Prediction methods and databases within chemoinformatics: emphasis on drugs and drug candidates

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Jonsdottir, Svava Osk; Jorgensen, FS; Brunak, Søren

2005-01-01

about drugs and drug candidates, and of databases with relevant properties. Access to experimental data and numerical methods for selecting and utilizing these data is crucial for developing accurate predictive in silico models. Many interesting predictive methods for classifying the suitability......MOTIVATION: To gather information about available databases and chemoinformatics methods for prediction of properties relevant to the drug discovery and optimization process. RESULTS: We present an overview of the most important databases with 2-dimensional and 3-dimensional structural information...... of chemical compounds as potential drugs, as well as for predicting their physico-chemical and ADMET properties have been proposed in recent years. These methods are discussed, and some possible future directions in this rapidly developing field are described....

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

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Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize

Integrative analysis to select cancer candidate biomarkers to targeted validation

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Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

2015-01-01

Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

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Xuefeng Ren

Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

Prediction of posthepatectomy liver failure using transient elastography in patients with hepatitis B related hepatocellular carcinoma.

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Lei, Jie-Wen; Ji, Xiao-Yu; Hong, Jun-Feng; Li, Wan-Bin; Chen, Yan; Pan, Yan; Guo, Jia

2017-12-29

It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P hepatocellular carcinoma.

Survival prediction model for postoperative hepatocellular carcinoma patients.

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Ren, Zhihui; He, Shasha; Fan, Xiaotang; He, Fangping; Sang, Wei; Bao, Yongxing; Ren, Weixin; Zhao, Jinming; Ji, Xuewen; Wen, Hao

2017-09-01

This study is to establish a predictive index (PI) model of 5-year survival rate for patients with hepatocellular carcinoma (HCC) after radical resection and to evaluate its prediction sensitivity, specificity, and accuracy.Patients underwent HCC surgical resection were enrolled and randomly divided into prediction model group (101 patients) and model evaluation group (100 patients). Cox regression model was used for univariate and multivariate survival analysis. A PI model was established based on multivariate analysis and receiver operating characteristic (ROC) curve was drawn accordingly. The area under ROC (AUROC) and PI cutoff value was identified.Multiple Cox regression analysis of prediction model group showed that neutrophil to lymphocyte ratio, histological grade, microvascular invasion, positive resection margin, number of tumor, and postoperative transcatheter arterial chemoembolization treatment were the independent predictors for the 5-year survival rate for HCC patients. The model was PI = 0.377 × NLR + 0.554 × HG + 0.927 × PRM + 0.778 × MVI + 0.740 × NT - 0.831 × transcatheter arterial chemoembolization (TACE). In the prediction model group, AUROC was 0.832 and the PI cutoff value was 3.38. The sensitivity, specificity, and accuracy were 78.0%, 80%, and 79.2%, respectively. In model evaluation group, AUROC was 0.822, and the PI cutoff value was well corresponded to the prediction model group with sensitivity, specificity, and accuracy of 85.0%, 83.3%, and 84.0%, respectively.The PI model can quantify the mortality risk of hepatitis B related HCC with high sensitivity, specificity, and accuracy.

Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder.

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Bartsch, Georg; Mitra, Anirban P; Mitra, Sheetal A; Almal, Arpit A; Steven, Kenneth E; Skinner, Donald G; Fry, David W; Lenehan, Peter F; Worzel, William P; Cote, Richard J

2016-02-01

Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor. Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction. The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set. Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

New candidate markers of head and neck squamous cell carcinoma progression

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Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

2017-09-01

The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk.

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Wang, Dan; Qi, Xiaoying; Liu, Fang; Yang, Chuanhua; Jiang, Wenguo; Wei, Xiaodan; Li, Xuri; Mi, Jia; Tian, Geng

2017-07-25

Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

Combination of c-reactive protein and squamous cell carcinoma antigen in predicting postoperative prognosis for patients with squamous cell carcinoma of the esophagus.

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Feng, Ji-Feng; Chen, Sheng; Yang, Xun

2017-09-08

We initially proposed a useful and novel prognostic model, named CCS [Combination of c-reactive protein (CRP) and squamous cell carcinoma antigen (SCC)], for predicting the postoperative survival in patients with esophageal squamous cell carcinoma (ESCC). Two hundred and fifty-two patients with resectable ESCC were included in this retrospective study. A logistic regression was performed and yielded a logistic equation. The CCS was calculated by the combined CRP and SCC. The optimal cut-off value for CCS was evaluated by X-tile program. Univariate and multivariate analyses were used to evaluate the predictive factors. In addition, a novel nomogram model was also performed to predict the prognosis for patients with ESCC. In the current study, CCS was calculated as CRP+6.33 SCC according to the logistic equation. The optimal cut-off value was 15.8 for CCS according to the X-tile program. Kaplan-Meier analyses demonstrated that high CCS group had a significantly poor 5-year cancer-specific survival (CSS) than low CCS group (10.3% vs. 47.3%, P <0.001). According to multivariate analyses, CCS ( P =0.004), but not CRP ( P =0.466) or SCC ( P =0.926), was an independent prognostic factor. A nomogram could be more accuracy for CSS (Harrell's c-index: 0.70). The CCS is a usefull and independent predictive factor in patients with ESCC.

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence

OpenAIRE

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

Background: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. Methods: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinform...

Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma.

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Yeh, Hsin-Chih; Jan, Hau-Chern; Wu, Wen-Jeng; Li, Ching-Chia; Li, Wei-Ming; Ke, Hung-Lung; Huang, Shu-Pin; Liu, Chia-Chu; Lee, Yung-Chin; Yang, Sheau-Fang; Liang, Peir-In; Huang, Chun-Nung

2015-01-01

To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract

Predicting microscopic extrauterine spread of endometrial carcinoma with MRI to support less invasive therapy

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Oishi Tanaka, Yumiko; Nishida, Masato; Minami, Rie; Yamaguchi, Masayuki; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Yoshizako, Takeshi

2000-06-01

Magnetic resonance imaging (MRI) provides precise staging of endometrial carcinoma. However, we have sometimes experienced patients with microscopic extrauterine extension in whom MRI showed the disease as being limited to the uterus. We studied indirect MRI signs for microscopic extrauterine spread of endometrial carcinoma which outwardly seemed to be limited to within the uterus. MRI studies and the clinical records of 100 patients with surgically proven endometrial carcinoma were retrospectively reviewed. We evaluated: MRI staging, tumor growing at the orifices of the fallopian tube in the uterine fundus, hydrosalpinx, and ascites, in each MRI study. Surgical specimens showed that 12 of the 100 patients had extrauterine spread, with 1 patient showing both ovarian extension and omental metastasis; there ovarian extension in 3, extension to the fallopian tubes in 3, omental metastasis in 1, and positive peritoneal cytology in 4. Tumor growing at the orifices of the fallopian tubes with deep myometrial invasion showed higher accuracy for predicting microscopic intrauterine spread (82.0%) although it was not significantly different from the accuracy of deep myometrial invasion anywhere within the uterus (75.0%). However, tumor growing at the orifices of the fallopian tubes in patients with stage Ia disease showed a high negative predictive value (89.7%). Hydrosalpinx had the highest specificity (98.9%) and accuracy (88.0%); however, it did not seem to be practical because it was observed in only 2 patients. Ascites in postmenopausal patients showed higher specificity (93.5%), although it was not considered to be useful in the premenopausal patients. Tumor extension at the orifices of the fallopian tubes in patients with stage Ia disease, and ascites in postmenopausal patients on MRI seemed to be predictive factors for microscopic extrauterine spread. (author)

The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma

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Xiao-Xia Zhu

2017-04-01

Interpretation: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

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Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Mei

2015-01-01

Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients. PMID:25624992

Review of Topical Treatment of Upper Tract Urothelial Carcinoma

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Kenneth G. Nepple

2009-01-01

Full Text Available A select group of patients with upper tract urothelial carcinoma may be appropriate candidates for minimally invasive management. Organ-preserving endoscopic procedures may be appropriate for patients with an inability to tolerate major surgery, solitary kidney, bilateral disease, poor renal function, small tumor burden, low-grade disease, or carcinoma in situ. We review the published literature on the use of topical treatment for upper tract urothelial carcinoma and provide our approach to treatment in the office setting.

Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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Farina M. Hanif

2014-10-01

Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

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Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

Predictive factors of occult neck metastasis in patients with oral squamous cell carcinoma

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Renato Fortes Bittar

Full Text Available ABSTRACT INTRODUCTION: It is well established that cervical lymph node metastasis is the most important prognostic factor in patients with oral squamous cell carcinoma of the upper aerodigestive tract. The definition of parameters and classifications that could separate patients in groups of low, intermediate and high-risk is being attempted for several years. OBJECTIVE: The objective of this study was to determine possible predictive factors related to the occurrence of occult cervical lymph node metastasis through the analysis of histopathological reports of surgical specimens obtained after oral squamous cell carcinoma resection and selective neck dissections of patients initially classified as N0. METHODS: This was a primary, retrospective, observational, case-control study. Histopathological reports were reviewed to determine if some findings were related to the occurrence of occult lymph node metastasis. The events analyzed were oral cavity subsites, pT-stage, muscular infiltration, desmoplasia, vascular emboli, perineural infiltration, tumor thickness and compromised margins. RESULTS: Occult cervical metastasis accounted for 19.10 percent of the cases. Desmoplasia, perineural infiltration, tumor thickness and pT4a stage are predictive factors of occult neck metastasis (p-value = 0.0488, 0.0326, 0.0395, 0.0488, respectively. CONCLUSION: The accurate definition of predictive factors of occult cervical metastasis may guide the selection of patients that should be referred to radiotherapy, avoiding the unnecessary exposure of low-risk patients to radiation and allowing a better regional control of the disease in those of moderate or high risk.

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

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Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

2018-01-01

Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

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Ganly, Ian; Amit, Moran; Kou, Lei

2015-01-01

BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METH...

Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

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Marchi, Fabio Albuquerque; Martins, David Correa; Barros-Filho, Mateus Camargo

2017-01-01

Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression...

Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

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Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

2014-01-01

Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716

Head and neck squamous cell carcinoma: usefulness of diffusion-weighted MR imaging in the prediction of a neoadjuvant therapeutic effect

International Nuclear Information System (INIS)

Kato, Hiroki; Tanaka, Osamu; Hoshi, Hiroaki; Kanematsu, Masayuki; Mizuta, Keisuke; Aoki, Mitsuhiro; Shibata, Toshiyuki; Yamashita, Tomomi; Hirose, Yoshinobu

2009-01-01

The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r=0.367 and 0.412, p<.05), and the ADCs showed a weak, inversed correlation (r=-0.384, p<.05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas. (orig.)

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

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Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

2017-12-01

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for

Does Enhancement or Perfusion on Preprocedure CT Predict Outcomes After Embolization of Hepatocellular Carcinoma?

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Borgheresi, Alessandra; Gonzalez-Aguirre, Adrian; Brown, Karen T; Getrajdman, George I; Erinjeri, Joseph P; Covey, Anne; Yarmohammadi, Hooman; Ziv, Etay; Sofocleous, Constantinos T; Boas, Franz Edward

2018-03-27

The objective of this study was to evaluate whether quantitative enhancement or perfusion measurements on preprocedure triphasic computed tomography (CT) can be used to predict response or overall survival after embolization of hepatocellular carcinoma. The institutional review board approved this retrospective review of 63 patients with hepatocellular carcinoma treated with particle embolization between March 2009 and December 2014. Quantitative enhancement and perfusion measurements were performed on the target tumor and the background liver on the triphasic CT performed before treatment. Microvascular invasion (MVI) and degree of differentiation were determined from a core biopsy specimen. Quantitative enhancement and perfusion values were then correlated with pathology (two-tailed t test), response to embolization on modified Response Evaluation Criteria In Solid Tumors (two-tailed t test), and overall survival after embolization (Cox proportional hazards model). Arterial enhancement did not predict immediate response or overall survival after embolization. The degree of differentiation or presence of MVI also did not predict immediate response or overall survival after embolization. However, high hepatic artery coefficient or low portal vein coefficient, both in the tumor (P = .011 and P = .004) and in the background liver (P = .015 and P = .009), were associated with worse survival. Hepatic artery coefficient, both in the tumor (P = .025) and in the background liver (P = .013), were independent predictors of survival in a multivariate model including the Child-Pugh score and the BCLC stage. Tumor and liver perfusion parameters estimated from preprocedure triphasic CT were predictive of survival after embolization. Arterial-phase enhancement and histology (degree of differentiation or MVI) did not predict immediate response or overall survival after particle embolization. Copyright © 2018 The Association of University Radiologists

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

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Kanika Gupta

2018-01-01

Full Text Available Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR Breast Imaging Reporting and Data System (BI-RADS Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001. The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma.

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Janice E Drew

Full Text Available Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2, proliferation (PCNA, CCND1, MS4A12, differentiation (B4GANLT2, CDX1, CDX2, apoptotic (CASP3, NOX1, NTN1, fibroblast (FSP1, COL1A1, structural (ACTG2, CNN1, DES, gene transcription (HDAC1, stem cell (LGR5, endothelial (VWF and mucin production (MUC2. Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.

Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

DEFF Research Database (Denmark)

Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

2007-01-01

and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic....... CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment....

Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

International Nuclear Information System (INIS)

Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

2013-01-01

Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

Diffusion-weighted magnetic resonance imaging for prediction of insignificant prostate cancer in potential candidates for active surveillance

International Nuclear Information System (INIS)

Kim, Tae Heon; Jeong, Jae Yong; Lee, Sin Woo; Sung, Hyun Hwan; Jeon, Hwang Gyun; Jeong, Byong Chang; Seo, Seong Il; Lee, Hyun Moo; Choi, Han Yong; Jeon, Seong Soo; Kim, Chan Kyo; Park, Byung Kwan

2015-01-01

To investigate whether the apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) could help improve the prediction of insignificant prostate cancer in candidates for active surveillance (AS). Enrolled in this retrospective study were 287 AS candidates who underwent DW-MRI before radical prostatectomy. Patients were stratified into two groups; Group A consisted of patients with no visible tumour or a suspected tumour ADC value > 0.830 x 10 -3 mm 2 /sec and Group B consisted of patients with a suspected tumour ADC value < 0.830 x 10 -3 mm 2 /sec. We compared pathological outcomes in each group. Group A had 243 (84.7 %) patients and Group B had 44 (15.3 %) patients. The proportion of organ-confined Gleason ≤ 6 disease and insignificant prostate cancer was significantly higher in Group A than Group B (61.3 % vs. 38.6 %, p = 0.005 and 47.7 % vs. 25.0 %, p = 0.005, respectively). On multivariate analysis, a high ADC value was the independent predictor of organ-confined Gleason ≤ 6 disease and insignificant prostate cancer (odds ratio = 2.43, p = 0.011 and odds ratio = 2.74, p = 0.009, respectively). Tumour ADC values may be a useful marker for predicting insignificant prostate cancer in candidates for AS. (orig.)

Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma.

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Celia Prior

Full Text Available To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC and to evaluate in vitro their mechanism of action in sunitinib resistance.We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41. The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101. In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance.TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074. High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance.We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies.

Human Papilloma Virus: Prevalence, distribution and predictive value to lymphatic metastasis in penile carcinoma

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Aluizio Goncalves da Fonseca

2013-07-01

Full Text Available Objectives To evaluate the prevalence, distribution and association of HPV with histological pattern of worse prognosis of penile cancer, in order to evaluate its predictive value of inguinal metastasis, as well as evaluation of other previous reported prognostic factors. Material and Methods Tumor samples of 82 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR. HPV status was correlated to histopathological factors and the presence of inguinal mestastasis. The influence of several histological characteristics was also correlated to inguinal disease-free survival. Results Follow-up varied from 1 to 71 months (median 22 months. HPV DNA was identified in 60.9% of sample, with higher prevalence of types 11 and 6 (64% and 32%, respectively. There was no significant correlation of the histological characteristics of worse prognosis of penile cancer with HPV status. Inguinal disease-free survival in 5 years did also not show HPV status influence (p = 0.45. The only independent pathologic factors of inguinal metastasis were: stage T ≥ T1b-T4 (p = 0.02, lymphovascular invasion (p = 0.04 and infiltrative invasion (p = 0.03. conclusions HPV status and distribution had shown no correlation with worse prognosis of histological aspects, or predictive value for lymphatic metastasis in penile carcinoma.

Indoor Tanning and the MC1R Genotype: Risk Prediction for Basal Cell Carcinoma Risk in Young People

OpenAIRE

Molinaro, Annette M.; Ferrucci, Leah M.; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

2015-01-01

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients...

Ring-enhancement pattern on contrast-enhanced CT predicts adenosquamous carcinoma of the pancreas: a matched case-control study.

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Imaoka, Hiroshi; Shimizu, Yasuhiro; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Tajika, Masahiro; Tanaka, Tsutomu; Ishihara, Makoto; Ogura, Takeshi; Obayashi, Tomohiko; Shinagawa, Akihide; Sakaguchi, Masafumi; Yamaura, Hidekazu; Kato, Mina; Niwa, Yasumasa; Yamao, Kenji

2014-01-01

Adenosquamous carcinoma of the pancreas (ASC) is a rare malignant neoplasm of the pancreas, exhibiting both glandular and squamous differentiation. However, little is known about its imaging features. This study examined the imaging features of pancreatic ASC. We evaluated images of contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). As controls, solid pancreatic neoplasms matched in a 2:1 ratio to ASC cases for age, sex and tumor location were also evaluated. Twenty-three ASC cases were examined, and 46 solid pancreatic neoplasms (43 pancreatic ductal adenocarcinomas, two pancreatic neuroendocrine tumors and one acinar cell carcinoma) were matched as controls. Univariate analysis demonstrated significant differences in the outline and vascularity of tumors on contrast-enhanced CT in the ASC and control groups (P outline, cystic changes, and the ring-enhancement pattern on contrast-enhanced CT were seen to have significant predictive powers by stepwise forward logistic regression analysis (P = 0.044, P = 0.010, and P = 0.001, respectively). Of the three, the ring-enhancement pattern was the most useful, and its predictive diagnostic sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ASC were 65.2%, 89.6%, 75.0% and 84.3%, respectively. These results demonstrate that presence of the ring-enhancement pattern on contrast-enhanced CT is the most useful predictive factor for ASC. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

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Mohammad R Nezami Ranjbar

Full Text Available This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS. Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS. Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes.

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Al-Hebshi, Nezar Noor; Li, Shiyong; Nasher, Akram Thabet; El-Setouhy, Maged; Alsanosi, Rashad; Blancato, Jan; Loffredo, Christopher

2016-07-15

The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations. Significantly mutated genes were identified with Oncodrive FM and the Youn and Simon's method. Candidate driver genes were nominated based on Gene Set Enrichment Analysis. The observed mutational spectrum was similar to that reported by the TCGA project. In addition to confirming known genes of OSCC (TP53, CDKNA2, CASP8, PIK3CA, HRAS, FAT1, TP63, CCND1 and FADD) the analysis identified several candidate novel driver events including mutations of NOTCH3, CSMD3, CRB1, CLTCL1, OSMR and TRPM2, amplification of the proto-oncogenes FOSL1, RELA, TRAF6, MDM2, FRS2 and BAG1, and deletion of the recently described tumor suppressor SMARCC1. Analysis also revealed significantly altered pathways not previously implicated in OSCC including Oncostatin-M signalling pathway, AP-1 and C-MYB transcription networks and endocytosis. There was a trend for higher number of mutations, amplifications and driver events in samples with history of shammah exposure particularly those that tested EBV positive, suggesting an interaction between tobacco exposure and EBV. The work provides further evidence for the genetic heterogeneity of oral cancer and suggests shammah-associated OSCC is characterized by extensive amplification of oncogenes. © 2016 UICC.

A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

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Hui-Hui Cao

Full Text Available Esophageal squamous cell carcinoma (ESCC has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR, phosphorylated Specificity protein 1 (p-Sp1, and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset and validated using an independent cohort of 185 specimens (validation dataset.The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001. Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset. Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

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Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

2016-01-01

It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

Science.gov (United States)

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas.

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Chao Ling

Full Text Available Previous genetic studies on colorectal carcinomas (CRC have identified multiple somatic mutations in four candidate pathways (TGF-β, Wnt, P53 and RTK-RAS pathways on populations of European ancestry. However, it is under-studied whether other populations harbor different sets of hot-spot somatic mutations in these pathways and other oncogenes. In this study, to evaluate the mutational spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes, including genes in the four candidate pathways, as well as several known oncogenes for other cancers. Candidate mutations were validated by Sanger sequencing, and we further used SIFT and PolyPhen-2 to assess potentially functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases. Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7, BRAF and PTEN in Chinese CRC patients. While most were previously reported in CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our study confirmed the existence of known somatic mutations in the four candidate pathways for CRC in Chinese patients. We also discovered a number of novel somatic mutations in these pathways, which may have implications for the pathogenesis of CRC.

Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

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Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

2017-02-21

The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

Maspin and MCM2 immunoprofiling in salivary gland carcinomas

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Helmy Iman M

2011-09-01

Full Text Available Abstract Background The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis. Materials and methods Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results. Results All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis. Conclusions Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

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Giridhar, Karthik V; Sosa, Carlos P; Hillman, David W; Sanhueza, Cristobal; Dalpiaz, Candace L; Costello, Brian A; Quevedo, Fernando J; Pitot, Henry C; Dronca, Roxana S; Ertz, Donna; Cheville, John C; Donkena, Krishna Vanaja; Kohli, Manish

2017-11-03

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only ( p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

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Xu, Dianbo; Wang, Danbo; Wang, Shuo; Tian, Ye; Long, Zaiqiu; Ren, Xuemei

2017-11-01

The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P 4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.

Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.

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Lee, Aimei; Rode, Anthony; Nicoll, Amanda; Maczurek, Annette E; Lim, Lucy; Lim, Seok; Angus, Peter; Kronborg, Ian; Arachchi, Niranjan; Gorelik, Alexandra; Liew, Danny; Warner, Fiona J; McCaughan, Geoffrey W; McLennan, Susan V; Shackel, Nicholas A

2016-02-01

The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

International Nuclear Information System (INIS)

Hanif, R.

2014-01-01

To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

MEDULLARY THYROID CARCINOMA

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V. S. Medvedev

2013-01-01

Full Text Available Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

Overexpression of Periostin and Lumican in Esophageal Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Peri, Suraj; Kumar, Ghantasala S. Sameer; Jacob, Harrys K.C.; Prasad, Thottethodi Subrahmanya Keshava; Mahmood, Riaz; Kumar, K. V. Veerendra; Kumar, M. Vijaya; Meltzer, Stephen J.; Montgomery, Elizabeth A.; Kumar, Rekha V.; Pandey, Akhilesh

2010-01-01

To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared to the adjacent normal epithelium. In the current study, we performed immunohistochemical analyses of protein products for two candidates genes identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM), using tissue microarrays. Increased expression of both periostin and lumican was observed in 100% of 137 different ESCC samples arrayed on tissue microarrays. Increased expression of periostin and lumican was observed in carcinoma as well as in stromal cell in the large majority of cases. These findings suggest that these candidates can be investigated in the sera of ESCC patients using ELISA or multiple reaction monitoring (MRM) type assays to further explore their utility as biomarkers

Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: Development and validation of a predictive score model

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Guo, Rui; Chen, Xiao-Zhong; Chen, Lei; Jiang, Feng; Tang, Ling-Long; Mao, Yan-Ping; Zhou, Guan-Qun; Li, Wen-Fei; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

2015-01-01

Background and purpose: The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized. Material and methods: Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set (n = 658), internal validation set (n = 658) and independent set (n = 652) using area under the receiver operating curve analysis. Results: Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score >1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P < 0.001), similar results were obtained in the other sets (P < 0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P = 0.02), independent set (0.73 vs. 0.67; P = 0.002) and all patients (0.71 vs. 0.67; P < 0.001). Conclusions: Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment

Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma.

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Huang, Ya-Qin; Liang, He-Yue; Yang, Zhao-Xia; Ding, Ying; Zeng, Meng-Su; Rao, Sheng-Xiang

2016-06-01

The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement.The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P histogram analyses-in particular for 1th percentile for PVP images-held promise for prediction of MVI of HCC.

1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

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Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

2017-03-01

To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

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Kamel Nermen A

2011-01-01

Full Text Available Abstract Background Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. Methods The study prospectively included 71 patients, (47 males, 24 females with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0 who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1, while 33 patients did not receive adjuvant radiotherapy (group 2. Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. Results The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03. The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p Conclusions Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

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Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

2014-08-01

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma.

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Rajakannu, Muthukumarassamy; Cherqui, Daniel; Ciacio, Oriana; Golse, Nicolas; Pittau, Gabriella; Allard, Marc Antoine; Antonini, Teresa Maria; Coilly, Audrey; Sa Cunha, Antonio; Castaing, Denis; Samuel, Didier; Guettier, Catherine; Adam, René; Vibert, Eric

2017-10-01

Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506-0.907) and 0

A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

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Dang My Nhi

2016-02-01

Full Text Available Severe dengue with severe plasma leakage (SD-SPL is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS. To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05, with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

Evaluation of candidate geomagnetic field models for IGRF-11

DEFF Research Database (Denmark)

Finlay, Chris; Maus, S.; Beggan, C. D.

2010-01-01

variations between candidates originate. A retrospective analysis of IGRF-10 main field candidates for epoch 2005.0 and predictive secular variation candidates for 2005.0–2010.0 using the new IGRF-11 models as a reference is also reported. The high quality and consistency of main field models derived using...

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

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Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-12-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

Gene targeting associated with the radiation sensitivity in squamous cell carcinoma by using microarray analysis

International Nuclear Information System (INIS)

Nimura, Yoshinori; Kumagai, Ken; Kouzu, Yoshinao; Higo, Morihiro; Kato, Yoshikuni; Seki, Naohiko; Yamada, Shigeru

2005-01-01

In order to identify a set of genes related to radiation sensitivity of squamous cell carcinoma (SCC) and establish a predictive method, we compared expression profiles of radio-sensitive/radio-resistant SCC cell lines, using the in-house cDNA microarray consisting of 2,201 human genes derived from full-length enriched SCC cDNA libraries and the Human oligo chip 30 K (Hitachi Software Engineering). Surviving fractions (SF) after irradiation of heavy iron were calculated by colony formation assay. Three pairs (TE2-TE13, YES5-YES6, and HSC3-HSC2), sensitive (SF1 0.6), were selected for the microarray analysis. The results of cDNA microarray analysis showed that 20 genes in resistant cell lines and 5 genes in sensitive cell lines were up regulated more than 1.5-fold compared with sensitive and resistant cell lines respectively. Fourteen out of 25 genes were confirmed the gene expression profiles by real-time polymerase chain reaction (PCR). Twenty-seven genes identified by Human oligo chip 30 K are candidate for the markers to distinguish radio-sensitive from radio-resistant. These results suggest that the isolated 27 genes are the candidates that might be used as specific molecular markers to predict radiation sensitivity. (author)

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

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Karthik V. Giridhar

2017-11-01

Full Text Available The Memorial Sloan Kettering Cancer Center (MSKCC prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR of 0.14, p < 0.0001, 95% confidence interval (CI 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34 were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001. Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Vascular involvement in pancreatic carcinoma. Pre-operative assessment by multislice CT angiography

International Nuclear Information System (INIS)

Ling Huawei; Guan Yongjing; Ding Bei; Lin Xiaozhu; Zhang Huan; Chen Kemin

2002-01-01

Objective: To study the value of multislice CT angiography (MSCTA) in the pre-operative assessment of vascular involvement in pancreatic carcinoma. Methods: 33 cases with pathologically proven pancreatic carcinoma underwent MSCTA prior to surgical intervention. The MSCTA findings in each of the 33 patients were evaluated prospectively by four radiologists. Vascular involvement of pancreatic carcinoma was validated at the time of surgery, which was a reference standard for comparison. Correlation was made between MSCTA findings and surgical results. Results: 11 out of 33 cases with pancreatic carcinoma were considered to be resectable by MSCTA with a positive predictive value of 82% in comparison with surgical findings. MSCTA also had high correlation with surgical results in assessing the non-resectability of pancreatic carcinoma (positive predictive value =95%). Conclusion: MSCTA could delineate the vascular involvement of pancreatic carcinoma with high accuracy and provided valuable information in the preoperative assessment of pancreatic carcinoma

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

International Nuclear Information System (INIS)

Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

2012-01-01

The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma.

Science.gov (United States)

Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

2012-09-27

The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

Co-registered perfusion SPECT/CT: Utility for prediction of improved postoperative outcome in lung volume reduction surgery candidates

International Nuclear Information System (INIS)

Takenaka, Daisuke; Ohno, Yoshiharu; Koyama, Hisanobu; Nogami, Munenobu; Onishi, Yumiko; Matsumoto, Keiko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2010-01-01

Purpose: To directly compare the capabilities of perfusion scan, SPECT, co-registered SPECT/CT, and quantitatively and qualitatively assessed MDCT (i.e. quantitative CT and qualitative CT) for predicting postoperative clinical outcome for lung volume reduction surgery (LVRS) candidates. Materials and methods: Twenty-five consecutive candidates (19 men and six women, age range: 42-72 years) for LVRS underwent preoperative CT and perfusion scan with SPECT. Clinical outcome of LVRS for all subjects was also assessed by determining the difference between pre- and postoperative forced expiratory volume in 1 s (FEV 1 ) and 6-min walking distance (6MWD). All SPECT examinations were performed on a SPECT scanner, and co-registered to thin-section CT by using commercially available software. On planar imaging, SPECT and SPECT/CT, upper versus lower zone or lobe ratios (U/Ls) were calculated from regional uptakes between upper and lower lung fields in the operated lung. On quantitatively assessed CT, U/L for all subjects was assessed from regional functional lung volumes. On qualitatively assessed CT, planar imaging, SPECT and co-registered SPECT/CT, U/Ls were assessed with a 4-point visual scoring system. To compare capabilities of predicting clinical outcome, each U/L was statistically correlated with the corresponding clinical outcome. Results: Significantly fair or moderate correlations were observed between quantitatively and qualitatively assessed U/Ls obtained with all four methods and clinical outcomes (-0.60 ≤ r ≤ -0.42, p < 0.05). Conclusion: Co-registered perfusion SPECT/CT has better correlation with clinical outcome in LVRS candidates than do planar imaging, SPECT or qualitatively assessed CT, and is at least as valid as quantitatively assessed CT.

Co-registered perfusion SPECT/CT: Utility for prediction of improved postoperative outcome in lung volume reduction surgery candidates

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Takenaka, Daisuke [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.j [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Koyama, Hisanobu [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Nogami, Munenobu [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Division of Image-Based Medicine, Institute of Biomedical Research and Innovation, 2-2, Minatojima Minamimachi Chuo-ku, Kobe, Hyogo, 650-0047 (Japan); Onishi, Yumiko [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Matsumoto, Keiko [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Department of Radiology, University of Yamanashi, 1110 Shimogato, Chuo, Yamanashi, 409-3898 (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan)

2010-06-15

Purpose: To directly compare the capabilities of perfusion scan, SPECT, co-registered SPECT/CT, and quantitatively and qualitatively assessed MDCT (i.e. quantitative CT and qualitative CT) for predicting postoperative clinical outcome for lung volume reduction surgery (LVRS) candidates. Materials and methods: Twenty-five consecutive candidates (19 men and six women, age range: 42-72 years) for LVRS underwent preoperative CT and perfusion scan with SPECT. Clinical outcome of LVRS for all subjects was also assessed by determining the difference between pre- and postoperative forced expiratory volume in 1 s (FEV{sub 1}) and 6-min walking distance (6MWD). All SPECT examinations were performed on a SPECT scanner, and co-registered to thin-section CT by using commercially available software. On planar imaging, SPECT and SPECT/CT, upper versus lower zone or lobe ratios (U/Ls) were calculated from regional uptakes between upper and lower lung fields in the operated lung. On quantitatively assessed CT, U/L for all subjects was assessed from regional functional lung volumes. On qualitatively assessed CT, planar imaging, SPECT and co-registered SPECT/CT, U/Ls were assessed with a 4-point visual scoring system. To compare capabilities of predicting clinical outcome, each U/L was statistically correlated with the corresponding clinical outcome. Results: Significantly fair or moderate correlations were observed between quantitatively and qualitatively assessed U/Ls obtained with all four methods and clinical outcomes (-0.60 {<=} r {<=} -0.42, p < 0.05). Conclusion: Co-registered perfusion SPECT/CT has better correlation with clinical outcome in LVRS candidates than do planar imaging, SPECT or qualitatively assessed CT, and is at least as valid as quantitatively assessed CT.

Cognitive Styles in Admission Procedures for Assessing Candidates of Architecture

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Casakin, Hernan; Gigi, Ariela

2016-01-01

Cognitive style has a strong predictive power in academic and professional success. This study investigated the cognitive profile of candidates studying architecture. Specifically, it explored the relation between visual and verbal cognitive styles, and the performance of candidates in admission procedures. The cognitive styles of candidates who…

Candidate Dosimetric Predictors of Long-Term Swallowing Dysfunction After Oropharyngeal Intensity-Modulated Radiotherapy

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Schwartz, David L.; Hutcheson, Katherine; Barringer, Denise; Tucker, Susan L.; Kies, Merrill; Holsinger, F. Christopher; Ang, K. Kian; Morrison, William H.; Rosenthal, David I.; Garden, Adam S.; Dong Lei; Lewin, Jan S.

2010-01-01

Purpose: To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia. Methods and Materials: Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2 (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields. Results: Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months. Conclusions: In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.

