Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2I0TIMe
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 5 Μαΐου 2018
Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy through Suppression of Src Signaling Pathway
Development and Validation of RAPID: A Patient-Specific Monte Carlo Three-Dimensional Internal Dosimetry Platform
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2HthFKY
Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial–Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2qBkQtz
Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy through Suppression of Src Signaling Pathway
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
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Development and Validation of RAPID: A Patient-Specific Monte Carlo Three-Dimensional Internal Dosimetry Platform
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
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Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial–Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
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UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy
Abstract
Purpose
To investigate the association between UDP-glucuronosyltransferase (UGT)1A polymorphisms and irinotecan-treatment efficacy in a Chinese population with metastatic colorectal cancer (mCRC).
Methods
The present study was based on a prospective multicenter trial of Chinese mCRC patients treated with irinotecan-based chemotherapy (NCT01282658, registered at http://www.clinicaltrials.gov). Fifteen single-nucleotide polymorphisms (SNPs) in four UGT1A genes were selected for genotyping in 164 patients. Kaplan–Meier and Cox regression analyses were used to assess the association between potential signatures and survival outcome.
Results
We found that UGT1A1*28 variant genotype was significantly associated with decreased progression-free survival (PFS) [adjusted hazard ratio (HR), 1.803; 95% confidence interval (CI), 1.217–2.671] and overall survival (OS) (adjusted HR 1.979; 95% CI 1.267–3.091) compared with wild-type genotype. Patients carrying (TA)7 allele showed a median PFS of 7.5 (95% CI 5.5–9.6) months compared with 9.8 (95% CI 8.6–10.9) months for patients with wild-type genotype. Median OSs were 13.3 (95% CI 10.3–16.2), and 20.8 (95% CI 18.7–23.0) months for (TA)6/7 or (TA)7/7, and (TA)6/6 patients, respectively. Similarly but more significantly, the copy number of haplotype III (composed by rs3755321-T, rs3821242-C, rs4124874-G and rs3755319-C) constructed among the selected SNPs also correlated with survival outcome.
Conclusions
UGT1A polymorphisms are predictive of survival outcome of irinotecan-treated Chinese mCRC patients. After validation, UGT1A polymorphisms might be helpful in facilitating stratification of mCRC patients for individualized treatment options.
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Phase II trial of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for untreated non-squamous non-small-cell lung cancer
Abstract
Purpose
We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC).
Methods
Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m2, days 1 and 8) plus pemetrexed (500 mg/m2, day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity. The primary endpoint was the 1-year survival rate. The secondary endpoints were progression-free survival (PFS), overall survival (OS), response in induction phase, and safety.
Results
From February 2012 to September 2014, 53 assessable patients were enrolled in this study. Thirty-eight (71.7%) patients completed induction therapy, while 35 (66.0%) received maintenance therapy. The 1-year survival rate was 67.7%. The median PFS and OS were 5.3 and 18.6 months, respectively. The response rate and disease control rate (DCR) during the induction phase were 37.7 and 86.8%, respectively. Eight patients (15.1%) discontinued the therapy due to adverse events (AEs) during the induction phase, but both hematological and non-hematological AEs were infrequent.
Conclusions
Treatment with induction chemotherapy of pemetrexed plus split-dose cisplatin showed a promising 1-year survival rate, DCR, and transition rate into maintenance phase. This regimen is feasible and well-tolerated. A phase III study comparing this regimen with conventional tri-weekly regimen is warranted.
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Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy
Abstract
Purpose
High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC.
Methods
Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups. Expression levels of TOR2a, CD68, YKL-39 and CCL18 genes were analyzed by qPCR, the amplification of TOR2a gene locus was assessed by the microarray assay. Clinical and pathological responses to neoadjuvant chemotherapy were assessed.
Results
We found that the average level of TOP2a expression in patients of DOX-Sense group was almost 10 times higher than in patients of DOX-Res group, and the expression of CD68 was 3 times higher in the DOX-Sense group compared to DOX-Res group. We demonstrated that expression levels of M2-derived cytokines but not the amount of TAM is indicative for clinical and pathological chemotherapy efficacy in breast cancer patients. Out of 8 patients from DOX-Sense group who did not respond to neoadjuvant chemotherapy (NAC), 7 patients had M2+ macrophage phenotype (YKL-39+CCL18− or YKL-39−CCL18+) and only one patient had M2− macrophage phenotype (YKL-39−CCL18−). In DOX-Res group, out of 14 patients who clinically responded to NAC 9 patients had M2− phenotype and only 5 patients had M2+ macrophage phenotype. Among pathological non-responders in DOX-Sense group, 19 (82%) patients had M2+ tumor phenotype and only 4 (18%) patients had M2− phenotype. In DOX-Res group, all 5 patients who pathologically responded to NAC had M2 phenotype (YKL-39−CCL18−). Unlike the clinical response to NAC, the differences in the frequency of M2+ and M2− phenotypes between pathologically responding and non-responding patients within DOX-Sense and DOX-Res groups were statistically significant.
Conclusions
Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.
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Sunitinib does not acutely alter left ventricular systolic function, but induces diastolic dysfunction
Abstract
Purpose
Cancer chemotherapies have improved the prognosis of cancer patients in recent years; however, their side effects on the cardiovascular systems have emerged as a major concern in the field of both cardiology and oncology. In particular, multi-targeted tyrosine kinase inhibitors are known to induce various types of cardiovascular adverse events including hypertension, QT-interval prolongation and heart failure, but their underlying mechanisms remain elusive. To explore how to better predict such drug-induced cardiovascular adverse events, we assessed the electropharmacological effects of sunitinib using the halothane-anesthetized dogs (n = 5), while plasma concentrations of cardiac enzymes including aspartate aminotransferase, lactate dehydrogenase, creatinine kinase and cardiac troponin I were measured.
Methods
Sunitinib was intravenously administered at 0.01 and 0.1 mg/kg for 10 min with 20 min interval.
Results
Sunitinib decreased the amplitude of maximum downstroke velocity of the left ventricular pressure, prolonged the isovolumic relaxation time and increased the left ventricular end-diastolic pressure in a dose-related manner without affecting the other cardiohemodynamic and electrophysiological variables. More importantly, sunitinib significantly elevated cardiac troponin I level for 30–60 min after the high dose without altering the other biomarkers.
Conclusions
Monitoring of the cardiac diastolic function together with cardiac troponin I after the start of sunitinib administration may become a reliable measure to predict the onset of sunitinib-induced cardiovascular adverse events.
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Exposure–response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer
Abstract
Purpose
Ramucirumab plus docetaxel improved survival in REVEL, a randomized phase 3 trial for patients with Stage IV non-small cell lung cancer after standard platinum-based chemotherapy. This exploratory analysis evaluated the exposure–response relationship of ramucirumab from REVEL.
Methods
Patients received ramucirumab (10 mg/kg) or placebo plus docetaxel (75 mg/m2) every 3 weeks. Pharmacokinetic samples were collected. A population pharmacokinetic analysis predicted ramucirumab minimum concentration after first-dose administration (Cmin,1) and average concentration at steady state (Cave,ss). Predicted Cmin,1 and Cave,ss were used to evaluate the relationship between ramucirumab exposure and efficacy and safety, respectively. Exposure–efficacy was assessed by Kaplan–Meier and Cox regression analyses; exposure–safety was assessed by ordered categorical analyses.
Results
Analyses included 376 patients treated with ramucirumab plus docetaxel and 366 patients treated with placebo plus docetaxel (364 for safety population). After adjusting for corresponding prognostic factors, the association between overall survival (OS) and Cmin,1 was statistically significant (p = 0.0110), although progression-free survival (PFS) showed a marginal association (p = 0.0515). At high ramucirumab exposures (Cmin,1), greater improvements (smaller hazard ratios) were seen for OS and PFS when stratified by Cmin,1 exposure quartiles. A statistically significant correlation was observed between ramucirumab Cave,ss and grade ≥ 3 febrile neutropenia and hypertension.
