scholarly journals Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5316
Author(s):  
Serdar Yavuzyigitoglu ◽  
Michael C. Y. Tang ◽  
Miguel Jansen ◽  
Kaspar W. Geul ◽  
Roy S. Dwarkasing ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Medical Center ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Growth Patterns ◽  
Mutation Status ◽  
Solitary Metastasis ◽  
Radiological Images ◽  
Metastatic Patterns ◽  
Chromosome 8P

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1- mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns.

Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
First Generation ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cancer Center ◽  
Free Survival ◽  
Alive With Disease ◽  
Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

scholarly journals The Tumorigenic Properties of EZH2 are Mediated by MiR-26a in Uveal Melanoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yao Li ◽  
Mingmei Zhang ◽  
Huayin Feng ◽  
Shaya Mahati
Keyword(s):  
Uveal Melanoma ◽  
Cell Function ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Polycomb Group ◽  
Luciferase Reporter ◽  
Polycomb Group Protein ◽  
Ezh2 Expression ◽  
Group Protein ◽  
Tumor Types

Background: The polycomb group protein enhancer of zeste homolog 2 (EZH2) has been found to be highly expressed in various tumors, and microRNA-26a (miR-26a) is often unmodulated in cancers. However, the functions of these two molecules in uveal melanoma (UM) and their relationships have not been reported.Methods: We explored the effects of the miR-26a–EZH2 axis in UM by examining the levels of miR-26a and EZH2. The EZH2 levels in various tumor types and the correlations between EZH2 levels and overall survival and disease-free survival were reanalyzed. The binding of miR-26a to the 3′-untranslated region of EZH2 mRNA was measured using the luciferase reporter assay. The regulation of EZH2 gene expression by miR-26a was also identified, and the effect of elevated EZH2 expression on UM cell function was further examined. Results: miR-26a was downregulated and EZH2 was upregulated in UM cells. Overexpression of miR-26a inhibited cell proliferation, and knockdown of EZH2 suppressed cell growth. EZH2 was a direct target of miR-26a in UM cells. The knockout of EZH2 mimicked the tumor inhibition of miR-26a in UM cells, whereas the reintroduction of EZH2 abolished this effect. In addition, a network of EZH2 and its interacting proteins (UBC, CDK1, HDAC1, SUZ12, EED) was found to participate in miR-26a-mediated tumor progression.Conclusion: The newly identified miR-26a–EZH2 axis may be a potential target for the development of treatment strategies for UM.

Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.

1990 ◽  
Vol 8 (9) ◽  
pp. 1466-1475 ◽  
Author(s):  
N Wolmark ◽  
H Rockette ◽  
D L Wickerham ◽  
B Fisher ◽  
C Redmond ◽  
...  
Keyword(s):  
Portal Vein ◽  
Treatment Failure ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Treated Group ◽  
Control Group ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Disease Free

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.

scholarly journals High Cysteinyl Leukotriene Receptor 1 Expression Correlates with Poor Survival of Uveal Melanoma Patients and Cognate Antagonist Drugs Modulate the Growth, Cancer Secretome, and Metabolism of Uveal Melanoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2950
Author(s):  
Kayleigh Slater ◽  
Aisling B. Heeran ◽  
Sandra Garcia-Mulero ◽  
Helen Kalirai ◽  
Rebeca Sanz-Pamplona ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lines ◽  
Uveal Melanoma ◽  
Therapeutic Potential ◽  
Unmet Need ◽  
Digital Pathology ◽  
Disease Free Survival ◽  
High Expression ◽  
Poor Overall Survival ◽  
Cysteinyl Leukotriene