Selecting Suitable Candidates for Predictive Maintenance

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Tiddens, Wieger Willem; Braaksma, Anne Johannes Jan; Tinga, Tiedo

2018-01-01

Predictive maintenance (PdM) or Prognostics and Health Management (PHM) assists in better predicting the future state of physical assets and making timely and better-informed maintenance decisions. Many companies nowadays ambition the implementation of such an advanced maintenance policy. However,

Mortality Predicted Accuracy for Hepatocellular Carcinoma Patients with Hepatic Resection Using Artificial Neural Network

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Herng-Chia Chiu

2013-01-01

Full Text Available The aim of this present study is firstly to compare significant predictors of mortality for hepatocellular carcinoma (HCC patients undergoing resection between artificial neural network (ANN and logistic regression (LR models and secondly to evaluate the predictive accuracy of ANN and LR in different survival year estimation models. We constructed a prognostic model for 434 patients with 21 potential input variables by Cox regression model. Model performance was measured by numbers of significant predictors and predictive accuracy. The results indicated that ANN had double to triple numbers of significant predictors at 1-, 3-, and 5-year survival models as compared with LR models. Scores of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC of 1-, 3-, and 5-year survival estimation models using ANN were superior to those of LR in all the training sets and most of the validation sets. The study demonstrated that ANN not only had a great number of predictors of mortality variables but also provided accurate prediction, as compared with conventional methods. It is suggested that physicians consider using data mining methods as supplemental tools for clinical decision-making and prognostic evaluation.

Mortality Predicted Accuracy for Hepatocellular Carcinoma Patients with Hepatic Resection Using Artificial Neural Network

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Chiu, Herng-Chia; Ho, Te-Wei; Lee, King-Teh; Chen, Hong-Yaw; Ho, Wen-Hsien

2013-01-01

The aim of this present study is firstly to compare significant predictors of mortality for hepatocellular carcinoma (HCC) patients undergoing resection between artificial neural network (ANN) and logistic regression (LR) models and secondly to evaluate the predictive accuracy of ANN and LR in different survival year estimation models. We constructed a prognostic model for 434 patients with 21 potential input variables by Cox regression model. Model performance was measured by numbers of significant predictors and predictive accuracy. The results indicated that ANN had double to triple numbers of significant predictors at 1-, 3-, and 5-year survival models as compared with LR models. Scores of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of 1-, 3-, and 5-year survival estimation models using ANN were superior to those of LR in all the training sets and most of the validation sets. The study demonstrated that ANN not only had a great number of predictors of mortality variables but also provided accurate prediction, as compared with conventional methods. It is suggested that physicians consider using data mining methods as supplemental tools for clinical decision-making and prognostic evaluation. PMID:23737707

Using transient elastography to predict hepatocellular carcinoma recurrence after radiofrequency ablation.

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Lee, Yu Rim; Park, Soo Young; Kim, Seung Up; Jang, Se Young; Tak, Won Young; Kweon, Young Oh; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Hur, Keun

2017-05-01

Liver stiffness (LS) value determined using transient elastography (TE) can be used to assess the degree of liver fibrosis. The study investigated whether TE can predict the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). This study retrospectively enrolled 228 patients with HCC who received TE and RFA as the first-line treatment for HCC between 2008 and 2015. Cox regression analysis was used to identify independent predictors of HCC recurrence. The median age of the study population (170 men and 58 women) was 61 years. During the study period, HCC recurrence and mortality developed in 125 (54.8%) and 37 (16.2%) patients after RFA, respectively. Liver cirrhosis, platelet count, multiple tumors, and LS value were the independent predictors of HCC recurrence. When the study population was stratified into early (measurement using TE can be a useful predictor of HCC recurrence after RFA. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Identification of potential prognostic microRNA biomarkers for predicting survival in patients with hepatocellular carcinoma

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Liao X

2018-04-01

Full Text Available Xiwen Liao,1 Guangzhi Zhu,1 Rui Huang,2 Chengkun Yang,1 Xiangkun Wang,1 Ketuan Huang,1 Tingdong Yu,1 Chuangye Han,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China Background: The aim of the present study was to identify potential prognostic microRNA (miRNA biomarkers for hepatocellular carcinoma (HCC prognosis prediction based on a dataset from The Cancer Genome Atlas (TCGA. Materials and methods: A miRNA sequencing dataset and corresponding clinical parameters of HCC were obtained from TCGA. Genome-wide univariate Cox regression analysis was used to screen prognostic differentially expressed miRNAs (DEMs, and multivariable Cox regression analysis was used for prognostic signature construction. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Results: Five miRNAs were regarded as prognostic DEMs and used for prognostic signature construction. The five-DEM prognostic signature performed well in prognosis prediction (adjusted P < 0.0001, adjusted hazard ratio = 2.249, 95% confidence interval =1.491–3.394, and time-dependent receiver–operating characteristic (ROC analysis showed an area under the curve (AUC of 0.765, 0.745, 0.725, and 0.687 for 1-, 2-, 3-, and 5-year HCC overall survival (OS prediction, respectively. Comprehensive survival analysis of the prognostic signature suggests that the risk score model could serve as an independent factor of HCC and perform better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of hsa-mir-139 and hsa-mir-5003 indicates that they were significantly enriched in multiple biological processes and pathways, including cell proliferation and cell migration

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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Zhang, Ping; Zhang, Zhiyuan; Zhou, Xiaojian; Qiu, Weiliu; Chen, Fangan; Chen, Wantao

2006-01-01

Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in cisplatin resistance

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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Zhang Ping

2006-09-01

Full Text Available Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Results Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. Conclusion The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis

Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters

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Hao, Ke; Sham, Pak C; Poon, Ronnie TP; Luk, John M; Lee, Nikki PY; Mao, Mao; Zhang, Chunsheng; Ferguson, Mark D; Lamb, John; Dai, Hongyue; Ng, Irene O

2009-01-01

Surgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters. We conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation set Our findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum α-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7). This described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new

Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.

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Lassus, Heini; Staff, Synnöve; Leminen, Arto; Isola, Jorma; Butzow, Ralf

2011-01-01

Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n=592), Aurora-A copy number by CISH (n=169), Aurora-A mRNA by real-time PCR (n=158) and DNA ploidy by flowcytometry (n=440). Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

Incidence, Mortality, and Predictive Factors of Hepatocellular Carcinoma in Primary Biliary Cirrhosis

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Kenichi Hosonuma

2013-01-01

Full Text Available Background. The study aims to analyze in detail the incidence, mortality using the standardized incidence ratio (SIR, and standardized mortality ratio (SMR of hepatocellular carcinoma (HCC in primary biliary cirrhosis (PBC, because no large case studies have focused on the detailed statistical analysis of them in Asia. Methods. The study cohorts were consecutively diagnosed at Gunma University and its affiliated hospitals. Age- or sex-specific annual cancer incidence and deaths were obtained from Japanese Cancer Registry and Death Registry as a reference for the comparison of SIR or SMR of HCC. Moreover, univariate analyses and multivariate analyses were performed to clarify predictive factors for the incidence of HCC. Results. The overall 179 patients were followed up for a median of 97 months. HCC had developed in 13 cases. SIR for HCC was 11.6 (95% confidence interval (CI, 6.2–19.8 and SMR for HCC was 11.2 (95% CI, 5.4–20.6 in overall patients. The serum albumin levels were a predictive factor for the incidence of HCC in overall patients. Conclusions. The incidence and mortality of HCC in PBC patients were significantly higher than those in Japanese general population. PBC patients with low serum albumin levels were populations at high risk for HCC.

Endogenous network states predict gain or loss of functions for genetic mutations in hepatocellular carcinoma.

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Wang, Gaowei; Su, Hang; Yu, Helin; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2016-02-01

Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by posteriori statistical association approaches. One may ponder the possibility of a priori determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (the endogenous molecular-cellular network theory), we found that the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. With hepatocellular carcinoma (HCC) as an example, we found that the normal hepatocyte and cancerous hepatocyte can be represented by robust stable states of one single endogenous network. These stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable predictions on accumulated and preferred mutation spectra in normal tissue. The validation of predicted cancer state mutation patterns demonstrates the usefulness and potential of a causal dynamical framework to understand and predict genetic mutations in cancer. © 2016 The Author(s).

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

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Saelen Marie

2012-09-01

Full Text Available Abstract Background The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC. Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Methods Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Results Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Conclusions Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation.

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Michael, Sushama; Travé, Gilles; Ramu, Chenna; Chica, Claudia; Gibson, Toby J

2008-02-15

KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C complex. While annotating the Eukaryotic Linear Motif resource (ELM, http://elm.eu.org/), we found that KEN motifs were significantly enriched in human protein entries with cell cycle keywords in the UniProt/Swiss-Prot database-implying that KEN-boxes might be more common than reported. Matches to short linear motifs in protein database searches are not, per se, significant. KEN-box enrichment with cell cycle Gene Ontology terms suggests that collectively these motifs are functional but does not prove that any given instance is so. Candidates were surveyed for native disorder prediction using GlobPlot and IUPred and for motif conservation in homologues. Among >25 strong new candidates, the most notable are human HIPK2, CHFR, CDC27, Dab2, Upf2, kinesin Eg5, DNA Topoisomerase 1 and yeast Cdc5 and Swi5. A similar number of weaker candidates were present. These proteins have yet to be tested for APC/C targeted destruction, providing potential new avenues of research.

Combination therapies in oral squamous cell carcinomas

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Krishnamurthi, S.; Shanta, V.

1982-01-01

The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

Consistent absence of BRAF mutations in salivary gland carcinomas

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Nooshin Mohtasham

2017-06-01

Full Text Available Introduction: Malignant salivary gland tumors are rare entities. Despite advances in surgery, radiation therapy and chemotherapy, the rate of the mortality and five-year survival has not been improved markedly over the last few decades. The activation of EGFR- RAS-RAF signaling pathway contributes to the initiation and progression of many human cancers, promising a key pathway for therapeutic molecules. Thus, the objective of this study was to evaluate BRAF mutations in salivary gland carcinomas. Methods: We designed PCR- RFLP (Polymerase Chain Reaction -Restriction Fragment Length Polymorphism and screened 50 salivary gland carcinomas (SGCs including mucoepidermoid carcinoma (MEC, adenoid cystic carcinoma (AdCC and polymorphous low grade adenocarcinoma (PLGA for the BRAF V600E mutation. Results: PCR-RFLP analyses demonstrated no mutation in BRAF exon 15 for SGC samples at position V600, which is the most commonly mutated site for BRAF in human cancer. Conclusions: According to our results SGCs didn’t acquire BRAF mutations that result in a constitutive activation of the signaling cascade downstream of EGFR, hence SGCs can be a good candidate for anti EGFR therapies.

Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate

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Ravinder eSingh

2016-02-01

Full Text Available Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3 and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64000 and provided 50% protection against a standardized lethal dose (10*8 CFU of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, IL-33, IFN-γ and IL-1β significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins.

Trimodal therapy in squamous cell carcinoma of the esophagus

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Matuschek C

2011-10-01

Full Text Available Abstract Patients with ESCC (squamous cell carcinoma of the esophagus are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.

Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

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Kakite, Suguru; Dyvorne, Hadrien A.; Lee, Karen M.; Jajamovich, Guido H.; Knight-Greenfield, Ashley; Taouli, Bachir

2015-01-01

To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p < 0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p < 0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC > 0.95, p < 0.002). D has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging

Development and evaluation of a prediction model for underestimated invasive breast cancer in women with ductal carcinoma in situ at stereotactic large core needle biopsy.

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Suzanne C E Diepstraten

Full Text Available BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. RESULTS: 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7% patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28, number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01, presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77, and microinvasion (OR 3.75, 95% CI 1.42-9.87. The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R(2, mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73, and fairly good calibration. CONCLUSION: The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.

Longitudinal change in renal function after nephroureterectomy in patients with upper tract urothelial carcinoma

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Chih-Yuan Chou

2015-06-01

Conclusion: In this study, it was found that the average renal function of the patients with upper tract urothelial carcinoma is not as good as the general population. More than half of the normal renal function patients have new onset chronic kidney disease after surgery. For preventing further deterioration of renal function, the implication of partial nephrectomy or segmental ureterectomy for selected patients with localized urothelial carcinoma should be re-examined. Besides, neoadjuvant chemotherapy should be considered for those who are not good candidates for local treatment.

Full Length Article Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology

International Nuclear Information System (INIS)

Zaakook, M.; Abu Sinna, E.; Ayoub, M.; El-Sheikh, S.

2013-01-01

Purpose: Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

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Kostianets Olga

2012-11-01

Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

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Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

2008-01-07

To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

GGPPS1 predicts the biological character of hepatocellular carcinoma in patients with cirrhosis

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Yu, De-cai; Liu, Jia; Chen, Jun; Shao, Jiao-jiao; Shen, Xiao; Xia, Hong-guang; Li, Chao-jun; Xue, Bin; Ding, Yi-tao

2014-01-01

Hepatocellular carcinoma (HCC) has been associated with diabetes and obesity, but a possible connection with the metabolic syndrome (MetS) and its potential interaction with hepatitis and cirrhosis are open to discussion. Our previous investigations have shown that GGPPS1 plays a critical role during hyperinsulinism. In this report, the expression and distribution of GGPPS1 in liver cancer, and its clinical significance were investigated. 70 patients with hepatocellular carcinoma (HCC) were included in this study. Three different types of tissues from each HCC patient were assembled immediately after surgical resection: tumor-free tissue >5 cm far from tumor edge (TF), adjacent nonmalignant tissue within 2 cm (AT), and tissue from the tumor (TT). Normal liver tissues from 10 liver transplant donors served as healthy control (HC) while 10 patients with liver cirrhosis as cirrhosis control (CC). The expression and distribution of GGPPS1 were detected by immunohistochemistry, western blots, or real-time PCR. The relationship between the expression of GGPPS1 and clinic pathologic index were analyzed. We found that GGPPS1 was intensified mainly in the cytoplasm of liver tumor cells. Both the expression of GGPPS1 mRNA and protein were upregulated in TT comparing to AT or TF. Meanwhile, HCC patients with cirrhosis had relative higher expression of GGPPS1. In addition, many pathologic characters show close correlation with GGPPS1, such as tumor stage, vessel invasion, and early recurrence. GGPPS1 may play a critical role during the development of HCC from cirrhosis and is of clinical significance for predicting biological character of HCC

Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma.

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Cheng-Bao Zhu

Full Text Available Transcatheter arterial chemoembolization (TACE is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC. Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS.The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001. The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively. Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001. In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP level (P = 0.006 and 0.016, respectively. Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients' outcomes.Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.

Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

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Kang, Ji Un; Koo, Sun Hoe; Kwon, Kye Chul; Park, Jong Woo; Kim, Jin Man

2009-01-01

The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown. High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs. Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

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Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata

2017-01-01

Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with

Early onset sebaceous carcinoma

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Kaltreider Sara A

2011-09-01

Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

Cryospray ablation (CSA in the palliative treatment of squamous cell carcinoma of the esophagus

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Johnston Mark H

2007-03-01

Full Text Available Abstract Background Esophageal carcinoma is the ninth most prevalent cancer worldwide with squamous cell carcinoma (SCCA and adenocarcinoma accounting for the vast majority of new cases (13,900 in 2003. Cure rates in the U.S. are less than 10%, similar to lung cancer. More than 50% of patients with esophageal carcinoma present with unresectable or metastatic disease, are not surgical candidates, or display disease progression despite the addition of neoadjuvant chemoradiotherapy to surgery. Need for improved palliation exits. Case presentation This case describes a 73-year-old African American male who presented with recurrent squamous cell carcinoma (SCCA of the esophagus who has a achieved complete remission for 24 months via endoscopic cryospray ablation. Conclusion Endoscopic cryo spray ablation warrants further investigation as a palliative treatment modality for esophageal cancer. This is the first reported case in the medical literature.

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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Joshua D. Campbell

2018-04-01

Full Text Available Summary: This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs from five sites associated with smoking and/or human papillomavirus (HPV. SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs, DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+ and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches. : Campbell et al. reveal that squamous cell cancers from different tissue sites may be distinguished from other cancers and subclassified molecularly by recurrent alterations in chromosomes, DNA methylation, messenger and microRNA expression, or by mutations. These affect squamous cell pathways and programs that provide candidates for therapy. Keywords: genomics, transcriptomics, proteomics, head and neck squamous cell carcinoma, lung squamous cell carcinoma, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, bladder carcinoma with squamous differentiation, human papillomavirus

Parametric response mapping of dynamic CT for predicting intrahepatic recurrence of hepatocellular carcinoma after conventional transcatheter arterial chemoembolization

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Choi, Seung Joon; Kim, Hyung Sik [Gachon University Gil Hospital, Department of Radiology, Incheon (Korea, Republic of); Kim, Jonghoon [Sungkyunkwan University, Department of Electronic Electrical and Computer Engineering, Suwon (Korea, Republic of); Seo, Jongbum [Yonsei University, Department of Biomedical Engineering, Wonju (Korea, Republic of); Lee, Jong-min [Hanyang University, Department of Biomedical Engineering, Seoul (Korea, Republic of); Park, Hyunjin [Sungkyunwkan University, School of Electronic and Electrical Engineering, Suwon (Korea, Republic of)

2016-01-15

The aim of our study was to determine the diagnostic value of a novel image analysis method called parametric response mapping (PRM) for prediction of intrahepatic recurrence of hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (TACE). This retrospective study was approved by the IRB. We recruited 55 HCC patients who achieved complete remission (CR) after TACE and received longitudinal multiphasic liver computed tomography (CT). The patients fell into two groups: the recurrent tumour group (n = 29) and the non-recurrent tumour group (n = 26). We applied the PRM analysis to see if this technique could distinguish between the two groups. The results of the PRM analysis were incorporated into a prediction algorithm. We retrospectively removed data from the last time point and attempted to predict the response to therapy of the removed data. The PRM analysis was able to distinguish between the non-recurrent and recurrent groups successfully. The prediction algorithm detected response to therapy with an area under the curve (AUC) of 0.76, while the manual approach had AUC 0.64. Adopting PRM analysis can potentially distinguish between recurrent and non-recurrent HCCs and allow for prediction of response to therapy after TACE. (orig.)

Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

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Karacali Bilge

2007-10-01

Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

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Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas J. [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He Jiwei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Keefe, Stephen M. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Tucker, Kai; Bekelman, Justin E. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David J. [Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-01-01

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

International Nuclear Information System (INIS)

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

2013-01-01

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage ≥pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage ≥pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in

Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

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Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

2017-11-01

To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Hepatocellular carcinoma in Danish patients

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Stefansdottir, Jenna; Christensen, Erik; Schiødt, Frank Vinholt

2017-01-01

OBJECTIVE: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival. METHODS...

Government instability shifts skin tone representations of and intentions to vote for political candidates.

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Stern, Chadly; Balcetis, Emily; Cole, Shana; West, Tessa V; Caruso, Eugene M

2016-01-01

Does government stability shift the way White and Black Americans represent and make voting decisions about political candidates? Participants judged how representative lightened, darkened, and unaltered photographs were of a racially ambiguous candidate ostensibly running for political office (Studies 1-3). When the governmental system was presented as stable, White participants who shared (vs. did not share) the candidate's political beliefs rated a lightened photo as more representative of the candidate, and Black participants who shared (vs. did not share) the candidate's political beliefs rated a darkened photo as more representative (Studies 1-3). However, under conditions of instability, both Whites and Blacks who shared (vs. did not share) the candidate's political beliefs rated a lightened photo as more representative (Study 3). Representations of (Studies 2 and 3) and actual differences in (Studies 4a and 4b) skin tone predicted intentions to vote for candidates, as a function of government stability and participants' race. Further evidence suggested that system stability shifted the motivations that guided voting decisions (Study 4a and 4b). When the system was stable, the motivation to enhance one's group predicted greater intentions to vote for lighter skinned candidates among Whites, and greater intentions to vote for darker skinned candidates among Blacks. When the system was unstable, however, lacking confidence in the sociopolitical system predicted intentions to vote for lighter skinned candidates among both Whites and Blacks. Implications for political leadership and social perception are discussed. (c) 2016 APA, all rights reserved).

Candidal carriage predicts candidiasis during topical immunosuppressive therapy: a preliminary retrospective cohort study.

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Tejani, Sara; Sultan, Ahmed; Stojanov, Ivan; Woo, Sook-Bin

2016-10-01

To determine (1) the prevalence of candidal carriage in patients with oral mucosal disease to be treated with topical immunosuppressive therapy, and (2) the incidence of oral candidiasis among carriers and noncarriers after initiation of therapy to assess any correlation between carriage and the development of candidiasis. Records of patients who underwent swab cultures for Candida between January 2009 and October 2014 at the Brigham and Women's Hospital in Boston, Massachusetts, were retrospectively reviewed. The prevalence of candidal carriage and incidence of candidiasis were determined by using descriptive statistics. Of 99 evaluable patients, 20 (20.2%) were Candida positive and 79 (79.8%) were Candida negative. Of 44 patients with follow-up, 7 (15.9%) were Candida positive and 37 (84.1%) were Candida negative; five (11.4%) developed candidiasis. Four of seven (57.1%) Candida-positive patients developed candidiasis, whereas only one of 37 (2.7%) Candida-negative patients developed candidiasis (P = .0012). The overall prevalence of candidal carriage was low (20.2%), and there was a significant difference in the incidence of candidiasis between carriers and noncarriers (P = .0012) after topical immunosuppressive therapy. Therefore, patients who are candidal carriers should be monitored closely for the development of secondary candidiasis and may be candidates for prophylactic antifungal therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictive factors of gastroduodenal toxicity in cirrhotic patients after three-dimensional conformal radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Kim, Haeyoung; Lim, Do Hoon; Paik, Seung Woon; Yoo, Byung Chul; Koh, Kwang Gheol; Lee, Joon Hyoek; Choi, Moon Seok; Park, Won; Park, Hee Chul; Huh, Seung Jae; Choi, Doo Ho; Ahn, Yong Chan

2009-01-01

Background and purpose: To identify predictive factors for the development of gastroduodenal toxicity (GDT) in cirrhotic patients treated with three-dimensional conformal radiotherapy (3D-CRT) for hepatocellular carcinoma (HCC). Materials and methods: We retrospectively analyzed dose-volume histograms (DVHs) and clinical records of 73 cirrhotic patients treated with 3D-CRT for HCC. The median radiation dose was 36 Gy (range, 30-54 Gy) with a daily dose of 3 Gy. The grade of GDT was defined by the Common Toxicity Criteria Version 2. The predictive factors of grade 3 GDT were identified. Results: Grade 3 GDT was found in 9 patients. Patient's age and the percentage of gastroduodenal volume receiving more than 35 Gy (V 35 ) significantly affected the development of grade 3 GDT. Patients over 50 years of age developed grade 3 GDT more frequently than patients under 50 years of age. The risk of grade 3 GDT grew exponentially as V 35 increased. The 1-year actuarial rate of grade 3 GDT in patients with V 35 35 ≥5% (4% vs. 48%, p 35 were the most predictive factors for the development of grade 3 GDT in patients treated with RT.

Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma

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Rasmussen, Gregers Brünnich; Håkansson, Katrin E; Vogelius, Ivan R

2017-01-01

.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has......OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous...... cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional...

Hepatocellular carcinoma: a systems biology perspective

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Lorenza Alice D'alessandro

2013-02-01

Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

Functional validation of candidate genes detected by genomic feature models

DEFF Research Database (Denmark)

Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

2018-01-01

to investigate locomotor activity, and applied genomic feature prediction models to identify gene ontology (GO) cate- gories predictive of this phenotype. Next, we applied the covariance association test to partition the genomic variance of the predictive GO terms to the genes within these terms. We...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated......Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...

Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

International Nuclear Information System (INIS)

Bae, Hyun-Mi; Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Yoon Jun; Heo, Dae Seog; Lee, Hyo-Suk

2011-01-01

Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively. PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein

New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

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Esfandiary, Ali; Ghafouri-Fard, Soudeh

2015-01-01

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

Disease-free survival after hepatic resection in hepatocellular carcinoma patients: a prediction approach using artificial neural network.

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Wen-Hsien Ho

Full Text Available BACKGROUND: A database for hepatocellular carcinoma (HCC patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. METHODS: The three prediction models included an artificial neural network (ANN model, a logistic regression (LR model, and a decision tree (DT model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC was used as the performance index for evaluating the three models. CONCLUSIONS: The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection.

Disease-Free Survival after Hepatic Resection in Hepatocellular Carcinoma Patients: A Prediction Approach Using Artificial Neural Network

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Ho, Wen-Hsien; Lee, King-Teh; Chen, Hong-Yaw; Ho, Te-Wei; Chiu, Herng-Chia

2012-01-01

Background A database for hepatocellular carcinoma (HCC) patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. Methods The three prediction models included an artificial neural network (ANN) model, a logistic regression (LR) model, and a decision tree (DT) model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively) were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups) were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC) was used as the performance index for evaluating the three models. Conclusions The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection. PMID:22235270

MO-DE-207B-05: Predicting Gene Mutations in Renal Cell Carcinoma Based On CT Imaging Features: Validation Using TCGA-TCIA Datasets

Energy Technology Data Exchange (ETDEWEB)

Chen, X; Zhou, Z; Thomas, K; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: The goal of this work is to investigate the use of contrast enhanced computed tomographic (CT) features for the prediction of mutations of BAP1, PBRM1, and VHL genes in renal cell carcinoma (RCC). Methods: For this study, we used two patient databases with renal cell carcinoma (RCC). The first one consisted of 33 patients from our institution (UT Southwestern Medical Center, UTSW). The second one consisted of 24 patients from the Cancer Imaging Archive (TCIA), where each patient is connected by a unique identi?er to the tissue samples from the Cancer Genome Atlas (TCGA). From the contrast enhanced CT image of each patient, tumor contour was first delineated by a physician. Geometry, intensity, and texture features were extracted from the delineated tumor. Based on UTSW dataset, we completed feature selection and trained a support vector machine (SVM) classifier to predict mutations of BAP1, PBRM1 and VHL genes. We then used TCIA-TCGA dataset to validate the predictive model build upon UTSW dataset. Results: The prediction accuracy of gene expression of TCIA-TCGA patients was 0.83 (20 of 24), 0.83 (20 of 24), and 0.75 (18 of 24) for BAP1, PBRM1, and VHL respectively. For BAP1 gene, texture feature was the most prominent feature type. For PBRM1 gene, intensity feature was the most prominent. For VHL gene, geometry, intensity, and texture features were all important. Conclusion: Using our feature selection strategy and models, we achieved predictive accuracy over 0.75 for all three genes under the condition of using patient data from one institution for training and data from other institutions for testing. These results suggest that radiogenomics can be used to aid in prognosis and used as convenient surrogates for expensive and time consuming gene assay procedures.

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

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Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P histogram parameters increased (all P histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma.

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Chen, Miao-Fen; Lee, Kuan-Der; Lu, Ming-Shian; Chen, Chih-Cheng; Hsieh, Ming-Ju; Liu, Yun-Hen; Lin, Paul-Yang; Chen, Wen-Cheng

2009-03-01

The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.

Giant basal cell carcinoma Carcinoma basocelular gigante

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Nilton Nasser

2012-06-01

Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

Radioimmune localization of occult carcinoma

International Nuclear Information System (INIS)

Duda, R.B.; Zimmer, A.M.; Rosen, S.T.; Gilyon, K.A.; Webber, D.; Spies, S.; Spies, W.; Merchant, B.

1990-01-01

Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan results in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer

Treatment of thyroid follicular carcinoma.

Science.gov (United States)

Ríos, Antonio; Rodríguez, José M; Parrilla, Pascual

2015-12-01

Differentiated thyroid carcinoma includes 2 different tumor types, papillary (PC) and follicular carcinoma (FC), and although similar, their prognosis is different. FC is uncommon, and this has led to it often being analyzed together with PC, and therefore the true reality of this tumor is difficult to know. As a result, the diagnostic and therapeutic management and the prognostic factors in differentiated carcinoma are more predictive of PC than FC. In this review we analyze the current state of many of the therapeutic aspects of this pathology. The best surgical technique and the usefulness of associated lymphadenectomy is also analyzed. Regarding post-surgical ablation with 131I, the indications, doses and usefulness are discussed. For the remaining therapies we analyze the few indications for radiotherapy and chemotherapy, and of new drugs such as tyrosine kinase inhibitors. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictive factors and prognosis for recurrent laryngeal nerve invasion in papillary thyroid carcinoma

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Chen W

2017-09-01

Full Text Available Wenjie Chen,1 Jianyong Lei,1 Jiaying You,2 Yali Lei,3 Zhihui Li,1 Rixiang Gong,1 Huairong Tang,3 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, 2West China School of Clinical Medicine, 3Health and Management Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Background: Recurrent laryngeal nerve (RLN invasion in papillary thyroid carcinoma (PTC is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients.Methods: A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid Surgery Center of West China Hospital of Sichuan University were reviewed. Demographics and clinical factors, imaging examination (ultrasonography characteristics, surgical details, postoperative pathological details, recurrence, and postoperative complications were recorded. Univariate and multivariate analyses were used to study the risk factors of RLN invasion, Kaplan–Meier method was performed to compare the outcomes of tumor recurrence.Results: Patients with RLN invasion had a higher recurrence rate than those in the control group (p<0.001. Multivariate analyses showed that age greater than 45 years (p<0.001, a largest tumor size bigger than 10 mm (p<0.001, clinical lymph node metastasis (cN1 (p<0.001, posterior focus (p<0.001, extrathyroidal extension (p<0.001, esophageal extension (p<0.001, tracheal extension (p<0.001, and preoperative vocal cord paralysis (p<0.001 were independent predictors for RLN invasion.Conclusion: PTC patients with RLN invasion have a negative prognosis and a higher recurrence rate. Meticulous operation and careful follow-up of patients with the above factors is recommended. Keywords: papillary thyroid carcinoma, recurrent laryngeal nerve invasion, predictive factors, lymph node metastases, Hashimoto’s thyroiditis

Surgery on spinal epidural metastases (SEM) in renal cell carcinoma: a plea for a new paradigm.

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Bakker, Nicolaas A; Coppes, Maarten H; Vergeer, Rob A; Kuijlen, Jos M A; Groen, Rob J M

2014-09-01

Prediction models for outcome of decompressive surgical resection of spinal epidural metastases (SEM) have in common that they have been developed for all types of SEM, irrespective of the type of primary tumor. It is our experience in clinical practice, however, that these models often fail to accurately predict outcome in the individual patient. To investigate whether decision making could be optimized by applying tumor-specific prediction models. For the proof of concept, we analyzed patients with SEM from renal cell carcinoma that we have operated on. Retrospective chart analysis 2006 to 2012. Twenty-one consecutive patients with symptomatic SEM of renal cell carcinoma. Predictive factors for survival. Next to established predictive factors for survival, we analyzed the predictive value of the Motzer criteria in these patients. The Motzer criteria comprise a specific and validated risk model for survival in patients with renal cell carcinoma. After multivariable analysis, only Motzer intermediate (hazard ratio [HR] 17.4, 95% confidence interval [CI] 1.82-166, p=.01) and high risk (HR 39.3, 95% CI 3.10-499, p=.005) turned out to be significantly associated with survival in patients with renal cell carcinoma that we have operated on. In this study, we have demonstrated that decision making could have been optimized by implementing the Motzer criteria next to established prediction models. We, therefore, suggest that in future, in patients with SEM from renal cell carcinoma, the Motzer criteria are also taken into account. Copyright © 2014 Elsevier Inc. All rights reserved.

Improving classification with forced labeling of other related classes: application to prediction of upstaged ductal carcinoma in situ using mammographic features

Science.gov (United States)

Hou, Rui; Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2018-02-01

Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure DCIS and upstaged DCIS can help avoid overtreatment and overdiagnosis. In this work, we propose to improve this classification performance with the aid of two other related classes: Atypical Ductal Hyperplasia (ADH) and Invasive Ductal Carcinoma (IDC). Our data set contains mammograms for 230 cases. Specifically, 66 of them are ADH cases; 99 of them are biopsy-proven DCIS cases, of whom 25 were found to contain invasive disease at the time of definitive surgery. The remaining 65 cases were diagnosed with IDC at core biopsy. Our hypothesis is that knowledge can be transferred from training with the easier and more readily available cases of benign but suspicious ADH versus IDC that is already apparent at initial biopsy. Thus, embedding both ADH and IDC cases to the classifier will improve the performance of distinguishing upstaged DCIS from pure DCIS. We extracted 113 mammographic features based on a radiologist's annotation of clusters.Our method then added both ADH and IDC cases during training, where ADH were "force labeled" or treated by the classifier as pure DCIS (negative) cases, and IDC were labeled as upstaged DCIS (positive) cases. A logistic regression classifier was built based on the designed training dataset to perform a prediction of whether biopsy-proven DCIS cases contain invasive cancer. The performance was assessed by repeated 5-fold CrossValidation and Receiver Operating Characteristic(ROC) curve analysis. While prediction performance with only training on DCIS dataset had an average AUC of 0.607(%95CI, 0.479-0.721). By adding both ADH and IDC cases for training, we improved the performance to 0.691(95%CI, 0.581-0.801).