Conclusions
An association was observed between ramucirumab exposure and efficacy. Higher ramucirumab exposure was associated with improved clinical outcomes and increased toxicity in this analysis. Two exposure–response prospective randomized trials are being conducted to address causation (NCT02443883 and NCT02514551), with encouraging preliminary results (Ajani et al. in Ann Oncol 28:abstr 698P, 2017).
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EML4–ALK rearrangement in squamous cell carcinoma shows significant response to anti-ALK inhibitor drugs crizotinib and alectinib
Abstract
EML4–ALK alterations are more common in adenocarcinomas and are rarely found in squamous cell histology. In documented cases, the majority of EML4–ALK translocations are identified in squamous cell histology and occur in patients with no or light smoking history. We report an EML4–ALK4 translocation in a 50-year-old patient with squamous cell carcinoma and an 18 pack-year smoking history. The patient had a near complete response in the CNS to alectinib treatment. Our observation suggests that EML4–ALK genomic testing may be clinically useful in patients with heavy smoking history.
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EGFL7 and RASSF1 promoter hypermethylation in epithelial ovarian cancer
Source:Cancer Genetics, Volumes 224–225
Author(s): Yanisa Rattanapan, Veerawat Korkiatsakul, Adcharee Kongruang, Takol Chareonsirisuthigul, Budsaba Rerkamnuaychoke, Anna Wongkularb, Sarikapan Wilailak
DNA methylation is one of the epigenetic mechanisms associated with gene expression and plays a key role as in activation and deactivation of oncogenes and tumor suppressor genes, respectively. This study employed DNA methylation array to identify methylated genes which are highly correlated with various phenotypes of epithelial ovarian cancer (EOC) in Thai patients and to quantify promoter CpG-island methylation of candidate genes. Tissues from patients with serous and non-serous EOC showed significantly higher promoter methylation of EGFL7 and RASSF1 compared to benign cases. These results indicate the potential of investigating promoter CpG-island methylation of cancer-associated genes as biomarkers of disease progression and even possibly of early detection.
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Checkpoint blockade after kidney transplantation
Source:European Journal of Cancer, Volume 96
Author(s): Mathieu Lesouhaitier, Caroline Dudreuilh, Mathilde Tamain, Nada Kanaan, Elodie Bailly, Delphine Legoupil, Clement Deltombe, Peggy Perrin, Guillaume Manson, Cécile Vigneau, Roch Houot
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Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study
Source:European Journal of Cancer, Volume 96
Author(s): N. Nabieva, T. Fehm, L. Häberle, J. de Waal, M. Rezai, B. Baier, G. Baake, H.-C. Kolberg, M. Guggenberger, M. Warm, N. Harbeck, R. Wuerstlein, J.-U. Deuker, P. Dall, B. Richter, G. Wachsmann, C. Brucker, J.W. Siebers, M. Popovic, T. Kuhn, C. Wolf, H.-W. Vollert, G.-P. Breitbach, W. Janni, R. Landthaler, A. Kohls, D. Rezek, T. Noesselt, G. Fischer, S. Henschen, T. Praetz, V. Heyl, T. Kühn, T. Krauss, C. Thomssen, A. Hohn, H. Tesch, C. Mundhenke, A. Hein, C.C. Hack, K. Schmidt, E. Belleville, S.Y. Brucker, S. Kümmel, M.W. Beckmann, D. Wallwiener, P. Hadji, P.A. Fasching
BackgroundEndocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment.Patients and methodsPost-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses.ResultsAmong 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84).ConclusionsThese results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration.Clinical Trials NumberCFEM345DDE19.
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A randomised-controlled trial of 1-year adjuvant chemotherapy with oral tegafur–uracil versus surgery alone in stage II colon cancer: SACURA trial
Source:European Journal of Cancer, Volume 96
Author(s): Chu Matsuda, Megumi Ishiguro, Satoshi Teramukai, Yoshiki Kajiwara, Shoichi Fujii, Yusuke Kinugasa, Yoshihiko Nakamoto, Masanori Kotake, Yoshiyuki Sakamoto, Kiyotaka Kurachi, Atsuyuki Maeda, Koji Komori, Naohiro Tomita, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Hidetaka Mochizuki, Yoko Nakagawa, Kenichi Sugihara
BackgroundEfficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur–uracil (UFT) to surgery alone for stage II colon cancer.MethodsPatients were randomly assigned to the surgery-alone group or UFT group (UFT at 500–600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729.ResultsA total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%.The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75–1.10; p = 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65–1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66–1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence.ConclusionsSuperiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT.Trial registrationClinicalTrials. Gov. #NCT00392899.
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Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer
Source:European Journal of Cancer, Volume 97
Author(s): S. Cavalieri, F. Perrone, R. Miceli, P.A. Ascierto, L.D. Locati, C. Bergamini, R. Granata, S. Alfieri, C. Resteghini, D. Galbiati, A. Busico, N. Paielli, R. Patuzzo, A. Maurichi, G. Gallino, R. Ruggeri, L. Mariani, M. Palla, L. Licitra, P. Bossi
BackgroundIn recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.MethodsPatients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.ResultsForty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3–4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.ConclusionsIn sSCC, dacomitinib showed activity similar to what was observed with anti–epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.
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A new look at the International Duration Evaluation of Adjuvant therapy (IDEA) classification—Defining novel predictive and prognostic markers in stage III colon cancer
Source:European Journal of Cancer, Volume 96
Author(s): Ofer Margalit, Ronac Mamtani, Yu-Xiao Yang, Kim A. Reiss, Talia Golan, Naama Halpern, Dan Aderka, Bruce Giantonio, Einat Shacham-Shmueli, Ben Boursi
BackgroundThe International Duration Evaluation of Adjuvant therapy (IDEA) pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. The overarching goal was to reduce chemotherapy-related toxicity, mainly oxaliplatin-induced neuropathy. Patients were classified into low-risk and high-risk groups, suggesting that low-risk patients may be offered only 3 months of treatment. We aimed to evaluate the benefit of monotherapy versus doublet chemotherapy in low and high IDEA risk groups.MethodsUsing the National Cancer Database (2004–2014), we identified 56,728 low-risk and 47,557 high-risk individuals with stage III colon cancer, according to the IDEA classification. We used multivariate Cox regression to evaluate the magnitude of survival differences between IDEA risk groups, according to treatment intensity (doublet versus monotherapy). In a secondary analysis, we examined the prognostic and predictive value of subgroups of age, tumour sidedness and lymph node ratio (LNR).ResultsLow and high IDEA risk groups derived similar benefit from doublet adjuvant chemotherapy as compared with monotherapy, with hazard ratios (HRs) of 0.83 (95% confidence interval [CI] 0.79–0.86) and 0.80 (95% CI 0.78–0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients older than 72 years (HR = 0.95, 95% CI 0.90–1.01) and high-risk patients older than 85 years (HR = 0.90, 95% CI 0.77–1.05). LNR and tumour sidedness were shown as additional prognostic, but not predictive, factors within the IDEA risk groups.ConclusionsIDEA risk classification per se does not predict for treatment benefit from doublet chemotherapy in stage III colon cancer. However, omission of oxaliplatin can be considered in IDEA low-risk patients older than 72 years.
