectable malignant biliary obstruction for cases in which endoscopic retrograde cholangiopancreatography (ERCP) failed at a high-volume center.

Methods

All 99 EUS-BD cases of unresectable malignant biliary obstruction at Sendai City Medical Center between February 2007 and September 2017 were retrospectively evaluated. ERCP is strictly prioritized over EUS-BD during the study period, and EUS-BD was performed in cases wherein ERCP was impossible or ineffective. Technical success, clinical success, adverse events, and time to recurrence of biliary obstruction were evaluated.

Results

EUS-BD was technically successful in 98% of the patients (97/99). The clinical success rate was 93% (90/97). Adverse events that were definitely related to the procedure were observed in ten patients (10%; peritonitis in six, acute cholecystitis in four). Of six patients with bile peritonitis, four suffered from mild localized peritonitis that improved with conservative treatment, whereas two developed pan-peritonitis that improved with additional intervention. Other three patients with a poor performance status succumbed shortly after the successful EUS-BD, with a possible association between the procedure and death. In the 68 patients with a bilioenteric stent, the median time to recurrence of biliary obstruction was 339 days (95% confidence interval (CI), 14–664 days) during the mean follow-up period of 136 ± 173 days.

Conclusion

EUS-BD was found to be feasible. However, there were a few patients with an unfavorable course after successful EUS-BD.

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Prognostic Factors for Operated Gallbladder Cancer

Abstract

Purpose

The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer.

Material and Method

We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis.

Results

The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS.

Conclusion

Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.

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Evaluation of Fecal M2PK as a Diagnostic Marker in Colorectal Cancer

Abstract

Background

Invasive colonoscopy is the gold standard for patients at risk for colorectal cancer. However, the need for non-invasive and specific markers is required.

Objective

To evaluate the sensitivity of the glycolytic pyruvate kinase isoenzyme type M2 dimer (M2PK) as a diagnostic biomarker for colorectal cancer (CRC) and adenomatous colorectal polyps (CRP) screening.

Design

Case-control.

Patients

Twenty patients with CRC, 20 patients with CRP (lack criteria for colonic cancer by biopsy), and 20 normal subjects.

Outcome

Complete blood count (CBC), erythrocyte sedimentation rate (ESR), tumor markers: carcino embryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), fecal occult blood test (FOBT), and fecal M2PK. Pelvic and abdominal ultrasound (US), colonoscopy, and a histopathological examination.

Results

Only weight loss and cachexia were significantly associated with CRC than CRP or control groups. M2PK was the most sensitive and specific test in differentiating CRC from CRP and the control subjects (sensitivity = 75%, specificity = 100%).

Limitations

(1) The selection of cases for three well-matched groups, as to perform colonoscopy in well-prepared cases and conditions. (2) Replicates in more than 20 cases for confirmation at the expense of enrolling new patients. (3) The cost associated with tumor markers analysis.

Conclusion

Fecal M2PK can be used as a precolonoscopy screening test for CRC patients, and is superior to other tumor markers, and in indicating the progress of colorectal adenomas > 1 cm. Thus being cost-effective and easy-to-perform test, it is a feasible tool to preselect patients who require colonoscopy.

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A Rapidly Developing Diffuse Large B cell Lymphoma of the Stomach

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Significance of Glypican-3 in Early Detection of Hepatocellular Carcinoma in Cirrhotic Patients

Abstract

Background

Egypt has high incidence of hepatocellular carcinoma (HCC). This is due to wide spread of hepatitis C virus (HCV) infection which is responsible for most of the cases of liver cirrhosis. The major diagnostic techniques for HCC include serum markers and various imaging modalities. Glypican 3 (GPC3) protein is highly expressed in HCC, but not in normal liver tissue. The significance of GPC3 as a predictor or diagnostic tool for human tumors other than HCC is unclear.

Aim

To quantitatively assess the role of GPC3 in diagnosis of HCC in comparison to α-fetoprotein (AFP), ultrasonography (US), and computerized tomography (CT).

Patients and Methods

This cross-sectional study enrolled 85 subjects: 40 cirrhotic patients with primary HCC, 30 cirrhotic patients without HCC, and 15 healthy individuals. All patients were recruited from the Gastroenterology and Tropical Departments and outpatient clinics of New Damietta Hospital during the period from November 2010 to August 2012.

Results

GPC3 is positive in some HCC patients with normal levels of AFP. AFP has lower sensitivity (67.5%) compared to higher sensitivity of GPC3 (82.5%), and near specificity (61.2%) to GPC3 (57.8%).

Conclusion and Significance

The combined serum AFP and GPC3 significantly increased the sensitivity of HCC diagnosis. Although GPC3 is better than AFP in diagnosis of HCC, it still lacks the 100% sensitivity and specificity because some patients have negative or normal level of GPC3 (below the cutoff point 1.5 ng/ml) despite being diagnosed by triphasic CT.

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Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition

Abstract

Background

Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy.

Case presentation

We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab.

Conclusion

Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.

https://ift.tt/2H0yMrm

Coordinated responses to individual tumor antigens by IgG antibody and CD8+ T cells following cancer vaccination

Abstract

Background

One of today's greatest hurdles for cancer immunotherapy is the absence of information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against tumor proteins. For CD8+ T cells in particular, patient-specific immune recognition and responses at the level of individual tumor antigens are rarely characterized. Because of this, some immunologists have turned to serum antibodies as an alternative measure of antigen-specific anti-tumor immunity. In this work, we sought to simultaneously interrogate serum IgG and CD8+ T cell recognition of individual tumor antigens to determine whether antigen-specific serum IgG antibodies provide a window into the behavior of antigen-specific CD8+ T cell responses. Using antibody-based assays to evaluate immune response repertoires and focus T cell antigen exploration could afford substantial advantages for discovering and monitoring the anti-cancer immune responses of patients enrolled on clinical trials.

