Pancreatic ductal adenocarcinoma(PDA)is known for its poor prognosis.Most of the patients are diagnosed with advanced stages,when no curative treatment is available.Currently,despite extensive ...clinical research on PDA,the median overall survival remains short.Diagnosis delay and primary chemo-resistance due to its intrinsic biological nature may explain the challenges to improve our results.Our knowledge about the molecular biology of PDA has exponentially increased during the last decades and its use for the development of biomarkers could help to reach better results in the clinical setting.These biomarkers could be the clue for the improvement in PDA clinical research by earlier detection strategies with diagnostic biomarkers,and by an individualization of treatment approach with prognostic and predictive biomarkers.This review summarizes the current knowledge about the molecular biology of PDA and the status of the most important prognostic and predictive biomarkers.
Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.
We prospectively studied 865 patients, aged ...54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up 95% confidence interval (CI) 34.22-40.8%, 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001).
The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.
Summary Thymic malignancies are extremely rare although usually affect young adults and continue to remain an important health problem. Like other rare diseases, progress in thymic malignancies has ...been slow and the treatment cornerstone still remains surgical resection. Next generation sequencing and other advances in molecular biology are shedding light onto the multiple genetic aberrations involved and have opened a new field for research with molecularly targeted therapies such as CKIT inhibitors or anti-EGFR therapies. In this review we will summarize the current knowledge in the pathophysiology, diagnosis, prognosis and latest advances in the management of thymomas and thymic carcinomas.
Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be ...identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines’ growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.
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•2 and 3D cellular models of AGS constitute a promising in vitro drug screening tool.•Several compounds have been validated as effective in AGS cell lines.•8AA would be the most interesting drug with which to continue development in AGS.•8AA shows promising anti-tumour activity in vitro.•8AA demonstrated in vitro proliferation, migration and invasion inhibition.
Approximately 20–30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine ...diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.
Background
Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive ...dysfunction in patients treated with adjuvant chemotherapy for colon cancer.
Patients and methods
We assessed cognitive function, quality of life, anxiety and depression, fatigue, and hemoglobin levels in colon cancer patients at three assessment points: pre-chemotherapy (
n
= 81), post-chemotherapy (
n
= 73), and after 6-month follow-up (
n
= 54). All patients were treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) for 6 months.
Results
Thirty patients (37 %) had cognitive impairment in the pre-chemotherapy evaluation, mainly in processing speed and psychomotor executive function (Trail Making Test A and B). At the end of treatment, the main domain affected was the verbal memory, with an acute decline detected in 56 % of patients. Fifty-four percent of the patients improved their dysfunction after 6 months of follow-up, whereas 18 (33 %) of them showed worsening in at least one test. Cognitive impairment was most common in older patients and in those with less years of education. Quality of life, anxiety, depression, fatigue, and hemoglobin did not influence the results of the cognitive tests.
Conclusions
Adjuvant FOLFOX4 in patients with colon cancer can have a negative effect on verbal memory. This deterioration is usually mild and transient.
This work reports the first electrochemical bioplatform developed for the multidetection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in DNA, DNA N6-methyladenine (6mA) and RNA ...N6-methyladenosine (m6A) methylations at global level. Direct competitive immunoassays were implemented on the surface of magnetic beads (MBs) and optimized for the single amperometric determination of different targets varying in length, sequence and number of methylations on screen-printed carbon electrodes. After evaluating the sensitivity and selectivity of such determinations and the confirmation of no cross-reactivity, a multiplexed disposable platform allowing the simultaneous determination of the mentioned four methylation events in only 45 min has been prepared. The multiplexed bioplatform was successfully applied to the determination of m6A in cellular total RNA and of 5-mC, 5-hmC and 6mA in genomic DNA extracted from tissues. The developed bioplatform showed its usefulness to discriminate the aggressiveness of cancerous cells and between healthy and tumor tissues of colorectal cancer patients.
First electrochemical bioplatform developed for the multidetection of 5-methyl-cytosine (5-mC) and 5-hydroxymethyl-cytosine (5-hmC) in DNA, N-6-methyladenosine in DNA (6 mA) and RNA (m6A) methylations at global level. Display omitted
•First multiplexed bioplatform for global detection of 5-mC, 5-hmC, 6 mA and m6A.•Competitive immunoassays implemented on MBs and amperometric detection at disposable electrodes.•Sensitive and selective multiplexed determination in only 45 min.•Analysis of cellular total RNA and genomic DNA extracted from tumor tissues.•Discriminate the aggressiveness of cancer cells and tumor tissues of cancer patients.
Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) ...analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.
Symptom Clusters in Advanced Cancer Jiménez, Ana, PhD; Madero, Rosario, PhD; Alonso, Alberto, PhD ...
Journal of pain and symptom management,
07/2011, Letnik:
42, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Context Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population. Objectives The aim of the present ...study was to explore SCs in advanced cancer, evaluate the characteristics associated with various clusters, and determine their relationship to survival. Methods This study included patients in the palliative care program of the Hospital Universitario La Paz from 2003 to 2005. The Edmonton Symptom Assessment System and a supplement including 13 other symptoms were used to detect symptoms. Principal component analysis was performed to determine symptom relationships and compare SCs with associated parameters. Results In total, 406 patients were included, 61% men and 39% women. The median age was 66.4 (range 18–95). The most common primaries were gastrointestinal (35%), lung (25%), genitourinary (8%), breast (5%), and head and neck (5%) carcinomas. The following clusters were identified: confusion (cognitive impairment, agitation, urinary incontinence), neuropsychological (anxiety, depression, and insomnia), anorexia-cachexia (anorexia, weight loss, and tiredness), and gastrointestinal (nausea and vomiting). The presence of these SCs was influenced by primary cancer site, gender, age, and performance status. Survival was related to the number of SCs present in a given patient: zero SC, 52 days; one SC, 38 days; two SCs, 23 days; and three to four SCs, 19 days; P < 0.001. Conclusion Different SCs can be identified in patients with advanced cancer. These SCs are influenced by primary cancer site, gender, age, and Eastern Cooperative Oncology Group performance status, and they can have prognostic value.
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