scholarly journals Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Te-Fu Tsai ◽  
Ji-Fan Lin ◽  
Yi-Chia Lin ◽  
Kuang-Yu Chou ◽  
Hung-En Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Expression Level ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Early Stage Disease ◽  
Stage Disease

Abstract Bladder cancer (BC) is the second most common urologic malignancy and the ninth most common malignancy worldwide. Surgical resection is the mainstay of treatment for patients with early-stage disease, whereas therapeutic options are limited for patients with advanced-stage or residual BC. Programmed cell death ligand-1 (PD-L1) is an important target for immunotherapy. It is known that PD-L1 is overexpressed in BC; a clinical trial involving PD-L1 immune checkpoint inhibitors in advanced BC is ongoing. In the present study, we used Western blot and quantitative real-time PCR (qPCR) to define the expression level of PD-L1 after cisplatin treatment in BC-derived cell lines. The signal activation was also evaluated by Western blot in BC-derived cell lines. We found that chemotherapeutic drug cisplatin can induce PD-L1 but not PD-L2 expression in BC-derived cell lines. Furthermore, the expression level of PD-L1 was increased in a dose- and time-dependent manner after cisplatin treatment. The cisplatin-induced PD-L1 expression is mainly mediated by ERK1/2 but not Akt/mTOR signal pathway. Moreover, we found that cisplatin activates transcription factor activator protein-1 (AP-1) to regulate PD-L1 expression. The chemotherapy drug such as cisplatin may trigger resistance of BC through PD-L1 up-regulation. The present study suggests that PD-L1 antibody should be used concomitantly with chemotherapy in the setting of advanced and metastatic BC.

Flow Cytometric Detection of ZAP-70 in Chronic Lymphocytic Leukemia: Correlation With Immunocytochemistry and Western Blot Analysis

2007 ◽  
Vol 131 (1) ◽  
pp. 50-56
Author(s):  
Graham W. Slack ◽  
Juanita Wizniak ◽  
Laith Dabbagh ◽  
Xinzhe Shi ◽  
Pascal Gelebart ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Specimen Processing

Abstract Context.—Expression of ZAP-70 in chronic lymphocytic leukemia (CLL) predicts worse clinical outcome in patients with early-stage disease. It has become important to include ZAP-70 in the immunophenotyping panel used to diagnose CLL, commonly performed by flow cytometry (FC). Nevertheless, the methodology used to detect ZAP-70 by FC has not been extensively evaluated. Objective.—To describe our FC method for detecting ZAP-70 in CLL and assess whether this assay is useful in estimating the ZAP-70 protein level in CLL cells. Design.—ZAP-70 expression was assessed by FC in 45 consecutive newly diagnosed CLL patients, and the results were correlated with those of immunocytochemistry and Western blot analysis. Results.—With >25% ZAP-70–positive B cells as the cutoff, the FC results had a perfect concordance with those of immunocytochemistry (39/39, 100%) and Western blot analysis (7/7, 100%). The use of autofluorescence controls was found to be superior to other alternatives. Overall, 19 (42%) of 45 cases were ZAP-70 positive in our series. Since only 7 cases (16%) had >20% to 30% ZAP-70–positive B cells, the cutoff of >25% readily separated CLL into positive and negative groups in most cases. ZAP-70 positivity was significantly associated with atypical morphology but not other laboratory parameters evaluated. Conclusions.—With proper specimen processing and the use of directly fluorescence-conjugated anti–ZAP-70 antibody, one can readily incorporate ZAP-70 into the routine FC study panel for CLL. Our data suggest that FC is a rapid and useful method to estimate the ZAP-70 protein expression level in CLL.

scholarly journals Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 421 ◽  
Author(s):  
Alain Mina ◽  
Chetan Vakkalagadda ◽  
Barbara Pro
Keyword(s):  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Close Monitoring ◽  
Early Stage Disease ◽  
Early Results ◽  
Stage Disease

Although Hodgkin lymphoma (HL) is highly curable with first-line therapy, relapses occur in approximately 10–20% of patients with early stage disease and 30–40% of patients with advanced stage disease. The standard approach for relapsed or refractory disease is salvage therapy, followed by consolidation with high dose therapy and autologous stem cell transplant (ASCT). Patients who achieve a complete response to salvage therapy prior to ASCT have better outcomes, thus recent studies have focused on incorporating newer agents in this setting. Major challenges in the management of relapsed patients remain how to choose and sequence the many salvage therapies that are currently available and how to best incorporate novel agents in the current treatment paradigms. In this article, we will summarize the most recent advances in the management of patients with recurrent HL and will mainly focus on the role of new agents approved and under investigation. Aside from brentuximab vedotin and checkpoint inhibitors, other novel agents and therapies are showing promising early results. However, at least with some of the newest targeted strategies, it is important to recognize that we are facing new challenges in terms of toxicities, which require very close monitoring and education of both the patient and treating physician.

