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1.
Consensus on molecular imaging and theranostics in prostate cancer.
Fanti, S, Minozzi, S, Antoch, G, Banks, I, Briganti, A, Carrio, I, Chiti, A, Clarke, N, Eiber, M, De Bono, J, et al
The Lancet. Oncology. 2018;(12):e696-e708
Abstract
Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.
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2.
Assessment of chemotherapy on various biochemical markers in breast cancer patients.
Paz, MFCJ, Gomes, AL, Islam, MT, Tabrez, S, Jabir, NR, Alam, MZ, Machado, KC, de Alencar, MVOB, Machado, KC, Ali, ES, et al
Journal of cellular biochemistry. 2018;(3):2923-2928
Abstract
Chemotherapy is a standard treatment method for the patients with locally advanced breast cancer. Lately, cyclophosphamide (CYP) and doxorubicin (DOX) are used as the major chemotherapeutic agents especially for the treatment of breast cancer. Till date, no serum biomarker has been able to provide an early diagnosis of breast cancer. This study aimed to assess inflammatory, cardiac, renal and hematological markers in 56 breast cancer patients (BCP) before, during and after termination of chemotherapy with CYP and DOX. Blood samples were collected from the patients at the each treatment stages mentioned above. These samples were assessed for interleukin 6 (IL-6), interleukin 10 (IL-10), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine, hemoglobin (Hb), leukocyte, platelet and Na+ /K+ -ATPase levels either by ELISA or colorimetric methods. The results suggest a significant increase in IL-6 level at all the stages in BCP as compared to control group. On the other hand, IL-10, CK and Na+ /K+ -ATPase levels were found to be significantly declined during all the stages. Moreover, the majority of hematological parameters remained unchanged throughout the treatment period with the exception of creatinine and Hb which showed slight modulation in their level at different stages. Based on the results, we conclude that breast cancer and co-treatment with CYP and DOX, interfere arious biological markers, thereby, showing the physiological imbalance.
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3.
Clinicopathological and prognostic significance of zinc finger antisense 1 overexpression in cancers: A meta-analysis.
Leng, Y, Luo, Q, Chen, X, Chen, F, Wang, X, Pan, Y
Medicine. 2018;(49):e13378
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Abstract
BACKGROUND An increasing number of studies have recently highlighted the role of zinc finger antisense 1(ZFAS1) as a prognostic marker in cancers. However, these results remain controversial. Hence, a meta-analysis was conducted to further investigate the effects of ZFAS1 expression on clinicopathological features and survival outcomes. METHOD All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library. All included articles evaluated the relationship between the expression levels of ZFAS1 and survival, or the range of pathological features in cancer patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to evaluate the effect of ZFAS1 expression on overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). The relationship between ZFAS1 expression and clinicopathological features was determined through pooled odds ratios (ORs) and 95% CIs. RESULTS In total 8 studies, which comprised of 820 patients, were qualified for analysis. Results revealed that the overexpression of ZFAS1 was significantly associated with poor OS (HR = 1.97, 95% CI: 1.53-2.54), worse RFS (HR = 1.95, 95% CI: 1.24-3.04) and worse DFS (HR = 2.35, 95% CI: 1.43-3.88) in cancers. Further subgroup analysis revealed that ZFAS1 overexpression was significantly correlated with poor OS in different cancer types, HR obtain methods and sample sizes. In addition, this meta-analysis revealed that the upregulated expression of ZFAS1 was significantly associated with lymph node metastasis, Tumor Node Metastasis (TNM) stage, and tumor size. CONCLUSIONS This meta-analysis revealed that the expression of ZFAS1 was associated with tumor prognosis. ZFAS1 could be used as a predictor for tumor progression in various cancers.
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Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: A systematic review and meta-analysis.