Methods

We vaccinated female BALB/c mice with a novel combination of an autophagosome-enriched vaccine derived from 4T1 mammary carcinoma along with poly-I:C adjuvant, then screened serum for IgG binding to arrays of 15mer peptides containing known mutation sites in 4T1. Simultaneously, we primed CD8+ T cell cultures from these same animals with 8-11mer peptides derived from these antigens. These primed T cells were then stimulated to measure recognition of the peptides or live 4T1 cells by IFNγ release.

Results

Vaccinated animals demonstrate increases in antigen-specific CD8+ T cell recognition of 4T1 tumor cells and peptides. For proteins confirmed in 4T1 cells and vaccine by mass spectrometry, there is a correlation between this increased CD8+ T cell IFNγ release and serum IgG binding to individual peptide antigens.

Conclusions

These results suggest it is possible to observe some features of a patient's antigen-specific T cell repertoire via an antibody surrogate, which has implications for tumor antigen discovery and clinical monitoring of antigen-specific anti-tumor immunity.

https://ift.tt/2qxCUUJ

Most-enhancing tumor volume by MRI radiomics predicts recurrence-free survival “early on” in neoadjuvant treatment of breast cancer

Abstract

Background

The hypothesis of this study was that MRI-based radiomics has the ability to predict recurrence-free survival "early on" in breast cancer neoadjuvant chemotherapy.

Methods

A subset, based on availability, of the ACRIN 6657 dynamic contrast-enhanced MR images was used in which we analyzed images of all women imaged at pre-treatment baseline (141 women: 40 with a recurrence, 101 without) and all those imaged after completion of the first cycle of chemotherapy, i.e., at early treatment (143 women: 37 with a recurrence vs. 105 without). Our method was completely automated apart from manual localization of the approximate tumor center. The most enhancing tumor volume (METV) was automatically calculated for the pre-treatment and early treatment exams. Performance of METV in the task of predicting a recurrence was evaluated using ROC analysis. The association of recurrence-free survival with METV was assessed using a Cox regression model controlling for patient age, race, and hormone receptor status and evaluated by C-statistics. Kaplan-Meier analysis was used to estimate survival functions.

Results

The C-statistics for the association of METV with recurrence-free survival were 0.69 with 95% confidence interval of [0.58; 0.80] at pre-treatment and 0.72 [0.60; 0.84] at early treatment. The hazard ratios calculated from Kaplan-Meier curves were 2.28 [1.08; 4.61], 3.43 [1.83; 6.75], and 4.81 [2.16; 10.72] for the lowest quartile, median quartile, and upper quartile cut-points for METV at early treatment, respectively.

Conclusion

The performance of the automatically-calculated METV rivaled that of a semi-manual model described for the ACRIN 6657 study (published C-statistic 0.72 [0.60; 0.84]), which involved the same dataset but required semi-manual delineation of the functional tumor volume (FTV) and knowledge of the pre-surgical residual cancer burden.

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Correlation of plasma concentration and adverse effects of bosutinib: standard dose or dose-escalation regimens of bosutinib treatment for patients with chronic myeloid leukemia

Abstract

Purpose

To investigate the exposure-toxicity relationship of bosutinib and to identify the target trough plasma concentration (C₀).

Methods

The toxicity and C₀ of bosutinib in Japanese chronic myeloid leukemia (CML) patients were monitored every 2 weeks for the first 3 months of treatment, and subsequently once a month during the 6 months after beginning 500 mg/day of standard dose (SD group, n = 10) or beginning 100 mg/day and increased by 100 mg every 2 weeks of dose escalation (DE group, n = 15).

Results

Nine of 10 patients (90%) in the SD group were not able to continue bosutinib therapy without interruption due to adverse events, compared to 2 patients (13.5%) in the DE group. The total duration of treatment interruption was 35 and 14 days in the SD and DE groups, respectively. The median time until liver dysfunction or diarrhea was day 28 and day 1 in the SD group, and day 53.5 and day 19 in the DE group, respectively. The cumulative dose of bosutinib was comparable between the SD and DE groups (51,700 vs. 53,550 mg, respectively). At 6 months, the median C₀ was 63.7 ng/mL and 63.0 ng/mL in the SD and DE groups, respectively. Liver dysfunction (all grades) and diarrhea (> grade 2) were prevalent in quartile 4 of C₀ (> 91.0 ng/mL), as calculated by the total C₀ distribution.

Conclusions

The DE regimen was better suited to avoid treatment interruption. The daily dose of bosutinib might be adjusted based on target C₀ to avoid adverse events by therapeutic drug monitoring in general practice.

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Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in classical Hodgkin lymphoma and promotes survival and migration

Abstract

Background

Methods

Results

Conclusion

https://ift.tt/2GZa2zP

Cancer mortality in Serbia, 1991–2015: an age-period-cohort and joinpoint regression analysis

Abstract

Background

Methods

Results

Conclusions

After two decades of increase, cancer mortality rates are finally declining in Serbia. Despite this, these rates place Serbia among the countries with the highest cancer mortality in the world.

https://ift.tt/2GXP3NT

Decreased macrophage inflammatory protein (MIP)-1α and MIP-1β increase the risk of developing nasopharyngeal carcinoma

Abstract

Background

The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.

Methods

The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case–control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case–control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein–Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test.