Metastatic uveal melanoma (UM) is a rare, but often lethal, form of ocular cancer arising from melanocytes within the uveal tract. UM has a high propensity to spread hematogenously to the liver, with up to 50% of patients developing liver metastases. Unfortunately, once liver metastasis occurs, patient prognosis is extremely poor with as few as 8% of patients surviving beyond two years. There are no standard-of-care therapies available for the treatment of metastatic UM, hence it is a clinical area of urgent unmet need. Here, the clinical relevance and therapeutic potential of cysteinyl leukotriene receptors (CysLT1 and CysLT2) in UM was evaluated. High expression of CYSLTR1 or CYSLTR2 transcripts is significantly associated with poor disease-free survival and poor overall survival in UM patients. Digital pathology analysis identified that high expression of CysLT1 in primary UM is associated with reduced disease-specific survival (p = 0.012; HR 2.76; 95% CI 1.21–6.3) and overall survival (p = 0.011; HR 1.46; 95% CI 0.67–3.17). High CysLT1 expression shows a statistically significant (p = 0.041) correlation with ciliary body involvement, a poor prognostic indicator in UM. Small molecule drugs targeting CysLT1 were vastly superior at exerting anti-cancer phenotypes in UM cell lines and zebrafish xenografts than drugs targeting CysLT2. Quininib, a selective CysLT1 antagonist, significantly inhibits survival (p < 0.0001), long-term proliferation (p < 0.0001), and oxidative phosphorylation (p < 0.001), but not glycolysis, in primary and metastatic UM cell lines. Quininib exerts opposing effects on the secretion of inflammatory markers in primary versus metastatic UM cell lines. Quininib significantly downregulated IL-2 and IL-6 in Mel285 cells (p < 0.05) but significantly upregulated IL-10, IL-1β, IL-2 (p < 0.0001), IL-13, IL-8 (p < 0.001), IL-12p70 and IL-6 (p < 0.05) in OMM2.5 cells. Finally, quininib significantly inhibits tumour growth in orthotopic zebrafish xenograft models of UM. These preclinical data suggest that antagonism of CysLT1, but not CysLT2, may be of therapeutic interest in the treatment of UM.

scholarly journals Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

2020 ◽  
Vol 37 (5) ◽  
pp. 593-605
Author(s):  
Florian E. Buisman ◽  
Eric P. van der Stok ◽  
Boris Galjart ◽  
Peter B. Vermeulen ◽  
Vinod P. Balachandran ◽  
...  
Keyword(s):  
New York ◽  
Liver Metastases ◽  
Preoperative Chemotherapy ◽  
Colorectal Liver Metastases ◽  
Systemic Chemotherapy ◽  
Disease Free Survival ◽  
Growth Patterns ◽  
Cancer Center ◽  
Pretreated Patients ◽  
Histopathological Growth Patterns

Abstract Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.37–0.73, p < 0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p = 0.19). In pretreated patients no significant effect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p = 0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p = 0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p < 0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this effect was only observed in patients that were not treated with chemotherapy.

MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients

2012 ◽  
Vol 97 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Ernie Marshall ◽  
Christopher Romaniuk ◽  
Paula Ghaneh ◽  
Helen Wong ◽  
Marie McKay ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Study ◽  
Uveal Melanoma ◽  
Hepatic Metastases ◽  
A Prospective Study

scholarly journals Systematic review of liver directed therapy for uveal melanoma hepatic metastases

HPB ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Alistair Rowcroft ◽  
Benjamin P.T. Loveday ◽  
Benjamin N.J. Thomson ◽  
Simon Banting ◽  
Brett Knowles
Keyword(s):  
Systematic Review ◽  
Uveal Melanoma ◽  
Hepatic Metastases

Predictors of Survival in CLL: Multivariate Analyses Reveal Significant Correlation with IgVH Gene Mutation Status, Clinical Stage, and Cellular CD38 (but Not Zap-70) Expression.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5010-5010
Author(s):  
Alicia D. Volkheimer ◽  
Marc C. Levesque ◽  
Bethany E. Beasley ◽  
Louis Diehl ◽  
Youwei Chen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Doubling Time ◽  
Multivariate Analyses ◽  
Medical Center ◽  
Clinical Stage ◽  
Leukemia Cell ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Binet Stage ◽  
Univariate Analyses