scholarly journals New Frontiers in the Medical Therapy of Hepatocellular Carcinoma

Chemotherapy ◽  
2022 ◽  
Author(s):  
Claudia Angela Maria Fulgenzi ◽  
Antonio D'Alessio ◽  
Thomas Talbot ◽  
Alessandra Gennari ◽  
Mark R. Openshaw ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Phase Iii ◽  
Early Stage Disease ◽  
Primary Liver Tumor ◽  
Phase Iii Clinical Trials ◽  
Stage Disease ◽  
Major Treatment

Background: Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and it rates fourth as a cause of cancer-related death. The presence of underlying liver disease and poor chemosensitivity pose major treatment challenges in the management of HCC. However, in the last few years the therapeutic scenario has substantially changed, and immunotherapy in the form of immune checkpoint inhibitors (ICPIs) has become an essential therapeutic strategy in this field. Summary: After controversial results of monotherapy, ICPIs have been mainly investigated in association with anti-angiogenic agents or as dual checkpoint inhibition. The combination of atezolizumab plus bevacizumab has become the new therapeutic standard for unresectable HCC. Currently, a number of ICPIs-based combinations are being studied in phase III clinical trials as front-line therapy for advanced HCC, with growing interest in integration of early-stage disease management in the form of adjuvant or neoadjuvant therapies. With most of the trials investigating ICPIs as first line treatment, the second line scenario relies mainly on tyrosine kinase inhibitors, which however, have not been formally trialed after ICPIs. Key messages: In this review we summarize the main therapeutic advances in the systemic management of HCC focusing on the most relevant ongoing trials. We also discuss the main issues arising from a such rapidly evolving field including therapeutic sequencing and patient stratification.

Clinical Profile of a New Monoclonal Antibody-Based Immunoassay for Tissue Polypeptide Antigen

1994 ◽  
Vol 9 (4) ◽  
pp. 231-238 ◽  
Author(s):  
M. Correale ◽  
H. Arnberg ◽  
P. Blockx ◽  
E. Bombardieri ◽  
M. Castelli ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bladder Cancer ◽  
Early Stage ◽  
Roc Curves ◽  
Preliminary Evaluation ◽  
Tissue Polypeptide Antigen ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Wide Range ◽  
Disease Stages

Our preliminary evaluation of a new monoclonal antibody-based assay for tissue polypeptide antigen (TPA) has shown it to be clinically equivalent to the polyclonal antibody-based assay for TPA. The new assay (TPA-M) employs three monoclonal antibodies to epitopes on cytokeratins 8, 18 and 19. This multicenter, multinational study included 266 patients with newly diagnosed carcinomas of the lung, breast, large bowel and urinary bladder. TPA values from the two assays were compared with three other cytokeratin markers (TPS, CYFRA 21–1 and TPACyk) and with the established reference markers for these malignancies (CEA and NSE for lung, CA 15–3 for breast, CEA and CA 19–9 for colorectal tumors). Analysis of receiver operating characteristic (ROC) curves in lung, colorectal and bladder cancer showed similar sensitivities for the two assays, ranging from 50% to 80% with a specificity of 95%. In breast cancer all the markers studied showed poor sensitivity. However, TPA determination by either method could discriminate advanced stage (stages III and IV) from early stage disease (stages 0 to II). TPA showed similar discriminating ability in bladder cancer. On the basis of the results obtained in our patient series, it seems that of the cytokeratin markers studied, TPA and TPA-M are the most sensitive and offer a wide range of clinical applications.

