scholarly journals CD44v6 expression is a novel predictive marker of therapy response and poor prognosis in gastric cancer patients

2018 ◽  
Author(s):  
Carla Pereira ◽  
Daniel Ferreira ◽  
Carolina Lemos ◽  
Diana Martins ◽  
Nuno Mendes ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Therapy Response ◽  
Predictive Marker ◽  
Response To Therapy ◽  
Conventional Chemotherapy ◽  
Poor Overall Survival ◽  
Cd44v6 Expression

AbstractLate diagnosis, modest treatment options and lack of predictive markers of therapy response dictate the poor overall survival (OS) of ∼1 year in most gastric cancer (GC) patients. We hypothesized that the level of CD44v6 expression in tumor cells could predict therapy response and prognosis in GC patients.We analyzed a surgical tumor series of GC patients for the extension of CD44v6 membranous immuno-expression, clinical-pathological features, patient survival, and response to therapy. By integrating this information, we assessed the value of CD44v6 expression to predict benefit from current treatment regimens and prognosis in GC patients. We used GC cell lines and mouse xenografts to assess and/validate the biological impact of CD44v6 expression in GC cells behavior.We demonstrated that GC patients whose tumors present higher levels of CD44v6 membranous expression benefit from adding chemotherapy to surgery as opposed to those without CD44v6 expression. Moreover, patients bearing CD44_high tumors presented worse OS than those bearing CD44_absent/low tumors, consolidating the role of CD44v6 expression as an independent factor of poor prognosis in this disease. Finally, ourin vitroand patients’ data pinpoints the CD44v6+ cell population as the driver of tumor recurrence following conventional chemotherapy, in heterogeneous tumors composed by CD44v6- and CD44v6+ cells.Our study pioneers the identification of CD44v6 as a potential predictive marker of response to conventional chemotherapy, and consolidates CD44v6 as an independent marker of poor prognosis in GC. Overall, our data strongly supports selection of patients with high CD44v6 expressing tumors for conventional chemotherapy with or without surgery, regardless of the TNM stage.

scholarly journals CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1249
Author(s):  
Gabriela M Almeida ◽  
Carla Pereira ◽  
Ji-Hyeon Park ◽  
Carolina Lemos ◽  
Sofia Campelos ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Therapy Response ◽  
Predictive Marker ◽  
Response To Treatment ◽  
Depth Of Invasion ◽  
Conventional Chemotherapy ◽  
Tumor Expression ◽  
Gastric Cancer Patients ◽  
Selection Of ◽  
Cd44v6 Expression

In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.

scholarly journals Increased Thioredoxin-1 Expression Promotes Cancer Progression and Predicts Poor Prognosis in Patients with Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wenjing Shang ◽  
Zhongdong Xie ◽  
Fengying Lu ◽  
Daoquan Fang ◽  
Tianbin Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Antitumor Effects ◽  
Thioredoxin 1

Background. Thioredoxin-1 (Trx-1) is a small redox protein, which plays an important role in many biological processes. Although increased expression of Trx-1 in various solid tumors has been reported, the prognostic significance and function of Trx-1 in human gastric cancer (GC) are still unclear. Here, we investigated the clinical and prognostic significance of Trx-1 expression and the function and mechanism of Trx-1 in human GC. Methods. We analyzed Trx-1 mRNA expression from the GEO database and Trx-1 protein expression in 144 GC tissues using immunohistochemistry. Effects of Trx-1 on GC cell were assessed in vitro and in vivo through Trx-1 knockdown or overexpression. The antitumor effects of the Trx-1 inhibitor, PX-12, on GC cells were investigated. PTEN and p-AKT expressions were evaluated by Western blotting. Results. Increased Trx-1 expression was found in GC tissues and associated with poor prognosis and aggressive clinicopathological characteristics in patients with GC. High Trx-1 expression predicted poor prognosis, and its expression was an independent prognostic factor for overall survival of GC patients. Knockdown of Trx-1 expression inhibited GC cell growth, migration, and invasion in vitro and tumor growth and lung metastasis in vivo. Conversely, overexpression of Trx-1 promoted GC cell growth, migration, and invasion. We also found that PX-12 inhibited GC cell growth, migration, and invasion. Overexpression of Trx-1 caused a decrease in PTEN and increase in p-AKT levels whereas silencing Trx-1 caused an increase in PTEN and decrease in p-AKT levels in GC cells. Inhibition of AKT signaling pathway by MK2206 also inhibited GC cell growth, migration, and invasion. Conclusion. Our results indicate that Trx-1 may be a promising prognostic indicator and therapeutic target for GC patients.

