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Background. The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated. Objectives. We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy. Materials and methods. We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic. Results. In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354). Conclusions. According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs. [ABSTRACT FROM AUTHOR]

Purpose: Cardiogenic shock still has a high mortality. In order to correctly manage these patients, it is useful to have available haemodynamic parameters, invasive and non‐invasive. The aim of this review is to show the current evidence on the use of echocardiographic aortic flow assessment by left ventricular outflow tract ‐ velocity time integral. Methods: Publications relevant to the discussion of echocardiographic aortic flow assessment by left ventricular outflow tract ‐ velocity time integral and cardiogenic shock, were retrieved from PubMed®. Results: Left ventricular outflow tract ‐ velocity time integral is an easily sampled and reproducible parameter that has already been shown to have prognostic value in various cardiovascular pathologies, including myocardial infarction and heart failure. Although there are still few data available in the literature, the LVOT‐VTI also seems to have an important role in CS from prognosis to guidance in the escalation/de‐escalation of vasoactive therapy and to support devices by allowing an estimate of patient's probability of response to fluid administration. Conclusion: Aortic flow assessment can become a very useful invasive parameter in the management of cardiogenic shock. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have been proven to be an effective treatment strategy for a variety of malignant tumors. However, only a subset of patients can benefit from ICIs due to factors such as drug resistance. Therefore, it is crucial to identify biomarkers that can accurately predict the efficacy of ICIs and provide a basis for individualized immunotherapy. In this study, we conducted a systematic review and meta-analysis to explore whether the chemokine interleukin 8 (IL-8) can be used as a biomarker to evaluate the efficacy of ICIs treatment. Methods: We conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, and Cochrane, to identify relevant articles published up to June 08, 2023. Our inclusion criteria were limited to cohort studies and clinical trials that reported hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS) and/or progression-free survival (PFS), as well as the objective response rate (ORR), in cancer patients with high and low IL-8 expression. For data analysis, we used Revman to generate forest plots, subgroup analysis, and assess publication bias. Additionally, Stata was utilized for sensitivity analysis and further examination of publication bias. Results: A total of 24 datasets, involving 3190 participants, were selected from 14 studies. The meta-analysis revealed a reduction in ORR, OS, and/or PFS in the high IL-8 group after treatment with ICIs compared to the low IL-8 group. Conclusion: IL-8 can serve as a biomarker for predicting the efficacy of ICIs. Patients with lower expression of IL-8 may benefit from ICIs treatment. [ABSTRACT FROM AUTHOR]

Hepatic metastasis is a clinical challenge for colorectal cancer (CRC). Senescent cancer cells accumulate in CRC favoring tumor dissemination. Whether this mechanism progresses also in metastasis is unexplored. Here, we integrated spatial transcriptomics, 3D‐microscopy, and multicellular transcriptomics to study the role of cellular senescence in human colorectal liver metastasis (CRLM). We discovered two distinct senescent metastatic cancer cell (SMCC) subtypes, transcriptionally located at the opposite pole of epithelial (e) to mesenchymal (m) transition. SMCCs differ in chemotherapy susceptibility, biological program, and prognostic roles. Mechanistically, epithelial (e)SMCC initiation relies on nucleolar stress, whereby c‐myc dependent oncogene hyperactivation induces ribosomal RPL11 accumulation and DNA damage response. In a 2D pre‐clinical model, we demonstrated that RPL11 co‐localized with HDM2, a p53‐specific ubiquitin ligase, leading to senescence activation in (e)SMCCs. On the contrary, mesenchymal (m)SMCCs undergo TGFβ paracrine activation of NOX4‐p15 effectors. SMCCs display opposing effects also in the immune regulation of neighboring cells, establishing an immunosuppressive environment or leading to an active immune workflow. Both SMCC signatures are predictive biomarkers whose unbalanced ratio determined the clinical outcome in CRLM and CRC patients. Altogether, we provide a comprehensive new understanding of the role of SMCCs in CRLM and highlight their potential as new therapeutic targets to limit CRLM progression. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers.

Background: Approximately 5% of COVID-19 patients suffer from near-fatal disease. Clinical and radiologic features may predict severe disease although with limited specificity and radiation hazard. Laboratory biomarkers are specific, simple, and point-of-care triage tools that can be used to predict the severity of the disease. This research aimed to study the role of inflammatory markers (serum ferritin, lactate dehydrogenase [LDH], D-dimer, and C-reactive protein [CRP]) in prognosticating COVID-19 patients. Methodology: This was a hospital-based retrospective study conducted on COVID-19 adult inpatients classified into three groups: mild disease-recovered (Group I), severe disease-recovered (Group II), and dead (Group III). Categorical outcomes were compared using the Chi-square test. Univariate binary logistic regression analysis was performed to test the association between the outcome and explanatory variables. An unadjusted odds ratio (OR) along with a 95% confidence interval was calculated. The utility of laboratory parameters (ferritin, LDH, neutrophil/lymphocyte ratio, D-dimer, and platelet/lymphocyte ratio) in predicting the severity of COVID-19 was assessed by the receiver operative curve analysis. P < 0.05 was considered statistically significant. Results: A total of 500 case records were analyzed. The mean age was 49.32 ± 17.1 years. About 72.4% were