Results

The levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1β in the highest categories were associated with a decreased risk of NPC in both the case–control study (MIP-1α: OR = 0.49, 95% CI = 0.26–0.95; MIP-1β: OR = 0.47, 95% CI = 0.22–1.00) and the nested case–control study (MIP-1α: OR = 0.13, 95% CI = 0.03–0.62; MIP-1β: OR = 0.20, 95% CI = 0.04–0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case–control study (MIP-1α: OR = 16.28, 95% CI = 7.11–37.23; MIP-1β: OR = 12.86, 95% CI = 5.9–28.05) and the nested case–control study (MIP-1α: OR = 86.12, 95% CI = 10.58–701.03; MIP-1β: OR = 115.44, 95% CI = 13.92–957.73).

Conclusions

Decreased preclinical MIP-1α and MIP-1β levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

https://ift.tt/2GZciXQ

Treatment of Colorectal Cancer: a Multidisciplinary Approach

Abstract

Background

Colorectal cancer is the third most prevalent cancer in the world, preceded by prostate and lung cancers in men (10%) and breast and lung cancers in women (9.4%). Colorectal cancer is the fourth leading cause of death in men (7.6%) and the third in women (8.6%). A multidisciplinary approach has radically changed the way we deal with this disease among all specialist fields.

Purpose

In this study, we propose comparing the multidisciplinary experience group (started in 2012) of S. Anna Hospital (University of Ferrara) with the previous approach to rectal cancer before the advent of the multidisciplinary program.

Results

We find that more study depth of neoplastic disease as well as of each individual patient leads to more accurate staging and to a weighted therapy based on the needs of the individual. All the studies were performed in accordance with the guidelines established by the European and Italian associations.

https://ift.tt/2qxCPjT

Prognostic Factors for Operated Gallbladder Cancer

Abstract

Purpose

Material and Method

We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis.

Results

Conclusion

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Clear Cell Sarcoma-Like Tumor of the Gastrointestinal Tract

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Metachronous Hepatic Angiosarcoma Presenting as a Mimic of Recurrent Hepatocellular Carcinoma

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Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression

Abstract

Purpose

Her-2 is an epidermal growth factor receptor expressed in some prostate cancers (PC) associated with outgrowth of the tumor. Dysregulation of some microRNAs is involved in the regulation of PC pathogenesis, whereas the role of miR-4319 in PC is unknown and addressed in the current study.

Methods

The levels of miR-4319 in PC tissues were determined by RT-qPCR and their association with patient survival was studied by Kaplan–Meier analysis. Targeted genes for miR-4319 were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. Growth of cells of overexpression or inhibition of miR-4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis-associated proteins.

Results

MiR-4319 levels were decreased in PC specimens, compared to corresponding normal prostate tissue. Lower levels of miR-4319 were correlated with poorer overall patients' survival. In vitro, the cell survival mediated with Her-2 against chemotherapy was inhibited by overexpression of miR-4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary prostate epithelial cells increased Her-2-dependent cell growth, while re-expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her-2-dependent resistance to EM-induced apoptosis.

Conclusion

The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling.

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Durable response to bevacizumab in adults with recurrent pilocytic astrocytoma

CNS Oncology, Ahead of Print.

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"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

Nutr Cancer. 2018 Apr 13;:1-12

Authors: Yadav U, Kumar P, Rai V

Abstract
Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including 12,043 DT cancer cases and 15,209 healthy controls were included in the present meta- analysis. Results of meta-analysis revealed a significant association between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models (T vs. C: OR = 1.21, 95% CI = 1.11-1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI = 1.22-1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12-1.35, p < 0.001; TT vs. CT + CC: OR = 1.36, 95% CI = 1.15-1.60, p < 0.001; CT vs. CC: OR = 1.16, 95% CI = 1.07-1.27, p < 0.001). In the stratified analysis based on cancer types, significant associations were observed between NQO1 C609T polymorphism and GC (OR = 1.38, 95% CI = 1.11-1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06-1.30, p = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99-1.35, p = 0.06). Furthermore, stratified analysis based on ethnicity indicated that there was a significant association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT vs. CC: OR = 1.55, 95% CI = 1.21-2.00, p ≤ 0.001) as well as in Caucasian populations (TT vs. CC: OR = 1.34, 95% CI = 1.04-1.73, p = 0.02). In conclusion, the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk factor for DT cancers, including GC and CRC.

PMID: 29652514 [PubMed - as supplied by publisher]

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Terminalia ferdinandiana Exell. Fruit and Leaf Extracts Inhibit Proliferation and Induce Apoptosis in Selected Human Cancer Cell Lines.

Terminalia ferdinandiana Exell. Fruit and Leaf Extracts Inhibit Proliferation and Induce Apoptosis in Selected Human Cancer Cell Lines.

Nutr Cancer. 2018 Apr 11;:1-15

Authors: Shalom J, Cock IE

Abstract
Terminalia spp. are characterized by their high antioxidant contents and several species have anticancer activity. This study examined T. ferdinandiana fruit and leaf extracts for antiproliferative and apoptotic activities against a panel of human carcinoma cell lines. All extracts inhibited Caco2, HeLa, Jeg-3, JAR, MC3T3-E1, and MG63 proliferation. The leaf ethyl acetate extract was the most potent inhibitor of proliferation (MC3T3-E1 IC50 = of 6 µg/ml; Caco2 IC50 = 102 µg/ml). Furthermore, IC50's < 500 µg/ml were determined against all cell lines tested against that extract. The methanolic leaf extract was also a potent inhibitor of cell proliferation (Jeg-3 IC50 = 147 µg/ml; MC3T3-E1 IC50 = 40 µg/ml). The fruit extracts were also good inhibitors of carcinoma cell proliferation. Cell imaging studies detected morphological features consistent with apoptosis in Caco2 cells exposed to the ethyl acetate, methanolic, and aqueous extracts. Caspase 3 activity was significantly elevated in Caco2 cells exposed to these extracts, indicating that apoptosis was induced. The leaf ethyl acetate extract contained a high diversity and relative abundance of tannins and flavonoids. All T. ferdinandiana fruit and leaf extracts displayed either no toxic or low toxicity in the Artemia franciscana bioassay and in a HDF viability assay.