Machine Learning Algorithms Outperform Conventional Regression Models in Predicting Development of Hepatocellular Carcinoma

Science.gov (United States)

Singal, Amit G.; Mukherjee, Ashin; Elmunzer, B. Joseph; Higgins, Peter DR; Lok, Anna S.; Zhu, Ji; Marrero, Jorge A; Waljee, Akbar K

2015-01-01

Background Predictive models for hepatocellular carcinoma (HCC) have been limited by modest accuracy and lack of validation. Machine learning algorithms offer a novel methodology, which may improve HCC risk prognostication among patients with cirrhosis. Our study's aim was to develop and compare predictive models for HCC development among cirrhotic patients, using conventional regression analysis and machine learning algorithms. Methods We enrolled 442 patients with Child A or B cirrhosis at the University of Michigan between January 2004 and September 2006 (UM cohort) and prospectively followed them until HCC development, liver transplantation, death, or study termination. Regression analysis and machine learning algorithms were used to construct predictive models for HCC development, which were tested on an independent validation cohort from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. Both models were also compared to the previously published HALT-C model. Discrimination was assessed using receiver operating characteristic curve analysis and diagnostic accuracy was assessed with net reclassification improvement and integrated discrimination improvement statistics. Results After a median follow-up of 3.5 years, 41 patients developed HCC. The UM regression model had a c-statistic of 0.61 (95%CI 0.56-0.67), whereas the machine learning algorithm had a c-statistic of 0.64 (95%CI 0.60–0.69) in the validation cohort. The machine learning algorithm had significantly better diagnostic accuracy as assessed by net reclassification improvement (pmachine learning algorithm (p=0.047). Conclusion Machine learning algorithms improve the accuracy of risk stratifying patients with cirrhosis and can be used to accurately identify patients at high-risk for developing HCC. PMID:24169273

BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma

International Nuclear Information System (INIS)

Henke, Lauren E; Pfeifer, John D; Ma, Changquing; Perkins, Stephanie M; DeWees, Todd; El-Mofty, Samir; Moley, Jeffrey F; Nussenbaum, Brian; Haughey, Bruce H; Baranski, Thomas J; Schwarz, Julie K; Grigsby, Perry W

2015-01-01

The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1–2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1–2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1–2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan–Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy

18F-fluorodeoxyglucose positron emission tomography for predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Su, Meng; Wei, Hangping; Lin, Ruifang; Zhang, Xuebang; Zou, Changlin; Zhao, Liang

2015-01-01

The aim of this study was to evaluate the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma (NPC). From July 2012 to March 2014, 46 NPC patients who had undergone PET scanning before receiving definitive intensity-modulated radiotherapy (IMRT) treatment in our hospital were enrolled. Factors potentially affecting tumor response to treatment were studied by multiple logistic regression analysis. After radiochemotherapy, 32 patients had a clinical complete response (CR), making the CR rate 69.6 %. Multiple logistic regression analysis demonstrated that the maximal standard uptake value (SUV max ) of the primary tumor was the only factor related to tumor response (p = 0.001), and that the logistic model had a high positive predictive value (90.6 %). The area under the receiver operating characteristic (ROC) curve was 0.809, with a best cutoff threshold at 10.05. Patients with SUV max ≤ 10 had a higher CR rate than those with SUV max > 10 (p < 0.001). The SUV max of the primary tumor before treatment is an independent predictor of tumor response in NPC. (orig.) [de

Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

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Thian-Sze Wong

2012-01-01

Full Text Available Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.

Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

OpenAIRE

de Faria, J

1985-01-01

The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

Treatment resistance in urothelial carcinoma: an evolutionary perspective.

Science.gov (United States)

Vlachostergios, Panagiotis J; Faltas, Bishoy M

2018-05-02

The emergence of treatment-resistant clones is a critical barrier to cure in patients with urothelial carcinoma. Setting the stage for the evolution of resistance, urothelial carcinoma is characterized by extensive mutational heterogeneity, which is detectable even in patients with early stage disease. Chemotherapy and immunotherapy both act as selective pressures that shape the evolutionary trajectory of urothelial carcinoma throughout the course of the disease. A detailed understanding of the dynamics of evolutionary drivers is required for the rational development of curative therapies. Herein, we describe the molecular basis of the clonal evolution of urothelial carcinomas and the use of genomic approaches to predict treatment responses. We discuss various mechanisms of resistance to chemotherapy with a focus on the mutagenic effects of the DNA dC->dU-editing enzymes APOBEC3 family of proteins. We also review the evolutionary mechanisms underlying resistance to immunotherapy, such as the loss of clonal tumour neoantigens. By dissecting treatment resistance through an evolutionary lens, the field will advance towards true precision medicine for urothelial carcinoma.

Prognosis and histology in Stage I nasopharyngeal carcinoma (NPC)

International Nuclear Information System (INIS)

Saw, D.; Ho, J.H.C.; Fong, M.; Chan, C.L.; Tse, C.H.; Lau, W.H.

1985-01-01

During 1969-1975, 212 new patients with Stage I nasopharyngeal carcinoma (NPC) with a tumor apparently confined to the nasopharynx were treated at Queen Elizabeth Hospital, Kowloon, Hong Kong. The initial histologies of 137 patients were available for review and further studies. The primary tumors were histologically classified into two major types - squamous cell carcinoma (35 patients) and undifferentiated carcinoma (102 patients). The latter was further divided into 4 sub-types: lymphoepithelioma of the Schmincke type, lymphoepithelioma of the Regaud type, spindle cell carcinoma, and undifferentiated carcinoma of the nasopharyngeal type. Such histological typing of the initial tumor was not of value in predicting the clinical outcome, whether in terms of 5-year crude or disease-free survival rate, or the tendency of the tumor to develop recurrence at the primary site, or distance metastases after a standardized course of radiation therapy. There is not significant correlation between the extent of mononuclear infiltration nor fibrosis in the tumor stroma and the survival or tumor control rates

LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma

Science.gov (United States)

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Huang, Yu-Jie; Chao, Pei-Ju; Ting, Hui-Min; Lee, Hsiao-Yi

2014-01-01

To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa. PMID:25163814

A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

International Nuclear Information System (INIS)

Reis, Patricia P; Simpson, Colleen; Goldstein, David; Brown, Dale; Gilbert, Ralph; Gullane, Patrick; Irish, Jonathan; Jurisica, Igor; Kamel-Reid, Suzanne; Waldron, Levi; Perez-Ordonez, Bayardo; Pintilie, Melania; Galloni, Natalie Naranjo; Xuan, Yali; Cervigne, Nilva K; Warner, Giles C; Makitie, Antti A

2011-01-01

Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC may aid in identifying a gene signature predictive of recurrence. We used a meta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets, in addition to our microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients. We identified 138 significantly over-expressed genes (> 2-fold, false discovery rate of 0.01) in OSCC. By penalized likelihood Cox regression, we identified a 4-gene signature with prognostic value for recurrence in our training set. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Over-expression of this 4-gene signature in histologically normal margins was associated with recurrence in our training cohort (p = 0.0003, logrank test) and in our independent validation cohort (p = 0.04, HR = 6.8, logrank test). Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. Our findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence

Expression of E-cadherin and vimentin in oral squamous cell carcinoma

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Zhou, Jingping; Tao, Detao; Xu, Qing; Gao, Zhenlin; Tang, Daofang

2015-01-01

The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome. PMID:26045832

Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma

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Zhao, Hui [Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Hepatopancreatobiliary Surgery, Nanjing Medical University Affiliated Wuxi Second People' s Hospital, Wuxi, Jiangsu (China); Hua, Ye [Department of Neurology, Nanjing Medical University Affiliated Wuxi Second People’s Hospital, Wuxi, Jiangsu (China); Dai, Tu [Department of Hepatopancreatobiliary Surgery, Nanjing Medical University Affiliated Wuxi Second People' s Hospital, Wuxi, Jiangsu (China); He, Jian; Tang, Min [Department of Radiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu (China); Fu, Xu; Mao, Liang [Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu (China); Jin, Huihan, E-mail: 45687061@qq.com [Department of Hepatopancreatobiliary Surgery, Nanjing Medical University Affiliated Wuxi Second People' s Hospital, Wuxi, Jiangsu (China); Qiu, Yudong, E-mail: yudongqiu510@163.com [Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu (China)

2017-03-15

Highlights: • This study aimed to establish a novel predictive scoring model of MVI in HCC patients. • Preoperative imaging features on CECT, such as intratumoral arteries, non-nodule type and absence of radiological tumor capsule were independent predictors for MVI. • The predictive scoring model is of great value in prediction of MVI regardless of tumor size. - Abstract: Purpose: Microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) cannot be accurately predicted preoperatively. This study aimed to establish a predictive scoring model of MVI in solitary HCC patients without macroscopic vascular invasion. Methods: A total of 309 consecutive HCC patients who underwent curative hepatectomy were divided into the derivation (n = 206) and validation cohort (n = 103). A predictive scoring model of MVI was established according to the valuable predictors in the derivation cohort based on multivariate logistic regression analysis. The performance of the predictive model was evaluated in the derivation and validation cohorts. Results: Preoperative imaging features on CECT, such as intratumoral arteries, non-nodular type of HCC and absence of radiological tumor capsule were independent predictors for MVI. The predictive scoring model was established according to the β coefficients of the 3 predictors. Area under receiver operating characteristic (AUROC) of the predictive scoring model was 0.872 (95% CI, 0.817-0.928) and 0.856 (95% CI, 0.771-0.940) in the derivation and validation cohorts. The positive and negative predictive values were 76.5% and 88.0% in the derivation cohort and 74.4% and 88.3% in the validation cohort. The performance of the model was similar between the patients with tumor size ≤5 cm and >5 cm in AUROC (P = 0.910). Conclusions: The predictive scoring model based on intratumoral arteries, non-nodular type of HCC, and absence of the radiological tumor capsule on preoperative CECT is of great value in the prediction of MVI

Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhao, Hui; Hua, Ye; Dai, Tu; He, Jian; Tang, Min; Fu, Xu; Mao, Liang; Jin, Huihan; Qiu, Yudong

2017-01-01

Highlights: • This study aimed to establish a novel predictive scoring model of MVI in HCC patients. • Preoperative imaging features on CECT, such as intratumoral arteries, non-nodule type and absence of radiological tumor capsule were independent predictors for MVI. • The predictive scoring model is of great value in prediction of MVI regardless of tumor size. - Abstract: Purpose: Microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) cannot be accurately predicted preoperatively. This study aimed to establish a predictive scoring model of MVI in solitary HCC patients without macroscopic vascular invasion. Methods: A total of 309 consecutive HCC patients who underwent curative hepatectomy were divided into the derivation (n = 206) and validation cohort (n = 103). A predictive scoring model of MVI was established according to the valuable predictors in the derivation cohort based on multivariate logistic regression analysis. The performance of the predictive model was evaluated in the derivation and validation cohorts. Results: Preoperative imaging features on CECT, such as intratumoral arteries, non-nodular type of HCC and absence of radiological tumor capsule were independent predictors for MVI. The predictive scoring model was established according to the β coefficients of the 3 predictors. Area under receiver operating characteristic (AUROC) of the predictive scoring model was 0.872 (95% CI, 0.817-0.928) and 0.856 (95% CI, 0.771-0.940) in the derivation and validation cohorts. The positive and negative predictive values were 76.5% and 88.0% in the derivation cohort and 74.4% and 88.3% in the validation cohort. The performance of the model was similar between the patients with tumor size ≤5 cm and >5 cm in AUROC (P = 0.910). Conclusions: The predictive scoring model based on intratumoral arteries, non-nodular type of HCC, and absence of the radiological tumor capsule on preoperative CECT is of great value in the prediction of MVI

Beyond the first episode: candidate factors for a risk prediction model of schizophrenia.

Science.gov (United States)

Murphy, Brendan P

2010-01-01

Many early psychosis services are financially compromised and cannot offer a full tenure of care to all patients. To maintain viability of services it is important that those with schizophrenia are identified early to maximize long-term outcomes, as are those with better prognoses who can be discharged early. The duration of untreated psychosis remains the mainstay in determining those who will benefit from extended care, yet its ability to inform on prognosis is modest in both the short and medium term. There are a number of known or putative genetic and environmental risk factors that have the potential to improve prognostication, though a multivariate risk prediction model combining them with clinical characteristics has yet to be developed. Candidate risk factors for such a model are presented, with an emphasis on environmental risk factors. More work is needed to corroborate many putative factors and to determine which of the established factors are salient and which are merely proxy measures. Future research should help clarify how gene-environment and environment-environment interactions occur and whether risk factors are dose-dependent, or if they act additively or synergistically, or are redundant in the presence (or absence) of other factors.

Coherent Raman Scattering Microscopy for Evaluation of Head and Neck Carcinoma.

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Hoesli, Rebecca C; Orringer, Daniel A; McHugh, Jonathan B; Spector, Matthew E

2017-09-01

Objective We aim to describe a novel, label-free, real-time imaging technique, coherent Raman scattering (CRS) microscopy, for histopathological evaluation of head and neck cancer. We evaluated the ability of CRS microscopy to delineate between tumor and nonneoplastic tissue in tissue samples from patients with head and neck cancer. Study Design Prospective case series. Setting Tertiary care medical center. Subjects and Methods Patients eligible were surgical candidates with biopsy-proven, previously untreated head and neck carcinoma and were consented preoperatively for participation in this study. Tissue was collected from 50 patients, and after confirmation of tumor and normal specimens by hematoxylin and eosin (H&E), there were 42 tumor samples and 42 normal adjacent controls. Results There were 42 confirmed carcinoma specimens on H&E, and CRS microscopy identified 37 as carcinoma. Of the 42 normal specimens, CRS microscopy identified 40 as normal. This resulted in a sensitivity of 88.1% and specificity of 95.2% in distinguishing between neoplastic and nonneoplastic images. Conclusion CRS microscopy is a unique label-free imaging technique that can provide rapid, high-resolution images and can accurately determine the presence of head and neck carcinoma. This holds potential for implementation into standard practice, allowing frozen margin evaluation even at institutions without a histopathology laboratory.

Concerted down-regulation of immune-system related genes predicts metastasis in colorectal carcinoma

International Nuclear Information System (INIS)

Fehlker, Marion; Huska, Matthew R; Jöns, Thomas; Andrade-Navarro, Miguel A; Kemmner, Wolfgang

2014-01-01

This study aimed at the identification of prognostic gene expression markers in early primary colorectal carcinomas without metastasis at the time point of surgery by analyzing genome-wide gene expression profiles using oligonucleotide microarrays. Cryo-conserved tumor specimens from 45 patients with early colorectal cancers were examined, with the majority of them being UICC stage II or earlier and with a follow-up time of 41–115 months. Gene expression profiling was performed using Whole Human Genome 4x44K Oligonucleotide Microarrays. Validation of microarray data was performed on five of the genes in a smaller cohort. Using a novel algorithm based on the recursive application of support vector machines (SVMs), we selected a signature of 44 probes that discriminated between patients developing later metastasis and patients with a good prognosis. Interestingly, almost half of the genes was related to the patients’ immune response and showed reduced expression in the metastatic cases. Whereas up to now gene signatures containing genes with various biological functions have been described for prediction of metastasis in CRC, in this study metastasis could be well predicted by a set of gene expression markers consisting exclusively of genes related to the MHC class II complex involved in immune response. Thus, our data emphasize that the proper function of a comprehensive network of immune response genes is of vital importance for the survival of colorectal cancer patients

Tissue-based quantitative proteome analysis of human hepatocellular carcinoma using tandem mass tags.

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Megger, Dominik Andre; Rosowski, Kristin; Ahrens, Maike; Bracht, Thilo; Eisenacher, Martin; Schlaak, Jörg F; Weber, Frank; Hoffmann, Andreas-Claudius; Meyer, Helmut E; Baba, Hideo A; Sitek, Barbara

2017-03-01

Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics. Proteomic differences between HCC and nontumorous liver tissue were studied by mass spectrometry. Among several significantly upregulated proteins, translocator protein 18 (TSPO) and Ras-related protein Rab-1A (RAB1A) were selected for verification by immunohistochemistry in an independent cohort. For RAB1A, a high accuracy for the discrimination of HCC and nontumorous liver tissue was observed. RAB1A was verified to be a potent biomarker candidate for HCC.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

2016-01-01

Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

Recurrence predictive models for patients with hepatocellular carcinoma after radiofrequency ablation using support vector machines with feature selection methods.

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Liang, Ja-Der; Ping, Xiao-Ou; Tseng, Yi-Ju; Huang, Guan-Tarn; Lai, Feipei; Yang, Pei-Ming

2014-12-01

Recurrence of hepatocellular carcinoma (HCC) is an important issue despite effective treatments with tumor eradication. Identification of patients who are at high risk for recurrence may provide more efficacious screening and detection of tumor recurrence. The aim of this study was to develop recurrence predictive models for HCC patients who received radiofrequency ablation (RFA) treatment. From January 2007 to December 2009, 83 newly diagnosed HCC patients receiving RFA as their first treatment were enrolled. Five feature selection methods including genetic algorithm (GA), simulated annealing (SA) algorithm, random forests (RF) and hybrid methods (GA+RF and SA+RF) were utilized for selecting an important subset of features from a total of 16 clinical features. These feature selection methods were combined with support vector machine (SVM) for developing predictive models with better performance. Five-fold cross-validation was used to train and test SVM models. The developed SVM-based predictive models with hybrid feature selection methods and 5-fold cross-validation had averages of the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the ROC curve as 67%, 86%, 82%, 69%, 90%, and 0.69, respectively. The SVM derived predictive model can provide suggestive high-risk recurrent patients, who should be closely followed up after complete RFA treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma.

Science.gov (United States)

A G, Deepa; Janardanan-Nair, Bindu; B R, Varun

2017-12-01

Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation. Key words: Immunohistochemistry, Oral leukoplakia, Oral submucous fibrosis, Podoplanin, Squamous cell carcinoma.

Psychometric Personality Differences Between Candidates in Astronaut Selection.

Science.gov (United States)

Mittelstädt, Justin M; Pecena, Yvonne; Oubaid, Viktor; Maschke, Peter

This paper investigates personality traits as potential factors for success in an astronaut selection by comparing personality profiles of unsuccessful and successful astronaut candidates in different phases of the ESA selection procedure. It is further addressed whether personality traits could predict an overall assessment rating at the end of the selection. In 2008/2009, ESA performed an astronaut selection with 902 candidates who were either psychologically recommended for mission training (N = 46) or failed in basic aptitude (N = 710) or Assessment Center and interview testing (N = 146). Candidates completed the Temperament Structure Scales (TSS) and the NEO Personality Inventory Revised (NEO-PI-R). Those candidates who failed in basic aptitude testing showed higher levels of Neuroticism (M = 49.8) than the candidates who passed that phase (M = 45.4 and M = 41.6). Additionally, candidates who failed in basic testing had lower levels of Agreeableness (M = 132.9) than recommended candidates (M = 138.1). TSS scales for Achievement (r = 0.19) and Vitality (r = 0.18) showed a significant correlation with the overall assessment rating given by a panel board after a final interview. Results indicate that a personality profile similar to Helmreich's "Right Stuff" is beneficial in astronaut selection. Influences of test anxiety on performance are discussed. Mittelstädt JM, Pecena Y, Oubaid V, Maschke P. Psychometric personality differences between candidates in astronaut selection. Aerosp Med Hum Perform. 2016; 87(11):933-939.

Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a western population

International Nuclear Information System (INIS)

Ferrari, Daris; Alterio, Daniela; Foa, Paolo; Codecà, Carla; Bertuzzi, Cecilia; Broggio, Francesca; Crepaldi, Francesca; Luciani, Andrea; Floriani, Irene; Ansarin, Mohssen; Chiesa, Fausto

2012-01-01

Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method. Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases

Visceral fat area predicts survival in patients with advanced hepatocellular carcinoma treated with tyrosine kinase inhibitors.

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Nault, Jean-Charles; Pigneur, Frédéric; Nelson, Anaïs Charles; Costentin, Charlotte; Tselikas, Lambros; Katsahian, Sandrine; Diao, Guoqing; Laurent, Alexis; Mallat, Ariane; Duvoux, Christophe; Luciani, Alain; Decaens, Thomas

2015-10-01

Anthropometric measurements have been linked to resistance to anti-angiogenic treatment and survival. Patients with advanced hepatocellular carcinoma treated with sorafenib or brivanib in 2008-2011 were included in this retrospective study. Anthropometric measurements were assessed using computed tomography and were correlated with drug toxicity, radiological response, and overall survival. 52 patients were included, Barcelona Clinic Liver Classification B (38%) and C (62%), with a mean value of α-fetoprotein of 29,554±85,654 ng/mL, with a median overall survival of 10.5 months. Sarcopenia was associated with a greater rate of hand-foot syndrome (P=0.049). Modified Response Evaluation Criteria In Solid Tumours (mRECIST) and Choi criteria were significantly associated with survival, but RECIST criteria were not. An absence of hand-foot syndrome and high-visceral fat area were associated with progressive disease as assessed by RECIST and mRECIST criteria. In multivariate analyses, high visceral fat area (HR=3.6; P=0.002), low lean body mass (HR=2.4; P=0.015), and presence of hand-foot syndrome (HR=1.8; P=0.004) were significantly associated with overall survival. In time-dependent multivariate analyses; only high visceral fat area was associated with survival. Visceral fat area is associated with survival and seems to be a predictive marker for primary resistance to tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Hypervelocity star candidates in Gaia DR1/TGAS

Science.gov (United States)

Marchetti, T.; Rossi, E. M.; Kordopatis, G.; Brown, A. G. A.; Rimoldi, A.; Starkenburg, E.; Youakim, K.; Ashley, R.

2018-04-01

Hypervelocity stars (HVSs) are characterized by a total velocity in excess of the Galactic escape speed, and with trajectories consistent with coming from the Galactic Centre. We apply a novel data mining routine, an artificial neural network, to discover HVSs in the TGAS subset of the first data release of the Gaia satellite, using only the astrometry of the stars. We find 80 stars with a predicted probability >90% of being HVSs, and we retrieved radial velocities for 47 of those. We discover 14 objects with a total velocity in the Galactic rest frame >400 km s-1, and 5 of these have a probability >50% of being unbound from the Milky Way. Tracing back orbits in different Galactic potentials, we discover 1 HVS candidate, 5 bound HVS candidates, and 5 runaway star candidates with remarkably high velocities, between 400 and 780 km s-1. We wait for future Gaia releases to confirm the goodness of our sample and to increase the number of HVS candidates.

The Glasgow Prognostic Score. An useful tool to predict survival in patients with advanced esophageal squamous cell carcinoma.

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Henry, Maria Aparecida Coelho de Arruda; Lerco, Mauro Masson; de Oliveira, Walmar Kerche; Guerra, Anderson Roberto; Rodrigues, Maria Aparecida Marchesan

2015-08-01

To evaluate the usefulness of the Glasgow Prognostic Score (GPS) in patients with esophageal carcinoma (EC). A total of 50 patients with EC were analyzed for GPS, nutritional and clinicopathologic parameters. Patients with CRP ≤ 1.0mg/L and albumin ≥ 3.5mg/L were considered as GPS = 0. Patients with only CRP increased or albumin decreased were classified as GPS = 1 and patients with CRP > 1.0mg/L and albumin L were considered as GPS = 2. GPS of 0, 1 and 2 were observed in seven, 23 and 20 patients, respectively. A significant inverse relationship was observed between GPS scores and the survival rate. The survival rate was greatest in patients with GPS = 0 and significantly higher than those from patients with GPS = 1 and GPS = 2. Minimum 12-month survival was observed in 71% patients with GPS = 0 and in 30% patients with GPS = 1. None of the patients with GPS = 2 survived for 12 months. A significant relationship between CRP or albumin individually and the survival rate was observed. No significant relationship among nutritional, clinic pathological parameters and survival was found. Glasgow Prognostic Score is an useful tool to predict survival in patients with esophageal carcinoma.

Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma.

Science.gov (United States)

Battistella, M; Mateus, C; Lassau, N; Chami, L; Boukoucha, M; Duvillard, P; Cribier, B; Robert, C

2010-02-01

Adnexal carcinomas are rare and diverse cutaneous tumours. They are locally aggressive and have the potential for distant metastasis. Metastatic adnexal carcinomas are very resistant to conventional chemotherapies. Sunitinib, an oral tyrosine kinase inhibitor, is reportedly effective for the treatment of various solid cancers. Its use in adnexal carcinomas has never been reported. The first patient had metastatic clear cell hidradenocarcinoma and was stabilized over 8 months with sunitinib, before she relapsed. The second patient had a metastatic malignant hair follicle tumour (trichoblastic carcinoma) and achieved a partial remission with sunitinib, and disease stabilized after 10 months. Dynamic contrast-enhanced ultrasound (DCE-US) performed to evaluate tumour vascularization during treatment depicted a dramatic and early decrease in the tumour blood volume. Sunitinib was effective in controlling the disease in our two patients. DCE-US using linear raw data may have an early predictive value for tumour response to sunitinib. Further studies involving larger cohorts of patients are warranted in order to confirm the efficacy of sunitinib in these rare tumours.

Predicting prognosis in hepatocellular carcinoma; comparison of staging system in pakistani cohort

International Nuclear Information System (INIS)

Sarwar, S.; Khan, A.A.

2015-01-01

To determine the clinical, biochemical and radiological prognostic indicators and to compare the performance of six staging systems in patients of hepatocellular carcinoma (HCC). Study Design:Descriptive study. Place and Duration of Study: Department of Gastroenterology, Doctors Hospital, Lahore, from October 2007 to December 2013. Methodology:Patients with HCC were included. Baseline clinical, hematological and radiological variables were noted. Patients were followed for 5 years or till death. Survival predictors were identified using Cox proportional hazard analysis and 6 prognostic staging systems were evaluated by determining homogeneity, discriminatory ability and monotonicity. Results: Of the 228 patients included, male to female ratio was 2.6/1 (165/63) and mean age was 56.5 ± 10.4 years. Majority of patients 189 (82.9%) were anti-HCV positive. Solitary HCC lesion was seen in 121 (53.1%) patients, 16 (7%) had 2 lesions while 73 (32%) had 3 or more lesions. Only 36 (15.8%) patients had palliative therapy for HCC. Survival rate was 45.2%, 25%, 12.3%, 7%, 2.2% and 1% for 6 months, 1, 2, 3, 4 and 5 years respectively. Male gender, portal vein thrombosis, serum albumin < 3.5 g/dl, tumor size =6 cm and alpha fetoprotein (AFP) =147 U/ml were bad prognostic indicators. OKUDA, GRETCH and early stages of CLIP had better homogeneity while CLIP showed superior discriminatory ability and monotonicity for predicting survival. Conclusion: Male gender, presence of portal vein thrombosis, low serum albumin, large tumor size and high AFP level are poor prognostic indicators in patients of HCC. CLIP has better performance in predicting mortality. (author)

Differentiated thyroid carcinomas: prediction of tumor invasion with MR imaging

International Nuclear Information System (INIS)

Takashima, S.; Takayama, F.; Wang, Q.; Kawakami, S.; Saito, A.; Sone, S.; Kobayashi, S.

2000-01-01

Purpose: To assess diagnostic accuracy for tumor invasion of surrounding organs by measurement of tumor circumferences on MR images in patients with differentiated thyroid carcinomas. Material and Methods: Surgical and MR imaging findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7 recurrent lesions) were retrospectively reviewed. The degrees of circumference of tumor encroachment to the organs were measured, and the measurements and morphologic diagnosis of tumor invasion made by a head and neck radiologist were compared with surgical and pathologic findings using receiver operating characteristic curves. Results: Diagnosis of tumor invasion by the radiologist was superior to the measurements of the carotid artery and cartilage, while the reverse was true for the trachea and esophagus. However, no statistical differences were noted between them for each structure. Optimal thresholds for tumor invasion were 90 deg or more for the cartilage (94% accuracy) and esophagus (86% accuracy), 135 deg or more for the trachea (86% accuracy), and 225 deg or more for the carotid artery (90% accuracy). Conclusion: Tumor invasion was more accurately diagnosed by measurement of tumor circumferences of each organ on MR images

Sonographic findings predictive of central lymph node metastasis in patients with papillary thyroid carcinoma: influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography.

Science.gov (United States)

Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo

2013-12-01

To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary thyroid carcinoma. The diagnostic performance of sonography for predicting metastasis was superior in chronic lymphocytic thyroiditis-negative patients than in positive patients.

Invasive Pleomorphic Lobular Carcinoma of the Breast: Pathologic, Clinical, and Therapeutic Considerations.

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Al-Baimani, Khalid; Bazzarelli, Amy; Clemons, Mark; Robertson, Susan J; Addison, Christina; Arnaout, Angel

2015-12-01

Pleomorphic lobular carcinoma is an uncommon form of breast cancer and a subtype of invasive lobular carcinoma. It has unique histopathologic features that translate to a more aggressive phenotype with an associated poor prognosis. Unlike classical invasive lobular carcinoma, it can lose estrogen and progesterone receptor expression and demonstrate HER-2/neu amplification. It remains to be determined, however, whether the pleomorphic histology independently predicts a worse outcome or whether other known associated negative prognostic factors such as larger tumor size, increased metastatic disease, and associated worse molecular subtypes commonly present in pleomorphic carcinoma account for the poor prognosis. Here we present an updated review of the unique pathologic and clinical features of pleomorphic lobular carcinoma needed to guide management for women with this subtype of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

Directory of Open Access Journals (Sweden)

D. Ben Sellem

2011-01-01

Full Text Available Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii generate statistical models capable of classifying borderline tumors and (iii establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate and mucinous (N-acetyl-lysine carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

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Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

2017-07-01

Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

Smoothened inhibitors in the treatment of advanced basal cell carcinomas.

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Kunstfeld, Rainer

2014-03-01

The Hedgehog pathway has been identified as a key element in the development of many forms of cancer. Smoothened (Smo) inhibitors are known to beneficially interfere with the Hedgehog pathway and are currently under investigation as anticancer drugs for many tumor entities. Reviewed here are the most recent developments in clinical research on Smo inhibitors for the treatment of advanced basal cell carcinoma (BCC). When reviewing the literature of the past 12 months, it is striking to see the rapid evolution of the field. Compounds that have been presented as powerful new drug candidates 12 months ago have now been discontinued, whereas new ones have emerged. Reports on 13 drug candidates have been identified: one marketed, vismodegib, eight currently under development (phase I-II) and four for which clinical investigation for BCC is currently not being pursued. Smo inhibitors are a promising drug class for the treatment of BCC. To date, most candidates are in early stage development and are expected to enter the market in approximately 5-8 years, if successful.

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

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Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

The Singapore Liver Cancer Recurrence (SLICER Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Soo Fan Ang

Full Text Available Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC. Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER Score, to predict outcomes of HCC patients who have undergone surgical resection.Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

Squamous Cell Carcinoma

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... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

International Nuclear Information System (INIS)

Jones, E. A.; Shenton, A.; Evans, D. G.; Sajid, M. I.

2011-01-01

Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome) is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden

Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

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Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

2016-09-01

The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

2014-01-01

Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. Identification of proteins differentially expressed in OSSC samples from patients sensitive or resistant. The samples were processed by LC-MS and analyzed with 2DICAL

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Yoon, H. [Sungkyunkwan Univ., Seoul (Korea, Republic of). Dept. of Health Sciences and Technology; Oh, D.; Park, H.C.; Han, Y.; Lim, D.H. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Kang, S.W. [Korea Univ., Seoul (Korea, Republic of). Dept. of Radiologic Science; Paik, S.W. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of). Dept. of Medicine

2013-07-15

Purpose: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). Patients and methods: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the {>=} grade 2 GD toxicity were investigated. Results: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V{sub 25} for stomach and V{sub 35} for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for {>=} grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V{sub 25} {<=} 6.3 % and 57.1 % for V{sub 25} > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V{sub 35} > 5.4 % and 45.9 % for V{sub 35} > 5.4 %. By multivariate analysis including the clinical factors, V{sub 25} for stomach and V{sub 35} for duodenum were the significant factors. Conclusion: EGD revealed that GD toxicity is common following RT for HCC. V{sub 25} for the stomach and V{sub 35} for the duodenum were the significant factors to predict {>=} grade 2 GD toxicity. (orig.)

Predicting Performance: A Comparison of University Supervisors' Predictions and Teacher Candidates' Scores on a Teaching Performance Assessment

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Sandholtz, Judith Haymore; Shea, Lauren M.

2012-01-01

The implementation of teaching performance assessments has prompted a range of concerns. Some educators question whether these assessments provide information beyond what university supervisors gain through their formative evaluations and classroom observations of candidates. This research examines the relationship between supervisors' predictions…

DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

DEFF Research Database (Denmark)

Conde, Ana R; Martins, Ana P; Brito, Miguel

2007-01-01

in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric...... preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.......Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved...

Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth.

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Seki, Mai; Sano, Takaaki; Yokoo, Satoshi; Oyama, Tetsunari

2016-04-01

In squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM), it is important to predict lymph node metastasis, including occult metastasis, before operating. The purpose of this study was for us to determine practical histopathologic parameters as predictive factors for lymph node metastasis in preoperative SCC biopsy specimens. We examined 91 cases of SCC for conventional histopathologic assessment and a new factor, tumor budding, and their relationship with lymph node metastasis. Significant factors via univariate analysis (p factoring into the decision as to whether neck dissection is indicated. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1582-E1590, 2016. © 2015 Wiley Periodicals, Inc.

Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

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Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

Judges' perception of candidates' organization and communication, in relation to oral certification examination ratings.