Background and Objectives: Bioelectrical-impedance analysis (BIA) is frequently used to estimate dry weight in hemodialysis (HD) patients. However, the clinical prognostic significance of BIA indicators is unclear. As a nutritional index, low phase angle (PA) might be an independent risk factor for predicting death in multiple chronic diseases. We performed this study to find relative influence factors of PA and other clinical prognostic significance. Methods and Study Design: The study involved 87 HD patients, 33 of whom were diabetic and 54 of whom were not. We measured body composition index, body water index and nutritional indicators and collected biochemical criteria. Then, we statistically analyzed the associations of these indices. After 1 year of follow-up, we recorded death, heart failure, hospitalization, cerebrovascular and cardiovascular events and other clinical outcomes. Results: We found a significant difference between the two groups in visceral-fat area, extracellular water/total body water (ECW/TBW) ratio and PA value. Two factors were negatively associated with PA: ECW/TBW ratio and HCO3- before HD. At 1 year, we noted that PA was associated with events such as heart failure or hospitalization. By further stratification and multivariate analysis adjusting for age, sex and months of dialysis, we found that low PA was an independent predictor of heart failure for diabetic HD patients. Conclusions: PA value was lower in Diabetic nephropathy (DN) HD patients, than that in non-DN HD patients. PA was mainly negatively associated with ECW/TBW ratio. It is a useful index for predicting heart failure in diabetic HD patients. [ABSTRACT FROM AUTHOR]

Background: Peritoneal sarcomatosis (PS) could occur in patients with retroperitoneal sarcomas (RPS). This study aimed to expand the understanding of PS on its characteristics and prognostic role, and develop a nomogram to predict its occurrence preoperatively. Methods: Data of 211 consecutive patients with RPS who underwent surgical treatment between 2011 and 2019 was retrospectively reviewed. First, the clinicopathological characteristics of PS were summarized and analyzed. Second, the disease-specific survival (DSS) and recurrence-free survival (RFS) of patients were analyzed to evaluate the prognostic role of PS. Third, preoperative imaging, nearly the only way to detect PS preoperatively, was combined with other screened risk factors to develop a nomogram. The performance of the nomogram was assessed. Results: Among the 211 patients, 49 (23.2%) patients had PS with an incidence of 13.0% in the primary patients and 35.4% in the recurrent patients. The highest incidence of PS occurred in dedifferentiated liposarcoma (25.3%) and undifferentiated pleomorphic sarcoma (25.0%). The diagnostic sensitivity of the preoperative imaging was 71.4% and its specificity was 92.6%. The maximum standardized uptake value (SUVmax) was elevated in patients with PS (P<0.001). IHC staining for liposarcoma revealed that the expression of VEGFR-2 was significantly higher in the PS group than that in the non-PS group (P = 0.008). Survival analysis (n =196) showed significantly worse DSS in the PS group than in non-PS group (median: 16.0 months vs. not reached, P < 0.001). In addition, PS was proven as one of the most significant prognostic predictors of both DSS and RFS by random survival forest algorithm. A nomogram to predict PS status was developed based on preoperative imaging combined with four risk factors including the presentation status (primary vs. recurrent), ascites, SUVmax, and tumor size. The nomogram significantly improved the diagnostic sensitivity compared to preoperative imaging alone (44/49, 89.8% vs. 35/49, 71.4%). The C-statistics of the nomogram was 0.932, and similar C-statistics (0.886) was achieved at internal cross-validation. Conclusion: PS is a significant prognostic indicator for RPS, and it occurs more often in recurrent RPS and in RPS with higher malignant tendency. The proposed nomogram is effective to predict PS preoperatively. [ABSTRACT FROM AUTHOR]

Background Anastomotic leakage after gastrointestinal surgery is a significant postoperative complication that leads to increased morbidity and mortality. C-reactive protein (CRP) has been used previously as a predictive marker of anastomotic leakage in gastrointestinal surgeries. Its short half-life makes it a reliable marker for postoperative complications, rapidly returning to normal values as the patient recovers. We conducted this study to evaluate the predictive accuracy of serum CRP levels in predicting anastomotic leaks in patients undergoing gastrointestinal repair surgeries. Methods Ninety-six gastrointestinal surgeries involving anastomoses and primary repairs were included in the study. CRP was taken serially from postoperative days (POD) 1 to 7. Patients were divided into two groups based on postoperative outcomes: leakage and non-leakage. The receiver operating characteristic (ROC) curve of CRP levels with leak and mortality was plotted to find a threshold value for leak and mortality. Results Out of 96 patients included in the study, Group B (non-leakage) consisted of 78 patients (81.3%), while Group A (leakage) comprised 18 patients (18.7%). ROC analysis identified a CRP cutoff of 127 mg/L on POD 5, with high sensitivity (80%) and high specificity (80%) indicating a high likelihood of leakage above this threshold. Conclusion This study underscores the importance of monitoring CRP levels in the postoperative period, particularly on POD 5, as a non-invasive and cost-effective tool for the early detection of anastomotic leaks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Rajendra Institute of Medical Sciences issued approval 238/26.10.2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mayank et al.)