Zhang, D, Liu, Z, Yin, X, Qi, X, Lu, B, Liu, Y, Hou, J
The International journal of biological markers. 2018;(3):266-274
Abstract
BACKGROUND Several studies have been conducted to evaluate the prognostic value of prothrombin induced by vitamin K absence-II (PIVKA-II) overexpression in hepatocellular carcinoma patients treated with curative ablation. However, the results remain controversial. The purpose of this meta-analysis was to explore the correlation between PIVKA-II expression and survival outcomes in these patients. METHODS We performed a systematic literature search in PubMed, EMBASE, Medline, Cochrane Library, and Web of Science to identify the relevant articles investigating the prognostic value of PIVKA-II in patients with hepatocellular carcinoma. Combined hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival and recurrence-free survival were calculated as the analysis endpoints. RESULTS A total of 15 cohorts encompassing 5647 patients were included. The results indicated that elevated PIVKA-II was significantly associated with poorer overall survival (HR 1.59; 95% CI 1.40, 1.82; P < 0.001) and recurrence-free survival (HR 1.76; 95% CI 1.42, 2.17; P < 0.001). Similar results were observed in the subgroup analysis based on sample size, analytical method, treatment modality, and cut-off value. CONCLUSIONS This meta-analysis suggests that elevated PIVKA-II is a predictor of unfavorable overall survival and recurrence-free survival in hepatocellular carcinoma patients receiving curative ablation. More rigorous studies are warranted to confirm the clinical utility of PIVKA-II in determining hepatocellular carcinoma prognosis.
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Translational opportunities for broad-spectrum natural phytochemicals and targeted agent combinations in breast cancer.
Dalasanur Nagaprashantha, L, Adhikari, R, Singhal, J, Chikara, S, Awasthi, S, Horne, D, Singhal, SS
International journal of cancer. 2018;(4):658-670
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Abstract
Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.
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Prognostic nomogram for patients with Nasopharyngeal Carcinoma incorporating hematological biomarkers and clinical characteristics.
Li, J, Chen, S, Peng, S, Liu, Y, Xing, S, He, X, Chen, H
International journal of biological sciences. 2018;(5):549-556
Abstract
Predictive models for survival prediction in individual cancer patients following the tumor, node, and metastasis (TNM) staging system are limited. The survival rates of patients who share TNM stage diseases are diversified. Therefore, we established a nomogram in which hematological biomarkers and clinical characteristics for predicting the overall survival (OS) of nasopharyngeal carcinoma (NPC) patients were incorporated. The clinicopathological and follow-up data of 690 NPC patients who were histologically diagnosed histologically at the Sun Yat-sen University Cancer Center between July 2007 and December 2011 were retrospectively reviewed. Data was randomly divided into primary (n = 460) and validation groups (n = 230). Cox regression analysis was used to identify prognostic factors for building the nomogram in primary cohorts. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index) and decision curve, and were compared with the TNM staging system, Epstein-Barr virus DNA copy numbers (EBV DNA), or TMN stage plus EBV DNA. The results were internally validated by assessment of discrimination and calibration using the validation cohorts at the same institution. Independent factors selected into the nomogram for OS included age [hazard ratio (HR): 1.765; 95% confidence interval (CI): 1.008-3.090)], TNM stage (HR: 1.899; 95% CI: 1.023-3.525), EBV DNA (HR: 1.322; 95% CI: 1.087-1.607), lactate dehydrogenase level (LDH) (HR: 1.784; 95% CI: 1.032-3.086), high sensitivity C-reactive protein (hs-CRP) (HR: 1.840; 95% CI: 1.039-3.258), high-density lipoprotein cholesterol (HDL-C) (HR: 0.503; 95% CI: 0.282-0.896), hemoglobin (HGB) (HR: 0.539; 95% CI: 0.309-0.939) and lymphocyte to lymphocyte ratio (LMR) (HR:0.531; 95% CI: 0.293-0.962). The C-index in the primary cohort and validation cohort were 0.800 and 0.831, respectively, and were statistically higher when compared to C-index values for TNM stage (0.672 and 0. 716), EBV DNA (0.668 and 0.688), and TNM stage+ EBV DNA (0. 732 and 0. 760), P < 0.001 for all. Moreover, the decision curve analyses demonstrated that the nomogram model had a higher overall net benefit compared to the TNM staging system, EBV DNA and TNM stage+ EBV DNA. Next, patients were divided into three distinct risk groups for OS based on total points (TPs) of the nomogram: a low-risk group (TPs ≤ 19.0), an intermediate risk group (19.0 < TPs ≤ 25.5) and a high risk group (TPs > 25.5), respectively. The nomogram predicting prognosis generated for NPC patients had a higher predictive power compared to the TNM staging system, EBV DNA, and TNM stage+ EBV DNA.
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Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer.