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Houston, James E; Myford, Carol M

2009-11-01

To determine (1) whether judges differed in the levels of severity they exercised when rating candidates' performance in an oral certification exam, (2) to what extent candidates' clinical competence ratings were related to their organization/communication ratings, and (3) to what extent clinical competence ratings could predict organization/communication ratings. Six hundred eighty-four physicians participated in a medical specialty board's 2002 oral examination. Ninety-nine senior members of the medical specialty served as judges, rating candidates' performances. Candidates' clinical competence ratings were analyzed using multifaceted Rasch measurement to investigate judge severity. A Pearson correlation was calculated to examine the relationship between ratings of clinical competence and organization/communication. Logistic regression was used to determine to what extent clinical competence ratings predicted organization/communication ratings. There were about three statistically distinct strata of judge severity; judges were not interchangeable. There was a moderately strong relationship between the two sets of candidate ratings. Higher clinical competence ratings were associated with an organization/communication rating of acceptable, whereas lower clinical competence ratings were associated with an organization/communication rating of unacceptable. The judges' clinical competence ratings correctly predicted 61.9% of the acceptable and 88.3% of the unacceptable organization/communication ratings. Overall, the clinical competence ratings correctly predicted 80% of the organization/communication ratings. The close association between the two sets of ratings was possibly due to a "halo" effect. Several explanations for this relationship were explored, and the authors considered the implications for their understanding of how judges carry out this complex rating task.

Assessment of potential solder candidates for high temperature applications

DEFF Research Database (Denmark)

pressure to eliminate lead containing materials despite the fact that materials for high Pb containing alloys are currently not affected by any legislations. A tentative assessment was carried out to determine the potential solder candidates for high temperature applications based on the solidification...... criterion, phases predicted in the bulk solder and the thermodynamic stability of chlorides. These promising solder candidates were precisely produced using the hot stage microscope and its respective anodic and cathodic polarization curves were investigated using a micro-electrochemical set up...

Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Wang, Chia-Chun; Cheng, Jason Chia-Hsien; Tsai, Chiao-Ling; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Hsieh, Min-Shu; Chang, Yih-Leong; Hsu, Feng-Ming

2015-01-01

Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

Discriminating dark matter candidates using direct detection

International Nuclear Information System (INIS)

Belanger, G.; Nezri, E.; Pukhov, A.

2009-01-01

We examine the predictions for both the spin-dependent and spin-independent direct detection rates in a variety of new particle physics models with dark matter candidates. We show that a determination of both spin-independent and spin-dependent amplitudes on protons and neutrons can in principle discriminate different candidates of dark matter up to a few ambiguities. We emphasize the importance of making measurements with different spin-dependent sensitive detector materials and the need for significant improvement of the detector sensitivities. Scenarios where exchange of new colored particles contributes significantly to the elastic scattering cross sections are often the most difficult to identify, the LHC should give an indication whether such scenarios are relevant for direct detection.

Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

Directory of Open Access Journals (Sweden)

Elizabeth A. Jones

2011-01-01

Full Text Available Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden.

The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

International Nuclear Information System (INIS)

Kang, Chung-Jan; Lin, Chien-Yu; Wang, Hung-Ming; Fan, Kang-Hsing; Ng, Shu-Hang; Lee, Li-Yu; Chen, I-How; Huang, Shiang-Fu

2011-01-01

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.

Science.gov (United States)

Henning, Judith E K; Deutschbein, Timo; Altieri, Barbara; Steinhauer, Sonja; Kircher, Stefan; Sbiera, Silviu; Wild, Vanessa; Schlötelburg, Wiebke; Kroiss, Matthias; Perotti, Paola; Rosenwald, Andreas; Berruti, Alfredo; Fassnacht, Martin; Ronchi, Cristina L

2017-11-01

Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Retrospective multicenter study. Referral centers of university hospitals. A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC. Copyright © 2017 Endocrine Society

Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

Science.gov (United States)

Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

2016-09-01

Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

International Nuclear Information System (INIS)

Mohamed, H.M.S.

2009-01-01

The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used (HepG2 liver carcinoma cell line, U251 brain carcinoma cell line, H460 Lung carcinoma cell line) in this study .cells were treated with Roscovitine in different concentrations ranging from 0.1μM to 100 μM before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, The cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages . Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trial

Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

International Nuclear Information System (INIS)

Noaman, E.; Sayed, H.M.; Medhat, A.M.; Morcos, N.Y.S.

2010-01-01

The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used liver carcinoma cell line (HepG2), brain carcinoma cell line (U251), Lung carcinoma cell line (H460) in this study cells were treated with Roscovitine in different concentrations ranging from 0.1 ?M to 100 ?M before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, the cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation exposure to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, Roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages. Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trials

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Gao, S.; Worm, J.; Guldberg, P.

2004-01-01

The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours...

Prognostic factors of follicular thyroid carcinoma.

Science.gov (United States)

Ríos, Antonio; Rodríguez, José M; Ferri, Belén; Martínez-Barba, Enrique; Torregrosa, Núria M; Parrilla, Pascual

2015-01-01

Most prognostic studies in differentiated carcinoma have included a high number of papillary carcinomas and few follicular carcinomas, and not all of their conclusions therefore apply to the latter. To analyze the prognostic factors of follicular thyroid carcinoma. Patients with histological diagnosis of follicular carcinoma who had undergone potentially curative surgery, had no disseminated disease at diagnosis, and had been followed up for at least 5 years. Tumor recurrence was defined as: 1) tumor lesions with cytological analysis suggesting malignancy and/or 2) patients with total thyroidectomy with thyroglobulin levels >2 ng/mL. Clinical, therapeutic, and histological parameters were analyzed to assess prognostic factors. Recurrence was found in 25 (38%) of the 66 study patients during a follow-up period of 99 ± 38 months. Most patients with recurrence (n=20) had increased Tg levels without anatomical location, and were initially treated with radioactive I131. In the remaining 5 cases, surgical excision of the lesion was performed, and three patients required surgery during the follow-up period. Two patients died due to the disease (3%), and two other patients (3%) currently have distant metastases. Mean disease-free interval was 154 ± 14 months, and rates of disease-free patients at 5, 10, 15, and 20 years were 71, 58, 58, and 58% respectively. Clinical factors influencing recurrence included 1) age (p=0.0035); 2) sex (p=0.0114); and 3) cervical pain (p=0.0026). Histological/surgical factors associated with recurrence included 1) infiltration into neighboring structures (p=0.0000); 2) type of carcinoma (p=0.0000); 3) size (p=0.0162); 4) vascular invasion (p=0.0085); and 5) adenopathies (p=0.046). In the multivariate study, cervical pain (p=0.018) and extrathyroid invasion (p=0.045) continued to be significant factors. In follicular carcinoma, rates of disease-free patients are 71% at 5 years and 58% at 10 years, and the main predictive factors are presence

Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma

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Lee SH

2015-02-01

Full Text Available Sang Hoon Lee,1 Seung Up Kim,1–3 Jeong Won Jang,4 Si Hyun Bae,4 Sanghun Lee,1,3 Beom Kyung Kim,1–3 Jun Yong Park,1–3 Do Young Kim,1–3 Sang Hoon Ahn,1–3 Kwang–Hyub Han1–31Department of Internal Medicine, 2Institute of Gastroenterology, Yonsei University College of Medicine, 3Liver Cirrhosis Clinical Research Center, 4Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground/purpose: Liver stiffness (LS measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC. We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA.Methods: This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.Results: This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months, 47 (42.3% patients experienced HCC de novo recurrence, and 18 (16.2% died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05. On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05. Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (95% CI, 1.148–84.211, P<0.05, together with total bilirubin.Conclusions: Our

Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

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Bova, Valentina; Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Diagnostic and Interventional Radiology (Italy); Vizzini, Giovanni Battista [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Hepatology (Italy); Luca, Angelo [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Diagnostic and Interventional Radiology (Italy)

2013-04-15

This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECIST criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.

Can radiological changes in lymph node volume during treatment predict success of radiation therapy in patients with locally advanced head and neck squamous cell carcinoma?

International Nuclear Information System (INIS)

Mishra, Sanju; Hammond, Alexander; Read, Nancy; Venkatesan, Varagur; Warner, Andrew; Winquist, Eric; Nichols, Anthony

2013-01-01

Assessment of nodal response after radiotherapy (RT) for head and neck squamous cell carcinoma is difficult, as both CT and positron emission tomography scanning have limited predictive value for residual disease. We sought to measure changes in nodal volume during RT to determine whether such changes are predictive of nodal disease control. Patients with locally advanced head and neck squamous cell carcinoma treated with 70Gy of radical RT (±chemotherapy or anti-epidermal growth factor receptor (EGFR) antibodies) were eligible. Baseline pre-RT scans and cone-beam CT scans done at the outset of treatment and at weeks 3, 5 and 7 (cone-beam CTs 1, 2, 3 and 4, respectively) were deformably coregistered, and 3D nodal volumes were measured. Thirty-eight eligible patients were identified. The main primary tumour site was oropharyngeal; most patients had stage IVa disease. Twenty-seven patients received concurrent platinum-based chemotherapy, 10 received only an EGFR inhibitor with RT and one received RT alone. Twelve patients had a failure in the neck. After week 1 of treatment, a 4% mean decrease in nodal volume was observed, increasing to 40% at week 7. Platinum-based chemotherapy achieved significantly greater decreases in nodal volume than EGFR inhibitors (44 vs. 25%; P=0.026). Advanced tumour stage predicted neck failure (P=0.002), but nodal volumes did not correlate with neck control. Changes in nodal volume are minimal initially during RT but accelerate during the latter weeks of therapy. This study suggests that chemotherapy achieves a greater decrease in nodal volume than EGFR inhibitors and that nodal changes do not predict disease control in the neck.

Basal Cell Carcinoma

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... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

Merkel Cell Carcinoma

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... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

DJ-1 and androgen receptor immunohistochemical expression in prostatic carcinoma: A possible role in carcinogenesis

International Nuclear Information System (INIS)

Osman, W.M.; Abd El Atti, R.M.; Abou Gabal, H.H.

2013-01-01

Background and Aim: Androgen plays a fundamental role in the growth and differentiation of prostate. Androgen receptor (AR) expression may represent a potential marker of prognosis in prostate cancer. However, there have been variable results regarding its ability to predict clinical progression. Despite the oncogenic properties of DJ-1, its significance in prostate cancer development and progression is not well understood. This research shed some light on the possible role of immunohistochemical expression of DJ-1 in clinically localized prostatic carcinoma in relation to the established role of AR and other clinico pathologic parameters. Materials and Methods: The immunohistochemical expression of AR and DJ-1 was evaluated in 129 samples including benign hyperplasia (n = 60) and prostatic carcinoma (n = 69). Results: The mean value of AR immunostaining was significantly higher in prostatic carcinomas than in benign hyperplasia (P = 0.001). A significant inverse correlation was found between AR immunostaining and the grade of prostatic carcinomas. A significantly higher median DJ-1 score was found in prostatic carcinoma than in benign hyperplasia (P = 0.0001). There was a significant direct correlation between AR and DJ-1 score (P = 0.0001). AR is more sensitive in predicting prostatic carcinoma than DJ-1 but DJ-1 is more specific than AR. Conclusion: AR nuclear expression was consistently present in benign and adenocarcinoma epithelium. But, there may be limited clinical use for AR expression in localized carcinoma due to its constant heterogeneity. DJ-1 with its oncogenic properties, specificity for prostatic carcinoma and homogenous expression gives an ideal complementary role to AR in the detection and treatment of prostatic carcinomas.

CLINICAL STUDY OF EARLY BREAST CARCINOMA

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Kiran Kumar

2016-01-01

Full Text Available Carcinoma of the breast is one of the commonest cancers occurring in female and accounts for 1/3rd of all the malignant diseases occurring in them. It is mainly a disease of the developed countries and accounts for 1,00,000 deaths annually. Breast carcinoma is classified as Early breast cancer, Locally advanced breast cancer and Metastatic breast cancer. By definition early stage breast cancer constitutes breast tumors of clinical stages I, IIa and T2N1M0. Early breast cancer is the one diagnosed by mammography. Women when approaches at this stage, they can go for breast conservation surgery. Not all women are candidates for this approach, and some require mastectomy as part of their treatment. AIM To observe the incidence of early breast carcinoma with particular reference to the time taken by the patients to seek medical advice after the symptoms have developed i.e. the average time taken by the patients to seek medical advice, their appropriate management and prognosis. MATERIALS AND METHODS This prospective study was conducted over a period of 2 years from Oct-2012 to Oct-2014 in 30 female patients aged between 25-65 years who were presented with lump in breast of size ≤5cms with or without pain, with or without lymph nodes to the outpatient department. All the patients were thoroughly asked about history, examined clinically, investigated, staged and managed by surgery either Breast Conservation Surgery or Modified Radical Mastectomy. Postoperative complications were recorded and followed up regularly. RESULTS The incidence of early breast cancer in this study was 0.98% with peak age incidence between 40-60 years and duration of symptoms <6 months in 18 patients. Breast Conservation Surgery + axillary dissection + Radiotherapy was done in 23%. Prognosis was good in these patients with no local recurrence and death. CONCLUSION The prognosis of early stage breast carcinoma patients in this study was good. To have long term tumor free and

Stating of cervical carcinoma using magnetic resonance imaging; Estadificacion del carcinoma de cervix por resonancia magnetica

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Oleaga, L.; Vela, M. C.; Grande, J.; Cura del, J. L.; Grande, D. [Hospital de Basurto. Bilbao (Spain)

1999-07-01

The infiltration of the parametrium represents one of the most important factors that determine the prediction and treatment of cervical carcinoma. Our objetive is to evaluate the utility of magnetic resonance imaging (MRI) in the staging of cervical carcinomas, to establish the reliability of this technique and to carry out a comparative study of the sequences used to demonstrate the parametrial invasion. We have carried out a retrospective study on 44 patients diagnosed with cervix neoplasia, using clinical exploration and performing a biopsy. the MRI studies have been carried out using a 1 Tesla magnet and the sequences used have been SE T1, Se proton density (PD) and T2 and dynamic GRE after administering gadolinium intravenously in the axial and sagital projections. The stages determined by MRI have been compared to the anatomopathological stages of the surgical specimens in cases where surgery was carried out and with the clinical stage in cases where no radical surgery was carried out. A diagnosis value of MRI has been determined to demonstrate the parametrial invasion, comparing the SE T2 sequence with the dynamic GE sequence with gadolinium. We calculate the volume of the tumour in the MRI studies to evaluate the difference of the volume between patients with tumoral stages that are clinically surgical and not surgical. MRI determines the invasion of the parametrium with a sensitivity of 88.8%, a specificity of 80% a positive value of 76.1%, a negative predictive value of 90.9% and a reliability of 83.7%. For the SE T2 sequences the sensitivity was 86.6%, the specifity 80%, the posistive predictive value 81.25%, the negative predictive value 85.7% and the reliability 83.3%. For the dynamic GE sequence with intravenous gadolinium the sensitivity was 86.6%, the specifity 86.6%, the posistive predictive value 86.6%, the negative predictive value 86.6% and the reliability 86.6%. The use of the dynamic GE sequence after the intravenous administration of

Hürthle cell carcinoma: current perspectives

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Ahmadi S

2016-11-01

Full Text Available Sara Ahmadi,1 Michael Stang,2 Xiaoyin “Sara” Jiang,3 Julie Ann Sosa2,4,5 1Division of Endocrinology, Department of Medicine, 2Section of Endocrine Surgery, Department of Surgery, 3Department of Pathology, Duke University Medical Center, 4Duke Cancer Institute, 5Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Abstract: Hürthle cell carcinoma (HCC can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI. HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. Keywords: thyroid cancer, thyroid nodule, follicular cell carcinoma, Hurthle cell lesion, minimally invasive HCC

Functional validation of candidate genes detected by genomic feature models

DEFF Research Database (Denmark)

Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

2018-01-01

Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated...

Localization of occult breast lesions: mammographic findings in non infiltrating carcinoma; Localizacion de lesiones ocultas de mama: hallazgos mamograficos del carcinoma no infiltrante

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Paul, L; Iribar, M; Vilarrasa, A; Lopez, M A; Hernandez, R; Carrasco, A [Departamento de Radiodiagnostico, Hospital Doce de Octubre, Madrid (Spain)

1995-08-01

A review was carried out of 169 biopsies of occult breast lesions, 32 of which were malignant. The radiological findings associated with in situ carcinomas were compared with those of malignant lesions in general. The signs that permit the detection of breast carcinoma in the earliest stages are described, and the positive predictive value of signs, such as a spicular form, clusters of microcalcifications, nodules and architectural disturbances, is discussed. Given the lack of specificity of these findings, many beginning lesions should be biopsied to ensure an early diagnosis of breast cancer. (Author)

Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

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Takashi Nagai

2016-03-01

Full Text Available Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

Gut-associated Lymphoid Tissue (GALT) Carcinoma or Dome Carcinoma?

Science.gov (United States)

Rubio, Carlos A; Schmidt, Peter T

2016-10-01

The vast majority of colorectal carcinomas (CRCs) evolve from mucosa not associated to lymphoid tissues aggregates via the adenoma-carcinoma sequence or via the serrated pathway. Rarely CRCs evolve from gut mucosa associated to lymphoid tissue (GALT). Based on the presence of a circumscribed elevation in the colorectal mucosa, GALT carcinomas are also referred to as dome carcinomas (DC). Descriptions of the surface mucosa covering 21 GALT-CRCs appearing in pathological reports were reviewed. Three of the 21 GALT-CRCs fulfilled the criteria of dome carcinoma. Of the remaining 18 GALT-CRCs, nine were described as polypoid lesions, five as plaque-like lesions, two as sessile elevated lesions or mass, one as ulcerated and one as histological finding. Hence, only 14.3% (n=3) of the 21 GALT-CRCs displayed a dome configuration, whereas the majority, 85.7% (n=18), exhibited structures other than dome shapes at gross or at histologic examination. It becomes apparent that by using "dome" in addressing carcinomas in the colorectal mucosa, many cases of GALT carcinomas might be overlooked. Another drawback of using the "dome" nomenclature is that dome-like outlines may be detected in small metastatic tumors in the submucosa or in small colorectal carcinomas not arising from GALT mucosa. Instead, by using "GALT carcinoma", that is the histologic diagnosis in addressing these neoplasias, all cases of GALT-CRCs will be included. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

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Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

2018-03-01

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; padvanced nasopharyngeal carcinoma and might be able to predict which patients benefit

Decreased expression of pyruvate dehydrogenase A1 predicts an unfavorable prognosis in ovarian carcinoma.

Science.gov (United States)

Li, Yaqing; Huang, Ruixia; Li, Xiaoli; Li, Xiaoran; Yu, Dandan; Zhang, Mingzhi; Wen, Jianguo; Goscinski, Mariusz Adam; Trope, Claes G; Nesland, Jahn M; Suo, Zhenhe

2016-01-01

Pyruvate dehydrogenase A1 (PDHA1) serves as a gate-keeper enzyme link between glycolysis and the mitochondrial citric acid cycle. The inhibition of PDHA1 in cancer cells can result in an increased Warburg effect and a more aggressive phenotype in cancer cells. This study was conducted to investigate the expression of PDHA1 in ovarian cancer and the correlation between PDHA1 expression and the prognosis of patients. The PDHA1 protein expression in 3 ovarian cancer cell lines (OVCAR-3, SKOV-3 and ES-2) and 248 surgically removed ovarian carcinoma samples was immunocytochemically examined. Statistical analyses were performed to evaluate the correlations between PDHA1 expression and the clinicopathological characteristics of the patients as well as the predictive value of PDHA1. The results showed the presence of variable expression of PDHA1 in the three ovarian cancer cell lines. Of the 248 ovarian cancer tissue specimens, 45 cases (18.1%) were negative in tumor cells for PDHA1, 162 cases (65.3%) displayed a low expression level, and 41 cases (16.5%) had a relatively high PDHA1 staining. The expression of PDHA1 was associated with the histological subtype ( P =0.004) and FIGO stage ( P =0.002). The median OS time in the PDHA1 negative group, low expression group and high expression group were 0.939 years, 1.443 years and 9.900 years, respectively. The median PFS time in the above three groups were 0.287 years, 0.586 years and 9.900 years, respectively. Furthermore, the high expression of PDHA1 in ovarian carcinoma cells was significantly associated with better OS and PFS by statistical analyses. Multivariate analyses showed that PDHA1 expression was also an independent prognostic factor for higher OS in ovarian cancer patients (HR=0.705, 95% CI 0.541-0.918, P =0.01). Our study indicated that the decreased expression of PDHA1 might be an independent prognostic factor in unfavorable outcomes.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanis, Lourdes [Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Cho, Sung-Ki [Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Saab, Sammy [Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024 (United States)

2016-11-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanic, Lourdes; Cho, Sung Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanic, Lourdes [Div. of Interventional Radiology, Dept. of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles (United States); Cho, Sung Ki [Div. of Interventional Radiology, Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Saab, Sammy [Div. of Hepatology, Dept. of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles (United States)

2016-07-15

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Science.gov (United States)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma.

Directory of Open Access Journals (Sweden)

Genta Sawada

Full Text Available Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC. Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes.We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

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Myklebost Ola

2007-01-01

Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy

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Hanamoto, Atsushi; Tatsumi, Mitsuaki; Takenaka, Yukinori; Hamasaki, Toshimitsu; Yasui, Toshimichi; Nakahara, Susumu; Yamamoto, Yoshifumi; Seo, Yuji; Isohashi, Fumiaki; Ogawa, Kazuhiko; Hatazawa, Jun; Inohara, Hidenori

2014-01-01

It is not well established whether pretreatment 18 F-FDG PET/CT can predict local response of head and neck squamous cell carcinoma (HNSCC) to chemoradiotherapy (CRT). We examined 118 patients: 11 with nasopharyngeal cancer (NPC), 30 with oropharyngeal cancer (OPC), and 77 with laryngohypopharyngeal cancer (LHC) who had completed CRT. PET/CT parameters of primary tumor, including metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and mean standardized uptake value (SUV max and SUV mean ), were correlated with local response, according to primary site and human papillomavirus (HPV) status. Receiver-operating characteristic analyses were made to access predictive values of the PET/CT parameters, while logistic regression analyses were used to identify independent predictors. Area under the curve (AUC) of the PET/CT parameters ranged from 0.53 to 0.63 in NPC and from 0.50 to 0.54 in OPC. HPV-negative OPC showed AUC ranging from 0.51 to 0.58, while all of HPV-positive OPCs showed complete response. In contrast, AUC ranged from 0.71 to 0.90 in LHC. Moreover, AUCs of MTV and TLG were significantly higher than those of SUV max and SUV mean (P < 0.01). After multivariate analysis, high MTV >25.0 mL and high TLG >144.8 g remained as independent, significant predictors of incomplete response compared with low MTV (odds ratio [OR], 13.4; 95% confidence interval [CI], 2.5–72.9; P = 0.003) and low TLG (OR, 12.8; 95% CI, 2.4–67.9; P = 0.003), respectively. In conclusion, predictive efficacy of pretreatment 18 F-FDG PET/CT varies with different primary sites and chosen parameters. Local response of LHC is highly predictable by volume-based PET/CT parameters

Low expression of c-Myc protein predicts poor outcomes in patients with hepatocellular carcinoma after resection.

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Ji, Fei; Zhang, Zhi-Heng; Zhang, Yi; Shen, Shun-Li; Cao, Qing-Hua; Zhang, Long-Juan; Li, Shao-Qiang; Peng, Bao-Gang; Liang, Li-Jian; Hua, Yun-Peng

2018-04-24

Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-β) signaling cascade. Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-β signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-β signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis. However, the prognostic significance of c-Myc in HCC is less understood METHODS: The expression of c-Myc protein and mRNA were measured by immunohistochemistry (IHC) and qRT- PCR, respectively. IHC was performed to detect TGF-β1 and ELF expression in HCC tissues. Their relationship with clinicopathological factors and overall survival (OS) and disease free survival (DFS) were examined. The expression of c-Myc protein and mRNA in HCC tissues were significantly higher in HCC area than those in normal liver tissues. However, the expression were low compared with those adjacent to HCC area. c-Myc protein was independently predictive of DFS and OS, and it was negatively correlated with tumor size (P = 0.031), tumor number (P = 0.038), and recurrence (P = 0.001). Low c-Myc expression was associated with short-term recurrence and poor prognosis. The predictive value of c-Myc combined with TGF-β1 or/and ELF was higher than that of any other single marker. Low c-Myc, high TGF-β1 or/and low ELF expression was associated with the worst DFS and OS. Low expression of c-Myc protein predicts poor outcomes in patients with HCC with hepatectomy. The combination of the expression of c-Myc, TGF-β1, and ELF can be used to accurately predict outcomes of patients with HCC.

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

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Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Alterations in cytokine levels in cervical carcinoma patients through radiation therapy

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Munagala, Radha; Nagarajan, B.

2008-01-01

Carcinoma cervix accounts for 86-90% of all genital cancers in Indian women. This is presented with prolonged infection and impairment of immune response even after completing the radiation therapy protocol. Increase in expression of IL-6 gene in invasive cervical carcinoma was observed against CIN and normal cervix. Evaluation of infiltrating lymphocytes TIL showed considerable CD3 + and CD4 + expression which predicted better prognosis and improved survival that was negated by increased IL-6. (author)

Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

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Lee, Jae Seo

2006-01-01

Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present

Reference miRNAs for miRNAome analysis of urothelial carcinomas.

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Nadine Ratert

Full Text Available BACKGROUND/OBJECTIVE: Reverse transcription quantitative real-time PCR (RT-qPCR is widely used in microRNA (miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma. METHODS: Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. PRINCIPAL FINDINGS: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. CONCLUSIONS: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p or three (miR-148b, miR-181b, and miR-874

Endometrial carcinoma: merit of magnetic resonance in pre-surgical staging; Carcinoma de endometrio: valor de la estadificacion prequirurgica por resonancia magnetica

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Fernandez, E.; Barrera, M. C.; Gervas, C.; Salvador, E.; Rivero, B. [Hospital Donostia. San sebastian (Spain); Sentis, M. [Corporacio Sanitaria Pare Tauli. Sabadell (Spain)

2003-07-01

To evaluate MR capacity in assessing deep myometrial and cervical infiltrations in cases of endometrial carcinoma. A series of 30 consecutively diagnosed endometrial cancer patients was pre-surgically evaluated by means of magnetic resonance (MR). TSE-T2 sequences with fat saturation and dynamic FFe sequence were used after gadolinium administration. A correlation with post-surgical histological stating was made. There were then determined sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the deep myometrial infiltration and cervical invasion. Cases of overestimation and underestimation were analyzed. Values obtained for myometrium and cervix were, respectively, S of 67% and 63%, SP of 89% and 91%, PPV of 80% and 71% and NPV of 80% and 87%. Two cases each were over valued for myometrial infiltration and cervix: four cases and 3 cases, respectively, were undervalues. MR stating in cases of endometrial carcinoma is a highly reliable diagnostic technique, but it does present certain limitations. (Author) 19 refs.

Carcinoma triquilemal: relato de caso Trichilemmal carcinoma: case report

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Miguel Roismann

2011-10-01

Full Text Available O carcinoma triquilemal é um tumor raro, que ocorre, geralmente, na pele exposta ao sol, principalmente face, couro cabeludo, pescoço e dorso das mãos, em indivíduos idosos, entre a 4ª e 9ª décadas de vida, sem predilação por sexo. O presente estudo mostra um caso de carcinoma triquilemal, recidivado, de difícil tratamento, em mesma topografia de um carcinoma basocelular tratado previamente com cirurgia e radioterapia.The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed skin, especially on the face, scalp, neck and back of hands, mainly in elderly subjects but commonly between the 4th and 9th decades of life. It is not a gender-based illness. This study shows a difficult to treat case of recurrent trichilemmal carcinoma on the same location of a basal-cell carcinoma previously treated with surgery and radiotherapy.

Prediction of nodal involvement in primary rectal carcinoma without invasion to pelvic structures: accuracy of preoperative CT, MR, and DWIBS assessments relative to histopathologic findings.

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Jun Zhou

Full Text Available OBJECTIVE: To investigate the accuracy of preoperative computed tomography (CT, magnetic resonance (MR imaging and diffusion-weighted imaging with background body signal suppression (DWIBS in the prediction of nodal involvement in primary rectal carcinoma patients in the absence of tumor invasion into pelvic structures. METHODS AND MATERIALS: Fifty-two subjects with primary rectal cancer were preoperatively assessed by CT and MRI at 1.5 T with a phased-array coil. Preoperative lymph node staging with imaging modalities (CT, MRI, and DWIBS were compared with the final histological findings. RESULTS: The accuracy of CT, MRI, and DWIBS were 57.7%, 63.5%, and 40.4%. The accuracy of DWIBS with higher sensitivity and negative predictive value for evaluating primary rectal cancer patients was lower than that of CT and MRI. Nodal staging agreement between imaging and pathology was fairly strong for CT and MRI (Kappa value = 0.331 and 0.348, P<0.01 but was relatively weaker for DWIBS (Kappa value = 0.174, P<0.05. The accuracy was 57.7% and 59.6%, respectively, for CT and MRI when the lymph node border information was used as the criteria, and was 57.7% and 61.5%, respectively, for enhanced CT and MRI when the lymph node enhancement pattern was used as the criteria. CONCLUSION: MRI is more accurate than CT in predicting nodal involvement in primary rectal carcinoma patients in the absence of tumor invasion into pelvic structures. DWIBS has a great diagnostic value in differentiating small malignant from benign lymph nodes.

Ultrasonographic detection of hepatocellular carcinoma: correlation of preoperative ultrasonography and resected liver pathology

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Lim, J.H.; Kim, S.H.; Lee, W.J.; Choi, D.; Kim, S.H.; Lim, H.K.

2006-01-01

AIM: The aim of this study was to determine the sensitivity of ultrasonography for detecting hepatocellular carcinoma in patients who underwent surgical liver resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103 patients who underwent hepatic resection surgery were retrospectively reviewed. The patients had chronic liver disease with good liver function and a relatively normal liver echotexture. The presence of a mass or masses in the resected part of the liver segments on preoperative ultrasonography was regarded as possible hepatocellular carcinoma, and these results were compared with the surgically resected hepatic lobes or segments. Accuracy for detection was assessed on a lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis. RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244 hepatic segments of 103 patients. One hundred and one of 157 hepatocellular carcinomas were detected using ultrasonography in 97 patients resulting in a sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was missed in each patient, a patient sensitivity being 94%. Using ultrasonography, 87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of 57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127 segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of 244 segments), positive predictive value was 97% (99 of 102 segments), and negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients with chronic liver disease and good hepatic function, ultrasonography has a sensitivity of 94% in the identification of affected patients, but for individual lesions, the sensitivity is only 64%

Multilocular cystic renal cell carcinoma: imaging and clinical correlation

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Xu Yong; Zhang Sheng

2013-01-01

Multilocular cystic renal cell carcinoma (MCRCC) is a subtype of clear cell renal cell carcinoma and has mild clinical symptoms and a favorable prognosis. Accordingly, nephron-sparing surgery is recommended as a therapeutic strategy. If histologic subtype of MCRCC can be predicted preoperatively with an acceptable level of accuracy, it may be important in predicting prognosis and make clinical management. Most MCRCCs show characteristic cross-sectional imaging findings and permit accurate diagnosis before the treatment. Cross -sectional imaging of MCRCC reveals a well -defined multilocular cystic mass with irregularly enhanced thickened septa and without enhanced intracystic solid nodule. It is often classified as Bosniak classification Ⅲ , which is significantly different from that of other renal cystic masses. The clinical, pathologic, and radiologic features of MCRCC were discussed and illustrated in this article. The role of the imaging preoperative evaluation for MCRCC, and management implications were emphasized. (authors)

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

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Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Perceived Social Support and Assertiveness as a Predictor of Candidates Psychological Counselors' Psychological Well-Being

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Ates, Bünyamin

2016-01-01

In this research, to what extent the variables of perceived social support (family, friends and special people) and assertiveness predicted the psychological well-being levels of candidate psychological counselors. The research group of this study included totally randomly selected 308 candidate psychological counselors including 174 females…

Tissue Biomarkers in Predicting Response to Sunitinib Treatment of Metastatic Renal Cell Carcinoma.

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Trávníček, Ivan; Branžovský, Jindřich; Kalusová, Kristýna; Hes, Ondřej; Holubec, Luboš; Pele, Kevin Bauleth; Ürge, Tomáš; Hora, Milan

2015-10-01

To identify tissue biomarkers that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Our study included 39 patients with mCRCC treated with sunitinib. Patients were stratified into two groups based on their response to sunitinib treatment: non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies before the initiation treatment with those performed at between 3rd and 7th months of treatment, depending on the patient. Histological samples of tumor tissue and healthy renal parenchyma, acquired during surgery of the primary tumor, were examined with immunohistochemistry to detect tissue targets involved in the signaling pathways of tumor growth and neoangiogenesis. We selected mammalian target of rapamycine, p53, vascular endothelial growth factor, hypoxia-inducible factor 1 and 2 and carbonic anhydrase IX. We compared the average levels of biomarker expression in both, tumor tissue, as well as in healthy renal parenchyma. Results were evaluated using the Student's t-test. For responders, statistically significant differences in marker expression in tumor tissue versus healthy parenchyma were found for mTOR (4%/16.7%; p=0.01031), p53 (4%/12.7%; p=0.042019), VEGF (62.7%/45%; p=0.019836) and CAIX (45%/15.33%; p=0.001624). A further significant difference was found in the frequency of high expression (more than 60%) between tumor tissue and healthy parenchyma in VEGF (65%/35%; p=0.026487) and CAIX (42%/8%; p=0.003328). CAIX was expressed at high levels in the tumor tissue in both evaluated groups. A significantly higher expression of VEGF in CRCC in comparison to healthy parenchyma can predict a better response to sunitinib. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept.