Background: The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated., Objectives: We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy., Material and Methods: We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic., Results: In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354)., Conclusion: According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.

Background: Approximately 5% of COVID-19 patients suffer from near-fatal disease. Clinical and radiologic features may predict severe disease although with limited specificity and radiation hazard. Laboratory biomarkers are specific, simple, and point-of-care triage tools that can be used to predict the severity of the disease. This research aimed to study the role of inflammatory markers (serum ferritin, lactate dehydrogenase [LDH], D-dimer, and C-reactive protein [CRP]) in prognosticating COVID-19 patients. Methodology: This was a hospital-based retrospective study conducted on COVID-19 adult inpatients classified into three groups: mild disease-recovered (Group I), severe disease-recovered (Group II), and dead (Group III). Categorical outcomes were compared using the Chi-square test. Univariate binary logistic regression analysis was performed to test the association between the outcome and explanatory variables. An unadjusted odds ratio (OR) along with a 95% confidence interval was calculated. The utility of laboratory parameters (ferritin, LDH, neutrophil/lymphocyte ratio, D-dimer, and platelet/lymphocyte ratio) in predicting the severity of COVID-19 was assessed by the receiver operative curve analysis. P < 0.05 was considered statistically significant. Results: A total of 500 case records were analyzed. The mean age was 49.32 ± 17.1 years. About 72.4% were <60 years and 301 male and 199 female patients were included. The comorbidity count included diabetes 168 (33.6%), hypertension 122 (24.4%), coronary artery disease 23 (4.6%), hypothyroidism 3 (6%), and others 33 (6.6%) The median levels of ferritin among the three groups differed significantly bearing higher levels in Group 3 (P < 0.001). Median LDH and D-dimer values of the three groups showed statistical significance (P < 0.001). Qualitative CRP was significantly associated with poor outcomes (P < 0.001). The odds of patients suffering severe COVID-19 rose with rising values of ferritin, LDH, and D-dimer (unadjusted OR: 1.007, 1.004, and 1.020). Conclusion: Onetime measurement of serum ferritin, LDH, D-dimer, and CRP performed between 7th and 10th day of symptoms significantly predicted outcomes for COVID-19 inpatients. [ABSTRACT FROM AUTHOR]

Considerable number of patients with metastatic urothelial carcinoma develop bone metastases. Immunecheckpoint inhibitors are approved, but their efficacy on bone metastasis has not been investigated. Data on 208 patients, treated with immunotherapy for advanced disease, were collected. Patients treated with immunotherapy for bone metastasis have a dismal prognosis compared to patients without bone involvement in terms of overall and progression-free survival. Background: Considerable numbers of patients with metastatic urothelial carcinoma (mUC) develop bone metastases (BoM). Their impact on the efficacy of immune-checkpoint inhibitors (ICIs) is not yet investigated. Methods: Between July 2014 and August 2020 data on pts treated with single-agent ICIs after failure of at least 1 previous line of chemotherapy for advanced disease, were retrospectively collected across 14 Italian centers. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UVA) and multivariable analysis (MVA). Results: A total of 208 evaluable patients treated with ICIs were identified, including 122 (59%) without BoM (BoM-) and 86 (41%) with bone metastases (BoM + ). After a median follow-up of 22.3 months, BoM + patients showed shorter OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], P = .005) and shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], P < .001). Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM + respectively. Within each Bellmunt score, OS and PFS of BoM + patients were shorter. Both presence of BoM and higher Bellmunt risk score were significantly associated with shorter OS and PFS in UVA and MVA. Conclusion: Patients treated with single-agent ICIs for BoM + mUC have a dismal prognosis compared to BoM-. Further research is needed to understand the mechanism behind these outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this review is to summarize the latest details considering the role of Dll4 in cancer, since recent data report that Dll4 has a major key role in tumor angiogenesis. Moreover, the authors try to seek any correlation between Dll4 and cancer stem cells in tumor development. Considering that cancer stem cells have proven to be implicated in the progression of many cancer types, any impact from Dll4 could lead to the alteration of cancer development. Additionally, the authors make a report on current advantages on immunotherapy and tumor-draining lymph nodes in cancer. Finally, this study analyzes toll like receptors, pattern recognition receptors that are capable of recognizing different molecules and activating different genes. These immunogenetic molecules have remarkable roles including angiogenesis promotion, while their activation can lead to either cancer progression or inhibition, representing a very promising therapeutic alliance for cancer treatment. The Notch signaling pathway regulates the development of embryonic and tissue homeostasis of various types of cells. It also controls cell proliferation, variation, fate and cell death because it emits short-range messages to nearby cells. The pathway plays an important role in the pathophysiology of various malignancies, controlling cancer creation. It also limits cancer development by adjusting preserved angiogenesis and cellular programs. One of the Notch signaling ligands (in mammals) is Delta-like ligand 4 (Dll4), which plays a significant role in the overall malignancies' advancement. Particularly, sequencing Notch gene mutations, including those of Dll4, have been detected in many types of cancers portraying information on the growth of particular gynecological types of tumors. The current research article examines the background theory that implies the ability of Dll4 in the development of endometrial and other cancer types, and the probable therapeutic results of Dll4 inhibition. [ABSTRACT FROM AUTHOR]