Evaluation of platelet distribution width as a diagnostic and prognostic biomarker in bladder neoplasm

2019 ◽  
Vol 15 (33) ◽  
pp. 3797-3807
Author(s):  
Lei Liu ◽  
Yajing Zhao ◽  
Jianfeng Cui ◽  
Shouzhen Chen ◽  
Benkang Shi
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Bladder Neoplasm ◽  
Platelet Distribution Width ◽  
Early Stage Disease ◽  
Distribution Width ◽  
Blood Indices ◽  
Stage Disease ◽  
Potential Biomarker

Aim: To evaluate the role of preoperative platelet distribution width (PDW) as a potential biomarker for distinguishing malignancy and tumor advantage of bladder neoplasm. Methods: The study included 210 subjects with bladder cancer, 76 subjects with urothelial papilloma and 132 healthy control subjects. Preoperative PDW along with other blood indices was evaluated. Results: PDW was higher in urothelial papilloma patients than that in bladder cancer patients (p < 0.001). Bladder cancer patients with advanced-stage disease exhibited lower PDW levels compared with patients with early stage disease. Conclusion: Reduced preoperative PDW level is an indicator of malignancy and advanced bladder cancer stages, suggesting it as a potential biomarker in bladder cancer diagnosis and prognosis.

scholarly journals Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events

ESMO Open ◽  
2019 ◽  
Vol 4 (4) ◽  
pp. e000472 ◽  
Author(s):  
Esmée P. Hoefsmit ◽  
Elisa A. Rozeman ◽  
John B. A. G. Haanen ◽  
Christian U. Blank
Keyword(s):  
Adverse Events ◽  
Autoimmune Diseases ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Future Research ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Cell Death Protein

Unprecedented successes regarding cancer immunotherapy have been achieved, in which therapeutic agents are used to target immune cells rather than cancer cells. The most effective immunotherapy to date is the group of immune checkpoint inhibitors (CPI), targeting, for example, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or programmed cell death protein (PD-1). TThe combination of these therapies (anti-PD-1 with anti-CTLA-4) induces high response rates, and seem to be increased further when applied in early-stage disease. However, combined CTLA-4 plus PD-1 blockade causes frequent high-grade immune-related adverse events (irAE). To date, research on biological mechanism of irAEs is scarce and no widely accepted biomarkers predicting onset of severe irAEs have been identified. The similarity of irAEs to autoimmune disorders fuels the hypothesis that irAEs may be linked to susceptible genetic loci related to various autoimmune diseases. In this review, we extensively searched for susceptible loci associated with various autoimmune diseases, and pooled them in groups most likely to be associated with CPI-induced irAEs. These sets could be used in future research on predicting irAEs and guide physicians in a more refined and personal manner.

scholarly journals Amyloid-beta and tau pathologies are both necessary to induce novel stage-specific microglia subtypes during Alzheimer's disease progression.

2021 ◽  
Author(s):  
Dong Won Kim ◽  
Kevin Tu ◽  
Alice Wei ◽  
Ashley Lau ◽  
Anabel Gonzalez-Gil ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Amyloid Β ◽  
Disease Stage ◽  
Dependent Manner ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Human Orthologue ◽  
Late Stages

It is unknown whether specific microglia are selectively induced by amyloid-β(Aβ), tau pathologies, or both in combination. To address this, we use single-cell RNA-sequencing to profile mice bearing both Aβ and tau pathologies during Alzheimer's disease (AD). We identify novel microglia subtypes induced in a disease stage-specific manner. We show that during early-stage disease, interferon signaling induces a subtype of microglia termed EADAM. During late-stage disease, a second microglia subtype termed LADAM is detected. While EADAM and LADAM-like microglia are observed in other neurodegenerative models, the magnitude and composition of subtype markers are distinct from microglia observed with AD-like pathology. The pattern of EADAM- and LADAM-associated gene expression is observed in microglia from human AD, during the early and late stages of disease, respectively. Furthermore, we observe that several siglec genes are selectively expressed in either EADAM or LADAM. Siglecg is expressed in white-matter-associated LADAM, and expression of the human orthologue of Siglecg is progressively elevated in AD-stage-dependent manner but not shown in non-AD tauopathy. Our findings imply that both Aβ and tau pathologies are required for disease stage-specific induction of EADAM and LADAM.

Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

2012 ◽  
Vol 109 ◽  
pp. 1-7 ◽  
Author(s):  
Michael Marberger ◽  
Jelle Barentsz ◽  
Mark Emberton ◽  
Jonas Hugosson ◽  
Stacy Loeb ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
Early Stage Disease ◽  
Prostate Cancer Diagnosis ◽  
Diagnosis And Management ◽  
Stage Disease ◽  
Novel Approaches ◽  
Improve Prostate Cancer

scholarly journals MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Tibor Szarvas ◽  
Michèle J. Hoffmann ◽  
Csilla Olah ◽  
Eszter Szekely ◽  
Andras Kiss ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Poor Overall Survival ◽  
Platinum Sensitivity ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.

Sign in / Sign up

Export Citation Format

Share Document