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Persisting inequalities in survival patterns of childhood neuroblastoma in Southern and Eastern Europe and the effect of socio-economic development compared with those of the US
Source:European Journal of Cancer, Volume 96
Author(s): Paraskevi Panagopoulou, Marios K. Georgakis, Margarita Baka, Maria Moschovi, Vassilios Papadakis, Sophia Polychronopoulou, Maria Kourti, Emmanuel Hatzipantelis, Eftichia Stiakaki, Helen Dana, Athanasios Tragiannidis, Evdoxia Bouka, Luis Antunes, Joana Bastos, Daniela Coza, Anna Demetriou, Domenic Agius, Sultan Eser, Raluca Gheorghiu, Mario Šekerija, Maciej Trojanowski, Tina Žagar, Anna Zborovskaya, Anton Ryzhov, Nick Dessypris, Daniel Morgenstern, Eleni Th Petridou
AimNeuroblastoma outcomes vary with disease characteristics, healthcare delivery and socio-economic indicators. We assessed survival patterns and prognostic factors for patients with neuroblastoma in 11 Southern and Eastern European (SEE) countries versus those in the US, including—for the first time—the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumours (NARECHEM-ST)/Greece.MethodsOverall survival (OS) was calculated in 13 collaborating SEE childhood cancer registries (1829 cases, ∼1990–2016) and Surveillance, Epidemiology, and End Results (SEER), US (3072 cases, 1990–2012); Kaplan–Meier curves were used along with multivariable Cox regression models assessing the effect of age, gender, primary tumour site, histology, Human Development Index (HDI) and place of residence (urban/rural) on survival.ResultsThe 5-year OS rates varied widely among the SEE countries (Ukraine: 45%, Poland: 81%) with the overall SEE rate (59%) being significantly lower than in SEER (77%; p < 0.001). In the common registration period within SEE (2000–2008), no temporal trend was noted as opposed to a significant increase in SEER. Age >12 months (hazard ratio [HR]: 2.8–4.7 in subsequent age groups), male gender (HR: 1.1), residence in rural areas (HR: 1.3), living in high (HR: 2.2) or medium (HR: 2.4) HDI countries and specific primary tumour location were associated with worse outcome; conversely, ganglioneuroblastoma subtype (HR: 0.28) was associated with higher survival rate.ConclusionsAllowing for the disease profile, children with neuroblastoma in SEE, especially those in rural areas and lower HDI countries, fare worse than patients in the US, mainly during the early years after diagnosis; this may be attributed to presumably modifiable socio-economic and healthcare system performance differentials warranting further research.
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Reporting of patient characteristics and stratification factors in phase 3 trials investigating first-line systemic treatment of metastatic colorectal cancer: A systematic review
Source:European Journal of Cancer, Volume 96
Author(s): Kaitlyn K.H. Goey, Remi Mahmoud, Halfdan Sørbye, Bengt Glimelius, Claus-Henning Köhne, Daniel J. Sargent, Cornelis J.A. Punt, Martijn G.H. van Oijen, Miriam Koopman
BackgroundPatient characteristics and stratification factors are important factors influencing trial outcomes. Uniform reporting on these parameters would facilitate cross-study comparisons and extrapolation of trial results to clinical practice. In 2007, standardisation on patient characteristics reporting and stratification in metastatic colorectal cancer (mCRC) trials was proposed. We investigated the reporting of prognostic factors and implementation of this proposal in mCRC trials published from 2005 to 2016.MethodsWe searched PubMed and Embase (January 2005 – June 2016) for first-line phase 3 mCRC trials. Patient characteristics reporting and use of stratification factors were extracted and analysed for adherence to the proposal from 2007.ResultsSixty-seven trials (35,315 patients) were identified, reporting 48 different patient characteristics (median: 9 [range: 5–18] per study). Age, gender, performance status (PS), primary tumour site and adjuvant chemotherapy were frequently reported (87%–100%), in contrast to laboratory values, such as alkaline phosphatase, lactate dehydrogenase and white blood cell count (10%–25%). We identified 29 different stratification factors (median: 3 [range: 1–9] per study). The most common strata were PS and treatment centre (>60%). A median of 8/12 (range: 4–11) of the proposed parameters was reported. Although the percentage of studies reporting each factor slightly increased over time, there was no significant correlation between publication year and adherence to the proposal from 2007.ConclusionsWe observed persistent heterogeneity in the reporting of patient characteristics and use of stratification factors in first-line mCRC trials. The proposal from 2007 has not led to increased uniformity of patient characteristics reporting and use of stratification over time. There is an urgent need to address this issue to improve the interpretation of trial results.
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Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site
Source:European Journal of Cancer, Volume 96
Author(s): Fabian Wolpert, Michael Weller, Anna Sophie Berghoff, Elisabeth Rushing, Lisa Michaela Füreder, Gregory Petyt, Henning Leske, Nicolaus Andratschke, Luca Regli, Marian Christoph Neidert, Roger Stupp, Rolf Stahel, Reinhard Dummer, Thomas Frauenfelder, Patrick Roth, Nicolas Reyns, Philipp Antonio Kaufmann, Matthias Preusser, Emilie Le Rhun
BackgroundIn 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS.MethodsWe screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation.ResultsFDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10−5, Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10−5; Wilcoxon's test). All observations were confirmed in the validation cohort.ConclusionsLung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA.
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Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT
Source:European Journal of Cancer, Volume 96
Author(s): Sebastian Giebel, Myriam Labopin, Michael Potter, Xavier Poiré, Henrik Sengeloev, Gerard Socié, Anne Huynh, Boris V. Afanasyev, Urs Schanz, Olle Ringden, Peter Kalhs, Dietrich W. Beelen, Antonio M. Campos, Tamás Masszi, Jonathan Canaani, Mohamad Mohty, Arnon Nagler
BackgroundAllogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome–positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014.ResultsIn univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)–based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01).ConclusionIn the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL.
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Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1
Source:European Journal of Cancer, Volume 96
Author(s): Ahmed Mekki, Laurent Dercle, Philip Lichtenstein, Aurélien Marabelle, Jean-Marie Michot, Olivier Lambotte, Jérôme Le Pavec, Eleonora De Martin, Corinne Balleyguier, Stéphane Champiat, Samy Ammari
BackgroundProgrammed death receptor-1 blocking antibodies (anti-PD1) are a new standard of care in many cancer types. Patients benefit from improved survival but have the risk of immune-related adverse events (irAE). We evaluated if medical imaging procedures, used for anti-tumour response assessment, can detect irAEs.Materials and methodsAll consecutive patients treated with anti-PD1 and with a medical imaging acquisition performed within 2 weeks with irAEs ≥2 were retrospectively included. Data were gathered from June 2014 to February 2017, and a central review was performed. The primary and secondary end-points were i) to evaluate the overall detection rate of irAEs by medical imaging and ii) to provide a comprehensive radiological description of irAEs.ResultsFifty-three patients (31 women, 22 men; average age: 61 years) were included. The primary tumour was melanoma (n = 32), lung cancer (n = 18) and other (n = 3). Patients were treated with nivolumab (n = 27) or pembrolizumab (n = 26). Of 74 medical imaging procedures analysed (ratio = 1.4 medical imaging per patient), 55 irAE were detected. The detection rate was overall: 74% (95 confidence interval: 63–84%), positron emission tomography with 18F-fludeoxyglucose integrated with computed tomography (18F-FDG PET/CT): 83% (n = 10/12), magnetic resonance imaging: 83% (n = 5/6), computed tomography scan: 79% (n = 19/24), ultrasonography: 70% (n = 19/27), standard X-rays: 40% (n = 2/5), lung/mediastinum: 100% (n = 7/7), enterocolitis: 100% (n = 8/8), hypophysitis: 100% (n = 3/3), thyroiditis: 75% (n = 15/20), hepatitis: 67% (n = 2/3), arthralgia or arthritis: 40% (n = 2/5) and pancreas: 28% (n = 2/7).ConclusionMedical imaging detected 74% of irAE in patients treated with anti-PD1. Beyond response assessment, medical imaging can detect irAE and guide towards specific management. We described the most frequent sites and patterns of imaging findings.