Background: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.Methods: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination.Results: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively.Conclusions: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma. [ABSTRACT FROM AUTHOR]

Background and Objective: Platelet-to-lymphocyte ratio (PLR) has been suggested to be associated with the progression of oral cancer with inconclusive results. The objective of the current study was to assess the prognostic role of oral cancer by meta-analysis.Method: PubMed, EMbase(Ovid), CNKI, WanFang Data, VIP, and CBM databases were searched up to August 24, 2018. Studies investigating the association between PLR and progression of oral cancer were included. Meta-analysis was performed by using Revman 5.3 software. The protocol of the study was registered on PROSPERO (CRD42018106836).Results: A total of five studies were included in the meta-analysis. The results of the meta-analysis showed that higher PLR was associated with the poor progress of oral cancer (overall survival: OR = 2.06, 95 CI: 1.49-2.86, P < 0.0001; disease-specific survival: OR = 2.12, 95 CI: 1.59-2.82, P < 0.00001).Conclusion: The current meta-analysis showed that higher PLR is a poor progression factor for oral cancer. However, larger sample, multi-center studies should be carried out in the future to validate the above conclusion. [ABSTRACT FROM AUTHOR]

The role of CXC chemokine receptors in tumors has been an increasingly researched focus in recent years. However, significant prognostic values of CXCR members in acute myeloid leukemia are yet to be explored profoundly. In this study, we firstly made an analysis of the relationship of CXCR family members and AML using samples from TCGA. Our results suggested that transcriptional expressions of CXCRs serve an important role in AML. CXCR transcript expressions, except CXCR1 expression, were significantly increased in AML. It displayed the expression pattern of CXCR members in different AML subtypes according to FAB classification. The correlations of CXCR transcript expression with different genotypes and karyotypes were also present. High CXCR2 expression was found to have a significantly worse prognosis compared with that of low CXCR2 expression, and CXCR2 was also found to be an independent prognostic factor. We also established a CXCR signature to identify high-risk subgroups of patients with AML. It was an independent prognostic factor and could become a powerful method to predict the survival rate of patients.

Abstract Background Galectin-3 as a β-galactoside-binding protein, has been found to be involved in tumor cell growth, anti-apoptosis, adhesion, angiogenesis, invasion, and distant metastases, indicating that it may play a pivotal role in cancer development and progression. However, their results remain debatable and inconclusive. Hence, this meta-analysis was performed to clarify the precise predictive value of galectin-3 in various cancers. Methods PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wanfang databases were searched comprehensively for eligible studies up to July 15, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated to demonstrate their associations. Results A total of 36 relevant studies were ultimately enrolled in this meta-analysis. Our results shed light on the significant association of elevated galectin-3 expression with reduced OS or DFS/RFS/PFS in overall cancer patients (pooled HR = 1.79, 95% CI 1.42–2.27, I 2= 67.3%, p

The role of CXC chemokine receptors in tumors has been an increasingly researched focus in recent years. However, significant prognostic values of CXCR members in acute myeloid leukemia are yet to be explored profoundly. In this study, we firstly made an analysis of the relationship of CXCR family members and AML using samples from TCGA. Our results suggested that transcriptional expressions of CXCRs serve an important role in AML. CXCR transcript expressions, except CXCR1 expression, were significantly increased in AML. It displayed the expression pattern of CXCR members in different AML subtypes according to FAB classification. The correlations of CXCR transcript expression with different genotypes and karyotypes were also present. High CXCR2 expression was found to have a significantly worse prognosis compared with that of low CXCR2 expression, and CXCR2 was also found to be an independent prognostic factor. We also established a CXCR signature to identify high-risk subgroups of patients with AML. It was an independent prognostic factor and could become a powerful method to predict the survival rate of patients. [ABSTRACT FROM AUTHOR]