Fukushima, H, Takemura, K, Suzuki, H, Koga, F
International journal of molecular sciences. 2018;(10)
Abstract
Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. In patients with cancer cachexia, anorexia, poor nutrition and systemic inflammation make the metabolic state more catabolic, resulting in sarcopenia. Thus, sarcopenia is considered as one of manifestations of cancer cachexia. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we summarized metabolic backgrounds of cancer cachexia and sarcopenia and definitions of sarcopenia based on computed tomography (CT) images. We conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients. Lastly, we discussed the impact of nutritional support, medication, and exercise on sarcopenia in cancer-bearing patients.
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The implication of diabetes metabolomics in the early diagnosis and pathogenesis of pancreatic cancer.
Lou, YB, Fan, FX, Mu, YC, Dong, X
Journal of biological regulators and homeostatic agents. 2018;(1):75-82
Abstract
The aim of this study was to analyze metabolite differences in pancreatic cancer and diabetic patients, to better diagnose these diseases. Gas chromatography-mass spectrometry was used to evaluate the metabolomic differences in blood samples of 50 pancreatic patients, 50 diabetic patients and 50 healthy people. Metabonomic data was analyzed with primary component analysis and discriminant analysis. The results show that pancreatic cancer patients, diabetic patients and healthy people can have significantly distinct metabolite profiles. Upregulated metabolites in the serum of the diabetic group included sugars (glucose, fructose), cholesterol, tyrosine and phosphoric acid and other substances, and down-regulation was observed in lactic acid, glycine, alanine, glutamine, proline, citric acid and other substances. It is indicated that identification of the most common changes in specific markers between the two diseases, can provide a new perspective and experimental basis for a better understanding of the metabolic differences and the pathogenesis of the two diseases in future. The present study sheds new light on the diagnosis of pancreatic cancer and diabetes.
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[Prognostic importance of albumin in oncology].
Deme, D, Telekes, A
Orvosi hetilap. 2018;(3):96-106
Abstract
Diminished serum albumin level can be observed in inflammatory processes. Serum albumin level also reduces - irrespective of the presence of malnutrition - in locally advanced or metastatic malignancies. Low serum albumin level may have an influence also on the results of anticancer therapy (e.g., drug pharmacokinetics, adverse drug reactions). Extensive data of the literature and empirical experience prove the better prognosis of patients involved in nutritional therapy. Based on the most relevent data of the literature, the authors summarize the studies which have revealed the close correlation between the baseline serum albumin level and the prognosis of malignant diseases. Orv Hetil. 2018; 159(3): 96-106.
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Membrane Proteome of Invasive Retinoblastoma: Differential Proteins and Biomarkers.
Danda, R, Ganapathy, K, Sathe, G, Madugundu, AK, Krishnan, UM, Khetan, V, Rishi, P, Gowda, H, Pandey, A, Subramanian, K, et al
Proteomics. Clinical applications. 2018;(5):e1700101
Abstract
PURPOSE Retinoblastoma (RB) is a pediatric ocular cancer which is caused due to the aberrations in the RB1 gene. The changes in the membrane proteomics would help in understanding the development of the retinoblastoma and could identify candidates for biomarkers and therapy. EXPERIMENTAL DESIGN Quantitative proteomics is performed on the enriched membrane fractions from pooled normal retina (n = 5) and pooled retinoblastoma tissues (n = 5). The proteins are tryptic-digested and tagged with iTRAQ labels. Orbitrap mass spectrometry is used to analyze and quantify the deregulated membrane proteins involved in the RB tumor progression. Immunohistochemistry (IHC) is used to further validate few of the differentially expressed proteins. RESULTS A total of 3122 proteins are identified of which, 663 proteins are found to be deregulated with ≥two fold change in the RB tumor compared to the retina. 282 proteins are upregulated and 381 are downregulated with ≥2 peptide identifications. Bioinformatic analysis revealed that, most of the proteins are involved in the transport, cellular communication, and growth. Overexpression of lamin B1 (LMNB1) and transferrin receptor (TFRC) are observed in RB tumors using IHC. CONCLUSION AND CLINICAL RELEVANCE The present study, is the first comprehensive quantitative membrane proteomic atlas of the differentially regulated proteins in RB compared to the retina. LMNB1 and TFRC could be potential biomarkers for this childhood cancer.