Background Autologous stem cell transplantation (ASCT) is a potential consolidation therapy for acute myeloid leukemia (AML). This study was designed to develop a prediction model for leukemia‐free survival (LFS) in a cohort of patients with de novo AML treated with ASCT during their first complete remission. Methods This was a registry study of 956 patients reported to the European Society for Blood and Marrow Transplantation. The primary outcome was LFS. Multivariate Cox regression modeling...
Cancers, Vol. 11, Pages 873: Multidisciplinary Management of Patients with Unresectable Hepatocellular Carcinoma: A Critical Appraisal of Current EvidenceCancers doi: 10.3390/cancers11060873Authors:Pierre M. GholamRenuka IyerMatthew S. JohnsonHepatocellular carcinoma (HCC) is a leading cause of new cancer diagnoses in the United States, with an incidence that is expected to rise. The etiology of HCC is varied and can lead to differences between patients in terms of presentation and natural history....
Purpose: Clinically aggressive meningiomas (MGMs) are rare but treatment-resistant tumors in need for more effective therapies. Since tumor-infiltrating T-lymphocytes (TILs) are essential for successful immunotherapy, we assessed TIL numbers and their activation status in primary (p-) and recurrent (r-)MGMs and their impact on survival. Experimental Design: Presence of TILs was analyzed in 202 clinically well-annotated cases (n = 123 pMGMs and n = 79 rMGMs) focusing on higher-grade MGMs (n = 97 WHO°II,...
Purpose: Uveal melanoma (UM) is a primary malignancy of the eye with oncogenic mutations in GNAQ, GNA11, or CYSLTR2, and additional mutations in BAP1 (usually associated with LOH of Chr 3), SF3B1 or EIF1AX. There are other characteristic chromosomal alterations, but their significance is not clear. Experimental Design: To investigate genes driving chromosomal alterations we integrated copy number, transcriptome and mutation data from three cohorts and followed up key findings. Results: We observed...
Observational findings suggest exercise is associated with improved outcomes in early-stage breast cancer. However, whether exercise has biological activity in patients with breast cancer has not been investigated. Pre-operative window of opportunity studies provide a setting in which to test the short-term effects of novel treatment strategies on validated surrogates.
Purpose: Mutant KRAS is a major driver of pancreatic oncogenesis and therapy resistance, yet KRAS inhibitors are lacking in the clinic. KRAS requires farnesylation for membrane localization and cancer-causing activity prompting the development of farnesyltransferase inhibitors (FTIs) as anti-cancer agents. However, KRAS becomes geranylgeranylated and active when cancer cells are treated with FTIs. To overcome this geranylgeranylation-dependent resistance to FTIs, we designed FGTI-2734, a RAS C-terminal...
Purpose: Uveal melanomas (UMs) are genetically simple tumors carrying few copy number alterations (CNAs) and a low mutation burden, except in rare MBD4-deficient, hypermutated cases. The genomics of UM metastatic progression has not been described. We assessed the genetic heterogeneity of primary and metastatic MBD4-proficient and deficient UMs. Experimental Design: We prospectively collected 75 metastatic and 16 primary samples from 25 consecutive UM patients, and performed whole-exome sequencing....
Purpose: LV305 is a modified, third generation, non-replicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the NY-ESO-1 cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1-expressing tumors. This phase 1 study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors. Experimental Design: Adults with previously-treated,...
Purpose: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer. Experimental Design: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells or both, per subtype and per antibody used; and its prognostic value for disease-free and overall survival. A pooled gene expression analysis...
Purpose: Radiation therapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing radiation therapy. No further clinical benefit has been achieved using alternative radiation strategies. Here we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG....
Irinotecan and topotecan have been widely used as anticancer drugs for the past 20 years. Due to their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes (TOP1CCs), camptothecins are also widely used to elucidate the DNA repair pathways associated with DNA-protein crosslinks and replication stress. This review summarizes the basic molecular mechanisms of action of TOP1 inhibitors, their current use and limitations as anticancer agents. We introduce new therapeutic...
Induction of antitumor responses by vaccines requires strong immunogens. Heterologous viral prime/boost immunization with the BN-CV301 vaccine promotes activation of immune responses that provide a clinical benefit to cancer patients. This viral platform may be used to harbor different antigens and prime tumor immunity potentially useful for combinatorial strategies.
Purpose: The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. The current study has used multi-omics approaches and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance. Experimental Design: Mass spectrometry-based proteomics and RNA-Seq was used to identify the signaling pathways involved in the escape of uveal melanoma cells from MEK inhibitor therapy. Mechanistic studies were...
Pseudouridine () is the most abundant RNA modification in cellular RNA present in tRNA/rRNA/snRNA and also in mRNA and long non-coding RNA. Elucidation of function in mRNA/lncRNA requires mapping and quantitative assessment of its modification fraction at single-base resolution. The most widely used mapping method for mRNA/lncRNA relies on its reaction with N-Cyclohexyl-N'-(2-morpholinoethyl)carbodiimide (CMC), forming an adduct with the base in RNA that is detectable by reverse transcription...