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Muenster, Uwe; Mueck, Wolfgang; van der Mey, Dorina; Schlemmer, Karl-Heinz; Greschat-Schade, Susanne; Haerter, Michael; Pelzetter, Christian; Pruemper, Christian; Verlage, Joerg; Göller, Andreas H; Ohm, Andreas

2016-05-01

The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed as immediate release (IR) tablet containing crystalline API, or if solubilization technology is needed to allow for sufficient oral bioavailability. pH-dependent VDADs of 22 and 83 compounds were plotted vs. the relative oral bioavailability (AUC solid vs. AUC solution formulation, Frel) in humans and rats, respectively. Furthermore, in order to investigate to what extent Frel rat may predict issues with solubility limited absorption in human, Frel rat was plotted vs. Frel human. Additionally, the impact of bile salts and lecithin on in vitro dissolution of poorly soluble compounds was tested and data compared to Frel rat and human. Respective in vitro - in vivo and in vivo - in vivo correlations were generated and used to build developability criteria. As a result, based on pH-dependent VDAD, Frel rat and in vitro dissolution in simulated intestinal fluid the IR formulation strategy within Pharmaceutical Research and Development organizations can be already set at late stage of drug discovery. Copyright © 2016 Elsevier B.V. All rights reserved.

The Predictive Validity of Teacher Candidate Letters of Reference

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Mason, Richard W.; Schroeder, Mark P.

2014-01-01

Letters of reference are widely used as an essential part of the hiring process of newly licensed teachers. While the predictive validity of these letters of reference has been called into question it has never been empirically studied. The current study examined the predictive validity of the quality of letters of reference for forty-one student…

CT determinants of prognosis in pancreatic carcinoma

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Schreiber, A.E.; Honda, H.; Berbaum, K.; Franken, E.A.; Lu, C.H.

1988-01-01

Abdominal CT scans of 61 patients with pathologically proved pancreatic carcinoma were analyzed to determine the radiographic features that predict length of survival. Excluded from study were patients who underwent definitive surgical procedures (Whipple procedure or pancreatectomy) or who received radiation or chemotherapy. Scans were evaluated in 18 radiographic and clinicopathologic categories. Multifactorial regression analysis indicated that the factors that most accurately predict the length of patient survival are (1) size, (2) associated lymphadenopathy, (3) hepatic metastasis, (4) hepatoduodenal ligament involvement, and (5) involvement of the mesentery and/or peritoneum

Immunohistochemical Expression of Tissue Inhibitor of Metalloproteinase-1 (Timp-1 in Invasive Breast Carcinoma

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Suada Kuskunović

2009-05-01

Full Text Available Tissue inhibitor of metalloproteinase-1 (TIMP-1 is a natural inhibitor of matrix metalloproteinas-es (MMPs. Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immuno-histochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010. Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023. Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005. TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

Accuracy of doppler ultrasound in diagnosis of endometrial carcinoma

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Batool, S.; Raza, S.; Manzur, S.

2013-01-01

Objective: To determine the accuracy of Doppler ultrasound in the diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding while taking histopathological findings as the gold standard. Methods: The cross-sectional study was done at the Department of Radiology, Bahawal Victoria Hospital, Bahawalpur, from April 1 to September 30, 2009, and comprised 128 patients above 50 years of age having history of post-menopausal bleeding and who were referred to the department. Name, age and hospital registration number were recorded on a proforma. Doppler ultrasound was performed and endometrial thickness and uterine artery resistive index were recorded on transabdominal ultrasonography. Patients with endometrial thickness of more than 5mm and uterine artery resistive index of less than 0.7 were considered to be having endometrial carcinoma. Histopathology findings were also recorded using the hospital registration number of the patient. The findings of Doppler ultrasound scan were validated with the findings of histopathology. Results: Of the 128 patients, 48 (37.5%) were between the ages of 51 and 55 years; 46 (35.93%) were in the 56-60 age group; and 34 (26.57%) were over 65 years. On the basis of Doppler ultrasound findings, 106 (82.8%) patients were diagnosed as having endometrial carcinoma, while 22 (17.19%) were declared negative. Ultrasonography results were compared with histopathology findings. The percentages of true positive, true negative, false positive and false negative were calculated. There were 103 (80.47%) true positive; 12 (9.37%) false positive; 10 (7.81%) true negative; and 3 (2.35%) false negative. Specificity, sensitivity, positive predictive value and negative predictive value were found to be 97.16%, 76%, 89.56% and 76.92% respectively. Conclusion: The use of Doppler ultrasonography in non-invasive diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding was quite useful with good

Metachronous colorectal carcinoma

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Bülow, Steffen; Svendsen, L B; Mellemgaard, A

1990-01-01

During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome

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Erkal, Haldun S.; Serin, Meltem; Cakmak, Ahmet

2001-01-01

Purpose: The present study reviews the experience in treatment of 447 patients with nasopharyngeal carcinomas, analyzing patient, tumor and treatment characteristics determining outcome. Materials and methods: There were 322 males and 125 females, their ages ranging from 7 to 85 years (median, 45 years). Two-hundred and seventy-two patients had World Health Organization (WHO) type 3 carcinomas, 123 patients had T4 tumors and 320 patients had metastatic cervical lymph nodes. Three-hundred and eight patients were treated with radiation therapy alone and 139 patients with chemotherapy in combination with radiation therapy. Cumulative radiation dose to primary tumor ranged from 50 to 76 Gy (median, 70 Gy) and radiation dose to metastatic cervical lymph nodes ranged from 46 to 74 Gy (median, 66 Gy). Results: Follow-up ranged from 0.1 to 19.5 years (mean, 7.6 years). Local complete response was achieved in 357 patients. In multivariate analysis, T-classification, cumulative radiation dose to primary tumor and treatment with chemotherapy in combination with radiation therapy predicted local response. Nodal complete response was achieved in 272 patients. In multivariate analysis, N-classification and radiation dose to metastatic cervical lymph nodes predicted nodal response. Local failure was observed in 70 patients, nodal failure in 35 patients and systemic failure in 114 patients. Overall survival, disease-free survival and disease-specific survival were 33, 32 and 37%, respectively, at 10 years. In multivariate analysis, age, T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted overall survival whereas T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted both disease-free survival and disease-specific survival. Conclusions: Radiation therapy alone appears to be an adequate and viable treatment for patients with early

Fasudil inhibits proliferation and migration of Hep-2 laryngeal carcinoma cells

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Zhang X

2018-02-01

Full Text Available Xiaowen Zhang,1 Nan Wu2 1Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; 2The Core Laboratory for Public Health Science and Practice, The First Affiliated Hospital of China Medical University, Shenyang, China Background: Rho-kinase signal pathway is a new target for cancer therapy. Fasudil, a selective Rho-kinase inhibitor, is found to exert antitumor effects on several types of cancer, but whether fasudil has antitumor effects on laryngeal carcinoma is still unknown. The aim of this study was to determine the effects of fasudil on laryngeal carcinoma and explore the underlying molecular mechanisms in this process. Methods: After treatment with fasudil, changes in biological behaviors, including the growth, proliferation, clone formation, apoptosis, and migration of human laryngeal carcinoma cells (Hep-2 cells were observed. The influences on apoptotic protease activity factor-1 (APAF-1-mediated apoptosis pathway and the activities of matrix metalloproteinases (MMP-2 and MMP-9 were measured by Western blotting and gelatin zymography assay. Results: Half-maximal inhibitory concentration of fasudil to Hep-2 cells was ~3.40×103 µM (95% CI: 2.53–4.66×103 µM. Moreover, fasudil treatment significantly decreased the ability of growth, proliferation, clone formation, and migration of Hep-2 cells, while remarkably increased the apoptosis rate. Furthermore, the expressions of APAF-1, caspase-9, and caspase-3 significantly increased in fasudil treatment group. Meanwhile, fasudil led to a remarkable decrease in the expressions and activities of MMP-2 and MMP-9. Conclusion: Our findings first demonstrate that fasudil not only inhibits the proliferation of laryngeal carcinoma cells through activating APAF-1-mediated apoptosis pathway, but also prevents migration by inhibiting the activities of MMP-2 and MMP-9. Therefore, fasudil is an attractive antitumor drug candidate for the treatment of laryngeal carcinoma

Recent advances in targeted drug therapy for hepatocellular carcinoma

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FAN Yongqiang

2018-02-01

Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

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Jing Liu

Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib

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Joon-Il Choi

2014-06-01

Full Text Available Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.

Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

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Mangolini, Alessandra; Bonon, Anna; Volinia, Stefano; Lanza, Giovanni; Gambari, Roberto; Pinton, Paolo; Russo, Gian Rosario; del Senno, Laura; Dell’Atti, Lucio; Aguiari, Gianluca

2014-01-01

Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma. PMID:25426415

Metastatic breast cancer to the liver with hepatoid features and Hep Par 1 antibody positive mimicking hepatocellular carcinoma.

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Affleck, Authur; Lyman, William B; Jacobs, W Carl; Livasy, Chad A; Martinie, John B; Iannitti, David A; Vrochides, Dionisios

2018-05-09

The hepatocyte paraffin 1 antibody (Hep Par 1) has a high positive predictive value for differentiating hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma. 1 We report a case of metastatic breast cancer to the liver with hepatoid histology and strong positive staining for Hep Par 1 mimicking hepatocellular carcinoma. To our knowledge, primary breast carcinoma staining Hep Par 1 positive has not been reported in the setting of hepatic metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

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Lee SH

2015-04-01

Full Text Available Sangheun Lee,1,* Beom Kyung Kim,2–5,* Seung Up Kim,2–5 Jun Yong Park,2–5 Do Young Kim,2–5 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

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Behl Susanne

2008-03-01

Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

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Shi, Bibo; Grimm, Lars J; Mazurowski, Maciej A; Baker, Jay A; Marks, Jeffrey R; King, Lorraine M; Maley, Carlo C; Hwang, E Shelley; Lo, Joseph Y

2018-03-01

The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

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Kevin Ten Haaf

2017-04-01

Full Text Available Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years. Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer.Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST participants (1,925 lung cancer cases and 884 lung cancer deaths and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths. Six-year lung cancer incidence and mortality risk predictions were assessed for (1 calibration (graphically by comparing the agreement between the predicted and the observed risks, (2 discrimination (area under the receiver operating characteristic curve [AUC] between individuals with and without lung cancer (death, and (3 clinical usefulness (net benefit in decision curve analysis by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81. The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a

EVALUATION OF P16INK4A PROTEIN AS A BIOMARKER FOR CERVICAL INTRAEPITHELIAL NEOPLASIA AND SQUAMOUS CELL CARCINOMA OF THE UTERINE CERVIX

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Biljana Đorđević

2011-06-01

Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well known. Interaction of HPV proteins with cellular regulatory proteins leads to up regulation of p16INK4A. The aim of this study was to evaluate p16INK4A protein as a biomarker for CIN lesions and squamous cell carcinoma on biopsy specimens of patients who underwent biopsy of the uterine cervix due to abnormal cytological finding.The authors analyzed biopsies from 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix. Expression of p16INK4A in CIN and invasive squamous cell carcinoma was immunohistochemically analyzed by using monoclonal anti-p16INK4A antibody.A total of 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix (mean age 40.2±11.5 years, range 20-74 years were analyzed. CIN I lesions were found in 27 (54%, CIN II/CIN III lesions in 9 (18%, and invasive squamous cell carcinoma in 14 (28% patients. Differences in the expression of p16INK4A between CIN I, CIN II/CIN III and squamous cell carcinoma were statistically significant (p<0.0001. Expression of p16INK4A showed low sensitivity (7%, specificity (8%, positive predictive value (8%, and negative predictive value (7% for CIN I. Sensitivity, specificity, positive predictive value, and negative predictive value of p16INK4A were 78%, 61%, 30%, and 93% for CIN II/CIN III, and 100%, 75%, 61%, and 100% for squamous cell carcinoma, respectively.Results of this study suggest that p16INK4A protein may be a sensitive biomarker for CIN II/CIN III lesions and invasive squamous cell carcinoma of the uterine cervix.

Assessment of Candidal carriage in patients with Type II Diabetes Mellitus

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RS Lamichhane

2015-03-01

Full Text Available Background: It is generally acknowledged that patients with diabetes mellitus are more susceptible to fungal infections, particularly with Candida albicans. Oral infection by Candida can result in a number of clinical lesions, including median rhomboid glossitis (central papillary atrophy, denture stomatitis, squamous cell carcinoma, Radiation therapy, immunocompromised status, etc. Different studies have shown that patients with diabetes mellitus have increased frequency of oral candidal carriage and increased risk of candidiasis, which is related to poor metabolic control, neutrophil dysfunction, reduced salivary flow, high glucose concentration in blood and saliva and in medications.Materials and Methods: Subjects of both the groups were given 10 ml of sterile normal saline and asked to rinse the mouth for one minute. The subjects were then asked to return the oral rinse in a sterile clean, broad-mouthed container which was capped, labelled and taken to the laboratory. The samples were then inoculated onto the culture medium (Sabouraud’s dextrose agar with Chloramphenicol with minimal delay (within 6-8 hours of collection of oral rinse. Candidal colonies were counted and compared with non-diabetics.Results: Statistically significant increase in colony forming units (p=0.0324 were obtainedin patients with diabetes mellitus.Conclusion: The results indicate significant increase in colonization and carriage of candida in the oral cavity among diabetics when compared with non-diabetics. However, further research using larger samples is required which may lend credibility to the suggestion of increased candidal CFUs in diabetics serving as a surrogate marker of serum glucose levels.Journal of Pathology of Nepal (2015 Vol. 5, 733-738

Radiotherapy of tonsillar and base of the tongue carcinoma. Prediction of local control

NARCIS (Netherlands)

Mak-Kregar, S.; Baris, G.; Lebesque, J. V.; Balm, A. J.; Hart, A. A.; Hilgers, F. J.

1993-01-01

119 patients with squamous cell carcinoma of the tonsillar region (68) and the base of the tongue (51), who received external radiotherapy with curative intent between 1966 and 1984, are analysed with respect to overall treatment results, local tumour control and prognostic factors. Radiation doses

The value of the combination of hemoglobin, albumin, lymphocyte and platelet in predicting platinum-based chemoradiotherapy response in male patients with esophageal squamous cell carcinoma.

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Cong, Lihong; Hu, Likuan

2017-05-01

The predictive value of HALP in esophageal cancer is currently unclear. We aimed to evaluate the value of HALP in predicting platinum-based definitive chemoradiotherapy response in male patients with esophageal squamous cell carcinoma. Data from all newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) were collected from January 1, 2010 to December 31, 2014 in Qilu Hospital. The treatment protocol was definitive chemoradiotherapy consisting of docetaxel plus cisplatin or carboplatin. The response assessment of the definitive chemoradiotherapy was based on computed tomography (CT) and barium meal test results. A total of 39 patients were included in the present study. The median value of HALP was 48.34. The chemoradiotherapy response rate of patients in the low HALP value group was 35%, compared with 78.95% of patients in the high HALP group (P=0.010). Additionally, the median progression-free survival in the 2 patient groups was significantly different (10.7 vs. 24.7m, P=0.041). In the multivariate analysis, patients with HALP higher than 48.34 had longer progression-free survival than patients with HALP of 48.34 or less (HR 2.745; 95% CI, 1.176-6.408; P=0.020). However, there was no significant difference for overall survival between the high HALP group and low HALP group. Our data suggested that pretreatment HALP could predict the platinum-based chemoradiotherapy response of tumors and progression free survival in male patients with ESCC. Therefore, HALP could be used in routine clinical practice to guide the therapeutic strategies for individual treatment in patients with ESCC. Copyright © 2017 Elsevier B.V. All rights reserved.

Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

DEFF Research Database (Denmark)

Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

2009-01-01

of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

The imunocytochemical advances in prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma

International Nuclear Information System (INIS)

Zelyins'ka, G.V.

2015-01-01

The topical issues is the problem of prognosis of metastasis radioiodine resistant metastasis. We offered the methods of prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma with the help of immunocytochemical detection of the cytokeratin 17 and thyroid peroxidase. With the purpose of prognosis of metastasis radioiodine resistibility the cytokeratin 17 is taped in punctates of primary papillary carcinomas. This approach allows predict response of metastases on radioiodine therapy to choose proper therapeutic approach

Diffusion-weighted MRI - a new parameter for advanced rectal carcinoma?

International Nuclear Information System (INIS)

Hein, P.A.; Lukas, P.; DeVries, A.F.; Pfeiffer, K.-P.

2003-01-01

Purpose: To evaluate the predictive value of apparent diffusion coefficient (ADC) on therapy outcome of combined chemoradiation in patients with primary carcinoma of the rectum. Materials and Method: Prior to standardized, combined, neoadjuvant chemoradiation, 16 patients with primary carcinoma of the rectum (cT3) were examined with magnetic resonance imaging (MRI). Diffusion weighted spin echo echo-planar images (SE-EPI) and contrast-enhanced T 1 -weighted spin echo (SE) images at 1.5 Tesla were obtained. The mean ADC of the tumor region was calculated and correlated with the therapy outcome substantiated by postsurgical histopathologic staging. Results: Tumor downstaging (pT0-2) occurred in 9 patients (therapy responders) and no down-staging (pT3) in 7 patients (therapy non-responders). The mean ADC measured 0.476±0.114 x 10 -3 mm 2 /s in the responder group and 0.703±0.085 x 10 -3 mm 2 /s in the non-responder group. Comparison of the mean ADC between the groups reached statistical significance (p=0.001). Conclusion: The mean ADC might be a new quantitative parameter to predict therapy outcome of combined preoperative chemoradiation in patients with primary carcinoma of the rectum. (orig.) [de

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.

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Na, Gun Hyung; Kim, Dong Goo; Han, Jae Hyun; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-06-07

To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria.

HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients.

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Wang, Jiajun; Liu, Li; Qu, Yang; Xi, Wei; Xia, Yu; Bai, Qi; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

2018-01-01

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort. In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.

ALMOST ALL OF KEPLER'S MULTIPLE-PLANET CANDIDATES ARE PLANETS

International Nuclear Information System (INIS)

Lissauer, Jack J.; Rowe, Jason F.; Bryson, Stephen T.; Howell, Steve B.; Jenkins, Jon M.; Kinemuchi, Karen; Koch, David G.; Marcy, Geoffrey W.; Adams, Elisabeth; Fressin, Francois; Geary, John; Holman, Matthew J.; Ragozzine, Darin; Buchhave, Lars A.; Ciardi, David R.; Cochran, William D.; Fabrycky, Daniel C.; Ford, Eric B.; Morehead, Robert C.; Gilliland, Ronald L.

2012-01-01

We present a statistical analysis that demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) indeed represent true, physically associated transiting planets. Binary stars provide the primary source of false positives among Kepler planet candidates, implying that false positives should be nearly randomly distributed among Kepler targets. In contrast, true transiting planets would appear clustered around a smaller number of Kepler targets if detectable planets tend to come in systems and/or if the orbital planes of planets encircling the same star are correlated. There are more than one hundred times as many Kepler planet candidates in multi-candidate systems as would be predicted from a random distribution of candidates, implying that the vast majority are true planets. Most of these multis are multiple-planet systems orbiting the Kepler target star, but there are likely cases where (1) the planetary system orbits a fainter star, and the planets are thus significantly larger than has been estimated, or (2) the planets orbit different stars within a binary/multiple star system. We use the low overall false-positive rate among Kepler multis, together with analysis of Kepler spacecraft and ground-based data, to validate the closely packed Kepler-33 planetary system, which orbits a star that has evolved somewhat off of the main sequence. Kepler-33 hosts five transiting planets, with periods ranging from 5.67 to 41 days.

Alternative dark matter candidates. Axions

International Nuclear Information System (INIS)

Ringwald, Andreas

2017-01-01

The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10 9 GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

DEFF Research Database (Denmark)

Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira Schreiner

2016-01-01

BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a co...

Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

International Nuclear Information System (INIS)

Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung

2011-01-01

Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase.

Science.gov (United States)

Honjo, Kie; Hiraki, Tsubasa; Higashi, Michiyo; Noguchi, Hirotsugu; Nomoto, Mitsuharu; Yoshimura, Takuya; Batra, Surinder K; Yonezawa, Suguru; Semba, Ichiro; Nakamura, Norifumi; Tanimoto, Akihide; Yamada, Sohsuke

2018-02-01

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

Science.gov (United States)

Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

hepatocellular carcinoma cells, which might predict hematogenous spreading metastasis in patients with hepatocellular carcinoma and may be a poor prognostic factor for hepatocellular carcinoma patients.

Oral Rigosertib for Squamous Cell Carcinoma

Science.gov (United States)

2017-06-22

Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in Taiwan - a cohort study.

Science.gov (United States)

Lee, Ya-Ling; Li, Wan-Chun; Tsai, Tung-Hu; Chiang, Hsin-Yu; Ting, Chin-Tsung

2016-04-19

Curative surgical resection (CSR) remains the most effective therapeutic intervention for patients with hepatocellular carcinoma (HCC); however, frequent post-surgical recurrence leads to high cancer related mortality. This study aimed to clarify the role of body mass index (BMI) and serum cholesterol level in predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC patients including 213 BMIhigh and 271 BMIlow patients were included. Overall survival (OS) and recurrence-free survival (RFS) rates were examined in patients with differential BMI and serum cholesterol level. The analysis showed that significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in groups with differential serum cholesterol levels among BMIlow and BMIhigh patients indicated that the BMIlow/Chollow patients exhibited the significant lower cumulative OS and RFS rates in comparison with the remaining subjects (P-value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the coexistence of low BMI and low serum cholesterol level could serve as prognostic factors to predict post-operative outcomes in HCC patients undergoing surgical hepatectomy.

ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Directory of Open Access Journals (Sweden)

Miao Yun

Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

Prioritization of candidate disease genes by topological similarity between disease and protein diffusion profiles.

Science.gov (United States)

Zhu, Jie; Qin, Yufang; Liu, Taigang; Wang, Jun; Zheng, Xiaoqi

2013-01-01

Identification of gene-phenotype relationships is a fundamental challenge in human health clinic. Based on the observation that genes causing the same or similar phenotypes tend to correlate with each other in the protein-protein interaction network, a lot of network-based approaches were proposed based on different underlying models. A recent comparative study showed that diffusion-based methods achieve the state-of-the-art predictive performance. In this paper, a new diffusion-based method was proposed to prioritize candidate disease genes. Diffusion profile of a disease was defined as the stationary distribution of candidate genes given a random walk with restart where similarities between phenotypes are incorporated. Then, candidate disease genes are prioritized by comparing their diffusion profiles with that of the disease. Finally, the effectiveness of our method was demonstrated through the leave-one-out cross-validation against control genes from artificial linkage intervals and randomly chosen genes. Comparative study showed that our method achieves improved performance compared to some classical diffusion-based methods. To further illustrate our method, we used our algorithm to predict new causing genes of 16 multifactorial diseases including Prostate cancer and Alzheimer's disease, and the top predictions were in good consistent with literature reports. Our study indicates that integration of multiple information sources, especially the phenotype similarity profile data, and introduction of global similarity measure between disease and gene diffusion profiles are helpful for prioritizing candidate disease genes. Programs and data are available upon request.

In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases

NARCIS (Netherlands)

Emanuels, AG; Koudstaal, J; Burger, MPM; Hollema, H

To offer more tailored treatment to individual patients with squamous cell carcinoma of the vulval more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in

Serum clusterin as a marker for diagnosing hepatocellular carcinoma

African Journals Online (AJOL)

Ragaa A. Ramadan

2014-06-20

Jun 20, 2014 ... tic sensitivity (95.5%) and negative predictive value (95.7%) over the single use of AFP. Conclusions: Although ... noma,12 urothelial bladder carcinoma,13 and prostate adeno- ... on top of chronic HCV infection-related cirrhosis (HCC group). ... examination and the Child-Pugh scoring system was used for.

Value Of Three Dimensional Power Doppler Ultrasound In Prediction Of Endometrial Carcinoma In Patients With Postmenopausal Bleeding

International Nuclear Information System (INIS)

Abou-Gabal, A.; Akl, Sh.A.; Hussain, Sh.H.; Allam, H.A.

2013-01-01

Objective: to determine whether endometrial volume or power Doppler indices as measured by 3D ultrasound imaging can discriminate between benign and malignant endometrium in women with postmenopausal bleeding and endometrial thickness > 5 mm. Study design: Eighty-four patients with postmenopausal bleeding and endometrial thickness > 5 mm underwent 3D power Doppler ultrasound examination of the corpus uteri. The endometrial volume was calculated, along with the vascularisation index (VI), flow index and vascularisation flow index (VFI) in the endometrium. The gold standard was the histological diagnosis of the endometrium. Results: There were 56 benign and 28 malignant endometrial. Endometrial thickness and volume were significantly larger in malignant than in benign endometrial, and flow indices in the endometrium were Significantly higher. The area under the ROC curve (AUC) of endometrial thickness was 0.83, that of endometrial volume 0.73, and that of the best power Doppler variable FI 0.93. The best logistic regression model for predicting malignancy contained the variables endometrial thickness and FI. Its AUC was 0.93. Conclusion: the diagnostic performance of endometrial volume measured by 3d imaging with regard to discriminating between benign and malignant endometrium was not superior to that of endometrial thickness measured by 2D ultrasound examination, but 3D power Doppler flow indices are good diagnostic tool in predicting endometrial carcinoma

Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia.

Science.gov (United States)

Michailidou, Evangelia; Tzimagiorgis, Georgios; Chatzopoulou, Fani; Vahtsevanos, Konstantinos; Antoniadis, Konstantinos; Kouidou, Sofia; Markopoulos, Anastasios; Antoniades, Dimitrios

2016-08-01

In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma. 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT-PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients. The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half. SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder. Copyright © 2016. Published by Elsevier Ltd.

Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

DEFF Research Database (Denmark)

Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

2016-01-01

Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

Directory of Open Access Journals (Sweden)

LU Fengmin

2017-07-01

Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

Science.gov (United States)

Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

2017-11-01

The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

Comparative genomics and prediction of conditionally dispensable sequences in legume-infecting Fusarium oxysporum formae speciales facilitates identification of candidate effectors.

Science.gov (United States)

Williams, Angela H; Sharma, Mamta; Thatcher, Louise F; Azam, Sarwar; Hane, James K; Sperschneider, Jana; Kidd, Brendan N; Anderson, Jonathan P; Ghosh, Raju; Garg, Gagan; Lichtenzveig, Judith; Kistler, H Corby; Shea, Terrance; Young, Sarah; Buck, Sally-Anne G; Kamphuis, Lars G; Saxena, Rachit; Pande, Suresh; Ma, Li-Jun; Varshney, Rajeev K; Singh, Karam B

2016-03-05

Soil-borne fungi of the Fusarium oxysporum species complex cause devastating wilt disease on many crops including legumes that supply human dietary protein needs across many parts of the globe. We present and compare draft genome assemblies for three legume-infecting formae speciales (ff. spp.): F. oxysporum f. sp. ciceris (Foc-38-1) and f. sp. pisi (Fop-37622), significant pathogens of chickpea and pea respectively, the world's second and third most important grain legumes, and lastly f. sp. medicaginis (Fom-5190a) for which we developed a model legume pathosystem utilising Medicago truncatula. Focusing on the identification of pathogenicity gene content, we leveraged the reference genomes of Fusarium pathogens F. oxysporum f. sp. lycopersici (tomato-infecting) and F. solani (pea-infecting) and their well-characterised core and dispensable chromosomes to predict genomic organisation in the newly sequenced legume-infecting isolates. Dispensable chromosomes are not essential for growth and in Fusarium species are known to be enriched in host-specificity and pathogenicity-associated genes. Comparative genomics of the publicly available Fusarium species revealed differential patterns of sequence conservation across F. oxysporum formae speciales, with legume-pathogenic formae speciales not exhibiting greater sequence conservation between them relative to non-legume-infecting formae speciales, possibly indicating the lack of a common ancestral source for legume pathogenicity. Combining predicted dispensable gene content with in planta expression in the model legume-infecting isolate, we identified small conserved regions and candidate effectors, four of which shared greatest similarity to proteins from another legume-infecting ff. spp. We demonstrate that distinction of core and potential dispensable genomic regions of novel F. oxysporum genomes is an effective tool to facilitate effector discovery and the identification of gene content possibly linked to host

Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites.

Science.gov (United States)

Morand, G B; Madana, J; Da Silva, S D; Hier, M P; Mlynarek, A M; Black, M J

2016-04-01

Merkel cell carcinoma is a rare, aggressive neurocutaneous malignancy. This study investigated whether patients with Merkel cell carcinoma in the head and neck had poorer outcomes than patients with Merkel cell carcinoma located elsewhere. A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montréal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method. Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis. Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy.

Gravitino, dark matter candidate and implications for big bang nucleosynthesis

International Nuclear Information System (INIS)

Bailly, S.

2008-11-01

The Standard Model of particle physics was developed in the seventies. Despite many experimental successes, it presents many problems that can only be solved with models beyond the Standard Model. Supersymmetry is an interesting candidate, postulating a new symmetry between fermions and bosons. This model can also have interesting applications in cosmology. It offers potentially good candidates for dark matter, what represents 25% of the energy density of the Universe, and its nature is unknown. Another cosmological problem is the lithium problems in Big Bang Nucleosynthesis describing the production of light elements in the first seconds of the Universe. The lithium abundance predicted by the theory is inconsistent with observations. I study a scenario in which a supersymmetric particle, the gravitino, is the candidate for dark matter and the production of this particle through the decay of other supersymmetric particles may solve the lithium problems. (author)

Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma.

Science.gov (United States)

Vasselli, J R; Yang, J C; Linehan, W M; White, D E; Rosenberg, S A; Walther, M M

2001-07-01

Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life. A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status

Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

International Nuclear Information System (INIS)

Chen, Ping-Ho; Tu, Hung-Pin; Ko, Ying-Chin; Shieh, Tien-Yu; Ho, Pei-Shan; Tsai, Chi-Cheng; Yang, Yi-Hsin; Lin, Ying-Chu; Ko, Min-Shan; Tsai, Pei-Chien; Chiang, Shang-Lun

2007-01-01

In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan. Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival. The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate. Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy

Endometrial carcinoma: merit of magnetic resonance in pre-surgical staging

International Nuclear Information System (INIS)

Fernandez, E.; Barrera, M. C.; Gervas, C.; Salvador, E.; Rivero, B.; Sentis, M.

2003-01-01

To evaluate MR capacity in assessing deep myometrial and cervical infiltrations in cases of endometrial carcinoma. A series of 30 consecutively diagnosed endometrial cancer patients was pre-surgically evaluated by means of magnetic resonance (MR). TSE-T2 sequences with fat saturation and dynamic FFe sequence were used after gadolinium administration. A correlation with post-surgical histological stating was made. There were then determined sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the deep myometrial infiltration and cervical invasion. Cases of overestimation and underestimation were analyzed. Values obtained for myometrium and cervix were, respectively, S of 67% and 63%, SP of 89% and 91%, PPV of 80% and 71% and NPV of 80% and 87%. Two cases each were over valued for myometrial infiltration and cervix: four cases and 3 cases, respectively, were undervalues. MR stating in cases of endometrial carcinoma is a highly reliable diagnostic technique, but it does present certain limitations. (Author) 19 refs

[Pulmonary sarcomatoid carcinoma].

Science.gov (United States)

Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

2016-01-01

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics. Copyright © 2016. Published by Elsevier Masson SAS.

Poorly Differentiated Thyroid Carcinoma.

Science.gov (United States)

Setia, Namrata; Barletta, Justine A

2014-12-01

Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

Alternative dark matter candidates. Axions

Energy Technology Data Exchange (ETDEWEB)

Ringwald, Andreas

2017-01-15

The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10{sup 9} GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

DEFF Research Database (Denmark)

Davis, Ian D; Xie, Wanling; Pezaro, Carmel

2017-01-01

BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... of therapy and change in IMDC prognostic category. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined......% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03). CONCLUSIONS: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy...

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

Science.gov (United States)

Eshghi, Naghmehossadat; Lundeen, Tamara F; MacKinnon, Lea; Avery, Ryan; Kuo, Phillip H

2018-05-01

An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

Alterations of the Human Skin N- and O-Glycome in Basal Cell Carcinoma and Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Uwe Möginger

2018-03-01

Full Text Available The glycome of one of the largest and most exposed human organs, the skin, as well as glycan changes associated with non-melanoma skin cancers have not been studied in detail to date. Skin cancers such as basal cell carcinoma (BCC and squamous cell carcinoma (SCC are among the most frequent types of cancers with rising incidence rates in the aging population. We investigated the healthy human skin N- and O-glycome and its changes associated with BCC and SCC. Matched patient samples were obtained from frozen biopsy and formalin-fixed paraffin-embedded tissue samples for glycomics analyses using two complementary glycomics approaches: porous graphitized carbon nano-liquid chromatography electro spray ionization tandem mass spectrometry and capillary gel electrophoresis with laser induced fluorescence detection. The human skin N-glycome is dominated by complex type N-glycans that exhibit almost similar levels of α2-3 and α2-6 sialylation. Fucose is attached exclusively to the N-glycan core. Core 1 and core 2 type O-glycans carried up to three sialic acid residues. An increase of oligomannose type N-glycans and core 2 type O-glycans was observed in BCC and SCC, while α2-3 sialylation levels were decreased in SCC but not in BCC. Furthermore, glycopeptide analyses provided insights into the glycoprotein candidates possibly associated with the observed N-glycan changes, with glycoproteins associated with binding events being the most frequently identified class.