PMID: 29641917 [PubMed - as supplied by publisher]

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Plantar melanoma is associated with certain poor prognostic histopathological factors, but not correlated with nodal involvement, recurrence, and worse survival

Abstract

Background

Plantar surface melanoma affects the Caucasian race less likely than it does other races, e.g., the Asians and the Blacks. So far, small numbers of researches on plantar melanoma have yielded controversial results. The aim of this study was to define the histopathological and clinical characteristics pertinent to plantar melanoma and to compare them with melanomas that emerged in other sites by using a large group of patients from a single institution.

Patients and methods

A total of 104 Turkish Caucasian plantar melanoma patients and 1065 patients with non-plantar melanomas were analyzed retrospectively.

Results

The plantar melanomas were found more frequently in females (p = 0.006) and in older patients (≥ 50 years old) (p = 0.002). Compared to melanomas in other sites, the plantar melanomas tended to have more acral lentiginous histopathology (p = 0.0001), deeper Clark invasion level (IV–V) (p = 0.01), and thicker Breslow depth (≥ 2 mm) (p = 0.05); and the plantar melanoma lesions were more likely ulcerated (p = 0.0001) and were correlated with more lymphovascular invasion (p = 0.001), fewer tumor infiltrating lymphocyte (p = 0.03), and less frequently associated with a preexisting melanocytic nevus (p = 0.01). However, no correlation was found between plantar localization and either nodal involvement or metastasis (p > 0.05). The recurrence free and overall survival times for plantar melanomas were similar to other sites (p > 0.05). 5-year overall survival rate in plantar melanoma patients were 59%.

Conclusion

Even though plantar melanoma is associated with certain poor histopathological factors, it is not correlated with nodal involvement, recurrence, and poor survival.

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Oncologist’s knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study

Abstract

Purpose

Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP.

Methods

Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline.

Results

A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines.

Conclusion

Despite oncologist's clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.

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Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide nanoparticles

Abstract

Objective

Using RGD10–NGR9 dual-targeting superparamagnetic iron oxide nanoparticles to evaluate their potential value in tumor angiogenesis magnetic resonance imaging (MRI) and the biodistribution in vitro and in vivo.

Materials and methods

Dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were designed and synthesized in our previous study. In vitro, prussian blue staining and phenanthroline colorimetry were conducted to evaluate binding affinity and adsorption of dual-targeting USPIO nanoparticles to αvβ3-integrin/APN positive cells. In vivo, a xenograft mouse tumor model was used to evaluate the potential of the dual-targeting nanoparticles as an MRI contrast agent. After intravenous injection, the contrast-to-noise ratio (CNR) values of MR images obtained were calculated at predetermined time-points. The iron level was detected to access the biodistribution and plasma half-time.

Results

In vitro, dual-targeting USPIO nanoparticles bound to proliferating human umbilical vein endothelia cells with high specificity. In vivo, contrast MRI of xenograft mice using dual-targeting nanoparticles demonstrated a significant decrease in signal intensity and a greater increase in CNR than standard MRI and facilitated the imaging of tumor angiogenesis in T2*WI. In terms of biodistribution, dual-targeting USPIO nanoparticles increased to 1.83 times in tumor lesions as compared to the control. And the plasma half-time was about 6.2 h.

Conclusion

A novel RGD10–NGR9 dual-targeting USPIO has a great potential value as a contrast agent for the identification of tumor angiogenesis on MRI, according to the high specific affinity in vitro and in vivo.

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Mucinous adenocarcinoma on perianal fistula. A rising entity?

Abstract

Introduction

Mucinous adenocarcinoma on perianal fistula is a rare entity; it could be underdiagnosed because it behaves often as a regular perianal fistula.

Materials and methods

We have recently treated four cases in our unit. We present them and review the literature, emphasizing on clinical characteristic and therapeutic options. The four patients were male with a mean age of 64. Three of them were classified as locally advances cases and therefore treated with neoadjuvant therapy.

Results

All of them underwent laparoscopic abdominoperineal escisión. Surgical specimens are described and clinical characteristic specified. Review of the literature shows that this disease has a very high potential risk of local recurrence and we must be aggressive with the resection. Sometimes plastic surgery is needed to reconstruct the perianal wound.

Conclusions

Mucinous adenocarcinoma associated with anal fistula is a rare disease. Neoadjuvant chemoradiotherapy followed by an adequate abdominoperineal excision may result in favourable outcomes.

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Urinary cell-free DNA as a prognostic marker for KRAS-positive advanced-stage NSCLC

Abstract

Background

KRAS mutations are prevalent in non-small cell lung cancer (NSCLC) but its clinical implications remain to be determined. Continual profiling of KRAS mutations in patients is challenging, and the study aims to determine the potential use of urinary DNA in disease predictions.

Methods

A total of 150 patients were recruited. To ascertain the clinical relevance of urinary DNA, matched tumor profiles were analyzed. Serial measurements were taken to gauge the reliability of the assay. These results were correlated to overall survival using the Kaplan–Meier estimate.