In B cell acute lymphoblastic leukemia (B-ALL), activation of Notch signaling leads to cell-cycle arrest and apoptosis. We aimed to harness knowledge acquired by understanding a mechanism of Notch-induced cell death to elucidate a therapeutically viable target in B-ALL. To this end, we identified that Notch activation suppresses Polo-like kinase 1 (PLK1) in a B-ALL specific manner. We identified that PLK1 is expressed in all subsets of B-ALL, and is highest in Philadelphia-like (Ph-like) ALL,...
CD205 is a type I transmembrane glycoprotein, member of C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 was robustly expressed and highly prevalent in a variety of solid malignancies from different histotypes. Immunohistochemistry (IHC) confirmed the increased expression of CD205 in pancreatic, bladder and triple negative breast cancer (TNBC) compared to that in the corresponding normal tissues. Using immunofluorescence microscopy, rapid internalization of the CD205...
Opinion statement The thymus is a key organ involved in establishing central immune tolerance. Thymic epithelial tumors (TETs) include thymomas and thymic carcinomas. Thymomas, which are histologically distinct from thymic carcinomas, lead to dysregulated thymopoiesis via decreased thymic epithelial expression of AIRE and MHC Class II, as well as via alterations in thymic architecture, thereby resulting in autoimmune complications that manifest as paraneoplastic disorders (PNDs)....
Psychometric Properties of the MICRA Questionnaire in Portuguese Individuals Carrying SDHx Mutations
Abstract This study aims to present the translation and cultural adaptation, as well as the psychometric characteristics of the Portuguese version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire in individuals with SDHx mutations. The questionnaire was translated and culturally adapted in accordance with the process recommended by the World Health Organization. As per suggestion of the authors of the original instrument, a joint, universal European...
Development of resistance to inhibitors of BRAF (BRAFi) and MEK (MEKi) remains a great challenge for targeted therapy in patients with BRAF-mutant melanoma. Here, we explored the role of miRNAs in melanoma acq...
Abstract Purpose Lately, awake surgery has been frequently adapted for glioblastoma (GBM). However, even with awake surgery, the expected long-term independence levels may not be achieved. We studied the characteristics of independence levels in GBM patients, and investigated the usefulness and parameter thresholds of awake surgery from the standpoint of functional outcomes. ...
Abstract Purpose Craniopharyngiomas occur in suprasellar locations that pose challenges for surgical management. This study evaluates the incidence of complications following craniotomy for craniopharyngioma in adults and investigates risk factors for these complications. Methods Patients who underwent craniotomy for excision of craniopharyngioma were identified...
Cancers, Vol. 11, Pages 872: Evaluating a Single Domain Antibody Targeting Human PD-L1 as a Nuclear Imaging and Therapeutic AgentCancers doi: 10.3390/cancers11060872Authors: Broos Lecocq Xavier Bridoux Nguyen Corthals Schoonooghe Lion Raes Keyaerts Devoogdt BreckpotThe PD-1:PD-L1 immune checkpoint axis is central in the escape of cancer cells from anticancer immune responses. Monoclonal antibodies (mAbs) specific for PD-L1 have been approved for treatment of various cancer types. Although PD-L1 blockade...
Abstract Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IV ADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin...
Localized renal cell carcinoma (RCC) has an associated risk of recurrence after nephrectomy. Several clinical risk models attempt to predict oncologic outcomes based on clinical and pathologic features. In addition, novel gene signatures have been developed to refine risk prediction based on tumor biology. Systemic therapies targeting angiogenic pathways that are effective in metastatic RCC failed to show an improvement in overall survival in the adjuvant setting. Immune checkpoint inhibitors have...
Background The identification of extrauterine disease is critical to the management of patients with high‐risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease. Methods Women with high‐risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy....
Cancers, Vol. 11, Pages 867: Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer ChemopreventionCancers doi: 10.3390/cancers11060867Authors: Goh Tan Goh Chan Pusparajah Lee GohThe search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents...
Cancers, Vol. 11, Pages 870: Synthesis and Enhanced Cellular Uptake In Vitro of Anti-HER2 Multifunctional Gold NanoparticlesCancers doi: 10.3390/cancers11060870Authors: Cruz KayserNanoparticle carriers offer the possibility of enhanced delivery of therapeutic payloads in tumor tissues due to tumor-selective accumulation through the enhanced permeability and retention effect (EPR). Gold nanoparticles (AuNP), in particular, possess highly appealing features for development as nanomedicines, such as...