Stating of cervical carcinoma using magnetic resonance imaging

International Nuclear Information System (INIS)

Oleaga, L.; Vela, M. C.; Grande, J.; Cura del, J. L.; Grande, D.

1999-01-01

The infiltration of the parametrium represents one of the most important factors that determine the prediction and treatment of cervical carcinoma. Our objective is to evaluate the utility of magnetic resonance imaging (MRI) in the staging of cervical carcinomas, to establish the reliability of this technique and to carry out a comparative study of the sequences used to demonstrate the parametrial invasion. We have carried out a retrospective study on 44 patients diagnosed with cervix neoplasia, using clinical exploration and performing a biopsy. the MRI studies have been carried out using a 1 Tesla magnet and the sequences used have been SE T1, Se proton density (PD) and T2 and dynamic GRE after administering gadolinium intravenously in the axial and sagital projections. The stages determined by MRI have been compared to the anatomo-pathological stages of the surgical specimens in cases where surgery was carried out and with the clinical stage in cases where no radical surgery was carried out. A diagnosis value of MRI has been determined to demonstrate the parametrial invasion, comparing the SE T2 sequence with the dynamic GE sequence with gadolinium. We calculate the volume of the tumour in the MRI studies to evaluate the difference of the volume between patients with tumoral stages that are clinically surgical and not surgical. MRI determines the invasion of the parametrium with a sensitivity of 88.8%, a specificity of 80% a positive value of 76.1%, a negative predictive value of 90.9% and a reliability of 83.7%. For the SE T2 sequences the sensitivity was 86.6%, the specifity 80%, the posistive predictive value 81.25%, the negative predictive value 85.7% and the reliability 83.3%. For the dynamic GE sequence with intravenous gadolinium the sensitivity was 86.6%, the specificity 86.6%, the positive predictive value 86.6%, the negative predictive value 86.6% and the reliability 86.6%. The use of the dynamic GE sequence after the intravenous administration of

Are all pelvic (nonuterine) serous carcinomas of tubal origin?

Science.gov (United States)

Przybycin, Christopher G; Kurman, Robert J; Ronnett, Brigitte M; Shih, Ie-Ming; Vang, Russell

2010-10-01

conventional criteria, 70%, 17%, and 13% of high-grade serous carcinomas qualified for classification as ovarian, peritoneal, and tubal in origin, respectively; however, using STIC as a supplemental criterion to define a case as tubal in origin, the distribution was modified to 28%, 8%, and 64%, respectively. Features of tumors in the ovary that generally suggest metastatic disease (bilaterality, small size, nodular growth pattern, and surface plaques) were identified with similar frequency in cases with and without STIC and were, therefore, not predictive of tubal origin. The findings, showing that nearly 60% of high-grade pelvic (nonuterine) serous carcinomas are associated with STICs, are consistent with the proposal that the fallopian tube is the source of a majority of these tumors. If these findings can be validated by molecular studies that definitively establish that STIC is the earliest form of carcinoma rather than intraepithelial spread from adjacent invasive serous carcinoma of ovarian or peritoneal origin, they will have important clinical implications for screening, treatment, and prevention.

Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

Institute of Scientific and Technical Information of China (English)

Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp

2011-01-01

Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma

OpenAIRE

Ricketts, Christopher J.; Morris, Mark R.; Gentle, Dean; Brown, Michael; Wake, Naomi; Woodward, Emma R.; Clarke, Noel; Latif, Farida; Maher, Eamonn R.

2012-01-01

In order to identify novel candidate tumor suppressor genes (TSGs) implicated in renal cell carcinoma (RCC), we performed genome-wide methylation profiling of RCC using the HumanMethylation27 BeadChips to assess methylation at >14,000 genes. Two hundred and twenty hypermethylated probes representing 205 loci/genes were identified in genomic CpG islands. A subset of TSGs investigated in detail exhibited frequent tumor methylation, promoter methylation associated transcriptional silencing an...

Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

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Kowalewska Magdalena

2012-06-01

Full Text Available Abstract Background Regional lymph node (LN status is a well-known prognostic factor for vulvar carcinoma (VC patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression. Methods Sentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+] and four histologically negative [LN(−] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(−, seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR in 71 LN samples. Results All of the seven genes in question were significantly increased in LN(+ compared to LN(− samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients. Conclusions Our findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients.

A systems biology-based classifier for hepatocellular carcinoma diagnosis.

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Yanqiong Zhang

Full Text Available AIM: The diagnosis of hepatocellular carcinoma (HCC in the early stage is crucial to the application of curative treatments which are the only hope for increasing the life expectancy of patients. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with HCC progression. However, those marker sets shared few genes in common and were poorly validated using independent data. Therefore, we developed a systems biology based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC diagnosis. METHODS AND RESULTS: In the Oncomine platform, genes differentially expressed in HCC tissues relative to their corresponding normal tissues were filtered by a corrected Q value cut-off and Concept filters. The identified genes that are common to different microarray datasets were chosen as the candidate markers. Then, their networks were analyzed by GeneGO Meta-Core software and the hub genes were chosen. After that, an HCC diagnostic classifier was constructed by Partial Least Squares modeling based on the microarray gene expression data of the hub genes. Validations of diagnostic performance showed that this classifier had high predictive accuracy (85.88∼92.71% and area under ROC curve (approximating 1.0, and that the network topological features integrated into this classifier contribute greatly to improving the predictive performance. Furthermore, it has been demonstrated that this modeling strategy is not only applicable to HCC, but also to other cancers. CONCLUSION: Our analysis suggests that the systems biology-based classifier that combines the differential gene expression and topological features of human protein interaction network may enhance the diagnostic performance of HCC classifier.

Liver stiffness value-based risk estimation of late recurrence after curative resection of hepatocellular carcinoma: development and validation of a predictive model.

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Kyu Sik Jung

Full Text Available Preoperative liver stiffness (LS measurement using transient elastography (TE is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC. We developed and validated a novel LS value-based predictive model for late recurrence of HCC.Patients who were due to undergo curative resection of HCC between August 2006 and January 2010 were prospectively enrolled and TE was performed prior to operations by study protocol. The predictive model of late recurrence was constructed based on a multiple logistic regression model. Discrimination and calibration were used to validate the model.Among a total of 139 patients who were finally analyzed, late recurrence occurred in 44 patients, with a median follow-up of 24.5 months (range, 12.4-68.1. We developed a predictive model for late recurrence of HCC using LS value, activity grade II-III, presence of multiple tumors, and indocyanine green retention rate at 15 min (ICG R15, which showed fairly good discrimination capability with an area under the receiver operating characteristic curve (AUROC of 0.724 (95% confidence intervals [CIs], 0.632-0.816. In the validation, using a bootstrap method to assess discrimination, the AUROC remained largely unchanged between iterations, with an average AUROC of 0.722 (95% CIs, 0.718-0.724. When we plotted a calibration chart for predicted and observed risk of late recurrence, the predicted risk of late recurrence correlated well with observed risk, with a correlation coefficient of 0.873 (P<0.001.A simple LS value-based predictive model could estimate the risk of late recurrence in patients who underwent curative resection of HCC.

Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

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Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

2017-10-03

Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

NARCIS (Netherlands)

K. ten Haaf (Kevin); J. Jeon (Jihyoun); M.C. Tammemagi (Martin); S.S. Han (Summer); C.Y. Kong (Chung Yin); S.K. Plevritis (Sylvia); E. Feuer (Eric); H.J. de Koning (Harry); E.W. Steyerberg (Ewout W.); R. Meza (Rafael)

2017-01-01

textabstractBackground: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most

Proton radiotherapy of skin carcinomas

International Nuclear Information System (INIS)

Umebayashi, Y.; Uyeno, K.; Otsuka, F.

1994-01-01

At the Proton Medical Research Centre, University of Tsukuba, a pilot study of proton-beam radiotherapy was performed in 12 patients with the following types of carcinoma: Bowen's disease (4), oral verrucous carcinoma (5), and squamous cell carcinoma (3). They received total doses of 51-99.2 Gy in fractions of 2-12.5 Gy. All tumours responded well to the treatment. All four lesions of Bowen's disease, three of the five oral verrucous carcinomas, and the three squamous cell carcinomas completely regressed following irradiation. Two squamous cell carcinomas recurred during the follow-up period. One recurrent squamous cell carcinoma was successfully treated by a salvage surgical operation, and in the other case the patient refused further therapy. In two verrucous carcinomas there was 90% regression of tumour volume. No severe radiation-related complication occurred. (Author)

Sentinel lymph node biopsy in patients with a needle core biopsy diagnosis of ductal carcinoma in situ: is it justified?

LENUS (Irish Health Repository)

Doyle, B

2012-02-01

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly with the introduction of population-based mammographic screening. DCIS is usually diagnosed non-operatively. Although sentinel lymph node biopsy (SNB) has become the standard of care for patients with invasive breast carcinoma, its use in patients with DCIS is controversial. AIM: To examine the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. METHODS: A retrospective analysis was performed of 145 patients with an NCB diagnosis of DCIS who had SNB performed at the time of primary surgery. The study focused on rates of SNB positivity and underestimation of invasive carcinoma by NCB, and sought to identify factors that might predict the presence of invasive carcinoma in the excision specimen. RESULTS: 7\\/145 patients (4.8%) had a positive sentinel lymph node, four macrometastases and three micrometastases. 6\\/7 patients had invasive carcinoma in the final excision specimen. 55\\/145 patients (37.9%) with an NCB diagnosis of DCIS had invasive carcinoma in the excision specimen. The median invasive tumour size was 6 mm. A radiological mass and areas of invasion <1 mm, amounting to "at least microinvasion" on NCB were predictive of invasive carcinoma in the excision specimen. CONCLUSIONS: SNB positivity in pure DCIS is rare. In view of the high rate of underestimation of invasive carcinoma in patients with an NCB diagnosis of DCIS in this study, SNB appears justified in this group of patients.

Validade da citologia e da biópsia orientada pela colposcopia no diagnóstico do carcinoma cervical pré-clínico Validity of cytology and colposcopy - guided biopsy for the diagnosis of preclinical cervical carcinoma

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Aldo Franklin Ferreira Reis

1999-05-01

,5 para displasia acentuada e carcinoma in situ, zero para displasia leve e moderada, zero para negativo e inflamatório e 0,4 para o conjunto de resultados negativos para invasão.Purpose: to evaluate the efficacy of cytology and colposcopy-directed biopsy to distinguish preclinical invasive cervical carcinoma from intraepithelial lesions. Patients and Methods: 441 patients submitted to conization, hysterectomy and Wertheim-Meigs operation from 1978 to 1995 in the University Hospital "Clementino Fraga Filho", Federal University of Rio de Janeiro, Cervical Pathology Outpatient Clinic. We estimated sensitivity, specificity, predictive values, likelihood ratio and confidence intervals of each study, which were divided into four classes: 1 normal and inflammatory; 2 mild and moderate dysplasias; 3 severe dysplasia and carcinoma in situ; 4 microcarcinoma and invasive carcinoma. Biopsies were analyzed as a whole and separated in accordance with the type of the colposcopic result (satisfactory and unsatisfactory. Results: cytology has shown sensitivity of 50%, specificity of 89%, positive predictive value of 63% and negative predictive value of 82%. The likelihood ratios were 4.4 for stromal invasion diagnosis, 0.7 for severe dysplasia and carcinoma in situ, 0.1 for mild and moderate dysplasia, 2.2 for normal and inflammatory report and 0.6 for the negative results for invasion as a whole. Satisfactory colposcopic guided biopsy white a visible lesion showed sensitivity of 59%, specificity of 100% positive predictive value of 100% and negative predictive value of 83%. Likelyohood ratios were: tending to infinity for invasion, 0.5 for severe dysplasia and carcinoma in situ, zero for mild and moderate dysplasia, zero for negative and inflammatory and 0.4 for all negative results for invasion.

Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma.

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Wang, Feng; Wang, Jun; Ju, Linlin; Chen, Lin; Cai, Weihua; Yang, Jialin

2018-01-01

Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p hepatocellular carcinoma.

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study

NARCIS (Netherlands)

Ansink, A. C.; Sie-Go, D. M.; van der Velden, J.; Sijmons, E. A.; de Barros Lopes, A.; Monaghan, J. M.; Kenter, G. G.; Murdoch, J. B.; ten Kate, F. J.; Heintz, A. P.

1999-01-01

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue

Citizen Candidates Under Uncertainty

OpenAIRE

Eguia, Jon X.

2005-01-01

In this paper we make two contributions to the growing literature on "citizen-candidate" models of representative democracy. First, we add uncertainty about the total vote count. We show that in a society with a large electorate, where the outcome of the election is uncertain and where winning candidates receive a large reward from holding office, there will be a two-candidate equilibrium and no equilibria with a single candidate. Second, we introduce a new concept of equilibrium, which we te...

Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

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Kathy Han

2007-01-01

Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

Predictive values of BI-RADS® magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS)

International Nuclear Information System (INIS)

Badan, Gustavo Machado; Piato, Sebastião; Roveda, Décio; Faria Castro Fleury, Eduardo de

2016-01-01

Purpose: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Materials and methods: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Results: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. Conclusion: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases.

Thymidylate Synthase, Thymidine Phosphorylase and Orotate Phosphoribosyl Transferase Levels as Predictive Factors of Chemotherapy in Oral Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Ogiuchi, Yosuke; Maruoka, Yasubumi; Ando, Tomohiro; Kobayashi, Makio; Ogiuchi, Hideki

2008-01-01

We conducted a clinicopathologic study on protein and mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) using biopsy tissue specimens before treatment. The mRNA levels have been measured in tumor cells microdissected from paraffin-embedded specimens (Danenberg Tumor Profile method: DTP method). We studied the mRNA and protein expression as effect predictive factors in chemotherapy. The subjects consisted of 20 cases of untreated oral squamous cell carcinoma who had undergone chemotherapy with TS-1 (16 males and 4 females, tongue in 8 cases, upper gingiva in 3 cases, lower gingiva in 3 cases, buccal mucosa in 5 cases and floor of the mouth in 1 case). TS gene expressions of the responders were lower than those for the nonresponders. Furthermore, regarding males who were less than 70 years of age, stage I and II, well differentiated type and tongue, TS mRNA expression of the responders were lower than that for the nonresponders. The mRNA expression of OPRT for the male responders was lower than that for the nonresponders. No remarkable difference was observed by immunohistochemistry. In this study, the measurement of the TS levels using the DTP method may potentially act as a predictive factor of antitumor effectiveness

Triple Test in Carcinoma Breast

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Sameer; Mukherjee, Arindam

2014-01-01

Introduction: The commonest clinical presentation in majority of breast pathology is a lump. A definite diagnosis of breast lump is very important for the surgeon to decide on the final course of treatment and also saves the patient from unnecessary physical, emotional and psychological trauma if there is a definite preoperative diagnosis of benign lesion. The present study was done to evaluate the effectiveness and relevance of “TRIPLE TEST”in diagnosis of carcinoma breast in rural labour class population. Materials and Methods: The present study was a prospective study conducted on patients over 35 years of age having palpable breast lumps presenting in the out patient department of general surgery, ESI Hospital Basaidarapur New Delhi, India. The duration of study was from May 2007 to June 2009 and a total of 100 cases were studied. Each patient was subjected to a detailed history, clinical breast examination ,diagnostic mammography and FNAC. In this study, the results of each modality was divided in three groups: benign, suspicious and malignant. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of each test was calculated individually and as combined. Result: Out of 100 patients enrolled in this study, 60 cases were benign and 40 cases were of malignant breast disease. The age of patients with carcinoma breast in the series varied from 35 years to 70 years. The highest incidence of malignancy noted was 30% in 41-50 years age group (4th decade) followed by 27.5% in 51-60 years age group (5th decade). The sensitivity of clinical examination was found to be 75%, specificity was 83.3%, positive predictive value (PPV) of 75% and diagnostic accuracy of 80%. The sensitivity, specificity, positive predictive value and diagnostic accuracy of mammography was calculated and was found to be 94.9% , 90% , 86% and 92% respectively. The sensitivity, specificity, positive predictive value and diagnostic accuracy of

Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

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Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

2014-01-01

Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

Are the uterine serous carcinomas underdiagnosed? Histomorphologic and immunohistochemical correlates and clinical follow up in high-grade endometrial carcinomas initially diagnosed as high-grade endometrioid carcinoma.

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Hu, Shaomin; Hinson, Jeff L; Matnani, Rahul; Cibull, Michael L; Karabakhtsian, Rouzan G

2018-02-01

Histologic subclassification of high-grade endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade endometrial carcinomas that were initially diagnosed as pure or mixed high-grade endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade endometrial carcinoma cases initially classified as pure high-grade endometrioid carcinoma (n=32), mixed high-grade endometrioid carcinoma/serous carcinoma (n=9) and mixed high-grade endometrioid carcinoma/clear cell carcinoma (n=2) were retrospectively stained with a panel of immunostains, including antibodies for p53, p16, estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade endometrial carcinoma cases initially diagnosed as high-grade endometrioid carcinoma were re-classified as serous carcinoma. All 17 cases showed negative staining for mammaglobin, while estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade endometrioid carcinoma cases. These results indicate that selected

Supermassive Black Hole Binary Candidates from the Pan-STARRS1 Medium Deep Survey

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Liu, Tingting; Gezari, Suvi

2018-01-01

Supermassive black hole binaries (SMBHBs) should be a common product of the hierarchal growth of galaxies and gravitational wave sources at nano-Hz frequencies. We have performed a systematic search in the Pan-STARRS1 Medium Deep Survey for periodically varying quasars, which are predicted manifestations of SMBHBs, and identified 26 candidates that are periodically varying on the timescale of ~300-1000 days over the 4-year baseline of MDS. We continue to monitor them with the Discovery Channel Telescope and the LCO network telescopes and thus are able to extend the baseline to 3-8 cycles and break false positive signals due to stochastic, normal quasar variability. From our imaging campaign, five candidates show persistent periodic variability and remain strong SMBHB candidates for follow-up observations. We calculate the cumulative number rate of SMBHBs and compare with previous work. We also compare the gravitational wave strain amplitudes of the candidates with the capability of pulsar timing arrays and discuss the future capabilities to detect periodic quasar and SMBHB candidates with the Large Synoptic Survey Telescope.

Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis.

Science.gov (United States)

Thompson, Henry J; Jiang, Weiqin; Zhu, Zongjian

2009-09-01

Evidence is strong that a reduction in risk for breast cancer is associated with moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor-associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy. (c) 2009 IUBMB

A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma

Science.gov (United States)

Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang

2015-01-01

Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236

Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma.

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Lee, Sang Hoon; Kim, Seung Up; Jang, Jeong Won; Bae, Si Hyun; Lee, Sanghun; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub

2015-01-01

Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA). This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence. This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238-7.842, Pmeasurement is a useful predictor of HCC de novo recurrence and overall survival after RFA.

The imbalance in expression of angiogenic and anti-angiogenic factors as candidate predictive biomarker in preeclampsia

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Pooneh Nikuei

2015-07-01

Full Text Available Preeclampsia is an important pregnancy disorder with serious maternal and fetal complications which its etiology has not been completely understood yet. Early diagnosis and management of disease could reduce its potential side effects. The vascular endothelial growth factor (VEGF family including VEGF-A is the most potent endothelial growth factor which induces angiogenesis and endothelial cell proliferation and has basic role in vasculogenesis. VEGF and its tyrosine kinase receptors (Flt1 and KDR are major factors for fetal and placental angiogenic development. Finding mechanisms involved in expression of angiogenic factors may lead to new prognostic and therapeutic points in management of preeclampsia. Recent researches, has shown capability of some anti-angiogenic factors as potential candidate to be used as early predictors for preeclampsia. Soluble fms-like tyrosin kinase-1 (sFlt1 is a truncated splice variant of the membrane-bound VEGF receptor Flt1, that is produced by the placenta and it can bind to angiogenic growth factors and neutraliz, their effects. It is also observed that the ratio of sFlt1 to placental growth factor is valuable as prognostic marker. In this review, VEGF family member’s role in angiogenesis is evaluated as biomarkers to be used for prediction of preeclampsia.

Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

LENUS (Irish Health Repository)

Hayes, B

2012-02-01

BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

Science.gov (United States)

Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

2013-07-01

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Ju-Yeon Cho

2016-12-01

Full Text Available Background/Aims Radiofrequency ablation (RFA is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC. However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. Methods In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. Results During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9% patients, with early massive recurrence in 27 patients (6.2%. The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. Conclusions Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.

Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

Science.gov (United States)

Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

2017-11-17

Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

Serum microRNAs in clear cell carcinoma of the ovary.

Science.gov (United States)

Chao, Angel; Lai, Chyong-Huey; Chen, Hua-Chien; Lin, Chiao-Yun; Tsai, Chia-Lung; Tang, Yun-Hsin; Huang, Huei-Jean; Lin, Chen-Tao; Chen, Min-Yu; Huang, Kuang-Gen; Chou, Hung-Hsueh; Chang, Ting-Chang; Chen, Shu-Jen; Wang, Tzu-Hao

2014-12-01

To identify candidate microRNAs (miRNAs) in the serum of patients with clear cell carcinomas in monitoring disease progression. The sera of patients with diagnosed ovarian clear cell carcinoma were collected from 2009 to 2012. Real-time quantitative polymerase chain reaction (PCR) analysis for 270 miRNAs was performed. To offset the potential extraction bias, an equal amount of Caenorhabditis elegans cel-miR-238 was added to each serum specimen before miRNA isolation. miRNA expression was analyzed using the ΔCt method, with cel-miR-238 as controls. Twenty-one patients with clear cell carcinoma were included. In the discovery phase on four pairs of pre- and postoperative sera, 18 differentially expressed miRNAs were selected from 270 miRNAs. In the validation phase on an independent set of 11 pairs of pre- and postoperative sera, 4 miRNAs (hsa-miR-130a, hsa-miR-138, hsa-miR-187, and hsa-miR-202) were confirmed to be higher in the preoperative sera. In the application phase, hsa-miR-130a remained consistent with the different time points in seven of the 10 patients during clinical follow-up periods. More importantly, in three patients, hsa-miR-130a levels were elevated in early disease recurrences before CA125 was found to be elevated. Hsa-miR-130a may be a useful serum biomarker for detecting recurrence of ovarian clear cell cancer, and warrants further studies. Copyright © 2014. Published by Elsevier B.V.

Predicting Treatment Response to Intra-arterial Therapies for Hepatocellular Carcinoma with the Use of Supervised Machine Learning-An Artificial Intelligence Concept.

Science.gov (United States)

Abajian, Aaron; Murali, Nikitha; Savic, Lynn Jeanette; Laage-Gaupp, Fabian Max; Nezami, Nariman; Duncan, James S; Schlachter, Todd; Lin, MingDe; Geschwind, Jean-François; Chapiro, Julius

2018-06-01

To use magnetic resonance (MR) imaging and clinical patient data to create an artificial intelligence (AI) framework for the prediction of therapeutic outcomes of transarterial chemoembolization by applying machine learning (ML) techniques. This study included 36 patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization. The cohort (age 62 ± 8.9 years; 31 men; 13 white; 24 Eastern Cooperative Oncology Group performance status 0, 10 status 1, 2 status 2; 31 Child-Pugh stage A, 4 stage B, 1 stage C; 1 Barcelona Clinic Liver Cancer stage 0, 12 stage A, 10 stage B, 13 stage C; tumor size 5.2 ± 3.0 cm; number of tumors 2.6 ± 1.1; and 30 conventional transarterial chemoembolization, 6 with drug-eluting embolic agents). MR imaging was obtained before and 1 month after transarterial chemoembolization. Image-based tumor response to transarterial chemoembolization was assessed with the use of the 3D quantitative European Association for the Study of the Liver (qEASL) criterion. Clinical information, baseline imaging, and therapeutic features were used to train logistic regression (LR) and random forest (RF) models to predict patients as treatment responders or nonresponders under the qEASL response criterion. The performance of each model was validated using leave-one-out cross-validation. Both LR and RF models predicted transarterial chemoembolization treatment response with an overall accuracy of 78% (sensitivity 62.5%, specificity 82.1%, positive predictive value 50.0%, negative predictive value 88.5%). The strongest predictors of treatment response included a clinical variable (presence of cirrhosis) and an imaging variable (relative tumor signal intensity >27.0). Transarterial chemoembolization outcomes in patients with HCC may be predicted before procedures by combining clinical patient data and baseline MR imaging with the use of AI and ML techniques. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

Energy Technology Data Exchange (ETDEWEB)

Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

2012-05-15

Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy.

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Henríquez-Hernández, Luis Alberto; Lloret, Marta; Pinar, Beatriz; Bordón, Elisa; Rey, Agustín; Lubrano, Amina; Lara, Pedro Carlos

2011-09-01

To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect. Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (PMVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins. Copyright © 2011 Elsevier Inc. All rights reserved.

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

National Research Council Canada - National Science Library

Griffith, Jeffrey K

2008-01-01

We are using an innovative, quantitative assay for telomere DNA content (TC) developed and characterized by the PI, to test the hypothesis that TC predicts the likelihood of disease recurrence in women with ductal carcinoma in situ (DCIS...

NT-proBNP is increased in differentiated thyroid carcinoma patients and may predict cardiovascular risk

NARCIS (Netherlands)

Klein Hesselink, Esther N; Horst-Schrivers, van der Anouk; van der Horst, Iwan C C; Bakker, Stephan J L; Muller Kobold, Anneke C.; Brouwers, Adrienne H; de Bock, Geertruida H; Gietema, Jourik A; Dullaart, Robin P F; Links, Thera P; Lefrandt, Joop D

INTRODUCTION: Chronic suppression of TSH in patients treated for differentiated thyroid carcinoma (DTC) may induce cardiac damage and increase risk for cardiovascular events and premature mortality. We aimed to compare circulating concentrations of N-terminal pro Brain Natriuretic Peptide

Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

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Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

2000-02-01

Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

Boomers versus Millennials: Online Media Influence on Media Performance and Candidate Evaluations

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Terri Towner

2016-09-01

Full Text Available Facebook posts, YouTube videos, tweets and wooing political bloggers have become standard practice in marketing political campaigns. Research has demonstrated the effect of new media on a host of politically-related behavior, including political participation, knowledge acquisition, group formation and self-efficacy. Yet, issues related to media trust, media performance and candidate evaluations have not been fully explored. In addition, much of the political marketing research looks exclusively at the Millennial age cohort, ignoring other age groups, particularly Baby Boomers. This case study addresses whether attention to traditional (i.e., television, hard-copy newspapers and radio and online media sources (i.e., political candidate websites, television network websites, online newspapers, Facebook, Twitter, YouTube, Tumblr and political blogs about the 2012 U.S. presidential campaign influences Millennials and Baby Boomers’ media trust and performance ratings, as well as candidate evaluations. Panel surveys were completed by both age cohorts, Millennials (n = 431 and Baby Boomers (n = 360, during the last two weeks of the presidential election. Findings indicate that traditional sources, specifically television, rather than online sources are significantly linked to media trust and performance ratings among both Boomers and Millennials. Attention to traditional media for campaign information predicts Boomers’ candidate evaluations, whereas Millennials’ candidate evaluations are influenced by online sources, such as Facebook and candidate websites.

Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)

International Nuclear Information System (INIS)

Higashi, Kotaro; Takase, Shuko; Ohguchi, Manabu; Seki, Hiroyasu; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Rikimaru, Shigeho.

1992-01-01

This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r=-0.701, p<0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy. (author)

Osteopontin expression in salivary gland carcinomas

DEFF Research Database (Denmark)

Bjørndal, Kristine; Larsen, Stine R; Godballe, Christian

2011-01-01

J Oral Pathol Med (2010) Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy......:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known...... prognostic factors in salivary gland carcinomas was insignificant. Conclusions:  Salivary gland carcinomas express OPN. The expression does not correlate with known prognostic factors....

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

Science.gov (United States)

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

FDG-PET/CT imaging for staging and target volume delineation in conformal radiotherapy of anal carcinoma

International Nuclear Information System (INIS)

Krengli, Marco; Inglese, Eugenio; Milia, Maria E; Turri, Lucia; Mones, Eleonora; Bassi, Maria C; Cannillo, Barbara; Deantonio, Letizia; Sacchetti, Gianmauro; Brambilla, Marco

2010-01-01

FDG-PET/CT imaging has an emerging role in staging and treatment planning of various tumor locations and a number of literature studies show that also the carcinoma of the anal canal may benefit from this diagnostic approach. We analyzed the potential impact of FDG-PET/CT in stage definition and target volume delineation of patients affected by carcinoma of the anal canal and candidates for curative radiotherapy. Twenty seven patients with biopsy proven anal carcinoma were enrolled. Pathology was squamous cell carcinoma in 20 cases, cloacogenic carcinoma in 3, adenocarcinoma in 2, and basal cell carcinoma in 2. Simulation was performed by PET/CT imaging with patient in treatment position. Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were drawn on CT and on PET/CT fused images. PET-GTV and PET-CTV were respectively compared to CT-GTV and CT-CTV by Wilcoxon rank test for paired data. PET/CT fused images led to change the stage in 5/27 cases (18.5%): 3 cases from N0 to N2 and 2 from M0 to M1 leading to change the treatment intent from curative to palliative in a case. Based on PET/CT imaging, GTV and CTV contours changed in 15/27 (55.6%) and in 10/27 cases (37.0%) respectively. PET-GTV and PET-CTV resulted significantly smaller than CT-GTV (p = 1.2 × 10 -4 ) and CT-CTV (p = 2.9 × 10 -4 ). PET/CT-GTV and PET/CT-CTV, that were used for clinical purposes, were significantly greater than CT-GTV (p = 6 × 10 -5 ) and CT-CTV (p = 6 × 10 -5 ). FDG-PET/CT has a potential relevant impact in staging and target volume delineation of the carcinoma of the anal canal. Clinical stage variation occurred in 18.5% of cases with change of treatment intent in 3.7%. The GTV and the CTV changed in shape and in size based on PET/CT imaging

Vitronectin in human breast carcinomas

DEFF Research Database (Denmark)

Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

2003-01-01

We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification...

Multicentricidade no carcinoma diferenciado da tireóide Multicentricity in the thyroid differentiated carcinoma

Directory of Open Access Journals (Sweden)

José Francisco Salles Chagas

2009-02-01

Full Text Available O tratamento cirúrgico de escolha no carcinoma diferenciado da tireóide sempre foi controverso. OBJETIVO: Analisar o acometimento tumoral do lobo contralateral da tireóide no carcinoma diferenciado, correlacionando risco e benefício com as complicações decorrentes da segunda intervenção. CASUÍSTICA E MÉTODO: Estudo retrospectivo, de 1998 a 2006, com 27 pacientes submetidos à tireoidectomia menos que total, sendo 21 lobectomias, cinco tireoidectomias subtotais e uma istmectomia. Foram analisados: gênero, idade, tipo de cirurgia, complicações, histopatológico do espécime cirúrgico e invasão do lobo contralateral. As idades variaram de 17 a 89 anos; o tipo histopatológico mais freqüente foi o carcinoma papilífero clássico (18 casos, seguido do carcinoma folicular (seis casos, do carcinoma papilífero variante folicular (dois casos e do carcinoma de células Hürthle (um caso. Vinte e um pacientes foram submetidos à totalização da tireoidectomia, 15 a 30 dias depois. RESULTADOS: A análise do lobo contralateral foi negativa para carcinoma em 16 (76,5% e positiva nos cinco restantes (23,8%. As complicações observadas foram: disfonia temporária (três casos e hipoparatireoidismo (dois casos, sendo um permanente. CONCLUSÃO: A totalização da tireoidectomia é um procedimento importante no tratamento do carcinoma bem diferenciado da tireóide pelo elevado acometimento contralateral (23,8%. A incidência de complicações é pequena.The treatment of choice for the well differentiated thyroid carcinoma has always been controversial. AIM: to analyze tumor invasion of the thyroid gland's contralateral lobe in cases of differentiated carcinoma, correlating risk/benefit with the complications of a second surgical approach. MATERIALS AND METHODS: Retrospective study, from 1998 to 2006, of 27 patients undergoing less than total thyroidectomy: lobectomy (21, subtotal thyroidectomy (5 or isthmusectomy (1. Gender, age, type of surgery

Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: preliminary data

Science.gov (United States)

Zhu, Zhe; Harowicz, Michael; Zhang, Jun; Saha, Ashirbani; Grimm, Lars J.; Hwang, Shelley; Mazurowski, Maciej A.

2018-02-01

Approximately 25% of patients with ductal carcinoma in situ (DCIS) diagnosed from core needle biopsy are subsequently upstaged to invasive cancer at surgical excision. Identifying patients with occult invasive disease is important as it changes treatment and precludes enrollment in active surveillance for DCIS. In this study, we investigated upstaging of DCIS to invasive disease using deep features. While deep neural networks require large amounts of training data, the available data to predict DCIS upstaging is sparse and thus directly training a neural network is unlikely to be successful. In this work, a pre-trained neural network is used as a feature extractor and a support vector machine (SVM) is trained on the extracted features. We used the dynamic contrast-enhanced (DCE) MRIs of patients at our institution from January 1, 2000, through March 23, 2014 who underwent MRI following a diagnosis of DCIS. Among the 131 DCIS patients, there were 35 patients who were upstaged to invasive cancer. Area under the ROC curve within the 10-fold cross-validation scheme was used for validation of our predictive model. The use of deep features was able to achieve an AUC of 0.68 (95% CI: 0.56-0.78) to predict occult invasive disease. This preliminary work demonstrates the promise of deep features to predict surgical upstaging following a diagnosis of DCIS.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

Science.gov (United States)

Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

2016-02-05

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

Dose response relationship in local radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

2001-01-01

In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

[Solitary hyperfunctioning thyroid gland carcinomas].