Results

A good overall concordance of 93% (consolidated results from serial measurements) was achieved between tumor tissue and urinary DNA profiling. Of the discordant KRAS cases, we observed subsequent positive detection during monitoring and very low concentrations of mutant DNA. In addition, we noted that KRAS-positive patients detected using urinary DNA have good prognostic utility. Interestingly, we also observed that the trend is highly correlative of the rate of change in KRAS mutant DNA concentrations and the period of monitoring.

Conclusions

Urinary DNA offered a non-invasive approach to probe NSCLC dynamics, and in our study we showed that it had predictive capabilities for KRAS-positive patients. Serial monitoring of urinary samples showed that it had a predictive role in identifying patients with worse outcome.

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Are endometrial cancer radiotherapy results age related?

Abstract

Objective

To analyze the impact of age on radiotherapy results based on cancer-specific survival (CSS), vaginal-cuff relapses (VCR) and complications analysis in 438 patients with endometrial carcinoma (EC) receiving postoperative radiotherapy (PRT) divided into three age groups for analysis.

Materials and methods

From 2003 to 2015, 438 patients with EC were treated with PRT and divided into three age groups: Group-1: 202 patients < 65 years; Group-2: 210 patients ≥ 65 and < 80 years; Group-3: 26 patients ≥ 80 years. Vaginal toxicity was assessed using the objective LENT-SOMA criteria and RTOG scores were recorded for the rectum, bladder, and small bowel. Statistics: Chi square and Student's t tests, Kaplan–Meier survival study for analysis of CSS.

Results

The mean follow-up was 5.6 years in Group-1, 5.6 years in Group-2 and 6.3 years in Group-3 (p = 0.38). No differences were found among the groups in distribution of stage, grade, myometrial invasion, Type 1 vs. 2 EC and VLSI (p = 0.97, p = 0.52, p = 0.35, p = 0.48, p = 0.76, respectively). There were no differences in rectal, bladder and vagina late toxicity (p = 0.46, p = 0.17, p = 0.75, respectively). A better CSS at 5 years was found in Group-1 (p = 0.006), and significant differences were found in late severe small bowel toxicity in Group-3 (p = 0.005). VCR was increased in Group-3 (p = 0.017).

Conclusions

Patients ≥ 65 years had a worse outcome in comparison to younger patients. Late vaginal, rectal and bladder toxicities were similar in the three groups, although an increase of severe late small bowel toxicity led to IMRT in patients ≥ 80 years. Further larger studies are needed including quality of life analysis in patients ≥ 80 years.

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Factors associated with anxiety and depression in cancer patients prior to initiating adjuvant therapy

Abstract

Objective

Anxiety and depression affect cancer patients' quality of life. Our objectives were to determine the prevalence of anxiety and depression and analyze the association between positive psychological factors, sociodemographic factors, and clinical factors in oncological patients initiating adjuvant treatment.

Methods

A prospective, multicenter cohort of 600 consecutive patients completed the Brief Symptom Inventory, Mini-Mental Adjustment to Cancer, Life Orientation Scale-Revised, and Multidimensional Scale of Perceived Social Support questionnaires.

Results

Prevalence of anxiety and depression was 49.8 and 36.6%, respectively. Women and younger individuals were more anxious and depressed than men and seniors. Employed participants suffered more anxiety than retirees, and singles exhibited more depression than married or partnered subjects. Logistic regression analysis showed that hope, optimism, social support, being male, and older were significantly associated with a lower risk of anxiety and depression (p < 0.001).

Conclusions

The high prevalence of anxiety and depression among Spaniards with cancer starting adjuvant chemotherapy suggests that more attention should be paid to mental health in these individuals. These findings are important for cancer patients because they can benefit from interventions that increase positive psychological factors such as hope, optimism, and social support to reduce anxiety and depression.

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Evaluation of waiting times for breast cancer diagnosis and surgical treatment

Abstract

Purpose

To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival.

Methods/patients

A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I–III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients' clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index.

Results

In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy–surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08–2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45–0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21–3.56, p = 0.008) condition a greater biopsy–surgery delay. No influence of delays on survival has been identified.

Conclusions

Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays.

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Successful Utilization of Mechanical Thrombectomy in a Presentation of Pediatric Acute Ischemic Stroke

Guidelines regarding the management of acute ischemic stroke (AIS) in the pediatric population using mechanical recanalization procedures are lacking. We present a case of a 14-year-old male diagnosed in the Emergency Department with an acute onset stroke who underwent successful mechanical clot removal by interventional radiology.

https://ift.tt/2qxQcS4

Durable response to bevacizumab in adults with recurrent pilocytic astrocytoma

CNS Oncology, Ahead of Print.

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"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

Nutr Cancer. 2018 Apr 13;:1-12

Authors: Yadav U, Kumar P, Rai V

PMID: 29652514 [PubMed - as supplied by publisher]

https://ift.tt/2HyFZft

Terminalia ferdinandiana Exell. Fruit and Leaf Extracts Inhibit Proliferation and Induce Apoptosis in Selected Human Cancer Cell Lines.

Terminalia ferdinandiana Exell. Fruit and Leaf Extracts Inhibit Proliferation and Induce Apoptosis in Selected Human Cancer Cell Lines.

Nutr Cancer. 2018 Apr 11;:1-15

Authors: Shalom J, Cock IE

PMID: 29641917 [PubMed - as supplied by publisher]

https://ift.tt/2HyQM9e

Plantar melanoma is associated with certain poor prognostic histopathological factors, but not correlated with nodal involvement, recurrence, and worse survival

Abstract

Background

Patients and methods

A total of 104 Turkish Caucasian plantar melanoma patients and 1065 patients with non-plantar melanomas were analyzed retrospectively.