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Avoidable cancers in the Nordic countries—The impact of alcohol consumption
Source:European Journal of Cancer
Author(s): Therese M-L. Andersson, Gerda Engholm, Eero Pukkala, Magnus Stenbeck, Laufey Tryggvadottir, Hans Storm, Elisabete Weiderpass
BackgroundAlcohol consumption is an important and preventable cause of cancer. The aim of this study was to quantify the proportion of the cancer burden in the Nordic countries linked to alcohol and estimate the potential for cancer prevention by changes in alcohol consumption.MethodsUsing the Prevent macro-simulation model, the number of cancer cases in the Nordic countries over a 30-year period (2016–2045) was modelled for six sites, under different scenarios of changing alcohol consumption, and compared to the projected number of cases if constant alcohol consumption prevailed. The studied sites were colorectal, post-menopausal breast, oral cavity and pharynx, liver, larynx as well as oesophageal squamous cell carcinoma. The alcohol consumption was based on the categories of non-drinkers/occasional drinkers, light drinkers (<=12.5 g alcohol per day), moderate drinkers (>12.5 and ≤ 50 g/day) and heavy drinkers (>50 g/day).ResultsAbout 83,000 cancer cases could be avoided in the Nordic countries in a 30-year period if alcohol consumption was entirely eliminated, which is 5.5% of the expected number of cases for the six alcohol-related cancer types. With a 50% reduction in the proportion with moderate alcohol consumption by year 2025, 21,500 cancer cases could be avoided. The number of avoidable cases was highest for post-menopausal breast and colorectal cancer, but the percentage was highest for oesophageal squamous cell carcinoma.ConclusionThe results from this study can be used to understand the potential impact and significance of primary prevention programmes targeted towards reducing the alcohol consumption in the Nordic countries.
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More is more? Pushing chemoradiotherapy of oesophageal squamous cell carcinoma forward
Source:European Journal of Cancer
Author(s): Florian Lordick
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Letter to the Editor: Central nervous system relapse rate and dose intensification in poor risk metastatic germ cell tumours—A comment on: ‘Patterns of relapse in poor prognosis germ cell tumours in the GETUG-13 trial: Implications for the assessment of brain metastases.’ by Loriot and colleagues
Source:European Journal of Cancer, Volume 95
Author(s): Constantine Alifrangis, Peter Wilson, Jonathan Shamash
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Role of perioperative chemotherapy in soft-tissue sarcomas: It's time to end a never-ending story
Source:European Journal of Cancer
Author(s): A. Italiano, E. Stoeckle
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Refining the use of cabazitaxel in metastatic castrate-resistant prostate cancer
Source:European Journal of Cancer
Author(s): Stéphane Culine
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Most adolescents' melanomas are conventional malignant adult-type melanomas
Source:European Journal of Cancer, Volume 95
Author(s): Klaus Rose, Jane M. Grant-Kels
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Immunotherapy-induced Addison's disease: A rare, persistent and potentially lethal side-effect
Source:European Journal of Cancer
Author(s): S. Hescot, M. Haissaguerre, P. Pautier, E. Kuhn, M. Schlumberger, A. Berdelou
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Low-level postoperative carcinoembryonic antigen improves survival outcomes stratification in patients with stage II colon cancer treated with standard adjuvant treatments
Source:European Journal of Cancer
Author(s): E. Auclin, T. André, J. Taieb, M. Benetkiewicz, A. de Gramont, D. Vernerey
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The International Cardioncology Society–ONE trial: Not all that glitters is for cardioncologists only
Source:European Journal of Cancer
Author(s): Giorgio Minotti
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Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG)
This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT).
https://ift.tt/2jy7uKV
Volumetric modulated arc therapy of head-and-neck cancer on a fast-rotating O-ring linac: Plan quality and delivery time comparison with a C-arm linac
Linac improvements in gantry speed, leaf speed and dose rate may increase the time-efficiency of volumetric modulated arc therapy (VMAT) delivery. The plan quality achievable with faster VMAT however remains to be investigated. In this study, a fast-rotating O-ring linac with fast-moving leaves is compared with a C-arm linac in terms of plan quality and delivery time for VMAT of head-and-neck cancer (HNC).
https://ift.tt/2FNw6rv
Multicentric Castleman’s disease in human immunodeficiency virus infection: two case reports
Castleman's Disease is a rare B-cell lymphoproliferative disease. It is mostly benign and is characterized by non-neoplastic lymph node hypertrophy, associated with infection by human herpesvirus-8 in people w...
https://ift.tt/2HRY4IO
Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker
Abstract
Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed. To discover a novel, sensitive, non-invasive biomarker of prostate cancer, through the fluorometric quantification and the electrophoretic analysis of seminal cfDNA in prostate cancer patients compared to healthy individuals. The concentration of seminal plasma cfDNA in prostate cancer patients was 2243.67 ± 1758 ng/μl, compared to 57.7 ± 4.8 ng/μl in healthy individuals (p < 0.05). Electrophoresis sites distribution patterns were different; ladder fragmentation was associated with prostate cancer patients and apoptotic electrophoretic fragmentation with healthy individuals. Human seminal fluid can be a valuable source of cfDNA in the setting of liquid biopsy procedures for the identification of novel oncological biomarkers. Seminal plasma cfDNA in prostate cancer patients is significantly more concentrated than that of age-matched, healthy controls. Fluorometric measurement and electrophoretic assessment allow a reliable quantification and characterization of seminal plasma cfDNA, which can be used routinely in prostate cancer screening programs.
https://ift.tt/2rmysIR
Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker
Abstract
Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed. To discover a novel, sensitive, non-invasive biomarker of prostate cancer, through the fluorometric quantification and the electrophoretic analysis of seminal cfDNA in prostate cancer patients compared to healthy individuals. The concentration of seminal plasma cfDNA in prostate cancer patients was 2243.67 ± 1758 ng/μl, compared to 57.7 ± 4.8 ng/μl in healthy individuals (p < 0.05). Electrophoresis sites distribution patterns were different; ladder fragmentation was associated with prostate cancer patients and apoptotic electrophoretic fragmentation with healthy individuals. Human seminal fluid can be a valuable source of cfDNA in the setting of liquid biopsy procedures for the identification of novel oncological biomarkers. Seminal plasma cfDNA in prostate cancer patients is significantly more concentrated than that of age-matched, healthy controls. Fluorometric measurement and electrophoretic assessment allow a reliable quantification and characterization of seminal plasma cfDNA, which can be used routinely in prostate cancer screening programs.
https://ift.tt/2rmysIR
Paroxysmal ocular movements – an early sign in Glut1 deficiency Syndrome
Abstract
The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.
https://ift.tt/2HU5QSc
PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population
Abstract
Background
PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile.
Methods
This study included 89 pediatric patients receiving standard treatment at Seoul National University Children's Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28. We performed immunohistochemistry assays for PD-1 and PD-L1. To characterize the gene expression, a custom immune-response focused gene panel was used.
Results
PD-1 expression was positive in 7 (35%) AT/RT, 7 (35%) EPN, 4 (19%) HGG, and 3 (11%) MBL patients. PD-L1 expression was positive in 8 (40%) AT/RT, 4 (20%) EPN, and 4 (19%) HGG; negative in all MBL patients. There was no statistically significant difference in the overall survival of PD-L1 positive patients. The gene expression analysis demonstrated differences in two clustering functional categories: cell–cell signaling and antigen presentation pathway.
Conclusions
AT/RT, EPN, and HGG showed a relatively higher expression rate of PD-L1 (19–40%). This suggests these tumor types might be good candidates for PD-1 checkpoint blockade. We determined that gene expression may potentially serve as a molecular tool in predicting which patients will respond to immunotherapy. Further investigation is required to better understand the predictive and prognostic role of PD-L1 in pediatric brain tumors.
https://ift.tt/2FLmvBu
Paroxysmal ocular movements – an early sign in Glut1 deficiency Syndrome
Abstract
The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.