scholarly journals The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9472
Author(s):  
María Alarcón ◽  
Wilda Olivares ◽  
Miguel Córdova-Delgado ◽  
Matías Muñoz-Medel ◽  
Tomas de Mayo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Area Under The Curve ◽  
Soft Agar ◽  
Poor Overall Survival ◽  
Clinicopathologic Characteristics ◽  
Non Invasive

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.

scholarly journals P09.05 177Lu-DOTATATE therapy in progressive meningioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii39-iii39
Author(s):  
M Müther ◽  
W Roll ◽  
B Zinnhardt ◽  
M Schäfers ◽  
K Rahbar ◽  
...  
Keyword(s):  
Stable Disease ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Therapy Response ◽  
Response To Therapy ◽  
Current Evidence ◽  
Promising Alternative ◽  
Multifocal Disease ◽  
Post Therapy

Abstract BACKGROUND Progressive meningioma is a challenging condition with a decreasing number of treatment options over the course of disease. Neurovascular involvement and multifocal disease often complicate surgical management. In addition, repeated radiotherapy carriers a risk of side effects. In somatostatin receptor expressing meningioma, peptide receptor radiotherapy (PPRT) with 177Lu-DOTATATE poses a promising alternative. However, current evidence is scarce. Hereby we present our single center experience of (PPRT) with 177Lu-DOTATATE in progressive meningioma. METHODS Eight patients (median age: 71 years; range 56–77) with progressive meningioma underwent PRRT using 177Lu-DOTATATE were included in this retrospective analysis. Response to therapy was assessed by interim and post-therapy 68Ga-DOTATATE-PET-CT and MRI. 177Lu-DOTATATE scintigraphies 48h p.i. were evaluated according to Krenning scale. Additionally, clinical outcome and follow up imaging were analyzed for progression free interval times. RESULTS Eight patients were included: Six patients with grade II and two patients with grade I meningiomas, according to the 2016 WHO classification. Six of eight patients harbored multifocal disease. One patients suffered systemic metastatic disease. Patients received a median of three cycles (range: 1 - 5) of PRRT with 177Lu-DOTATATE (mean injected dose 7.1 GBq) between 1/2015 and 1/2019. Tumor uptake in 48h p.i. 177Lu-Scintigraphies was heterogeneous (Krenning scale; median: 3; range: 1–4). Post-therapy imaging scheduled eight weeks after completion of therapy showed progressive disease in five patients, three patients had stable disease. Median follow-up post therapy response evaluation was 24 months in patients with stable disease. Median time to progression was 10 months. CONCLUSION In this cohort of eight progressive meningioma patients 177Lu-DOTATATE therapy showed heterogeneous efficacy.

Trace FVIII Augments Rfviia Induced Thrombin Generation and Improves Hemostasis in Hemophilia A Patients with Inhibitors: A clinical Cohort Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 40-40
Author(s):  
Tami Livnat ◽  
Uri Martinowitz ◽  
Shirley Azar-Avivi ◽  
Ariela Zivelin ◽  
Gili Kenet
Keyword(s):  
Thrombin Generation ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Therapy Response ◽  
Response To Therapy ◽  
Individual Therapy ◽  
Severe Bleeding ◽  
Inhibitor Level