Background: Sorafenib is a multikinase inhibitor used to treat advanced hepatocellular carcinoma (HCC). Recently, a preclinical trial has shown that response to sorafenib is associated with a metabolic shift towards aerobic glycolysis. To test this observation in humans, we decided to conduct a proof-of-concept trial investigating the role of metabolic shift detected on [18F]FDG PET/CT in predicting survival and tumor response in HCC patients treated with sorafenib. Methods: We prospectively enrolled advanced HCC patients candidate to sorafenib and undergoing [18F]FDG PET/CT at baseline, at 24 h, and at day 7 following treatment start. Response evaluation was obtained after 8 weeks according to Response Evaluation Criteria in Solid Tumors (RECIST). All clinical variables and metabolic parameters (i.e., SUVmax; metabolic tumor volume, MTV; total lesion glycolysis, TLG; and their variations, Δ) were compared with those of treatment response and correlated to progression-free (PFS) and overall survival (OS). Results: For this proof-of-concept trial, between August 2016 and August 2018, 13 patients (10 male, 3 female, median age 69) were enrolled. Considering the entire cohort, we demonstrated a significant negative correlation between ΔSUVmax at 24 h and 1 week (rho = − 0.733, p = 0.016). The metabolic shift, as expected, demonstrated median SUVmax, MTV, and TLG after 1 week lower in patients with a stable disease than a progressive disease (p = 0.019). Metabolic parameters and ECOG performance status (PS) resulted significantly correlated to PFS and OS at univariate analysis. On multivariate analysis, only median MTV at 1 week resulted as an independent prognostic factor for PFS (p = 0.033). Conclusions: As hypothesized, [18F]FDG PET/CT resulted in able to evaluate metabolic shift at 24 h and early treatment response already 1 week after treatment start. Moreover, metabolic parameters and ECOG PS resulted in predictive and prognostic factors to PFS and OS, with MTV at 1 week appearing as an independent predictive factor for PFS. [ABSTRACT FROM AUTHOR]

Objectives: MET protein expression has been reported to be in relevance with the survival of NSCLC patients in various studies, yet the results were inconsistent. The purpose of our study set out to determine the prognostic role of both c-MET and p-MET expression among NSCLC that underwent surgical resection.Methods: Data were obtained from retrospective cohort studies by searching on PubMed, Cochrane Library, EMBASE and Web of Science, and a meta-analysis was performed to assess the prognostic role of MET expression among NSCLC.Results: Totally 18 literatures including 5,572 surgically resected NSCLC cases staged I-IV were included for data synthesis. The positive rate of c-MET and p-MET was 1,753/4,315 and 135/1,257. The pooled hazard ratios (HRs) regarding c-MET and p-MET expression for overall survival (OS) was 1.623 (95% CI: 1.176–2.240, p = 0.003) and 1.710 (95% CI: 0.823–3.533, p = 0.15), respectively. Subgroup analysis results on Asian (HR = 2.115, p < 0.001), adenocarcinoma (HR = 2.220, p < 0.001) and rabbit polyclonal antibodies (HR = 2.107, p < 0.001) etc. were also indicative.Conclusion: C-MET over-expression among NSCLC patients that underwent surgical resection is a prognostic factor that indicated adverse survival on OS. Whereas, p-met didn't appear to have an impact on the prognosis of NSCLC. The studies are need and the topic could be re-valued by then.

Objectives: MET protein expression has been reported to be in relevance with the survival of NSCLC patients in various studies, yet the results were inconsistent. The purpose of our study set out to determine the prognostic role of both c-MET and p-MET expression among NSCLC that underwent surgical resection. Methods: Data were obtained from retrospective cohort studies by searching on PubMed, Cochrane Library, EMBASE and Web of Science, and a meta-analysis was performed to assess the prognostic role of MET expression among NSCLC. Results: Totally 18 literatures including 5,572 surgically resected NSCLC cases staged I-IV were included for data synthesis. The positive rate of c-MET and p-MET was 1,753/4,315 and 135/1,257. The pooled hazard ratios (HRs) regarding c-MET and p-MET expression for overall survival (OS) was 1.623 (95% CI: 1.176–2.240, p = 0.003) and 1.710 (95% CI: 0.823–3.533, p = 0.15), respectively. Subgroup analysis results on Asian (HR = 2.115, p < 0.001), adenocarcinoma (HR = 2.220, p < 0.001) and rabbit polyclonal antibodies (HR = 2.107, p < 0.001) etc. were also indicative. Conclusion: C-MET over-expression among NSCLC patients that underwent surgical resection is a prognostic factor that indicated adverse survival on OS. Whereas, p-met didn't appear to have an impact on the prognosis of NSCLC. The studies are need and the topic could be re-valued by then. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC. miR-31 seems also to play important regulatory functions in ICC and it directly regulates BAP-1 expression in lung cancer. In this study, tissue expression of BAP-1, PBRM-1, S100P, and miR-31 was investigated in ICC and correlated with clinical-pathological features. Sixty-one consecutive patients who underwent curative hepatic resection for ICC were enrolled. None received any therapy prior to surgery. Immunostaining for BAP-1, PBRM-1, and S100P, and in situ hybridization for miR-31 were performed, using tissue microarray slides. A strong retained expression of BAP-1 and PBRM-1 was associated with a reduced overall (p = 0.04 and p = 0.002, respectively) and disease-free survival (p = 0.05 and p = 0.02, respectively). An overexpression of S100P was related to a reduced overall survival (p = 0.005). The multivariate analyses identified the presence of perineural invasion and the retained PBRM-1 expression as independent predictors of worse overall [p = 0.02, hazard ratio (HR) = 2.25 (1.16-4.39) and p = 0.001, HR = 3.13 (1.56-6.28), respectively] and disease-free survivals [p = 0.03, HR = 2.43 (1.09-5.4) and p = 0.03, HR = 2.51 (1.11-5.67), respectively]. An overexpression of S100P was predictive of a worse overall survival [p = 0.02, HR = 1.66 (1.08-2.55)]. High levels of miR-31 were significantly associated to a low expression of BAP-1 protein (p = 0.03). In ICC, a retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that microRNA (miR)-760 serves an important role in various cancer types. However, to the best of our knowledge, its role in hepatocellular carcinoma (HCC) has not been fully elucidated. The current study investigated the prognostic role of miR-760 in HCC by using the Kaplan-Meier plotter database. The current data indicated that low expression of miR-760 was associated with higher overall survival (OS) for all patients with HCC from both the RNA-seq [hazard ratio (HR)=2.04; 95% confidence interval (CI)=1.44–2.89; P=4.9×10−5] and the non-commercial spotted microarray (HR=1.71; CI=1.05–2.76; P=0.028). In the RNA-seq platform, a lower expression of miR-760 was strongly associated with improved OS in male patients with HCC, but not in female patients with HCC. Additionally, low expression of miR-760 was associated with improved OS in patients with stage I, II and III HCC, and was associated with improved OS in Asian and Caucasian patients. The current results indicated that miR-760 serves as an oncogene for HCC and high expression of miR-760 is significantly associated with tumor progression and poor prognosis in patients with HCC. [ABSTRACT FROM AUTHOR]