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PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population
Abstract
Background
PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile.
Methods
This study included 89 pediatric patients receiving standard treatment at Seoul National University Children's Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28. We performed immunohistochemistry assays for PD-1 and PD-L1. To characterize the gene expression, a custom immune-response focused gene panel was used.
Results
PD-1 expression was positive in 7 (35%) AT/RT, 7 (35%) EPN, 4 (19%) HGG, and 3 (11%) MBL patients. PD-L1 expression was positive in 8 (40%) AT/RT, 4 (20%) EPN, and 4 (19%) HGG; negative in all MBL patients. There was no statistically significant difference in the overall survival of PD-L1 positive patients. The gene expression analysis demonstrated differences in two clustering functional categories: cell–cell signaling and antigen presentation pathway.
Conclusions
AT/RT, EPN, and HGG showed a relatively higher expression rate of PD-L1 (19–40%). This suggests these tumor types might be good candidates for PD-1 checkpoint blockade. We determined that gene expression may potentially serve as a molecular tool in predicting which patients will respond to immunotherapy. Further investigation is required to better understand the predictive and prognostic role of PD-L1 in pediatric brain tumors.
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Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats
Abstract
Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9–10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.
https://ift.tt/2jv61ox
Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats
Abstract
Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9–10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.
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Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)
A35 is a novel synthetic cyclizing-berberine recently patented as an antitumor compound. Based on its dual targeting topoisomerase (top) activity, A35 might overcome the resistance of single-target top inhibit...
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Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation
Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the ...
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Vaginal brachytherapy for endometrial cancer
Abstract
Background
There is limited information about survival effect of vaginal brachytherapy (VBT) and its comparison to external beam pelvic radiotherapy (EBRT) and no radiotherapy (no-RT) of endometrial cancer patients.
Patients and methods
We performed a multicenter retrospective registry study of 1550 patients with endometrial cancer treated by no-RT (n = 702), VBT (n = 430) and EBRT ± VBT (n = 418). The outcome measure was overall survival.
Results
RT did not improve the overall survival of patients with a low risk of recurrence. In univariate analysis, the survival effect of VBT was significant in patients with intermediate and high risk of recurrence (HR 0.42, CI 0.29–0.60, p < 0.0001). EBRT ± VBT demonstrated no survival effect in these groups. Multivariate analysis showed that VBT (HR 0.50, CI 0.36–0.71) significantly reduced the mortality risk in patients with an intermediate and high risk compared with no-RT after adjustment for age, tumor grading, tumor stage, lymphadenectomy, adjuvant therapy and comorbidities. Matching for age, histological type, tumor stage, tumor grade, and performance status between patients treated with no-RT and VBT was performed. The matching analysis again demonstrated the favorable survival effect of VBT compared to no-RT on overall survival with an absolute risk reduction of 17.7%. Notably, in a further 106 matched pairs, EBRT ± VBT did not demonstrate any survival effect over VBT among patients at intermediate and high risk of recurrence.
Conclusions
VBT should be performed in patients at intermediate and high risk of recurrence of endometrial cancer, after operative determination of lymph node status.
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Vaginal brachytherapy for endometrial cancer
Abstract
Background
There is limited information about survival effect of vaginal brachytherapy (VBT) and its comparison to external beam pelvic radiotherapy (EBRT) and no radiotherapy (no-RT) of endometrial cancer patients.
Patients and methods
We performed a multicenter retrospective registry study of 1550 patients with endometrial cancer treated by no-RT (n = 702), VBT (n = 430) and EBRT ± VBT (n = 418). The outcome measure was overall survival.
Results
RT did not improve the overall survival of patients with a low risk of recurrence. In univariate analysis, the survival effect of VBT was significant in patients with intermediate and high risk of recurrence (HR 0.42, CI 0.29–0.60, p < 0.0001). EBRT ± VBT demonstrated no survival effect in these groups. Multivariate analysis showed that VBT (HR 0.50, CI 0.36–0.71) significantly reduced the mortality risk in patients with an intermediate and high risk compared with no-RT after adjustment for age, tumor grading, tumor stage, lymphadenectomy, adjuvant therapy and comorbidities. Matching for age, histological type, tumor stage, tumor grade, and performance status between patients treated with no-RT and VBT was performed. The matching analysis again demonstrated the favorable survival effect of VBT compared to no-RT on overall survival with an absolute risk reduction of 17.7%. Notably, in a further 106 matched pairs, EBRT ± VBT did not demonstrate any survival effect over VBT among patients at intermediate and high risk of recurrence.
Conclusions
VBT should be performed in patients at intermediate and high risk of recurrence of endometrial cancer, after operative determination of lymph node status.
https://ift.tt/2wlSpFg
Identifying risk factors for L’Hermitte’s sign after IMRT for head and neck cancer
L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high.
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Identifying risk factors for L’Hermitte’s sign after IMRT for head and neck cancer
L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high.
https://ift.tt/2Ih6x7u
A review of HPRT and its emerging role in cancer
Abstract
Hypoxanthine guanine phosphoribosyltransferase (HPRT) is a common salvage housekeeping gene with a historically important role in cancer as a mutational biomarker. As an established and well-known human reporter gene for the evaluation of mutational frequency corresponding to cancer development, HPRT is most commonly used to evaluate cancer risk within individuals and determine potential carcinogens. In addition to its use as a reporter gene, HPRT also has important functionality in the body in relation to purine regulation as demonstrated by Lesch–Nyhan patients whose lack of functional HPRT leads to significant purine overproduction and further neural complications. This regulatory role, in addition to an established connection between other salvage enzymes and cancer development, points to HPRT as an emerging influence in cancer. Recent work has shown that not only is the enzyme upregulated within malignant tumors, it also has significant surface localization within some cancer cells. With this is mind, HPRT has the potential to become a significant biomarker not only for the characterization of cancer, but also for its potential treatment.
https://ift.tt/2rmFv5j
A review of HPRT and its emerging role in cancer
Abstract
Hypoxanthine guanine phosphoribosyltransferase (HPRT) is a common salvage housekeeping gene with a historically important role in cancer as a mutational biomarker. As an established and well-known human reporter gene for the evaluation of mutational frequency corresponding to cancer development, HPRT is most commonly used to evaluate cancer risk within individuals and determine potential carcinogens. In addition to its use as a reporter gene, HPRT also has important functionality in the body in relation to purine regulation as demonstrated by Lesch–Nyhan patients whose lack of functional HPRT leads to significant purine overproduction and further neural complications. This regulatory role, in addition to an established connection between other salvage enzymes and cancer development, points to HPRT as an emerging influence in cancer. Recent work has shown that not only is the enzyme upregulated within malignant tumors, it also has significant surface localization within some cancer cells. With this is mind, HPRT has the potential to become a significant biomarker not only for the characterization of cancer, but also for its potential treatment.
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Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ
Abstract
Purpose
The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS.
Methods
The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992–2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed.
Results
Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82–1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60–0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53–1.37 for left-sided versus right-sided RT).