Cancers, Vol. 11, Pages 868: Uptake of Ranibizumab but Not Bevacizumab into Uveal Melanoma Cells Correlates with a Sustained Decline in VEGF-A Levels and Metastatic ActivitiesCancers doi: 10.3390/cancers11060868Authors: Tura Pawlik Rudolf Ernesti Stutzer Grisanti RanjbarDespite the implication of vascular endothelial growth factor-A (VEGF-A) in the pathophysiology of uveal melanoma (UM), the anti-VEGF-A antibody bevacizumab yielded conflicting results on UM growth. Here, we evaluated whether bevacizumab...
Cancers, Vol. 11, Pages 869: Automated Definition of Skeletal Disease Burden in Metastatic Prostate Carcinoma: A 3D Analysis of SPECT/CT ImagesCancers doi: 10.3390/cancers11060869Authors: Fiz Dittmann Campi Weissinger Sahbai Reimold Stenzl Piana Sambuceti la FougèreTo meet the current need for skeletal tumor-load estimation in castration-resistant prostate cancer (CRPC), we developed a novel approach based on adaptive bone segmentation. In this study, we compared the program output with existing...
Cancers, Vol. 11, Pages 871: Meta-Enrichment Analyses to Identify Advanced Gastric Cancer Patients Who Achieve a Higher Response to S-1/CisplatinCancers doi: 10.3390/cancers11060871Authors: Takeuchi Jaffer A Fang Pfeiffer Takeuchi van Laarhoven The Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study (FLAGS) and the Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial (DIGEST) have shown that...
Publication date: July–August 2019Source: Reports of Practical Oncology & Radiotherapy, Volume 24, Issue 4Author(s): Trine Egegaard, Julie Rohold, Christian Lillelund, Gitte Persson, Morten QuistAbstractAimTo examine the feasibility of an individual, supervised, structured moderate-to-high intensity cycle ergometer exercise training immediately before radiotherapy in patients undergoing concomitant chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC).BackgroundLung cancer...
Publication date: August 2019Source: European Journal of Cancer, Volume 117Author(s): Luca Mazzarella, Bruno Achutti Duso, Dario Trapani, Carmen Belli, Paolo D'Amico, Emanuela Ferraro, Giulia Viale, Giuseppe CuriglianoAbstract'First-generation' immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core...
Publication date: August 2019Source: European Journal of Cancer, Volume 117Author(s): Joo-Hyun Park, Do-Hoon Kim, Yong-Gyu Park, Do-Young Kwon, Moonyoung Choi, Jin-Hyung Jung, Kyungdo HanAbstractIntroductionThe association between Parkinson's disease (PD) and cancer development is controversial, especially in Asia. Therefore, we conducted a nationwide population-based cohort study to assess the overall cancer risk and risk for specific cancers in patients with PD in Korea.MethodsUsing data from the...
Publication date: August 2019Source: European Journal of Cancer, Volume 117Author(s): Matejka Rebolj, Oleg Blyuss, Kee Seng Chia, Stephen W. DuffyAbstractAimBreast density is a risk factor for breast cancer. As density changes across a woman's life span, we studied for how long a single density measurement taken in (post-)menopausal women remains informative.MethodsWe used data from Singaporean women who underwent a single mammography screen at age 50–64 years. For each case with breast cancer diagnosed...
Publication date: August 2019Source: European Journal of Cancer, Volume 117Author(s): Carmen Criscitiello, Giuseppe Curigliano
Publication date: August 2019Source: European Journal of Cancer, Volume 117Author(s): M. Wakkee, S. van Egmond, M. Louwman, P. Bindels, J. van der Lei, T. Nijsten, L. HollesteinAbstractBackgroundHigh incidence rates of keratinocyte carcinoma (KC) in Western countries put pressure on healthcare systems. The aim of this study was to describe clinical practice in order to identify areas for improvement.MethodsA random selection of patients from the Integrated Primary Care Information database who consulted...
Publication date: Available online 21 June 2019Source: European Journal of Surgical OncologyAuthor(s): Mohammad Alyami, Frederic Mercier, Matthieu Siebert, Pierre-Emmanuel Bonnot, Nathalie Laplace, Laurent Villeneuve, Guillaume Passot, Olivier Glehen, Naoual Bakrin, Vahan KepenekianAbstractBackgroundPIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment.MethodsAll...
Publication date: Available online 20 June 2019Source: European Journal of Surgical OncologyAuthor(s): Ambria S. Moten, Huaqing Zhao, Charles M. Intenzo, Alliric I. WillisAbstractBackgroundWe sought to identify treatment disparities existing prior to publication of the 2015 American Thyroid Association Management Guidelines in order to identify patients with papillary thyroid cancer (PTC) at risk for receiving inadequate treatment.MethodsPatients diagnosed with PTC from 2011 to 2013 were identified...
Cancers, Vol. 11, Pages 866: Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung AdenocarcinomasCancers doi: 10.3390/cancers11060866Authors:Chien-Hung GowMin-Shu HsiehYen-Ting LinYi-Nan LiuJin-Yuan ShihBRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative...
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