Science.gov (United States)

Zivaljevic, V; Zivic, R; Diklic, A; Krgovic, K; Kalezic, N; Vekic, B; Stevanovic, D; Paunovic, I

2011-08-01

Thyroid gland carcinomas usually appear as afunctional and hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid carcinoma with scintigraphic hyperfunctional lesions have also been reported. The aim of our retrospective study was to elucidate the frequency of carcinomas in patients operated for solitary hyperfunctional thyroid nodules and to represent their demographic and clinical features. During one decade (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid nodules in the Centre for Endocrine Surgery in Belgrade. Malignancy was revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases papillary microcarcinomas were found adjacent to dominant hyperfunctional adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma in one. All 3 patients were preoperatively hyperthyroid. In both patients with follicular carcinoma we performed lobectomies. In the third case we carried out a total thyroidectomy considering the intraoperative frozen section finding of a papillary carcinoma. According to our results the frequency of solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the possibility that a hyperfunctional nodule is malignant should be considered in the treatment of such lesions. © Georg Thieme Verlag KG Stuttgart ˙ New York.

Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Zhang ZG

2015-12-01

Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

Science.gov (United States)

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Heimdal, John-Helge; Kross, Kenneth; Klementsen, Beate; Olofsson, Jan; Aarstad, Hans Jørgen

2008-01-01

This study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease. Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis. All patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS) (t = 2.03; p < 0.05) and MCP-1 (SFM) (t = 2.49; p < 0.05) compared to controls. Increased in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; p < 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; p < 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; p < 0.05). In HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors

Decomposing the Relationship Between Candidates' Facial Appearance and Electoral Success

DEFF Research Database (Denmark)

Laustsen, Lasse

2014-01-01

Numerous studies show that candidates’ facial competence predicts electoral success. However, a handful of other studies suggest that candidates’ attractiveness is a stronger predictor of electoral success than facial competence. Furthermore, the overall relationship between inferences from...... candidates’ faces and electoral success is challenged in two ways: (i) non-facial factors in candidate photos such as clothing and hair style as well as (ii) parties’ nomination strategies are suggested as potential confounds. This study is based on original data about all 268 candidates running in three...... local elections in 2009 in Denmark and supports a two-component structure of the relationship between candidates’ facial appearance and their electoral success. Facial competence is found to mediate a positive relationship between candidates’ attractiveness and electoral success, but simultaneously...

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma.

Science.gov (United States)

Nakahira, Mitsuhiko; Saito, Naoko; Yamaguchi, Hiroshi; Kuba, Kiyomi; Sugasawa, Masashi

2014-05-01

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut-off value of mean ADC for HPV(+) OPSCC of 1.027 × 10(-3) mm(2)/s yielded sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.

Carcinoma vulvar

Directory of Open Access Journals (Sweden)

Yamit Peñas Zayas

2015-11-01

Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

ALMOST ALL OF KEPLER'S MULTIPLE-PLANET CANDIDATES ARE PLANETS

Energy Technology Data Exchange (ETDEWEB)

Lissauer, Jack J.; Rowe, Jason F.; Bryson, Stephen T.; Howell, Steve B.; Jenkins, Jon M.; Kinemuchi, Karen; Koch, David G. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Marcy, Geoffrey W. [Astronomy Department, University of California, Berkeley, CA 94720 (United States); Adams, Elisabeth; Fressin, Francois; Geary, John; Holman, Matthew J.; Ragozzine, Darin [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Buchhave, Lars A. [Niels Bohr Institute, University of Copenhagen, DK-2100, Copenhagen (Denmark); Ciardi, David R. [Exoplanet Science Institute/Caltech, Pasadena, CA 91125 (United States); Cochran, William D. [Department of Astronomy, University of Texas, Austin, TX 78712 (United States); Fabrycky, Daniel C. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Ford, Eric B.; Morehead, Robert C. [University of Florida, 211 Bryant Space Science Center, Gainesville, FL 32611 (United States); Gilliland, Ronald L., E-mail: Jack.Lissauer@nasa.gov [Space Telescope Science Institute, Baltimore, MD 21218 (United States); and others

2012-05-10

We present a statistical analysis that demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) indeed represent true, physically associated transiting planets. Binary stars provide the primary source of false positives among Kepler planet candidates, implying that false positives should be nearly randomly distributed among Kepler targets. In contrast, true transiting planets would appear clustered around a smaller number of Kepler targets if detectable planets tend to come in systems and/or if the orbital planes of planets encircling the same star are correlated. There are more than one hundred times as many Kepler planet candidates in multi-candidate systems as would be predicted from a random distribution of candidates, implying that the vast majority are true planets. Most of these multis are multiple-planet systems orbiting the Kepler target star, but there are likely cases where (1) the planetary system orbits a fainter star, and the planets are thus significantly larger than has been estimated, or (2) the planets orbit different stars within a binary/multiple star system. We use the low overall false-positive rate among Kepler multis, together with analysis of Kepler spacecraft and ground-based data, to validate the closely packed Kepler-33 planetary system, which orbits a star that has evolved somewhat off of the main sequence. Kepler-33 hosts five transiting planets, with periods ranging from 5.67 to 41 days.

High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

Science.gov (United States)

Pu, Meng; Wang, Jianlin; Huang, Qike; Zhao, Ge; Xia, Congcong; Shang, Runze; Zhang, Zhuochao; Bian, Zhenyuan; Yang, Xishegn; Tao, Kaishan

2017-07-01

Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

Multifocal hyperfunctioning thyroid carcinoma without metastases.

Science.gov (United States)

Nishida, Akiko T; Hirano, Shigeru; Asato, Ryo; Tanaka, Shinzo; Kitani, Yoshiharu; Honda, Nobumitsu; Fujiki, Nobuya; Miyata, Kouji; Fukushima, Hideyuki; Ito, Juichi

2008-09-01

Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.

Molecular characterisation of sinonasal carcinomas and their clinical implications.

Science.gov (United States)

López, Fernando; Llorente, José Luis; Costales, María; García-Inclán, Cristina; Pérez-Escuredo, Jhudit; Alvarez-Marcos, César; Hermsen, Mario; Suárez, Carlos

2013-01-01

Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose management is difficult and complex, leading to high morbidity and mortality despite improvements in the field of surgery and radiotherapy. An elevated number of these tumours can be attributed to occupational exposure. In comparison with other head and neck malignancies, studies of molecular changes in these tumours are infrequent. This review was focused on findings about the epidemiology and molecular and phenotypic characterisation of sinonasal carcinomas, which can potentially be useful for diagnosis and treatment. The increasing knowledge about the molecular biology that underlies their carcinogenesis may help to identify precursor lesions, prognostic markers and markers that predict chemoradiotherapy response and, finally, to identify potential molecular targets that will expand treatment options. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Radiotherapy of bronchogenic carcinoma

International Nuclear Information System (INIS)

Heilmann, H.P.

1982-01-01

Radiotherapy of branchogenic carcinoma comprises; palliative treatment, postoperative or pre-operative radiotherapy, radiotherapy as part of a combination of chemotherapy and radiotherapy of small cell carcinoma and curative radiotherapy of non-operable non-small cell carcinoma. Atelectasis and obstruction are indications for palliative radiotherapy. Postoperative radiotherapy is given only in cases of incomplete resection or mediastinal metastases. In the treatment of small cell carcinoma by combined irradiation and chemotherapy the mediastinum and primary tumour are irradiated, generally after chemotherapy, and the C.N.S. receives prophylactic radiotherapy. Curative radiotherapy is indicated in cases of non-operable small cell carcinoma. Irradiation with doses of 60-70 Gy produced 5-years-survival rates of 10-14% in cases classified as T 1 -T 2 N 0 M 0 . (orig.) [de

Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

2015-12-15

This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

International Nuclear Information System (INIS)

Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

2015-01-01

This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Ingrid Leguerney

2017-01-01

Full Text Available Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87, p=0.0003 and AUC (R=0.81, p=0.0013. The percentage of vessel tissue area was significantly reduced (p<0.01 in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

Ultrasound-guided diffuse optical tomography (DOT) of invasive breast carcinoma: Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status?

Energy Technology Data Exchange (ETDEWEB)

Zhu, Qingli, E-mail: qinglizhu@gmail.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Xiao, Mengsu, E-mail: xiaomengsu_2000@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); You, Shanshan, E-mail: shanshan_0531@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Zhang, Jing, E-mail: zhang.jing1029@163.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Jiang, Yuxin, E-mail: yuxinjiangxh@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Lai, Xingjian, E-mail: lxjpumch@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Dai, Qing, E-mail: qingdai_2000@yahoo.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China)

2012-11-15

Objectives: To prospectively study the ultrasound-guided near-infrared diffuse optical tomography (DOT) findings of the total haemoglobin concentration (THC) detected in invasive breast carcinomas and its contribution to the prediction of axillary lymph node (LN) status. Methods: A total of 195 invasive breast carcinomas were prospectively studied with DOT before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Tumour size and THC level were correlated with LN status by a logistic regression analysis. Results: One hundred twenty-four patients (63.59%) was LN(-) and 71 (36.41%) was LN(+). The average THC was significantly higher in the LN(+) group than in the LN(-) group (252.94 {+-} 69.19 {mu}mol/L versus 203.86 {+-} 83.13 {mu}mol/L, P = 0.01). A multivariate analysis showed an independent relationship between the probability of axillary metastasis, elevated THC level (P = 0.01), and tumour size (P = 0.001). The odds ratio with THC {>=} 140 {mu}mol/L was 13.651 (1.781-104.560), whereas that of tumour size with a 1 cm increment was only 1.777 (1.283-2.246). Conclusions: The THC level and the tumour size are independent and preoperative predictors of axillary nodal status; these variables may improve the diagnosis of patients with lymph node metastasis.

CT in the staging of bronchogenic carcinoma

International Nuclear Information System (INIS)

McLoud, T.C.; Kosiuk, J.P.; Templeton, P.A.; Shepard, J.O.; Moore, E.H.; Mathisen, D.J.; Wain, J.C.; Grillo, H.C.

1989-01-01

The authors previously presented a study of the accuracy of CT in the staging of bronchogenic carcinoma by means of correlative lymph node mapping and sampling in 85 patients. This study has now been extended to include 143 patients. Abnormal nodes (greater than or equal to 1 cm) were localized according to the ATS classification of regional lymph node mapping. One hundred thirty-eight patients underwent mediastinoscopy and 116, thoracotomy. In each case, lymph node groups 2R, 4R, 2L, 4L (paratracheal), 7 (subcarinal), and 5 (aorticopulmonary) underwent biopsy on the appropriate sides. Hilar nodes were resected with the surgical specimen. A total of 554 nodes were sampled. Overall sensitivity of CT for all the lymph node groups was similar to the previous study and was 40.5% with a specificity of 84.2%. Sensitivity was highest for group 5 (83%), and lowest for the subcarinal area (25%) (group 7). Specificity ranged from 71% for 10R hilar nodes to 90% for the subcarinal nodes. The positive predictive value was 34% and the negative predictive value was 87%. This study corroborates the authors' previous results and shows that when careful correlation of individual lymph nodes groups identified on CT is done with those sampled at surgery, the accuracy of CT in staging bronchogenic carcinoma is limited

Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site

DEFF Research Database (Denmark)

Møller, Anne Kirstine Hundahl; Pedersen, Karen Damgaard; Abildgaard, Julie Rafn

2010-01-01

tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine.......Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract...

Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.

Science.gov (United States)

Ritterhouse, Lauren L; Howitt, Brooke E

2016-09-01

This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Most of the benefits from genomic selection can be realised by genotyping a proportion of selection candidates

DEFF Research Database (Denmark)

Henryon, Mark; Berg, Peer; Sørensen, Anders Christian

2012-01-01

allocated to male and female candidates at ratios of 100:0, 75:25, 50:50, 25:75, and 0:100. For genotyped candidates, a direct-genomic value (DGV) was sampled with reliabilities 0.10, 0.50, and 0.90. Ten sires and 300 dams with the highest breeding values after genotyping were selected at each generation......We reasoned that there are diminishing marginal returns from genomic selection as the proportion of genotyped selection candidates is increased and breeding values based on a priori information are used to choose the candidates that are genotyped. We tested this premise by stochastic simulation...... of breeding schemes that resembled those used for pigs. We estimated rates of genetic gain and inbreeding realized by genomic selection in breeding schemes where candidates were phenotyped before genotyping and 0-100% of the candidates were genotyped based on predicted breeding values. Genotypings were...

Carcinoma basocelular em localizações incomuns Basal cell carcinoma in unusual locations

Directory of Open Access Journals (Sweden)

Ane Beatriz Mautari Niwa

2006-10-01

Full Text Available Os autores apresentam cinco pacientes que desenvolveram carcinomas basocelulares em locais incomuns de ocorrência desse tumor. O objetivo é relatar a raridade topográfica da neoplasia cutânea e discutir o conceito de localização incomum para o carcinoma basocelular.The authors present five patients who develop basal cell carcinomas in sites this tumor rarely occurs. The aim is to report the rare location of this frequent cutaneous malignancy and to briefly discuss the concept of unusual location of basal cell carcinoma.

Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma

International Nuclear Information System (INIS)

Levine, E.L.; Renehan, A.; Gossiel, R.; Davidson, S.E.; Roberts, S.A.; Chadwick, C.; Wilks, D.P.; Potten, C.S.; Hendry, J.H.; Hunter, R.D.; West, C.M.L.

1995-01-01

Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy

Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma

Science.gov (United States)

2012-01-01

Background Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. Methods We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. Results The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0

Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Li, Shau-Hsuan; Huang, Yung-Cheng; Huang, Wan-Ting; Lin, Wei-Che; Liu, Chien-Ting; Tien, Wan-Yu; Lu, Hung-I

2012-01-01

Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.003, univariately) and overall survival (P = 0

CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

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Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

2018-02-23

Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.

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Yurugi, Yohei; Wakahara, Makoto; Matsuoka, Yuki; Sakabe, Tomohiko; Kubouchi, Yasuaki; Haruki, Tomohiro; Nosaka, Kanae; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Shiomi, Tatsushi; Nakamura, Hiroshige; Umekita, Yoshihisa

2017-01-01

Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

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Grimm, Lars J; Ghate, Sujata V; Hwang, E Shelley; Soo, Mary Scott

2017-11-01

The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS). We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded. In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications. Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

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Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Warty Carcinoma Penis: An Uncommon Variant

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Sushma Thapa

2017-01-01

Full Text Available Penile carcinoma frequency varies widely in different parts of the world and comprises 1–10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%–10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the “verruciform” group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6×4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis.

Cholangiographic evaluation of bile duct carcinoma

International Nuclear Information System (INIS)

Nichols, D.A.; MacCarty, R.L.; Gaffey, T.A.

1983-01-01

Cholangiograms and clinical histories of 82 patients with biopsy-proved bile duct carcinoma were reviewed. The carcinomas were classified according to morphologic findings and clinical outcome. Ulcerative colitis and antecedent inflammatory disease of the biliary tree, particularly primary sclerosing cholangitis, seem to predispose to the development of bile duct carcinoma. Focal stenotic lesions were the most common morphologic type (62/82). Polypoid carcinomas and diffuse sclerosing carcinomas were less common and of about equal frequency. Prognosis was best for patients with polypoid carcinomas and worst for those with diffuse sclerosing carcinomas. In 69 cases (84%), the tumors involved the intrahepatic or proximal extrahepatic ducts, makin curative resection difficult or impossible. Patients with carcinomas limited to the more distal extrahepatic bile ducts had a longer average survival and a higher probability of surgical cure. Proper management of patients with bile duct carcinoma requires a complete and accurate cholangiographic evaluation of the morphology, location, and extent of the disease

Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis

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Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

2015-01-01

Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

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Duan, X-Y.; Wang, W.; Li, M.; Li, Y.; Guo, Y-M. [PET-CT Center, The First Affiliated Hospital of Xi' an, Jiaotong University, Xi' an, Shaanxi (China)

2015-02-03

{sup 18}F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. {sup 18}F-FDG PET/CT scans were performed and different SUV parameters (SUV{sub max}, SUV{sub avg}, SUV{sub T/L}, and SUV{sub T/A}) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV{sub max}, SUV{sub avg}, and SUV{sub T/L} of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV{sub T/L} was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV{sub max} was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV{sub T/L} appeared to be most useful overall, but SUV{sub max} was the best index for adenocarcinoma tumor differentiation.

Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

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Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar

2017-12-01

The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53 and NF-kappa B in human tongue carcinoma - BLCAP overexpression induces S phase arrest and apoptosis

NARCIS (Netherlands)

Yao, Jun; Duan, Li; Fan, Mingwen; Yuan, Jianhuan; Wu, Xinxing

Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor suppressor gene identified from the human bladder carcinoma. Our previous studies have shown that BLCAP overexpression could inhibit cell growth by inducing apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor

Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis.

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Nam, Seon Young; Lee, Hye Seung; Jung, Gyung-Ah; Choi, Jimi; Cho, Sung Jin; Kim, Min Kyu; Kim, Woo Ho; Lee, Byung Lan

2003-12-01

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (pSmad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.

Integrative analysis of gene expression and DNA methylation using unsupervised feature extraction for detecting candidate cancer biomarkers.

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Moon, Myungjin; Nakai, Kenta

2018-04-01

Currently, cancer biomarker discovery is one of the important research topics worldwide. In particular, detecting significant genes related to cancer is an important task for early diagnosis and treatment of cancer. Conventional studies mostly focus on genes that are differentially expressed in different states of cancer; however, noise in gene expression datasets and insufficient information in limited datasets impede precise analysis of novel candidate biomarkers. In this study, we propose an integrative analysis of gene expression and DNA methylation using normalization and unsupervised feature extractions to identify candidate biomarkers of cancer using renal cell carcinoma RNA-seq datasets. Gene expression and DNA methylation datasets are normalized by Box-Cox transformation and integrated into a one-dimensional dataset that retains the major characteristics of the original datasets by unsupervised feature extraction methods, and differentially expressed genes are selected from the integrated dataset. Use of the integrated dataset demonstrated improved performance as compared with conventional approaches that utilize gene expression or DNA methylation datasets alone. Validation based on the literature showed that a considerable number of top-ranked genes from the integrated dataset have known relationships with cancer, implying that novel candidate biomarkers can also be acquired from the proposed analysis method. Furthermore, we expect that the proposed method can be expanded for applications involving various types of multi-omics datasets.

HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

International Nuclear Information System (INIS)

Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

2012-01-01

Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip® HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

International Nuclear Information System (INIS)

Clark, Brenda G.; Souhami, Luis; Roman, Ted N.; Chappell, Rick; Evans, Michael D.C.; Fowler, Jack F.

1997-01-01

Purpose: The aim of this work is to investigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors. Methods and Materials: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m 2 was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the confounding effect of the cisplatin. Results: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at approximately 125 Gy 3 corresponding to a brachytherapy dose of approximately 8 Gy per fraction. This value is approximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The data from the group of patients treated without cisplatin is comparable to the data from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison. Conclusion: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external beam irradiation in the head and neck region

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

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Lionel Kankeu Fonkoua

2018-03-01

Full Text Available Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC. Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2 amplification and programmed death-ligand 1 (PD-L1 expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS on molecular profile (MP-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets.

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Kankeu Fonkoua, Lionel; Yee, Nelson S

2018-03-09

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

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Matloub, Azza Abdelmageed; Salama, Alaa Hamed; Aglan, Hadeer Ahmed; AbouSamra, Mona Mahmoud; ElSouda, Sahar Salah Mohamed; Ahmed, Hanaa Hamdy

2018-04-01

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant Chemotherapy in Patients with Nasopharyngeal Carcinoma

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Guo-Yi Zhang

2015-01-01

Full Text Available Purpose. To explore the potential of diffusion-weighted (DW magnetic resonance imaging (MRI using apparent diffusion coefficient (ADC for predicting the response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC. Methods and Materials. Ninety-two consecutive patients with NPC who underwent three cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and anatomical MRI were performed before and after neoadjuvant chemotherapy prior to radiotherapy. Pretreatment ADCs and percentage increases in ADC after chemotherapy were calculated for the primary lesions and metastatic adenopathies. Receiver operating characteristic curve analysis was used to select optimal pretreatment ADCs. Results. Pretreatment mean ADCs were significantly lower for responders than for nonresponders (primary lesions, P=0.012; metastatic adenopathies, P=0.013. Mean percentage increases in ADC were higher for responders than for nonresponders (primary lesions, P=0.008; metastatic adenopathies, P<0.001. The optimal pretreatment primary lesion and metastatic adenopathy ADCs for differentiating responders from nonresponders were 0.897 × 10−3 mm2/sec and 1.031 × 10−3 mm2/sec, respectively. Conclusions. NPC patients with low pretreatment ADCs tend to respond better to neoadjuvant chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging biomarker of response to neoadjuvant chemotherapy.

Transplantable pancreatic acinar carcinoma

International Nuclear Information System (INIS)

Warren, J.R.; Reddy, J.K.

1981-01-01

Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with [3H]-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with [3H]-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed

Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

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Shi, Bibo; Hou, Rui; Mazurowski, Maciej A.; Grimm, Lars J.; Ren, Yinhao; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2018-02-01

Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

Quantitative proteomic analysis for novel biomarkers of buccal squamous cell carcinoma arising in background of oral submucous fibrosis

International Nuclear Information System (INIS)

Liu, Wen; Zeng, Lijuan; Li, Ning; Wang, Fei; Jiang, Canhua; Guo, Feng; Chen, Xinqun; Su, Tong; Xu, Chunjiao; Zhang, Shanshan; Fang, Changyun

2016-01-01

In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches. We compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis. In total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs. The present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy. The online version of this article (doi:10.1186/s12885-016-2650-1) contains supplementary material, which is available to authorized users

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

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Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

2016-10-20

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2 H -furo[3,2- b ][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

Candidate OP Phyla: Importance, Ecology and Cultivation Prospects.

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Rohini Kumar, M; Saravanan, V S

2010-10-01

OP phyla were created in the domain bacteria, based on the group of 16S rRNA gene sequences recovered from the Obsidian Pool. However, due to the lack of cultured representative it is referred to as candidate phyla. Wider ecological occurrence was predicted for the OP phyla, especially OP3, OP10 and OP11. Recently, members of phylum OP5 and OP10 were cultured, providing clues to their cultivation prospects. At last the bioprospecting potentials of the OP members are discussed herein.

Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

International Nuclear Information System (INIS)

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.; Patel, Vyomesh; Gutkind, J. Silvio; Yamada, Kenneth M.; Berrier, Allison L.

2011-01-01

Research highlights: → Proteomics of clustered integrin αβ1, α v β, α 6 β receptors in oral carcinoma. → p130Cas, Dek, Src and talin regulate oral carcinoma invasion. → p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin αβ1, α v β or α 6 β receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

Results of high energy x-ray therapy of gastric carcinoma, 3. Early gastric carcinoma (Tl carcinoma)

Energy Technology Data Exchange (ETDEWEB)

Yamada, S; Asakawa, H; Otawa, H; Matsumoto, K [Miyagi Seijinbyo Center (Japan)

1981-11-01

A total of 25 cases with early gastric carcinoma, of which 10 cases were followed by gastrectomy, were given a combined radiotherapy with 5-Fu, Ft 207 or MFC at Miyagi Seijinbyo Center. Histologic examinations of biopsy specimens revealed the disappearance of cancer cells in five (42%) of 12 cases and those of serial specimens of the resected stomach showed the complete disappearance of cancer cells in three (27%) of 11 lesions (10 cases). Five year survival rate in 15 non-resected cases was only 30%. From these results, it was suggested that a combined radiotherapy of early gastric carcinoma should not be chosen as a curative treatment procedure but it might be valuable, if early carcinoma was thought to be inoperable because of other medical reasons.

A Preoperative Measurement of Serum MicroRNA-125b May Predict the Presence of Microvascular Invasion in Hepatocellular Carcinomas Patients

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Mei Liu

2016-06-01

Full Text Available The high recurrence rate remains a major problem that strongly influenced the prognosis of hepatocellular carcinoma (HCC patients who received hepatectomy. The presence of microvascular invasion (MVI is regarded as the most important risk factor that contributes to the postoperative recurrence. Our previous study has hinted that serum microRNA-125b (miR-125b was associated with MVI. The aim of the present study was to identify whether serum miR-125b can serve as a biomarker to reliably predict microvascular invasion (MVI preoperatively. MiR-125b was quantified in 108 HCC patients’ serum before they received surgery by quantitative real-time PCR (qRT-PCR. Our results revealed that MVI was associated with relapse free survival (RFS of postoperative HCC patients; surgical margin width was associated with postoperative RFS in MVI present patients, but not in the patients without MVI. Multivariate analysis revealed that miR-125b, tumor size and AFP were the independent predictive factors associated with MVI in this cohort (P = .001, .001, .003, respectively. The probability of the predictive accuracy of miR-125b was 76.95% (51.32% specificity and 87.50% sensitivity, which was almost equal to the classifier established by combination of AFP and tumor size (78.82% probability, 65.63% specificity and 84.21% sensitivity. Furthermore, the combination of tumor size, AFP and miR-125b yielded a ROC curve area of 86.68% (72.37% specificity and 84.38% sensitivity. Our study indicated that serum miR-125b can be used to predict MVI of HCC patients before they received hepatic resection. Therefore, miR-125b can potentially guide individualized treatment, which helps HCC patients, with or without MVI, to benefit from different surgical approach.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.

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Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P

2017-06-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.

Female urethral carcinoma

International Nuclear Information System (INIS)

Saitoh, Masahiko; Kondo, Atsuo; Sakakibara, Toshihumi

1988-01-01

Urethral carcinoma in 2 females has been treated with irradiation together with adjunct chemotherapy. In case 1, a 73-year-old female with squamous cell carcinoma was successfully treated with irradiation of 4,000 rad and peplomycin of 60 mg intravenously given. She has been free from the disease for the past 43 months. In case 2, a 61-year-old female with transitional cell carcinoma was initially treated with irradiation of 5,000 rad together with peplomycin 90 mg, which was followed by another 5,000 rad irradiation. The tumor recurred and the patient was operated on for cystourethrectomy and partial resection of the vagina. A further chemotherapy of cisplatin, peplomycin, and mitomycin C was instituted. She died of the tumor recurrence 23 months after the first visit to our clinic. Diagnosis and treatment modalities on the female urethral carcinoma are briefly discussed. (author)

Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

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Haltas Hacer

2012-08-01

Full Text Available Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744

Diversifying Selection in the Wheat Stem Rust Fungus Acts Predominantly on Pathogen-Associated Gene Families and Reveals Candidate Effectors

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Jana eSperschneider

2014-09-01

Full Text Available Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defence proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialised gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control.

Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

Science.gov (United States)

Kim, Hwi Young; Lee, Dong Hyeon; Lee, Jeong-Hoon; Cho, Young Youn; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

2018-03-20

Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values). This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

Does multifocal papillary micro-carcinoma require radioiodine ablation?

International Nuclear Information System (INIS)

Punda, A.; Markovic, V.; Eterovic, D.

2015-01-01

Full text of publication follows. Background: the thyroid carcinomas smaller than 1 cm (micro-carcinomas) comprise a significant fraction of papillary carcinomas. Excluding clinical micro-carcinomas, which present as metastatic disease, the micro-carcinomas diagnosed by ultrasound/FNAC or incidentally have very good prognosis. However, whether or not these papillary micro-carcinomas require post-surgical radioiodine ablation remains a matter of debate. Hypothesis: multi-focality is present in majority of clinical papillary micro-carcinomas and this characteristic can be used to identify the subset of non-clinical micro-carcinomas with greater malignant potential. Methods: the data on types of differentiated thyroid carcinomas diagnosed in the period 2008-2011 in the University Hospital Split were collected. Results: there were 359 patients with thyroid carcinoma, 329 (92%) of which had papillary carcinoma. About 61% (202/329) of papillary carcinomas were micro-carcinomas; most of them were diagnosed by ultrasound/FNAC (134/202= 66%), the rest were incidentalomas (48/202=24%) and clinical micro carcinomas (20/202=10%). Sixty percent (12/20) of patients with clinical micro-carcinoma and 23 patients with non-clinical micro-carcinoma (23/182=13%) had multifocal disease. Conclusion: multifocal disease is a frequent characteristic of clinical papillary thyroid micro-carcinomas, suggesting that multi-focality presents an early stage of non-clinical micro-carcinomas with more aggressive behaviour. Thus multifocal, but not uni-focal papillary micro-carcinomas may require radioiodine ablation. (authors)

Hyperthermo-chemo-radiotherapy for patients with carcinoma of the esophagus and prediction of the clinical remedial value using the in vitro succinate dehydrogenase inhibition test

International Nuclear Information System (INIS)

Matsuda, Hiroyuki; Sugimachi, Keizo; Ohno, Shinji; Mori, Masaki; Kuwano, Hiroyuki; Maehara, Yoshihiko

1989-01-01

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable (n=88) and unresectable (n=36) carcinoma of the esophagus. The histopathological effectiveness, and the long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemoradiotherapy (CR therapy). A correlation between the hyperthermia sensitivity test, using the in vitro succinate dehydrogenase inhibition test, and the clinical remedial value was also examined in malignant tissues from 47 patients with esophageal cancer, and treated with HCR therapy. In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (69%) compared with that in cases treated by CR therapy (48%) (P<0.05). The long term results of patients with both resectable and unresectable carcinoma, given HCR therapy were significanly better than those given CR therapy (P<0.05). On the other hand, the clinical remedial value, determined radiographically showed a correlation rate of 77% to the hyperthermia sensitivity test. Thus, the HCR therapy resulted in not only a higher histopathological effectiveness rate but also a significantly longer survival without severe side effects, and this hyperthermia sensitivity test using the succinate dehydrogenase inhibition test facilitates prediction of the outcome of the HCR therapy. (author)

Optimized candidal biofilm microtiter assay

NARCIS (Netherlands)

Krom, Bastiaan P.; Cohen, Jesse B.; Feser, Gail E. McElhaney; Cihlar, Ronald L.

Microtiter based candidal biofilm formation is commonly being used. Here we describe the analysis of factors influencing the development of candidal biofilms such as the coating with serum, growth medium and pH. The data reported here show that optimal candidal biofilm formation is obtained when

Deep Learning Questions Can Help Selection of High Ability Candidates for Universities

Science.gov (United States)

Mellanby, Jane; Cortina-Borja, Mario; Stein, John

2009-01-01

Selection of students for places at universities mainly depends on GCSE grades and predictions of A-level grades, both of which tend to favour applicants from independent schools. We have therefore developed a new type of test that would measure candidates' "deep learning" approach since this assesses the motivation and creative thinking…

Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: friends or foes?

Science.gov (United States)

Agahozo, Marie Colombe; Hammerl, Dora; Debets, Reno; Kok, Marleen; van Deurzen, Carolien H M

2018-02-20

In the past three decades, the detection rate of ductal carcinoma in situ of the breast has dramatically increased due to breast screening programs. As a consequence, about 20% of all breast cancer cases are detected in this early in situ stage. Some ductal carcinoma in situ cases will progress to invasive breast cancer, while other cases are likely to have an indolent biological behavior. The presence of tumor-infiltrating lymphocytes is seen as a promising prognostic and predictive marker in invasive breast cancer, mainly in HER2-positive and triple-negative subtypes. Here, we summarize the current understanding regarding immune infiltrates in invasive breast cancer and highlight recent observations regarding the presence and potential clinical significance of such immune infiltrates in patients with ductal carcinoma in situ. The presence of tumor-infiltrating lymphocytes, their numbers, composition, and potential relationship with genomic status will be discussed. Finally, we propose that a combination of genetic and immune markers may better stratify ductal carcinoma in situ subtypes with respect to tumor evolution.

Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.

Science.gov (United States)

Misawa, Yuki; Misawa, Kiyoshi; Kawasaki, Hideya; Imai, Atsushi; Mochizuki, Daiki; Ishikawa, Ryuji; Endo, Shiori; Mima, Masato; Kanazawa, Takeharu; Iwashita, Toshihide; Mineta, Hiroyuki

2017-07-01

The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51-6.75 (p = 0.002); 2.24, 1.06-4.76 (p = 0.035); and 2.56, 1.09-6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.

Ultrasound manifestation of hepatocellular carcinoma

International Nuclear Information System (INIS)

Hwang, M. S.; Yoo, H. S.; Park, C. Y.; Choi, H. J.; Moon, Y. M.; Lee, S. I.

1982-01-01

With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns

Ultrasound manifestation of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hwang, M S; Yoo, H S; Park, C Y; Choi, H J; Moon, Y M; Lee, S I [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1982-06-15

With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns.

Anaplastic carcinoma

International Nuclear Information System (INIS)

Parikh, D.M.; Agarwal, S.; Rao, R.S.

1999-01-01

Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

Radiosensitivity of hepatocellular carcinoma

International Nuclear Information System (INIS)

Hennequin, C.; Quero, L.; Rivera, S.

2011-01-01

The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

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Kristiansen Glen

2007-06-01

Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

Analysis of PGY-1 Pharmacy Resident Candidate Letters of Recommendation at an Academically Affiliated Residency Program.