Conclusions
The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.
https://ift.tt/2JUjAZO
Association of Parkinson’s disease with industry sectors: a French nationwide incidence study
Abstract
In order to identify working environments at risk for Parkinson's disease (PD), we investigated the relation between the importance of industry sectors, used as a surrogate for occupational exposures, and PD incidence in French cantons. The number of incident PD cases (2010–2014) in 3689 cantons of metropolitan France was determined using drug claims from French National Health Insurance databases. The proportions of workers in 38 industry sectors in 2006 were calculated for each canton. Associations between the proportions of workers in industry sectors and PD age/sex-standardized incidence ratios were examined using incidence rate ratios (IRR) and 95% confidence intervals (CI) estimated with multilevel negative binomial regressions with a random intercept at the canton-level and adjusted for smoking, deprivation index, and density of neurologists. We then used two-step semi-Bayes hierarchical regression (HR) to include prior information about exposure to pesticides, metals, and solvents in each industry sector. We identified 112,625 incident cases. PD incidence was higher in areas characterized by high proportions of workers in "Agriculture, forestry and fishing" (IRRHR = 1.042; CI 95% = 1.014–1.070; p-TrendHR = 0.004), "Manufacture of textiles, wearing apparel, leather and related products" (IRRHR = 1.024; CI 95% = 1.005–1.044; p-TrendHR = 0.010), and "Manufacture of basic metals and fabricated metal products, except machinery and equipment" (IRRHR = 1.024; CI 95% = 1.003–1.046; p-TrendHR = 0.071). This nationwide study, based on a comprehensive analysis of industry sectors, shows significant associations between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and PD incidence that may be targeted in further epidemiological studies to replicate and better understand these associations.
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The heart of the matter: years-saved from cardiovascular and cancer deaths in an elite athlete cohort with over a century of follow-up
Abstract
To quantify the years of life saved from cardiovascular (CVD), cancer and overall deaths among elite athletes according to their main type of physiological effort performed in the Olympic Games. All French athletes participating in the Games from 1912 to 2012, with vital status validated and cause of death (if concerned) identified by the national registries were included (n = 2814, 455 died) and classified according to 6 groups of effort: POWER (continuous effort < 45 s); INTERMEDIATE (45 s ≤ continuous effort < 600 s); ENDURANCE (continuous effort ≥ 600 s); POLYVALENT (participating in different events entering different classifications), INTERMITTENT (intermittent effort, i.e. team sports); PRECISION (targeting events). The theoretical years-lost method was adapted to calculate gains in longevity (years-saved) according to specific-risks under the competing risks model and was implemented in R software. Considering overall-deaths, all groups significantly saved, on average, 6.5 years of life (95% CI 5.8–7.2) compared to the general population. This longevity advantage is mainly driven by a lower risk of cancer which, isolated, contributed to significantly save 2.3 years of life (95% CI 1.2–1.9) on average in each group. The risk of CVD-related mortality in the ENDURANCE and PRECISION groups is not significantly different from the general population. The other groups significantly saved, on average, 1.6 years of life (95% CI 1.2–1.9) from CVD death. The longevity benefits in elite athletes are associated with the type of effort performed during their career, mainly due to differences on the CVD-risk of death.
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Association of Parkinson’s disease with industry sectors: a French nationwide incidence study
Abstract
In order to identify working environments at risk for Parkinson's disease (PD), we investigated the relation between the importance of industry sectors, used as a surrogate for occupational exposures, and PD incidence in French cantons. The number of incident PD cases (2010–2014) in 3689 cantons of metropolitan France was determined using drug claims from French National Health Insurance databases. The proportions of workers in 38 industry sectors in 2006 were calculated for each canton. Associations between the proportions of workers in industry sectors and PD age/sex-standardized incidence ratios were examined using incidence rate ratios (IRR) and 95% confidence intervals (CI) estimated with multilevel negative binomial regressions with a random intercept at the canton-level and adjusted for smoking, deprivation index, and density of neurologists. We then used two-step semi-Bayes hierarchical regression (HR) to include prior information about exposure to pesticides, metals, and solvents in each industry sector. We identified 112,625 incident cases. PD incidence was higher in areas characterized by high proportions of workers in "Agriculture, forestry and fishing" (IRRHR = 1.042; CI 95% = 1.014–1.070; p-TrendHR = 0.004), "Manufacture of textiles, wearing apparel, leather and related products" (IRRHR = 1.024; CI 95% = 1.005–1.044; p-TrendHR = 0.010), and "Manufacture of basic metals and fabricated metal products, except machinery and equipment" (IRRHR = 1.024; CI 95% = 1.003–1.046; p-TrendHR = 0.071). This nationwide study, based on a comprehensive analysis of industry sectors, shows significant associations between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and PD incidence that may be targeted in further epidemiological studies to replicate and better understand these associations.
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The heart of the matter: years-saved from cardiovascular and cancer deaths in an elite athlete cohort with over a century of follow-up
Abstract
To quantify the years of life saved from cardiovascular (CVD), cancer and overall deaths among elite athletes according to their main type of physiological effort performed in the Olympic Games. All French athletes participating in the Games from 1912 to 2012, with vital status validated and cause of death (if concerned) identified by the national registries were included (n = 2814, 455 died) and classified according to 6 groups of effort: POWER (continuous effort < 45 s); INTERMEDIATE (45 s ≤ continuous effort < 600 s); ENDURANCE (continuous effort ≥ 600 s); POLYVALENT (participating in different events entering different classifications), INTERMITTENT (intermittent effort, i.e. team sports); PRECISION (targeting events). The theoretical years-lost method was adapted to calculate gains in longevity (years-saved) according to specific-risks under the competing risks model and was implemented in R software. Considering overall-deaths, all groups significantly saved, on average, 6.5 years of life (95% CI 5.8–7.2) compared to the general population. This longevity advantage is mainly driven by a lower risk of cancer which, isolated, contributed to significantly save 2.3 years of life (95% CI 1.2–1.9) on average in each group. The risk of CVD-related mortality in the ENDURANCE and PRECISION groups is not significantly different from the general population. The other groups significantly saved, on average, 1.6 years of life (95% CI 1.2–1.9) from CVD death. The longevity benefits in elite athletes are associated with the type of effort performed during their career, mainly due to differences on the CVD-risk of death.
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Association of Parkinson’s disease with industry sectors: a French nationwide incidence study
Abstract
In order to identify working environments at risk for Parkinson's disease (PD), we investigated the relation between the importance of industry sectors, used as a surrogate for occupational exposures, and PD incidence in French cantons. The number of incident PD cases (2010–2014) in 3689 cantons of metropolitan France was determined using drug claims from French National Health Insurance databases. The proportions of workers in 38 industry sectors in 2006 were calculated for each canton. Associations between the proportions of workers in industry sectors and PD age/sex-standardized incidence ratios were examined using incidence rate ratios (IRR) and 95% confidence intervals (CI) estimated with multilevel negative binomial regressions with a random intercept at the canton-level and adjusted for smoking, deprivation index, and density of neurologists. We then used two-step semi-Bayes hierarchical regression (HR) to include prior information about exposure to pesticides, metals, and solvents in each industry sector. We identified 112,625 incident cases. PD incidence was higher in areas characterized by high proportions of workers in "Agriculture, forestry and fishing" (IRRHR = 1.042; CI 95% = 1.014–1.070; p-TrendHR = 0.004), "Manufacture of textiles, wearing apparel, leather and related products" (IRRHR = 1.024; CI 95% = 1.005–1.044; p-TrendHR = 0.010), and "Manufacture of basic metals and fabricated metal products, except machinery and equipment" (IRRHR = 1.024; CI 95% = 1.003–1.046; p-TrendHR = 0.071). This nationwide study, based on a comprehensive analysis of industry sectors, shows significant associations between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and PD incidence that may be targeted in further epidemiological studies to replicate and better understand these associations.