Background: An abnormal frontal QRS-T angle (fQRSTa) is associated with increased risk of death in primary and secondary cardiovascular prevention. The aim of this study was to evaluate the fQRSTa prognostic role in patients undergoing myocardial revascularization and/or cardiac valve surgery.Methods: We enrolled and prospectively followed for 48 ± 26 months 939 subjects with available QRS and T axis data; mean age was 68 ± 12 years, 449 patients (48%) underwent myocardial revascularization, 333 (35%) cardiac valve surgery, 94 (10%) valve plus bypass graft surgery and 63 (7%) cardiac surgery for other cardiovascular (CV) diseases. The ECG variables were collected at the end of the cardiac rehabilitation program and fQRSTa was considered normal if <60°, abnormal if >120°, borderline otherwise. Endpoints were overall and CV mortality.Results: The fQRSTa was normal in 333 patients (36%), borderline in 285 (30%) and abnormal in 321 (34%). Overall (p = 0.012) and cardiovascular (p = 0.007) mortality were significantly higher in patients with abnormal fQRSTa even after adjusting separately for gender, PR-, QTc- intervals, presence of right or left bundle branch block and left atrial volume index. The predictive value was confirmed in patients with stable coronary artery disease (SCAD), not in patients with acute coronary syndrome or valve disease. SCAD patients with abnormal both fQRSTa and QRS axis had higher risk of overall (hazard ratio = 2.9, p < 0.0001) and CV (hazard ratio = 4.4, p < 0.0001) mortality compared with SCAD patients with normal fQRSTa, even after multivariate adjustment for age, gender, ECG intervals, left-ventricle ejection fraction and mass index.Conclusions: In SCAD patients undergoing myocardial revascularization, abnormal fQRSTa is independent predictor of overall and CV mortality. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma (SCC) of the uterine cervix is a leading cause of morbidity and mortality among women. The alterations of Phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl2) and p53 expression seem to be significant in the development of various types of cancers. The altered expressions of PTEN, Bcl2 and p53 and their involvement in cancer of the uterine cervix are not well recognized. Aim: This study aimed at examining the expression patterns of PTEN, Bcl2 and p53 proteins and comparing them with the grade and stage of cervical cancer. Materials and Methods: Tissue blocks of SCC and ten cases of inflammatory lesions of the uterine cervix were examined immunohistochemically for the expression of PTEN, Bcl2 and p53 proteins. Results: Loss of PTEN expression was identified in 45.33% of cervical SCC and high expression was found in inflammatory lesions (p ≤ 0.05). PTEN expression was significantly associated with the clinical stage of SCC (61.36% and 45.16% in stages I–II and III–IV, respectively) (p < 0.05), but not with the degree of differentiation of the SCC. The expression of Bcl2 was significantly high (60%) in cancer cases than in control cases (p < 0.05). Bcl2 did not show any significant association with the histologic type and clinical stage of the SCC of the uterine cervix. The expression of p53 protein was significantly high (57.33%)) in cancer tissue, and no expression was noted in control cases (p < 0.05). Moreover, the expression pattern of p53 protein in cervical cancer tissue samples was not linked with the patient age, grade and stage of the cervical SCC (p > 0.05). Conclusion: The reduced expression of PETN and overexpressions of Bcl2 and p53 might play an indispensable role in carcinogenesis of cervical SCC. Moreover, a relationship was detected between PTEN expression and clinical stage of the cervical SCC. [ABSTRACT FROM AUTHOR]

Aim: The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). Materials and methods: From the databases of two centers including 31,500 F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. Results: Recurrent GCT was confirmed in 47 of 52 patients with pathological F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from 'wait and watch' to new chemotherapy in six patients and the 'wait-and-watch' approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). Conclusion: F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process. [ABSTRACT FROM AUTHOR]