Results

Conclusion

Even though plantar melanoma is associated with certain poor histopathological factors, it is not correlated with nodal involvement, recurrence, and poor survival.

https://ift.tt/2y1JSYc

Oncologist’s knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study

Abstract

Purpose

Methods

Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline.

Results

Conclusion

https://ift.tt/2yUR9q7

Urinary cell-free DNA as a prognostic marker for KRAS-positive advanced-stage NSCLC

Abstract

Background

Methods

Results

Conclusions

https://ift.tt/2fQCeoS

Are endometrial cancer radiotherapy results age related?

Abstract

Objective

Materials and methods

Results

Conclusions

https://ift.tt/2HtyWV6

Factors associated with anxiety and depression in cancer patients prior to initiating adjuvant therapy

Abstract

Objective

Methods

Results

Conclusions

https://ift.tt/2GW8hPV

General recommendations paper on the management of older patients with cancer: the SEOM geriatric oncology task force’s position statement

Abstract

Population aging is associated with greater numbers of older people with cancer. Thanks to treatment advances, not only are more seniors diagnosed with cancer, but there are also more and more older cancer survivors. This upward trend will continue. Given the heterogeneity of aging, managing older patients with cancer poses a significant challenge for Medical Oncology. In Spain, a Geriatric Oncology Task Force has been set up within the framework of the Spanish Society for Medical Oncology (SEOM). With the aim of generating evidence and raising awareness, as well as helping medical oncologists in their training with respect to seniors with cancer, we have put together a series of basic management recommendations for this population. Many of the patients who are assessed in routine clinical practice in Oncology are older. CGA is the basic tool by means of which to evaluate older people with cancer and to understand their needs. Training and the correct use of recommendations regarding treatment for comorbidities and geriatric syndromes, support care, and drug–drug interactions and toxicities, including those of antineoplastic agents, as detailed in this article, will ensure that this population is properly managed.

https://ift.tt/2Hm19NL

Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression

Abstract

Purpose

Methods

Results

Conclusion

The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling.

https://ift.tt/2Hm16S5

Evaluation of waiting times for breast cancer diagnosis and surgical treatment

Abstract

Purpose

To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival.

Methods/patients

Results

Conclusions

https://ift.tt/2v4byLE

Computer-Based Readability Testing of Information Booklets for German Cancer Patients

Abstract

Understandable health information is essential for treatment adherence and improved health outcomes. For readability testing, several instruments analyze the complexity of sentence structures, e.g., Flesch-Reading Ease (FRE) or Vienna-Formula (WSTF). Moreover, the vocabulary is of high relevance for readers. The aim of this study is to investigate the agreement of sentence structure and vocabulary-based (SVM) instruments. A total of 52 freely available German patient information booklets on cancer were collected from the Internet. The mean understandability level L was computed for 51 booklets. The resulting values of FRE, WSTF, and SVM were assessed pairwise for agreement with Bland–Altman plots and two-sided, paired t tests. For the pairwise comparison, the mean L values are L_FRE = 6.81, L_WSTF = 7.39, L_SVM = 5.09. The sentence structure-based metrics gave significantly different scores (P < 0.001) for all assessed booklets, confirmed by the Bland–Altman analysis. The study findings suggest that vocabulary-based instruments cannot be interchanged with FRE/WSTF. However, both analytical aspects should be considered and checked by authors to linguistically refine texts with respect to the individual target group. Authors of health information can be supported by automated readability analysis. Health professionals can benefit by direct booklet comparisons allowing for time-effective selection of suitable booklets for patients.

https://ift.tt/2v9XW1g

Computer-Based Readability Testing of Information Booklets for German Cancer Patients

Abstract

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Assessment of Radiology Training During Radiation Oncology Residency

Abstract

A strong foundation in diagnostic imaging is essential to the practice of radiation oncology. This study evaluated radiology training in radiation oncology residency. An online survey was distributed to current radiation oncology residents in the USA by e-mail in 2017. Responses were summarized using frequency and percentages and compared with chi-square test and Spearman's rank correlation when appropriate. One hundred five residents completed the survey. Although most residents felt that a strong knowledge base in diagnostic radiology was moderately or extremely important (87%, n = 90/104), the majority were only somewhat confident in their radiology skills (61%, n = 63/104) and were only somewhat, minimally, or not at all satisfied with their training (79%, n = 81/103). Although there was an association between increasing post-graduate training and confidence level (p = 0.01062, ρ = 0.24959), the majority of graduating residents feel only somewhat confident in radiology skills (63%, n = 12/19). Residents were most commonly exposed to radiology via multidisciplinary conferences (96%, n = 100/104), though only 15% (n = 16/104) of residents ranked these as the most beneficial component of their radiology training and 13% (n = 13/101) of residents felt these were the least beneficial. Most residents (60%, n = 63/105) believe there is a need for dedicated radiology training during residency, preferring monthly formal didactics (68%, n = 71/105) co-taught by a radiologist and radiation oncologist (58%, n = 61/105). Radiation oncology residents feel their radiology training is suboptimal, suggesting a need for more guidance and standardization of radiology curriculum. A preferred option may be monthly didactics co-taught by radiologists and radiation oncologists; however, future studies should assess the effectiveness of this model.

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Sociodemographic disparities in the occurrence of medical conditions among adolescent and young adult Hodgkin lymphoma survivors

Abstract

Purpose

Hodgkin lymphoma (HL) survivors experience high risks of second cancers and cardiovascular disease, but no studies have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in adolescent and young adult (AYA) survivors.