https://ift.tt/2HVEcAu
The heart of the matter: years-saved from cardiovascular and cancer deaths in an elite athlete cohort with over a century of follow-up
Abstract
To quantify the years of life saved from cardiovascular (CVD), cancer and overall deaths among elite athletes according to their main type of physiological effort performed in the Olympic Games. All French athletes participating in the Games from 1912 to 2012, with vital status validated and cause of death (if concerned) identified by the national registries were included (n = 2814, 455 died) and classified according to 6 groups of effort: POWER (continuous effort < 45 s); INTERMEDIATE (45 s ≤ continuous effort < 600 s); ENDURANCE (continuous effort ≥ 600 s); POLYVALENT (participating in different events entering different classifications), INTERMITTENT (intermittent effort, i.e. team sports); PRECISION (targeting events). The theoretical years-lost method was adapted to calculate gains in longevity (years-saved) according to specific-risks under the competing risks model and was implemented in R software. Considering overall-deaths, all groups significantly saved, on average, 6.5 years of life (95% CI 5.8–7.2) compared to the general population. This longevity advantage is mainly driven by a lower risk of cancer which, isolated, contributed to significantly save 2.3 years of life (95% CI 1.2–1.9) on average in each group. The risk of CVD-related mortality in the ENDURANCE and PRECISION groups is not significantly different from the general population. The other groups significantly saved, on average, 1.6 years of life (95% CI 1.2–1.9) from CVD death. The longevity benefits in elite athletes are associated with the type of effort performed during their career, mainly due to differences on the CVD-risk of death.
https://ift.tt/2HQvFTj
An online randomized controlled trial, with or without problem-solving treatment, for long-term cancer survivors after hematopoietic cell transplantation
Abstract
Purpose
This randomized controlled trial examines the efficacy of INSPIRE, an INternet-based Survivorship Program with Information and REsources, with or without problem-solving treatment (PST) telehealth calls, for survivors after hematopoietic cell transplantation (HCT).
Methods
All adult survivors who met eligibility criteria were approached for consent. Participants completed patient-reported outcomes at baseline and 6 months. Those with baseline impaired scores on one or more of the outcomes were randomized to INSPIRE, INSPIRE + PST, or control with delayed INSPIRE access. Outcomes included Cancer and Treatment Distress, Symptom Checklist-90-R Depression, and Fatigue Symptom Inventory. Planned analyses compared arms for mean change in aggregated impaired outcomes and for proportion of participants improved on each outcome.
Results
Of 1306 eligible HCT recipients, 755 (58%) participated, and 344 (45%) had one or more impaired scores at baseline. We found no reduction in aggregated outcomes for either intervention (P > 0.3). In analyses of individual outcomes, participants randomized to INSPIRE + PST were more likely to improve in distress than controls (45 vs. 20%, RR 2.3, CI 1.0, 5.1); those randomized to INSPIRE alone were marginally more likely to improve in distress (40 vs. 20%, RR 2.0, CI 0.9, 4.5).
Conclusions
The INSPIRE online intervention demonstrated a marginal benefit for distress that improved with the addition of telehealth PST, particularly for those who viewed the website or were age 40 or older.
Implications for Cancer Survivors
Online and telehealth programs such as INSPIRE offer opportunities to enhance HCT survivorship outcomes, particularly for mood, though methods would benefit from strategies to improve efficacy.
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An online randomized controlled trial, with or without problem-solving treatment, for long-term cancer survivors after hematopoietic cell transplantation
Abstract
Purpose
This randomized controlled trial examines the efficacy of INSPIRE, an INternet-based Survivorship Program with Information and REsources, with or without problem-solving treatment (PST) telehealth calls, for survivors after hematopoietic cell transplantation (HCT).
Methods
All adult survivors who met eligibility criteria were approached for consent. Participants completed patient-reported outcomes at baseline and 6 months. Those with baseline impaired scores on one or more of the outcomes were randomized to INSPIRE, INSPIRE + PST, or control with delayed INSPIRE access. Outcomes included Cancer and Treatment Distress, Symptom Checklist-90-R Depression, and Fatigue Symptom Inventory. Planned analyses compared arms for mean change in aggregated impaired outcomes and for proportion of participants improved on each outcome.
Results
Of 1306 eligible HCT recipients, 755 (58%) participated, and 344 (45%) had one or more impaired scores at baseline. We found no reduction in aggregated outcomes for either intervention (P > 0.3). In analyses of individual outcomes, participants randomized to INSPIRE + PST were more likely to improve in distress than controls (45 vs. 20%, RR 2.3, CI 1.0, 5.1); those randomized to INSPIRE alone were marginally more likely to improve in distress (40 vs. 20%, RR 2.0, CI 0.9, 4.5).
Conclusions
The INSPIRE online intervention demonstrated a marginal benefit for distress that improved with the addition of telehealth PST, particularly for those who viewed the website or were age 40 or older.
Implications for Cancer Survivors
Online and telehealth programs such as INSPIRE offer opportunities to enhance HCT survivorship outcomes, particularly for mood, though methods would benefit from strategies to improve efficacy.
https://ift.tt/2rmgeHv
Endoscopic self-expandable metal stent placement for malignant afferent loop obstruction caused by peritoneal recurrence after total gastrectomy
Abstract
Afferent loop obstruction (ALO) caused by cancer recurrence after total gastrectomy (TG) can be managed by either surgical or non-surgical treatment. The general condition of patients with recurrent gastric cancer is often poor, so a less invasive non-surgical treatment is desirable. We report the case of a 75-year-old male who had undergone TG for gastric cancer 6 months previously and who presented at our hospital with abdominal pain and vomiting. Abdominal computed tomography scan showed a dilated afferent loop, and additionally a low-density lesion around jejunojejunal anastomosis, suggesting that ALO is associated with peritoneal recurrence. A self-expandable metal stent (SEMS) was endoscopically placed to treat ALO after decompression of the dilated afferent loop using an intestinal tube. He retained a good quality of life until his death due to cancer progression 5 months after the SEMS placement. Our case indicates that SEMS could be a less invasive alternative to surgery, and may confer a better quality of life for patients with ALO due to cancer recurrence after TG. This is the valuable report of case in which endoscopic metallic stent placement succeeded for ALO caused by peritoneal recurrence after TG.
https://ift.tt/2KB9LkG
Endoscopic self-expandable metal stent placement for malignant afferent loop obstruction caused by peritoneal recurrence after total gastrectomy
Abstract
Afferent loop obstruction (ALO) caused by cancer recurrence after total gastrectomy (TG) can be managed by either surgical or non-surgical treatment. The general condition of patients with recurrent gastric cancer is often poor, so a less invasive non-surgical treatment is desirable. We report the case of a 75-year-old male who had undergone TG for gastric cancer 6 months previously and who presented at our hospital with abdominal pain and vomiting. Abdominal computed tomography scan showed a dilated afferent loop, and additionally a low-density lesion around jejunojejunal anastomosis, suggesting that ALO is associated with peritoneal recurrence. A self-expandable metal stent (SEMS) was endoscopically placed to treat ALO after decompression of the dilated afferent loop using an intestinal tube. He retained a good quality of life until his death due to cancer progression 5 months after the SEMS placement. Our case indicates that SEMS could be a less invasive alternative to surgery, and may confer a better quality of life for patients with ALO due to cancer recurrence after TG. This is the valuable report of case in which endoscopic metallic stent placement succeeded for ALO caused by peritoneal recurrence after TG.
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Incorporation of the technologist’s opinion for arbitration of discrepant assessments among radiologists at screening mammography
Abstract
Purpose
We determined whether the addition of the technologist's opinion may be helpful in deciding if discordant readings at blinded double reading should be recalled.
Methods
A consecutive series of 99,013 digital screening mammograms, obtained between July 2013 and January 2015, were included. All mammograms were first interpreted by a technologist and then double read in a blinded fashion by a team of 13 screening radiologists. All concordant and discordant positive readings among radiologists were recalled.
Results
Out of 3562 recalls, 998 women were recalled after a discordant reading. Of these women, 337 (33.8%) had a positive technologist assessment, of which 40 (11.9%) were diagnosed with breast cancer. Sixty women with a negative technologist assessment (60/661, 9.1%) were diagnosed with breast cancer (p = 0.16). Recall rate would have decreased with technologist arbitration (3.6% vs. 2.9%, p < 0.001). Cancer detection rate decreased with 8.5%, from 7.1/1000 screens to 6.5/1000 screens (p = 0.10). Among women with a positive technologist assessment, the probability of breast cancer was highest in case of suspicious microcalcifications and lowest for suspicious masses (30.4% (17/56) versus 7.0% (16/212), p < 0.001). Breast cancers were diagnosed in all groups of mammographic abnormalities, except in women with a suspicious asymmetry and a negative technologist assessment.