Background and Purpose: The natural history of optic pathway glioma (OPG) is highly variable and unpredictable. We present a pilot study of the prognostic role of conventional and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the evaluation of OPG.Methods: We retrospectively reviewed 17 patients with 20 pretreatment OPG lesions who underwent conventional and DCE MRI between January 2010 and December 2016. Conventional MRI was evaluated for enhancement pattern, cystic component, optic nerve tortuosity, optic nerve dural ectasia, and optic nerve perineural thickening. The DCE MRI data were analyzed for quantitative parameters using the two-compartment pharmacokinetic model (Ktrans , kep , and ve ) and for semiquantitative parameters based on time-signal intensity curve (AUC60 , peak, and wash-in). The results were compared with the clinically progressive or nonprogressive tumor.Results: Five progressive OPGs and 15 nonprogressive OPGs were included. Conventional MRI findings of diffuse enhancement and cystic component were significantly correlated with progressive OPGs (both P = .01). Conventional MRI yielded sensitivity of 60%, specificity of 100%, and accuracy of 90%. Ktrans , kep , and ve as well as AUC60 , peak, and wash-in were significantly higher in progressive OPGs (P < .05). Using DCE MRI increased diagnostic performance up to a sensitivity of 100%, specificity of 93%, and accuracy of 95%.Conclusion: DCE MRI accurately distinguished progressive and nonprogressive OPGs, with high sensitivities and specificities. DCE MRI has a significant prognostic role in predicting progressive OPGs, thus making it useful for the identification of patients who need close clinical and imaging follow-up. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of metabolic parameters analyzed at baseline and at interim FDG-PET in predicting disease outcome in unresectable MPM patients receiving pemetrexed-based chemotherapy. A consecutive series of MPM patients treated between February 2004 and July 2013 with first-line pemetrexed-based chemotherapy, and evaluated by FDG-PET and CT scan at baseline and after two cycles of chemotherapy, was reviewed. Best CT scan response was assessed according to modified RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were correlated with FDG-PET parameters, such as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and percentage changes in SUVmax (∆SUV) and TLG (∆TLG). Overall, 142 patients were enrolled; 77 (54%) received talc pleurodesis before chemotherapy. Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS ( P < 0.05) in both group of patients (treated and untreated with pleurodesis). In 65 patients not receiving pleurodesis, SUVmax reduction ≥25% (∆SUV ≥ 25%) and TLG reduction ≥30% (∆TLG ≥ 30%) were significantly associated with longer PFS ( P < 0.05). Patients showing both ∆SUV ≥ 25% and ∆TLG ≥ 30% responses had a significant reduction in the risk of disease progression (HR:0.31, P < 0.001) and death (HR:0.52, P = 0.044). Neither ∆SUV nor ∆TLG showed similar association with survival outcomes in patients treated with pleurodesis. Our study confirmed the prognostic role of baseline FDG-PET in a large series of MPM patients treated with first-line pemetrexed-based chemotherapy. Moreover, use of ∆SUV ≥ 25% and ∆TLG ≥ 30% as cut-off values to define early metabolic response supported the role of FDG-PET in predicting disease outcome and treatment response in patients not receiving pleurodesis. [ABSTRACT FROM AUTHOR]

Aim: A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. Materials and Methods: Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. Results: PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for SUVmax < 6 vs. 15 % for SUVmax > 6, p = 0.018; 2-year PFS 66 % for TLG < 8.5 vs. 18 % for TLG > 8.5, p = 0.09). Conclusion: A very good diagnostic performance for FDG PET/CT was confirmed in patients with suspected recurrent BC. FDG PET/CT allowed for a change in treatment decision in about 40 % of cases and showed an important prognostic value in assessing PFS and OS. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma (SCC) of the uterine cervix is a leading cause of morbidity and mortality among women. The alterations of Phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl2) and p53 expression seem to be significant in the development of various types of cancers. The altered expressions of PTEN, Bcl2 and p53 and their involvement in cancer of the uterine cervix are not well recognized. Aim: This study aimed at examining the expression patterns of PTEN, Bcl2 and p53 proteins and comparing them with the grade and stage of cervical cancer. Materials and Methods: Tissue blocks of SCC and ten cases of inflammatory lesions of the uterine cervix were examined immunohistochemically for the expression of PTEN, Bcl2 and p53 proteins. Results: Loss of PTEN expression was identified in 45.33% of cervical SCC and high expression was found in inflammatory lesions (p ≤ 0.05). PTEN expression was significantly associated with the clinical stage of SCC (61.36% and 45.16% in stages I⁻II and III⁻IV, respectively) (p < 0.05), but not with the degree of differentiation of the SCC. The expression of Bcl2 was significantly high (60%) in cancer cases than in control cases (p < 0.05). Bcl2 did not show any significant association with the histologic type and clinical stage of the SCC of the uterine cervix. The expression of p53 protein was significantly high (57.33%)) in cancer tissue, and no expression was noted in control cases (p < 0.05). Moreover, the expression pattern of p53 protein in cervical cancer tissue samples was not linked with the patient age, grade and stage of the cervical SCC (p > 0.05). Conclusion: The reduced expression of PETN and overexpressions of Bcl2 and p53 might play an indispensable role in carcinogenesis of cervical SCC. Moreover, a relationship was detected between PTEN expression and clinical stage of the cervical SCC.