Methods

Data for 5,085 patients aged 15–39 when diagnosed with HL during 1996–2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to hospitalization data. We examined the impact of race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the occurrence of medical conditions (≥ 2 years after diagnosis) and the impact of medical conditions on survival using multivariable Cox proportional hazards regression.

Results

Twenty-six percent of AYAs experienced at least one medical condition and 15% had ≥ 2 medical conditions after treatment for HL. In multivariable analyses, Black HL survivors had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.05–1.78] and circulatory system diseases (HR = 1.58, CI 1.17–2.14); Hispanics had a higher likelihood of endocrine diseases [HR = 1.24 (1.04–1.48)]. AYAs with public or no insurance (vs. private/military) had higher likelihood of circulatory system diseases, respiratory system diseases, chronic kidney disease/renal failure, liver disease, and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had higher likelihood of respiratory system and endocrine diseases. AYAs with these medical conditions or second cancers had an over twofold increased risk of death.

Conclusion

Strategies to improve health care utilization for surveillance and secondary prevention among AYA HL survivors at increased risk of medical conditions may improve outcomes.

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Interactions of coffee consumption and postmenopausal hormone use in relation to breast cancer risk in UK Biobank

Abstract

Purpose

We investigated the association of coffee consumption with postmenopausal breast cancer risk, overall and by the status of postmenopausal hormone therapy (PMH).

Methods

This study included 126,182 postmenopausal women (2,636 with breast cancer and 123,546 without) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Information on breast cancer risk factors and coffee consumption was collected at baseline and updated during follow-up. We used Cox proportional hazards regression to evaluate associations between coffee consumption and breast cancer, overall and in stratified analyses by woman's PMH status (none, past, current).

Results

In the overall analysis, coffee consumption was not associated with breast cancer risk (Hazard Ratio [HR] 1.00, 95% CI 0.91–1.11 for 2–3 cups/day, and HR 0.98, 95% CI 0.87–1.10 for ≥ 4 cups/day, p-trend = 0.69). Women with no PMH history who consumed ≥ 4 cups/day had a 16% reduced risk of breast cancer as compared to women who consumed < 7 cups/week (HR 0.84, 95% CI 0.71–1.00). Among women with past PMH, those consuming ≥ 4 cups/day had a 22% greater risk of breast cancer than women consuming < 7 cups/week (HR 1.22, 95% CI 1.01–1.47). No association was found among current PMH users. We found no significant interaction between PMH and coffee consumption (p = 0.24).

Conclusions

Coffee consumption might be associated with increased breast cancer risk in women who used hormones in the past. Further studies are warranted to confirm these findings and elucidate potential biological mechanisms underlying the observed associations.

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Risk sharing agreements, present and future

Francisco R Gonçalves, Susana Santos, Catarina Silva and Gabriela Sousa

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Association of Elements with Schizophrenia and Intervention of Selenium Supplements

Abstract

The purpose of this study is to explore more trace elements (zinc, potassium, copper, iron, boron, manganese, selenium, chromium and cadmium elements) in addition to calcium, magnesium, lead and arsenic in the sera of patients with schizophrenia and the general population in China and to determine the effect of selenium on schizophrenia patients. Participants were collected from the Pingyin County Mental Health Hospital and Pingyin County. A t test was used to analyse the differences between schizophrenia patients and healthy subjects, and element content differences in gender. Logistic multivariate regression analysis was applied to analyse the influence of elements to schizophrenia. Repeated measures analysis of variance was used to analyse differences in the elements after 1 and 3 months. Mn, Se, Cd, Pb, Ca, Cu and Fe were lower than those in the normal group, and B, Cr, As, K and Mg were higher than those in the control group. The odd ratios (ORs) of serum As and serum K were 2.624 and 1.035, respectively. The ORs of sera Cr, Mn, Se, Ca and Cu were all below one. After intervention of 'selenium weikang' about 1 and 3 months, the serum As was decreased and the serum selenium and copper were increased. Cr, Mn, Se, Ca and Cu might have beneficial, statistically significant effects on schizophrenia. Elements As and K might be harmful to schizophrenia with statistical significance. After selenium supplementation, the schizophrenia patients improved in some factors, like the appetite and memory, and the As element decreased.

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Effects of Se and Cd Co-treatment on the Morphology, Oxidative Stress, and Ion Concentrations in the Ovaries of Laying Hens

Abstract

This study aims at revealing the effects of the combined treatment of selenium and cadmium on ovary morphology, oxidative stress, and 28 kinds of ion concentrations in laying hens. In this experiment, 128 healthy 31-week-old chickens were selected and divided into four treatment groups, three of which were separately fed the basic diets supplemented with either Se or Cd or both Se and Cd for 90 days, and the remaining group was fed the basic diet and treated as a control. The chickens were sacrificed for collecting ovarian tissues. Morphological structure and ultrastructure analysis of ovaries in the Cd-treated group revealed ovarian damage, with decreased activities of SOD and GPx, along with increased levels of MDA and H₂O₂. Cd treatment also resulted in disturbances in ion balance. The concentrations of Ca, Ti, Cu, Zn, and Ba were significantly reduced, while the concentrations of Fe, Mo, and Cd were significantly increased when compared with the control group. Interestingly, the damages caused by cadmium were alleviated in the Se+Cd-treated group. These results indicate that selenium can alleviate cadmium-induced ovarian damages.