Abstract Abstract 40 Treatment of Hemophilia A patients with inhibitors is challenging, as correlation between inhibitor level and hemostatic response to therapy may be limited. Thrombin generation (TG) assays may be used to monitor hemostasis and/or predict patients' response to various bypass agents. Since combination of excess FVIII and bypassing agents may potentiate improved TG in inhibitor plasma tested in-vitro, we aimed to define the therapeutic feasibility of co-administration of rFVIIa and FVIII in hemophilia A patients with inhibitors. Patients and Methods: Following consent, blood was sampled from 15 hemophilia patients (age: 0.5–46y) with inhibitor (0.5–668 BU). Platelet poor plasma (PPP) was prepared, spiked and incubated with excess FVIII. Ex-vivo kinetics of FVIII neutralization over time was evaluated by sequential measurements of residual FVIII activity. We then used recalcification induced-TG (performed in PPP supplemented with 4μM phospholipids), to measure the ex-vivo response to increasing concentrations of FVIII (0–200%) and rFVIIa (0–6.8μg/ml), alone or in combination. Based upon these ex-vivo studies, an individually tailored therapeutic regimen of concomitant bolus doses of rFVIIa and FVIII was applied to nine hemophilia patients with inhibitors. Results: FVIII ex- vivo measurements post incubation detected either rapid or slow neutralization- not correlating with inhibitor level. Flat baseline TG curves were recorded for all inhibitor patients, with variable responses to FVIII and/or rFVIIa. Combined spiking with FVIII and rFVIIa dramatically increased rFVIIa induced ETP (762.7 ±305.7 as compared to 339.3±179.9 nM/min with rFVIIa only) and peak height (48.7±23.6 vs 23.7±16.6) in all patients' plasma samples. Based upon individual ex vivo assays, concomitant bolus doses of rFVIIa (120–200 mcg/kg) and FVIII (50–100 U/Kg), were applied to 9 patients, for a total of 333 episodes during study period (February 2010-Septemeber 2012). Patients during immune tolerance received rFVIIa prophylaxis with combined rFVIIa/FVIII dosing applied 3 times weekly. For most mild- moderate joint bleeds hemostasis was defined as satisfactory following a single combined dose. Severe bleeding episodes or target joint bleeds responded to 2–8 (median:3) combined doses, applied every 12 hours. During study period the median number of spontaneous joint bleeds decreased from 4 to 1 per month. Neither thrombosis nor any other complications evolved. Conclusions: Prediction of individual therapy response may be achieved by pre-analytical studies, assessing FVIII neutralization kinetics as well as ex-vivo TG responses to combined bypass/FVIII therapy. Such studies enabled treatment of inhibitor patients according to individually tailored regimens. We confirmed for the first time that the in- vitro advantage of combining FVIII and rFVIIa, indeed accounts for improved hemostasis and may safely be applied to inhibitor patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Adult Neuroblastoma Complicated by Increased Intracranial Pressure: A Case Report and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Patrick L. Stevens ◽  
Douglas B. Johnson ◽  
Mary Ann Thompson ◽  
Vicki L. Keedy ◽  
Haydar A. Frangoul ◽  
...  
Keyword(s):  
Case Report ◽  
Intracranial Pressure ◽  
Pediatric Population ◽  
Adult Population ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Response To Therapy ◽  
Cell Transplant ◽  
Increased Intracranial Pressure ◽  
Poor Overall Survival

Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures. The patient was treated with systemic chemotherapy, I131metaiodobenzylguanidine (MIBG) radiotherapy, and autologous stem cell transplant (SCT). Unfortunately the patient’s response to therapy was limited and she subsequently died. We aim to review neuroblastoma in the context of increased intracranial pressure and the limited data of neuroblastoma occurring in the adult population, along with proposed treatment options.

scholarly journals JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level

2020 ◽  
Author(s):  
Da Huang ◽  
Fan Xiao ◽  
Fuzhou Hua ◽  
Zhenzhong Luo ◽  
Zhaoxia Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Predictive Marker ◽  
Cancer Proliferation ◽  
Poor Overall Survival ◽  
Downstream Target ◽  
Cellular Analysis

Abstract Background: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. Methods: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis(RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. Results: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. Conclusions: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

scholarly journals Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas

2020 ◽  
Vol 7 (1) ◽  
pp. e000505
Author(s):  
Emoke Papp ◽  
Anita Steib ◽  
Elhusseiny MM Abdelwahab ◽  
Judit Meggyes-Rapp ◽  
Laszlo Jakab ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Therapy Response ◽  
Clinical Decision ◽  
Response To Therapy ◽  
Solid Tumours ◽  
Chemosensitivity Test ◽  
Pleural Effusions ◽  
In Vitro Chemosensitivity ◽  
Lung Adenocarcinomas

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.

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