Science.gov (United States)

McLaughlin, Milena M; Masic, Dalila; Gettig, Jacob P

2018-04-01

Letters of recommendation (LORs) are a critical component for differentiating among similarly qualified pharmacy residency candidates. These letters contain information that is difficult to ascertain from curricula vitae and pharmacy school transcripts. LOR writers may use any words or phrases appropriate for each candidate as there is no set framework for LORs. The objective of this study was to characterize descriptive themes in postgraduate year 1 (PGY-1) pharmacy residency candidates' LORs and to examine which themes of PGY-1 pharmacy residency candidates' LORs are predictive of an interview invitation at an academically affiliated residency program. LORs for candidates from the Pharmacy Online Residency Centralized Application System (PhORCAS) from 2013 and 2014 for the Midwestern University PGY-1 Pharmacy Residency were analyzed. LOR characteristics and descriptive themes were collected. All scores for candidate characteristics and overall PhORCAS recommendation were also recorded. A total of 351 LORs for 111 candidates from 2013 (n = 47 candidates) and 2014 (n = 64 candidates) were analyzed; 36 (32.4%) total candidates were offered an interview. Themes that were identified as predictors of an interview included a higher median (interquartile range) number of standout words (3 words [1.3-4] vs 3.8 words [2.5-5.5], P < .01) and teaching references (3.7 words [2.7-6] vs 5.7 words [3.7-7.8], P = .01). For this residency program, standout words and teaching references were important when offering interviews.

Carcinoma arising in thyroglossal remnants

NARCIS (Netherlands)

van Vuuren, P. A.; Balm, A. J.; Gregor, R. T.; Hilgers, F. J.; Loftus, B. M.; Delprat, C. C.; Rutgers, E. J.

1994-01-01

Three patients with a papillary carcinoma arising in a thyroglossal duct cyst are presented and the literature is reviewed. This rare malignancy is seen mostly in women between the ages of 20 and 50 years. The distribution of carcinoma subtypes differs from that of thyroid carcinomas and

Correlative study of dynamic MRI and tumor angiogenesis in gastric carcinoma

International Nuclear Information System (INIS)

Tang Qunfeng; Shen Junkang; Feng Yizhong; Qian Minghui; Chai Yuhai

2004-01-01

Objective: To investigate the correlation between the dynamic MRI enhancement characteristics and tumor angiogenesis in gastric carcinoma. Methods: Histopathological slides of 30 patients underwent CD34 and vascular endothelial growth factor (VEGF) immunohistochemical staining. Microvessel density (MVD) and VEGF protein expression were analyzed with their relationship to pathological features. The dynamic MRI characteristics, including the maximum contrast enhancement ratio (CERmax), were correlatively studied with MVD and VEGF expression. Results: In 30 cases, MVD was 13.00 to 68.25 per vision field with an average of 42.95 ±14.79. The low expression rate of VEGF was 30% (9/30), while the high expression rate of VEGF was 70% (21/30). MVD and VEGF expression correlated with lymph node metastasis (P>0.05), but their relationships to the degree of differentiation and depth of invasion were not significant (P>0.05). MVD was related to TNM-staging of gastric carcinoma (P>0.05). The expression of VEGF between the stage I and IV had significant differences (P>0.05). MVD was higher in VEGF-high expression than in VEGF-low expression [(47.30 ± 14.16) per vision versus (32.81 ± 11.25) per vision]. CERmax was significantly correlated with MVD (r=0.556, P=0.0014). The distribution features and shape of microvessels within gastric carcinoma were related to the enhancement characteristics such as irregular enhancement and delaminated enhancement. The correlation between CERmax and expression of VEGF was not significant (t=-0.847, P=0.404). Conclusion: The manifestations on dynamic MR images can reflect the distribution features and shape of microvessels within gastric carcinoma. Dynamic MR imaging may prove to be a valuable means in estimating the MVD of gastric carcinoma noninvasively, and further predicting the biological behavior of gastric carcinoma and judging the prognosis. (authors)

Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

OpenAIRE

Haltas, Hacer; Bayrak, Reyhan; Yenidunya, Sibel; Kosehan, Dilek; Sen, Meral; Akin, Kayihan

2012-01-01

Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The ...

Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

OpenAIRE

Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

2013-01-01

Introduction Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation ...

A clinical study of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Ito, Zenya; Wada, Tetsuro; Senarita, Masamitsu

1999-01-01

Forty-four patients of nasopharyngeal carcinoma, treated in Tsukuba University Hospital between March 1988 and March 1998, were reviewed in order to assess the adequacy of our treatment protocol. Most of the cases except 5 were histologically diagnosed as squamous cell carcinoma including 25 of lymphoepithelioma (poorly-differentiated squamous cell carcinoma). Thirty-two out of 39 squamous cell carcinoma cases have fallen into Stage IV category (UICC, 1987) , and all of the non-squamous cell carcinoma cases were also categorized as Stage IV. The basic protocol for nasopharyngeal squamous cell carcinoma was the combination of full-dose irradiation and chemotherapy using cisplatin/carboplatin and peplomycin. The metastatic cervical lymphnodes in 9 cases, too massive to control by this treatment, were surgically dissected after the treatment. Recurrence was noted in 9 cases who were rehospitalized and salvaged medically and/or surgically. As a consequence, the overall 5-year survival rate was 71.4% for squamous cell carcinoma. On the other hand, only one of the 5 non-squamous cell carcinoma cases died of the disease. (author)

Predictive values of BI-RADS{sup ®} magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS)

Energy Technology Data Exchange (ETDEWEB)

Badan, Gustavo Machado, E-mail: gustavobadan@hotmail.com [Breast Imaging Service of Radiology Depatment—Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP (Brazil); Piato, Sebastião [Mastology Division—Gynecology and Obstetrics Department (Brazil); Roveda, Décio; Faria Castro Fleury, Eduardo de [Breast Imaging Service of Radiology Depatment—Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP (Brazil)

2016-10-15

Purpose: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Materials and methods: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Results: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. Conclusion: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases.

Prognostic value of HMGA2, P16, and HPV in oral squamous cell carcinomas

DEFF Research Database (Denmark)

Loeschke, S.; Ohlmann, A. K.; Bräsen, Jan Hinrich

2016-01-01

Purpose Molecular markers are only occasionally used in diagnostics of oral squamous cell carcinoma (OSCC), even though they could influence decision making in individually designed cancer therapies. We analyzed the predictive value of the markers HPV, p16, and HMGA2 and the TNM classification...... in regard to survival and recurrence rates. Material and methods A total of 91 OSCC cases were included in this study, with a follow up of up to 131 months. HPV-DNA was present in 7 carcinomas. p16 was detected by immunohistochemical staining in 14 samples. HMGA2 expression was determined by real...

Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

Directory of Open Access Journals (Sweden)

Yu-Li Su

Full Text Available We developed a novel inflammation-based model (NPS, which consisted of a neutrophil to lymphocyte ratio (NLR and platelet count (PC, for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC.We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS.In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001 or PC (P < .0001. The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001. Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002.The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

Thyroid cancer - medullary carcinoma

Science.gov (United States)

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network

Science.gov (United States)

Yao, Qianlan; Xu, Yanjun; Yang, Haixiu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Sun, Zeguo; Shi, Xinrui; Feng, Li; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

2015-01-01

The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. PMID:26598063

WIF-1 and Ihh Expression and Clinical Significance in Patients With Lung Squamous Cell Carcinoma and Adenocarcinoma.

Science.gov (United States)

Zhang, Yue; Hu, Chunhong

2016-10-31

This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (PIhh protein expression survived significantly shorter than patients with negative Ihh protein expression. In contrast, no significant difference in mean survival was observed in patients with lung squamous cell carcinoma and adenocarcinoma with positive and negative WIF-1 protein expression (P>0.05). Ihh is a marker for poor prognosis in patients with lung squamous cell carcinoma and adenocarcinoma. WIF-1 is not a predictive marker for lung cancer.

The cld mutation: narrowing the critical chromosomal region and selecting candidate genes.

Science.gov (United States)

Péterfy, Miklós; Mao, Hui Z; Doolittle, Mark H

2006-10-01

Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the tw73 haplotype on mouse Chromosome 17. While the cld mutation results in lipase proteins that are inactive, aggregated, and retained in the endoplasmic reticulum (ER), it maps separately from the lipase structural genes. We have narrowed the gene critical region by about 50% using the tw18 haplotype for deletion mapping and a recombinant chromosome used originally to map cld with respect to the phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs). To identify the affected gene, we have selected candidates based on their known role in associated biological processes, cellular components, and molecular functions that best fit with the predicted function of the cld gene. A secondary approach was based on differences in mRNA levels between mutant (cld/cld) and unaffected (+/cld) cells. Using both approaches, we have identified seven functional candidates with an ER localization and/or an involvement in protein maturation and folding that could explain the lipase deficiency, and six expression candidates that exhibit large differences in mRNA levels between mutant and unaffected cells. Significantly, two genes were found to be candidates with regard to both function and expression, thus emerging as the strongest candidates for cld. We discuss the implications of our mapping results and our selection of candidates with respect to other genes, deletions, and mutations occurring in the cld critical region.

miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.

Science.gov (United States)

Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen

2012-09-01

Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

NARCIS (Netherlands)

Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

2005-01-01

Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

Science.gov (United States)

Schultz, Luciana; Albadine, Roula; Hicks, Jessica; Jadallah, Sana; DeMarzo, Angelo M; Chen, Ying-Bei; Nielsen, Matthew E; Neilsen, Matthew E; Gonzalgo, Mark L; Sidransky, David; Schoenberg, Mark; Netto, George J

2010-12-01

Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. Mean length of follow-up was 62.6 months (range, 1-182 months). Disease progression, overall survival (OS), and disease-specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). In a second model substituting organ-confined disease and lymph node status for TNM stage grouping, phosS6 and c-myc remained independent predictors of DSS (P=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression

Issue-Advocacy versus Candidate Advertising: Effects on Candidate Preferences and Democratic Process.

Science.gov (United States)

Pfau, Michael; Holbert, R. Lance; Szabo, Erin Alison; Kaminski, Kelly

2002-01-01

Examines the influence of soft-money-sponsored issue-advocacy advertising in U.S. House and Senate campaigns, comparing its effects against candidate-sponsored positive advertising and contrast advertising on viewers' candidate preferences and on their attitude that reflect democratic values. Reveals no main effects for advertising approach on…

A fourteen-year review of radical cystectomy for transitional cell carcinoma demonstrating the usefulness of the concept of lymph node density

Directory of Open Access Journals (Sweden)

Chi W. Cheng

2006-10-01

Full Text Available OBJECTIVE: We studied the long-term outcome of radical cystectomy for transitional cell carcinoma and evaluated prognostic factors for disease specific survival. MATERIALS AND METHODS: A retrospective review was carried out for all cystectomies performed for transitional cell carcinoma between 1989 and 2002. Disease specific survival was correlated to patient, pathological and operative factors as well as to adjuvant therapy. RESULTS: Of the 133 cystectomies included, 100 were male and 33 were female patients. The median age was 69 years (range 43 to 86. The median follow up was 20 months (range 0 to 158. With univariate analysis, pT stage, N stage, lymph node density, carcinoma in-situ, surgical margin and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. On the other hand, with multivariate analysis, only pT stage, lymph node density and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. Within the group of node positive disease, lymph node density also predicted disease specific survival with both univariate and multivariate analyses. Patients with lymph node density 20% or below showed better disease specific survival. CONCLUSIONS: pT stage and lymph node density were found to be the most important predictive factors for disease specific survival after cystectomy in the Asian population.

Identification of Novel Human Breast Carcinoma (MDA-MB-231 Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library

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Elena Lenci

2016-10-01

Full Text Available The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

Study on specificity of colon carcinoma-associated serum markers and establishment of SVM prediction model

Directory of Open Access Journals (Sweden)

Lu Li

2017-03-01

Full Text Available We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Logistic regression and Bhattacharyya distance were used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. Through Logistic regression, three indexes, CEA, HSP60 and CA199, were screened out. Using Bhattacharyya distance, four indexes with the largest Bhattacharyya distance were screened out, including CEA, NSE, AFP, and CA724. The specificity of the combination of the above six indexes was higher than that of other combinations, so did the accuracy of the established SVM identification model. Using Logistic regression and Bhattacharyya distance for detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

International Nuclear Information System (INIS)

Lin, Hui; Lin, Huan-Xin; Ge, Nan; Wang, Hong-Zhi; Sun, Rui; Hu, Wei-Han

2013-01-01

The combined predictive value of plasma uric acid and primary tumor volume in nasopharyngeal carcinoma (NPC) patients receiving intensity modulated radiation therapy (IMRT) has not yet been determined. In this retrospective study, plasma uric acid level was measured after treatment in 130 histologically-proven NPC patients treated with IMRT. Tumor volume was calculated from treatment planning CT scans. Overall (OS), progression-free (PFS) and distant metastasis-free (DMFS) survival were compared using Kaplan-Meier analysis and the log rank test, and Cox multivariate and univariate regression models were created. Patients with a small tumor volume (<27 mL) had a significantly better DMFS, PFS and OS than patients with a large tumor volume. Patients with a high post-treatment plasma uric acid level (>301 μmol/L) had a better DMFS, PFS and OS than patients with a low post-treatment plasma uric acid level. Patients with a small tumor volume and high post-treatment plasma uric acid level had a favorable prognosis compared to patients with a large tumor volume and low post-treatment plasma uric acid level (7-year overall OS, 100% vs. 48.7%, P <0.001 and PFS, 100% vs. 69.5%, P <0.001). Post-treatment plasma uric acid level and pre-treatment tumor volume have predictive value for outcome in NPC patients receiving IMRT. NPC patients with a large tumor volume and low post-treatment plasma uric acid level may benefit from additional aggressive treatment after IMRT

Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

Science.gov (United States)

Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

2016-01-26

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Early prediction of response to cetuximab and radiotherapy by FDG-PET/CT for the treatment of a locoregionally advanced squamous cell carcinoma of the hypopharynx

Directory of Open Access Journals (Sweden)

Mindaugas Grybauskas

2014-01-01

Full Text Available Cetuximab (CTX is used for the concurrent treatment with radiotherapy (RT in squamous cell carcinoma of head and neck (HNSCC. There are no reliable clinical predictive markers of effectiveness of CTX at yet. We describe the clinical case of patient who received a CTX/RT to cure locoregionally advanced hypopharyngeal SCC. 2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography and computed tomography (18FDG-PET/CT was performed before the treatment and repeated 10 days after CTX induction dose. A repeated 18FDG-PET/CT scan showed dramatic decrease of metabolic parameters. Patient had a complete response after treatment and is still alive and cured after 5 years.

Dynamic CT of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-03-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. Detecting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. The dynamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma.

Emerging therapies for thyroid carcinoma.

LENUS (Irish Health Repository)

Walsh, S

2012-02-01

Thyroid carcinoma is the most commonly diagnosed endocrine malignancy. Its incidence is currently rising worldwide. The discovery of genetic mutations associated with the development of thyroid cancer, such as BRAF and RET, has lead to the development of new drugs which target the pathways which they influence. Despite recent advances, the prognosis of anaplastic thyroid carcinoma is still unfavourable. In this review we look at emerging novel therapies for the treatment of well-differentiated and medullary thyroid carcinoma, and advances and future directions in the management of anaplastic thyroid carcinoma.

Mammary carcinoma diagnostics and therapy

International Nuclear Information System (INIS)

Fischer, Uwe; Baum, Friedemann

2014-01-01

The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.

Management of small hepatocellular carcinoma in cirrhosis: Focus on portal hypertension

Science.gov (United States)

Hernandez-Gea, Virginia; Turon, Fanny; Berzigotti, Annalisa; Villanueva, Augusto

2013-01-01

The incidence of hepatocellular carcinoma (HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality. Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency, and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan. Patients with small HCC can be candidates for potential curative treatments: liver transplantation, surgical resection and percutaneous ablation, depending on the presence of portal hypertension and co-morbidities. This review will analyze recent advancements in the clinical management of these individuals, focusing on issues related to the role of portal hypertension, the debate between resection and ablative therapies and the future impact of molecular technologies. PMID:23482437

Outcome of superficial squamous cell carcinoma of the esophagus: a clinicopathological study

Directory of Open Access Journals (Sweden)

Maria Aparecida Coelho de Arruda Henry

2013-05-01

Full Text Available PURPOSE: To analyze the clinicopathological features and outcome of patients with pathologically proven superficial squamous cell carcinoma of the esophagus. METHODS: A total of 234 consecutive cases of esophageal carcinoma in a 15-year period were reviewed. RESULTS: Superficial esophageal cancer was found in five patients (2.1%. They were four men and one woman and the mean age was 52.5 years. Smoking and alcohol were the main risk factors. Achalasia due to Chagas disease occurred in one patient and a second primary tumor developed in the larynx in another patient. Four patients underwent esophagectomy and one patient received chemoradiotherapy. The histopathologic diagnosis was of squamous cell carcinoma in all cases. Intramucosal tumor (Tis was identified in three cases and superficially invasive carcinoma in two cases. Four patients are free of disease with survival times of two, four, six and nine years. The patient who developed laryngeal cancer died six years after esophagectomy. CONCLUSION: Long-term survival in patients with esophageal cancer is related to early diagnosis. Therefore, a less aggressive surgical approach, such as endoscopic resection, may be a good option for these patients, if depth of tumor invasion can be accurately predicted by the new imaging tools.

Influences of general self-efficacy and weight bias internalization on physical activity in bariatric surgery candidates.

Science.gov (United States)

Hübner, Claudia; Baldofski, Sabrina; Zenger, Markus; Tigges, Wolfgang; Herbig, Beate; Jurowich, Christian; Kaiser, Stefan; Dietrich, Arne; Hilbert, Anja

2015-01-01

Physical activity (PA) seems to be important for long-term weight loss after bariatric surgery; however, studies provide evidence for insufficient PA levels in bariatric patients. Research found self-efficacy to be associated with PA and weight bias internalization, for which an influence on mental and physical health has been shown in recent studies. The purpose of the present study was to investigate the influence of general self-efficacy on PA, mediated by weight bias internalization. In 179 bariatric surgery candidates, general self-efficacy, weight bias internalization, and different intensities of PA were assessed by self-report questionnaires. Structural equation modeling was used to analyze the assumed mediational relationship. After controlling for sociodemographic variables, weight bias internalization fully mediated the association between general self-efficacy and moderate-intense as well as vigorous-intense PA. Lower general self-efficacy predicted greater weight bias internalization, which in turn predicted lower levels of moderate-intense and vigorous-intense PA. The results suggest an influence of weight bias internalization on preoperative PA in bariatric surgery candidates. Subsequently, implementation of interventions addressing weight bias internalization in the usual treatment of bariatric surgery candidates might enhance patients' preoperative PA, while longitudinal analyses are needed to further examine its predictive value on PA after bariatric surgery. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Birth characteristics and childhood carcinomas.

Science.gov (United States)

Johnson, K J; Carozza, S E; Chow, E J; Fox, E E; Horel, S; McLaughlin, C C; Mueller, B A; Puumala, S E; Reynolds, P; Von Behren, J; Spector, L G

2011-10-25

Carcinomas in children are rare and have not been well studied. We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57,966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). White compared with 'other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR(per 5-year age increase)=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01-1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01-1.33). Gestational age birth weight, and birth order were not significantly associated with childhood carcinomas. This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

Science.gov (United States)

Hynds, Robert E; Janes, Sam M

2017-09-01

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

CT volumetry for gastric carcinoma: association with TNM stage.

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Hallinan, James T P D; Venkatesh, Sudhakar K; Peter, Luke; Makmur, Andrew; Yong, Wei Peng; So, Jimmy B Y

2014-12-01

We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage. This institutional review board-approved retrospective study was performed on 153 patients who underwent a staging CT study for histologically confirmed GC. CT volumetry was performed by drawing regions of interest including abnormal thickening of the stomach wall. Reproducibility of tumour volume (Tvol) between two readers was assessed. Correlation between Tvol and TNM/peritoneal staging derived from histology/surgical findings was evaluated using ROC analysis and compared with CT evaluation of TNM/peritoneal staging. Tvol was successfully performed in all patients. Reproducibility among readers was excellent (r = 0.97; P = 0.0001). The median Tvol of GC showed an incremental trend with T-stage (T1 = 27 ml; T2 = 32 ml; T3 = 53 ml and T4 = 121 ml, P volumetry may provide useful adjunct information for preoperative staging of GC. CT volumetry of gastric carcinoma is feasible and reproducible. Tumour volume 95.7 ml predicts metastatic gastric cancer with 87% sensitivity and 78.5% specificity (P = 0.0001). CT volumetry may be a useful adjunct for staging gastric carcinoma.

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF): incremental validity in predicting early postoperative outcomes in spine surgery candidates.

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Marek, Ryan J; Block, Andrew R; Ben-Porath, Yossef S

2015-03-01

A substantial proportion of individuals who undergo surgical procedures to relieve spine pain continue to report significant pain and dysfunction after recovery. Psychopathology and patient expectations have been linked to poor results, leading to an increasing reliance on presurgical psychological screening (PPS) as part of the surgical diagnostic process. The original Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1943) and the MMPI-2 (Butcher, Graham, Ben-Porath, Tellegen, & Dahlstrom, 2001) were among the measures most commonly used in PPS evaluations and research. This study focuses on the newest version of the test, the MMPI-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011; Tellegen & Ben-Porath, 2008/2011) as a predictor of outcomes for spine surgery candidates. Using a sample of 172 men and 210 women who underwent a PPS, we examined the ability of MMPI-2-RF scale scores to predict early surgical outcomes independent of other presurgical risk factors identified by other means, as well as patients' presurgical expectations. MMPI-2-RF results accounted for up to 11% of additional variance in measures of early postoperative functioning. MMPI-2-RF scales that assess for emotional/internalizing problems, specifically Demoralization, measures of somatoform dysfunction, and interpersonal problems contributed most to the prediction of diminished outcome. 2015 APA, all rights reserved

Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

International Nuclear Information System (INIS)

Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang

2006-01-01

Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD 5 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD 5 ) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended

Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment.

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Reiner, Caecilia S; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

2016-03-01

To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE). Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders. According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8). Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

The Role of Diffusion-Weighted Imaging (DWI in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC: The New Era of Functional Imaging Biomarkers

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Johannes M. Ludwig

2015-11-01

Full Text Available Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC. Current response assessment is mainly based on: (1 changes in size, which is at times unreliable and lag behind the result of therapy; and (2 contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI techniques, such as diffusion-weighted imaging (DWI have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement, which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

Circulating miRNAs as biomarkers for oral squamous cell carcinoma recurrence in operated patients

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Yan, Yan; Wang, Xuan; Venø, Morten Trillingsgaard

2017-01-01

MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC...

Interval Between Hysterectomy and Start of Radiation Treatment Is Predictive of Recurrence in Patients With Endometrial Carcinoma

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Cattaneo, Richard [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Hanna, Rabbie K. [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States); Jacobsen, Gordon [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States)

2014-03-15

Purpose: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with endometrial carcinoma. We analyzed the impact of the time interval between hysterectomy and RT initiation in patients with endometrial carcinoma. Methods and Materials: In this institutional review board-approved study, we identified 308 patients with endometrial carcinoma who received adjuvant RT after hysterectomy. All patients had undergone hysterectomy, oophorectomy, and pelvic and para-aortic lymph node evaluation from 1988 to 2010. Patients' demographics, pathologic features, and treatments were compared. The time interval between hysterectomy and the start of RT was calculated. The effects of time interval on recurrence-free (RFS), disease-specific (DSS), and overall survival (OS) were calculated. Following univariate analysis, multivariate modeling was performed. Results: The median age and follow-up for the study cohort was 65 years and 72 months, respectively. Eighty-five percent of the patients had endometrioid carcinoma. RT was delivered with high-dose-rate brachytherapy alone (29%), pelvic RT alone (20%), or both (51%). Median time interval to start RT was 42 days (range, 21-130 days). A total of 269 patients (74%) started their RT <9 weeks after undergoing hysterectomy (group 1) and 26% started ≥9 weeks after surgery (group 2). There were a total of 43 recurrences. Tumor recurrence was significantly associated with treatment delay of ≥9 weeks, with 5-year RFS of 90% for group 1 compared to only 39% for group 2 (P<.001). On multivariate analysis, RT delay of ≥9 weeks (P<.001), presence of lymphovascular space involvement (P=.001), and higher International Federation of Gynecology and Obstetrics grade (P=.012) were independent predictors of recurrence. In addition, RT delay of ≥9 weeks was an independent significant predictor for worse DSS and OS (P=.001 and P=.01, respectively). Conclusions: Delay in administering adjuvant RT after

Carcinoma multiplex

International Nuclear Information System (INIS)

Shah, S. A.; Riaz, U.; Zahoor, I.; Jalil, A.; Zubair, M.

2013-01-01

Multiple primaries in a single patient are uncommon, though not very rare. The existence of such cancers in two un-related, non-paired organs is even more un-common. Here, we present a case of 55 years old male who presented to us with a mucoepidermoid carcinoma of the parotid gland and was operated. Later on, he presented with a large cystic swelling in the pelvis which turned out to be pseudomyxoma peritonei. A review of slides and immunohistochemistry indicated it to be adenocarcinoma colon. He presented again with recurrent mucoepidermoid carcinoma of the parotid which was operated successfully with the use of myocutaneous flap for wound closure. He is currently undergoing chemotherapy. In order to establish a separate mono-clonal etiology of both tumours, immunohistochemistry was performed. To the best of our knowledge, carcinoma multiplex in the colon and the parotid has never been reported before. (author)

High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta

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Clark Taane G

2010-04-01

Full Text Available Abstract Background Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. Results Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%. Conclusions Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes

Oblimersen in Treating Patients With Merkel Cell Carcinoma

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2013-06-03

Recurrent Neuroendocrine Carcinoma of the Skin; Stage I Neuroendocrine Carcinoma of the Skin; Stage II Neuroendocrine Carcinoma of the Skin; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Neuroendocrine Carcinoma of the Skin

Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

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Sansing, Hope A. [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States); Sarkeshik, Ali; Yates, John R. [Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA (United States); Patel, Vyomesh; Gutkind, J. Silvio [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yamada, Kenneth M. [Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Berrier, Allison L., E-mail: allison.berrier@gmail.com [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States)

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

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Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

2017-03-01

The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

Cryotherapy for hepatocellular carcinoma

DEFF Research Database (Denmark)

Awad, Tahany; Thorlund, Kristian; Gluud, Christian

2009-01-01

BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

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Teik Hin Tan

2016-07-01

Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

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Tae Sook Hwang

2015-01-01

Full Text Available Follicular variant of papillary thyroid carcinoma (FVPTC, particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6% had a point mutation in one of the BRAF V600E (n=57, BRAF K601E (n=11, or RAS (n=64 genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital subtraction angiography

International Nuclear Information System (INIS)

Schubert, R.A.; Soeldner, J.; Kaiser, W.A.; Steiner, T.; Schubert, J.

1998-01-01

Renal cell carcinoma in a horseshoe kidney is an unusual entity. To our knowledge, only 123 cases have been published to date. We report the first bilateral case of two clear-cell carcinomas in an asymmetrically fused kidney. Optimum preservation of renal function after radical tumor removal requires accurate preoperative imaging. Since the vascular supply in fusion anomalies is extremely variable, angiography is mandatory. Magnetic resonance imaging was most suitable to predict the tumor extent and localization, because it simultaneously gave the most comprehensive anatomical overview of the malformation. (orig.)

Dynamic CT of hepatocellular carcinoma

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-01-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. 1 Decting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. 2 The dinamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. 3 The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma. (author)

Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

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Kiichiro Kaji

Full Text Available Squamous cell carcinoma antigen recognized by T cells 3 (SART3, a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC.The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315 were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ enzyme-linked immunospot and cytotoxic T lymphocyte (CTL assays using peripheral blood mononuclear cells (PBMCs in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677.The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677.

Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

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Liu, Changmei; Yang, Fangmei

2015-09-01

Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification.

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Ahn, Sung-Min; Jang, Se Jin; Shim, Ju Hyun; Kim, Deokhoon; Hong, Seung-Mo; Sung, Chang Ohk; Baek, Daehyun; Haq, Farhan; Ansari, Adnan Ahmad; Lee, Sun Young; Chun, Sung-Min; Choi, Seongmin; Choi, Hyun-Jeung; Kim, Jongkyu; Kim, Sukjun; Hwang, Shin; Lee, Young-Joo; Lee, Jong-Eun; Jung, Wang-Rim; Jang, Hye Yoon; Yang, Eunho; Sung, Wing-Kin; Lee, Nikki P; Mao, Mao; Lee, Charles; Zucman-Rossi, Jessica; Yu, Eunsil; Lee, Han Chu; Kong, Gu

2014-12-01

Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P = 0.038 and P = 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P = 0.017). RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. © 2014 by the American Association for the Study of Liver Diseases.

Prediction of local failures with a combination of pretreatment tumor volume and apparent diffusion coefficient in patients treated with definitive radiotherapy for hypopharyngeal or oropharyngeal squamous cell carcinoma

International Nuclear Information System (INIS)

Ohnishi, Kayoko; Shioyama, Yoshiyuki; Hatakenaka, Masamitsu

2011-01-01

The purpose of this study was to investigate the clinical factors for predicting local failure after definitive radiotherapy in oropharyngeal or hypopharyngeal squamous cell carcinoma. Between July 2006 and December 2008, 64 consecutive patients with squamous cell carcinoma of the hypopharynx or the oropharynx treated with definitive radiotherapy were included in this study. Clinical factors, such as pretreatment hemoglobin (Hb) level, T-stage, gross tumor volume of primary tumors (pGTV), and maximum standardized uptake value (SUV max ) on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), were evaluated for the correlation with local failure. A subset analysis of 32 patients with MR images including diffusion-weighted images (DWI) as a pretreatment evaluation was also performed. The Kaplan-Meier curves, the log-rank test, and the Cox proportional hazards model were used to evaluate these clinical factors. Eleven of 64 patients experienced local recurrence, with a median follow-up time of 15 months. In the univariate analysis, Hb level (p=0.0261), T-stage (p=0.012), pGTV (p=0.0025), and SUV max (p=0.024) were significantly associated with local failure. In the multivariate analysis, pGTV (p=0.0070) remained an adverse factor for local control. In the subset analysis of 32 patients with DWI, the median apparent diffusion coefficient (ADC) value of primary tumors on DWI was 0.79 x 10 -3 mm 2 /s (range, 0.40-1.60 x 10 -3 mm 2 /s). Patients with a high ADC value (>0.79 x 10 -3 mm 2 /s) had a significantly lower local control rate than patients with a low ADC value (100% vs. 44%, p=0.0019). The rate of local failure among patients with a large pGTV and a high ADC value was 55% (6/11), whereas no local failures occurred (0%, 0/21) among patients with a small pGTV or a low ADC. These results suggest that a combination of a large tumor volume and a high ADC value could be predictive of local recurrence after definitive radiotherapy in hypopharyngeal or

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation

International Nuclear Information System (INIS)

Arthur, Douglas W.; Schmidt-Ullrich, Rupert K.; Friedman, Richard B.; Wazer, David E.; Kachnic, Lisa A.; Amir, Cyrus; Bear, Harry D.; Hackney, Mary Helen; Smith, Thomas J.; Lawrence, Walter

1999-01-01

Purpose: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. Methods and Materials: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. Results: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for

A clinical study of oropharyngeal carcinoma. Chemoradioselection by TAR therapy

International Nuclear Information System (INIS)

Wada, Tetsuro; Yoshimura, Tomonori; Ohara, Hirotatsu

2013-01-01

The data of 91 patients with oropharyngeal carcinoma treated at the University of Tsukuba Hospital between 2002 and 2011 were reviewed. The mean age (±standard deviation) was 62.5 (±10.2) years and the male-female ratio was 5.5 : 1. The tumor originated from the lateral wall in 58 cases (63.7%), the anterior wall in 22 cases (24.2%), the superior wall in 8 cases (8.8%), and the posterior wall in 3 cases (3.3%). Six cases were revealed to be positive for human papilloma virus (HPV) among the 7 cases examined. Only supportive care was administered in 12 cases. The remaining 79 cases were treated, and the disease-specific 5-year survival rate was 55.6%. Smoking and alcohol consumption were significantly related to the disease-specific survival rate. At our department, chemoradiotherapy is initiated with 45 Gy of radiation concurrently with a novel oral fluoropyrimidine derivative (Teysuno, Taiho Phamaceutical Co., Ltd.) and vitamin A (TAR therapy), to improve the rate of curative surgical resection and select appropriate candidates for further definitive chemoradiotherapy to allow organ preservation (chemoradioselection). Chemoselection by induction chemotherapy, or chemoradioselection by initial concurrent chemoradiotherapy is considered to be important to make individualized treatment selection for patients with oropharyngeal carcinoma, because of the highly variable response to definitive chemoradiotherapy among cases. (author)

Palliation of Dysphagia in Carcinoma Esophagus

OpenAIRE

Ramakrishnaiah, Vishnu Prasad Nelamangala; Malage, Somanath; Sreenath, G.S.; Kotlapati, Sudhakar; Cyriac, Sunu

2016-01-01

Esophageal carcinoma has a special place in gastrointestinal carcinomas because it contains two main types, namely, squamous cell carcinoma and adenocarcinoma. Carcinoma esophagus patients require some form of palliation because of locally advanced stage or distant metastasis, where it cannot be subjected to curable treatment with surgery and chemoradiation. Many modalities of palliation of dysphagia are available, but the procedure with least morbidity, mortality, and long-term palliation of...