Abstract One of the complexities of chronic lymphocytic leukemia (CLL) is that some patients die early from the disease, while others identically staged by conventional means may live more than two decades. This has led to a search for prognostic indicators that correlate better with eventual survival. Candidate markers include Rai stage, Binet stage, lymphocyte doubling time (DT), immunoglobulin heavy chain V region (IgVH) mutation status, and leukemia cell CD38 and Zap-70 expression. To determine which of these markers correlate best with survival in univariate and multivariate analyses, we examined these parameters in 150 CLL patients from a VA medical center and a university medical center. CLL cells were purified from patients not receiving active treatment with WBC &gt;20,000/uL by deleting T cells, monocytes, neutrophils, and erythrocytes using antibodies against CD2, CD3, CD16, CD36, CD56, and glycophorin A, and centrifugation over ficoll-Hypaque (CLL purity &gt; 97%). In univariate analyses, patients with advanced stage on presentation had shorter survival than those with low stage [14.0 yr for high modified Rai stage vs. 25.3 yr for low stage (p = 0.013), and 13.8 yr, 13.4, and 25.3 yr for Binet stages C, B, and A, respectively (p = 0.033)]. Patients with a lymphocyte DT &gt;3 yr survived twice as long (22.6 yr) as those with a DT &lt;3 yr (11.3 yr) (p = 0.004). There was a strong relationship of IgVH mutation status with survival (median survival 22.6 yr for mutated, 9.4 yr for unmutated; p = 0.0006). Likewise, cellular CD38 expression significantly correlated with survival (CD38 neg 25.3 yr, CD38 pos 13.4 yr, p = 0.008). Zap-70 expression determined by quantitative immunoblot [Zap-70/actin ratio (anti-Zap-70 antibody from Upstate; clone 2F3.2)] was not significantly related to survival (Zap-70 pos 20.8 yr, Zap-70 neg 22.6 yr). Other parameters found not to be related to eventual survival were WBC on presentation, maximum WBC reached before treatment, and time from diagnosis to initial treatment. IgVH mutation status was significantly related to lymphocyte DT, CD38 expression, and Zap-70 expression. In multivariate analyses using the proportional hazards model, IgVH mutation status (p = 0.001), cellular CD38 expression (p = 0.025), and Binet stage (p = 0.026) were significantly associated with survival (with p = 0.0002 overall for these three parameters in the model), but Zap-70 had no significant relationship to survival in the model. Thus, in contrast to other reports, cellular Zap-70 expression does not correlate with various parameters of disease severity (including survival) in our cohort of CLL patients. In summary, our univariate analyses show significant correlations of advanced clinical stage, short lymphocyte doubling time, high CD38 expression, and unmutated IgVH with short survival. However, multivariate analyses show that only IgVH gene mutation status, clinical stage at presentation, and cellular CD38 expression correlate significantly with survival.

MicroRNA alterations associated with BRAF status in melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8565-8565
Author(s):  
Michelle W. Ma ◽  
Joshua Andrew Farhadian ◽  
Erica Brooke Friedman ◽  
Eleazar Vega-Saenz de Miera ◽  
Douglas Hanniford ◽  
...  
Keyword(s):  
Tumor Suppressors ◽  
Braf Mutation ◽  
Target Genes ◽  
Medical Center ◽  
Differentially Expressed ◽  
New York University ◽  
Gene Target ◽  
Significant Differential Expression ◽  
Mutation Status ◽  
Differentially Expressed Mirnas

8565 Background: We hypothesize that BRAF mutations result in microRNA (miRNA) alterations which contribute to orchestrating the mutant BRAF’s oncogenic effects in melanoma. Our study is the first to examine the association between the BRAF mutation status in primary melanomas and the expression of miRNAs that target known tumor suppressors. Methods: 84 prospectively accrued melanoma patients at New York University Langone Medical Center were studied. DNA and total RNA were extracted from consecutive sections of formalin-fixed paraffin-embedded primary tissues. BRAF mutation status was determined by DNA sequencing. RNA was hybridized to miRCURY miRNA microarrays containing 1314 probes. Normalized miRNA data were analyzed using the t-test (p<0.05) to identify differentially expressed miRNAs between BRAFmut vs. BRAFwt cases. Those with an average fold change (FC) > 2 were selected for predicted (TargetScan, PicTar) and validated (miRWalk) gene target analysis, and overlapping genes targeted by ≥ 2 miRNAs were analyzed using pathway-mapping algorithms (KEGG, BioCarta, PANTHER). Results: 48 (57%) primaries were BRAFwt and 36 (43%) were BRAFmut (26 V600E, 4 V600K, 1 V600R, 1 V600D, 4 other). 30 miRNAs met the criteria for statistically significant differential expression and FC thresholding: let-7i, miR-23c, -26a/b, -27b, -34a, -98, -126*, -141, -148a, -181b, -195, -199a-3p, -199a/b-5p, -200a/b/c, -203, -205, -455-3p, -491-3p, -606, -641, -646, -1297, -4301; miRPlus-C1070, -C1110, -G1246-3p (average FC: 2.3-3.5, all increased in BRAFmut vs. BRAFwt). Predicted and validated target gene analysis revealed 317 genes, of which 110 (35%) were convergent targets of ≥ 2 miRNAs. Pathway analyses of the predicted, validated, and convergent target genes pointed to the potential impact of BRAFmut-associated miRNAs on known tumor suppressors FAS, PTEN, and TNF and the p53 pathway. Conclusions: Differentially expressed miRNAs in BRAFmut vs. BRAFwt primaries target genes with known roles in melanoma biology and/or treatment response. These miRNAs warrant further study as potential effectors of the BRAFmut oncogenic program.

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