Conclusions
Assessment by a technologist does not provide a significant discriminating ability in case of a discordant radiologist reading and, taking into account the decrease in cancer detection rate, does not appear to be a suitable arbitration strategy for discordant recalls at blinded double reading.
https://ift.tt/2HRf69Y
Cancers, Vol. 10, Pages 133: Translation Control by p53
Cancers, Vol. 10, Pages 133: Translation Control by p53
Cancers doi: 10.3390/cancers10050133
Authors: Justina Kasteri Dibash Das Xuelin Zhong Leah Persaud Ashleigh Francis Hilal Muharam Moira Sauane
The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth.
https://ift.tt/2FKDUuj
Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome
Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome
Cancers doi: 10.3390/cancers10050134
Authors: Ingeborg E. de Kruijff Anna M. Timmermans Michael A. den Bakker Anita M.A.C. Trapman-Jansen Renée Foekens Marion E. Meijer-Van Gelder Esther Oomen-de Hoop Marcel Smid Antoinette Hollestelle Carolien H.M. van Deurzen John A. Foekens John W.M. Martens Stefan Sleijfer
CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment (n = 551). 11% of the tumors showed CD146 expression. CD146 expression was most prevalent in triple-negative cases (64%, p < 0.001). In univariable analysis, CD146 expression was a prognostic factor for both metastasis-free survival (MFS) (p = 0.020) and overall survival (OS) (p = 0.037), but not in multivariable analysis (including age, tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67). No correlation between CD146 and EMT nor difference in outcome to first-line tamoxifen was seen. In this large series, our data showed that CD146 is present in primary breast cancer and is a pure prognostic factor for MFS and OS in breast cancer patients. We did not see an association between CD146 expression and EMT nor on outcome to tamoxifen.
https://ift.tt/2roVYoz
Cancers, Vol. 10, Pages 133: Translation Control by p53
Cancers, Vol. 10, Pages 133: Translation Control by p53
Cancers doi: 10.3390/cancers10050133
Authors: Justina Kasteri Dibash Das Xuelin Zhong Leah Persaud Ashleigh Francis Hilal Muharam Moira Sauane
The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth.
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Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome
Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome
Cancers doi: 10.3390/cancers10050134
Authors: Ingeborg E. de Kruijff Anna M. Timmermans Michael A. den Bakker Anita M.A.C. Trapman-Jansen Renée Foekens Marion E. Meijer-Van Gelder Esther Oomen-de Hoop Marcel Smid Antoinette Hollestelle Carolien H.M. van Deurzen John A. Foekens John W.M. Martens Stefan Sleijfer
CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment (n = 551). 11% of the tumors showed CD146 expression. CD146 expression was most prevalent in triple-negative cases (64%, p < 0.001). In univariable analysis, CD146 expression was a prognostic factor for both metastasis-free survival (MFS) (p = 0.020) and overall survival (OS) (p = 0.037), but not in multivariable analysis (including age, tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67). No correlation between CD146 and EMT nor difference in outcome to first-line tamoxifen was seen. In this large series, our data showed that CD146 is present in primary breast cancer and is a pure prognostic factor for MFS and OS in breast cancer patients. We did not see an association between CD146 expression and EMT nor on outcome to tamoxifen.
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Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy
Abstract
Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.
https://ift.tt/2JXanQH
Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy
Abstract
Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.
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Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain
Abstract
Background
The Douleur Neuropathique 4 questionnaire (DN4) is a simple and objective tool developed by the French Neuropathic Pain Group to screen for neuropathic pain.
Methods
This prospective observational study was undertaken in three hospitals to assess the validity of a Japanese translation of the DN4. We first translated the DN4 into Japanese using a forward–backward method. Pain specialists then examined patients independently and diagnosed them with neuropathic or non-neuropathic pain, according to the International Association for the Study of Pain definitions. The Japanese version of the DN4 questionnaire was then given to each patient.
Results
Of 187 patients that met our inclusion criteria, 100 and 87 were diagnosed with neuropathic and non-neuropathic pain, respectively. The test–retest intra-class correlation coefficient (95% confidence interval) was 0.827 (0.769–0.870). Among patients with identical diagnoses of neuropathic or non-neuropathic pain, receiver-operating characteristic curve analysis revealed an area under the curve of 0.89. A cut-off point of equal or greater than 4 resulted in a sensitivity of 71% and specificity of 92%.
Conclusion
The Japanese version of the DN4 was found to be a helpful tool for discriminating between neuropathic and non-neuropathic pain.
https://ift.tt/2rlcNkX
Ambient air emissions of polycyclic aromatic hydrocarbons and female breast cancer incidence in US
Abstract
To examine ambient air pollutants, specifically polycyclic aromatic hydrocarbons (PAHs), as a factor in the geographic variation of breast cancer incidence seen in the US, we conducted an ecological study involving counties throughout the US to examine breast cancer incidence in relation to PAH emissions in ambient air. Age-adjusted incidence rates of female breast cancer from the surveillance, epidemiology, and end results (SEER) program of the US National Cancer Institute were collected and analyzed using SEER*Stat 8.3.2. PAH emissions data were obtained from the Environmental Protection Agency. Linear regression analysis was performed using SPSS 23 software for Windows to analyze the association between PAH emissions and breast cancer incidence, adjusting for potential confounders. Age-adjusted incidence rates of female breast cancer were found being significantly higher in more industrialized metropolitan SEER regions over the years of 1973–2013 as compared to less industrialized regions. After adjusting for sex, race, education, socioeconomic status, obesity, and smoking prevalence, PAH emission density was found to be significantly associated with female breast cancer incidence, with the adjusted β of 0.424 (95% CI 0.278, 0.570; p < 0.0001) for emissions from all sources and of 0.552 (95% CI 0.278, 0.826; p < 0.0001) for emissions from traffic source. This study suggests that PAH exposure from ambient air could play a role in the increased breast cancer risk among women living in urban areas of the US. Further research could provide insight into breast cancer etiology and prevention.
https://ift.tt/2wlkc8O
Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors
Abstract
Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.
https://ift.tt/2jw9rr3
Ambient air emissions of polycyclic aromatic hydrocarbons and female breast cancer incidence in US
Abstract
To examine ambient air pollutants, specifically polycyclic aromatic hydrocarbons (PAHs), as a factor in the geographic variation of breast cancer incidence seen in the US, we conducted an ecological study involving counties throughout the US to examine breast cancer incidence in relation to PAH emissions in ambient air. Age-adjusted incidence rates of female breast cancer from the surveillance, epidemiology, and end results (SEER) program of the US National Cancer Institute were collected and analyzed using SEER*Stat 8.3.2. PAH emissions data were obtained from the Environmental Protection Agency. Linear regression analysis was performed using SPSS 23 software for Windows to analyze the association between PAH emissions and breast cancer incidence, adjusting for potential confounders. Age-adjusted incidence rates of female breast cancer were found being significantly higher in more industrialized metropolitan SEER regions over the years of 1973–2013 as compared to less industrialized regions. After adjusting for sex, race, education, socioeconomic status, obesity, and smoking prevalence, PAH emission density was found to be significantly associated with female breast cancer incidence, with the adjusted β of 0.424 (95% CI 0.278, 0.570; p < 0.0001) for emissions from all sources and of 0.552 (95% CI 0.278, 0.826; p < 0.0001) for emissions from traffic source. This study suggests that PAH exposure from ambient air could play a role in the increased breast cancer risk among women living in urban areas of the US. Further research could provide insight into breast cancer etiology and prevention.
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