Background/Aims: Although the diagnostic value of fluorine-18 2-fluoro-2-deoxy-D-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDGPET/ CT) in patients with colorectal cancer (CRC) has been reported, the association between the F-18-FDG uptake in metastatic lymph nodes (FDG LN ) and clinicopathological variables has not been fully investigated. We evaluated the diagnostic value of F-18-FDG-PET/CT in detecting LN metastasis from CRC, and the relationship between F-18-FDG-PET/ CT-detecting LN metastasis and prognosis. Methods: We retrospectively analyzed the medical records of 370 patients who underwent preoperative F-18-FDG-PET/CT, followed by surgical resection for CRC between January 2007 and December 2010. We analyzed the sensitivity, specificity, and accuracy of F-18-FDG-PET/CT and CT in diagnosing metastatic LNs. Survival was analyzed in 115 patients with stage III CRC. Results: The sensitivity, specificity, and accuracy for detecting metastatic LNs using F-18-FDG-PET/CT were 56.8, 90.3, and 74.2%, and those for contrast-enhanced CT were 38.4, 95.5, and 65.0%, respectively. The accuracy of F-18-FDGPET/ CT was significantly associated with tumor depth and lymphatic involvement. In the survival analysis, cancer-specific survival and the disease-free survival were significantly shorter in patients with stage III CRC with FDG LN than in those without FDG LN . Conclusion: F-18-FDG-PET/CT had low sensitivity and high specificity for detecting metastatic LNs from CRC. FDG LN independently predicted poor prognosis in patients with stage III CRC. [ABSTRACT FROM AUTHOR]

Background: Regenerating gene (REG) family is composed of antiapoptotic factors and growth factors that affect epithelial cells within the digestive system. Regenerating gene-I has been studied in different cancers. However, it has never been studied in head and neck cancer. We investigated the expression of REG-I in head and neck SCC and its relevance to patient survival rates. Methods: Untreated biopsy specimens of 60 patients with stage IV head and neck SCC were collected, and the expression of REG-I was evaluated using immunohistochemistry. The association between REG-I expression and clinico-pathological features or survival status of the patients was assessed by Chi-square test, Fisher's exact test and Kaplan-Meier method. Cox proportional hazard model was used to identify the independent prognostic factors. Results: Incidence of lymphatic permeation, vascular invasion and pathological lymph nodes was significantly higher in REG-I negative group (p = 0.008, 0.030 and 0.015, respectively). Overall and cancer-free survival rates were significantly higher in REG-I positive group (p = 0.000434 and 1.0847E-8, respectively). Univariate analysis showed that REG-I was an independent prognostic factor for predicting long-term overall survival (p = 0.002), and multivariate analysis showed that REG-I and lymphatic permeation were independent prognostic factors for predicting long-term disease-free survival (p = 0.001 and 0.022, respectively). Conclusion: Our results showed for the first time that, REG-I is expressed in head and neck SCC. REG-I expression is associated with a longer survival status. We conclude that, REG-I might be a prognostic marker in head and neck SSC and should be further investigated. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) plays a key role in progression to metastatic castration-resistant prostate cancer (mCRPC). Despite the recent progress in targeting persistent AR activity with the next-generation hormonal therapies (abiraterone acetate and enzalutamide), resistance to these agents limits therapeutic efficacy for many patients. Several explanations for response and/or resistance to abiraterone acetate and enzalutamide are emerging, but growing interest is focusing on importance of AR splice variants (AR-Vs) and in particular of AR-V7. Increasing evidences highlight the concept that variant expression could be used as a potential predictive biomarker and a therapeutic target in advanced prostate cancer. Therefore, understanding the mechanisms of treatment resistance or sensitivity can help to achieve a more effective management of mCRPC, increasing clinical outcomes and representing a promising and engaging area of prostate cancer research. [ABSTRACT FROM AUTHOR]

Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A), a recently identified oncogene, has emerged as a potential drug target for a range of different tumor types. High CIP2A expression has been reported in almost all solid organ cancers and in some hematological tumors and is associated with high grade and poor prognosis. Notably, high CIP2A expression is determined in over 70% of tumor patient samples in the majority of human cancers. High expression of CIP2A has also been proposed as a useful biomarker that predicts therapeutic response to chemotherapeutics such as Bortezomib, Erlotinib, Checkpoint Kinase 1 inhibitors and pro-senescence based therapies. In this review, we highlight, critically evaluate and discuss the ambiguity in CIP2A's prognostic role in different human cancers and its role in modulating response and resistance to chemotherapeutics. [ABSTRACT FROM AUTHOR]

Background: In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS). Methods: We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis. Results: The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (≤6; p = 0.0017). Patients with a high iSUV (>6) had a longer OS compared to those with a low iSUV (≤6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV >6 (hazard ratio = 0.26). Conclusion: Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]