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The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men

Abstract

Manganese is an essential nutrient that may play a role in the production of inflammatory biomarkers. We examined associations between estimated dietary manganese intake from food/beverages and supplements with circulating biomarkers of inflammation. We further explored whether estimated dietary manganese intake affects DNA methylation of selected genes involved in the production of these biomarkers. We analyzed 1023 repeated measures of estimated dietary manganese intakes and circulating blood inflammatory biomarkers from 633 participants in the Normative Aging Study. Using mixed-effect linear regression models adjusted for covariates, we observed positive linear trends between estimated dietary manganese intakes and three circulating interleukin proteins. Relative to the lowest quartile of estimated intake, concentrations of IL-1β were 46% greater (95% CI − 5, 126), IL-6 52% greater (95% CI − 9, 156). and IL-8 32% greater (95% CI 2, 71) in the highest quartiles of estimated intake. Estimated dietary manganese intake was additionally associated with changes in DNA methylation of inflammatory biomarker-producing genes. Higher estimated intake was associated with higher methylation of NF-κβ member activator NKAP (Q4 vs Q1: β = 3.32, 95% CI − 0.6, 7.3). When stratified by regulatory function, higher manganese intake was associated with higher gene body methylation of NF-κβ member activators NKAP (Q4 vs Q1: β = 10.10, 95% CI − 0.8, 21) and NKAPP1 (Q4 vs Q1: β = 8.14, 95% CI 1.1, 15). While needed at trace amounts for various physiologic functions, our results suggest estimated dietary intakes of manganese at levels slightly above nutritional adequacy contribute to inflammatory biomarker production.

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sEcad and EGF Levels Increased in Urine of Non-ferrous Metal Workers and Medium of Uroepithelial Cell Line Treated by Arsenic

Abstract

Inorganic arsenic (iAs) is a carcinogen and could increase the risks of bladder, lung, and skin cancer. Mining and smelting of non-ferrous metals are common occupational arsenic exposures. In this study, 125 individuals working in non-ferrous metal smelting plants were separated into two groups according to urinary total arsenic (TAs) levels: group 1, TAs < 100 μg/g Cr; group 2, TAs ≥ 100 μg/g Cr. Demographic characteristics of participants were obtained by questionnaire interview. Levels of E-cadherin soluble ectodomain fragment (sEcad) and epidermal growth factor (EGF) in workers urine were determined by ELISA test. We found that concentrations of sEcad and EGF present in urine were significantly elevated in the high urinary arsenic group 2 compared with the low urinary arsenic group 1. Urinary levels of the shedding of E-cadherin soluble ectodomain fragment (sEcad) and epidermal growth factor (EGF) were positively related to the concentrations of iAs in urine after adjusting for the confounding effects. A positive correlation between sEcad and EGF concentrations in urine was also observed. In order to verify the effects of iAs on sEcad and EGF, the human uroepithelial cell line (SV-HUC-1) was treated with NaAsO₂ for 24 h in vitro. sEcad and EGF levels in the 4 μM NaAsO₂-treated SV-HUC-1 cell medium significantly increased compared to the control group. In conclusion, urinary levels of sEcad and EGF increased in higher urinary arsenic workers of non-ferrous metal plants and are closely associated with urinary iAs concentration. The results suggested that sEcad and EGF may potentially be preclinical prognostic factors of bladder injury and early detection in arsenic exposure individuals.

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Building a Culture of Excellence in Cancer Education: a Message from Your President

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Awareness of HPV and Cervical Cancer Prevention Among University Health Sciences Students in Cyprus

Abstract

Cervical cancer is preventable; however, despite the existence of primary and secondary means of prevention, its incidence is still higher in certain socioeconomic groups and countries, suggesting gaps in cervical cancer prevention. The objective of this study was to evaluate the knowledge and awareness of health sciences university students in Cyprus regarding HPV and cervical cancer in order to better guide the future development of educational programs to improve cervical cancer prevention. This was a cross-sectional study of 178 university health sciences students in Cyprus using a validated questionnaire on HPV and cervical cancer prevention. Analysis of the completed questionnaires revealed moderate levels of knowledge and awareness with an overall mean score of 23.32 out of 33 on HPV and 8.12 out of 13 on cervical cancer, a score of 9.25 out of 14 on HPV vaccines, and a score of 5.93 out of 9 on cervical cancer screening. Older students achieved higher scores compared to younger students (mean score of 6.76 for 18–22 years old, 9.44 for 23–28 years old, and 10.25 for 29–38 years old; p < 0.001). The study found several gaps in the students' knowledge and awareness on cervical cancer prevention. We suggest the design of education programs targeting this population possibly by incorporation of cervical cancer prevention education within students' curriculum to increase knowledge such that the spread of the virus is minimized and these health sciences students are prepared to educate their communities as part of their future practice in health professions.

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Biospecimen Education Among Pacific Islanders in Southern California

Abstract

Despite increasing rates of cancer, biospecimen donations for cancer research remains low among Pacific Islanders (PIs). To address this disparity, researchers partnered with PI community organizations to develop and test a theory-based culturally tailored educational intervention designed to raise awareness about the issues surrounding biospecimen research. A total of 219 self-identified PI adults in Southern California were recruited to participate in a one-group pre-post design study. Participants completed questionnaires that assessed their knowledge and attitude regarding biospecimen research before and after viewing an educational video and receiving print materials. Results showed that participants' overall knowledge and attitude increased significantly from pre-test to post-test (p < .0001). Over 98% of participants also reported that they would be willing to donate at least one type of biospecimen sample. Efforts such as these that utilize culturally tailored education interventions may be instrumental in improving biospecimen donation rates in the PI community as well as other minority populations.

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