scholarly journals Prognostic value of p53, c-ErbB2 and tunel data in upper urothelial carcinoma associated with Balkan nephropathy

2014 ◽  
Vol 66 (2) ◽  
pp. 641-649 ◽  
Author(s):  
Marina Savin ◽  
Z. Dzamic ◽  
M. Baralic ◽  
Sanja Radojevic-Skodric ◽  
Jelena Marinkovic ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Balkan Nephropathy ◽  
Apoptosis Detection ◽  
Environmental Toxin ◽  
Her 2 ◽  
Epidermal Growth

A characteristic tumor suppressor protein 53 (p53) mutational profile of genotoxic action of aristolochic acid was identified in the upper urothelial carcinoma (UUTT) associated with Balkan nephropathy (BEN). In the present study, we examined the prognostic value of tissue-based molecular markers in overall-survival (OS) risk after surgical treatment of UUTT, adjusted for gender, age and urological characteristics in 32 patients with BEN. Immunohistochemical examination of p53, the proliferation cell nuclear antigen (PCNA), the human epidermal growth factor receptor 2 (c-ErbB2; also known as HER-2/neu) proto-oncogene and the in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis detection were used to examine serial tumor sections. The median OS-time was 60 months for UUTT operation; the mortality rate (18.7%) was related to (new) disease (re)occurrence or invasion in 12-216 months. High-grade (p=0.029), TUNEL>0.36%+ cells (p=0.010), and c-ErbB2+ cells (p=0.014) can define the risk of tumor invasion. Patients with Balkan nephropathy that develop UUTT at a stage greater than pT1 (with apoptosis TUNEL+ cells >0.36% and p53+ cells greater than 10%) were at high risk of poor-OS after the tumor surgery (h(x)=6.35; p=0.045). The obtained data present evidence for p53, cErbB2 and apoptosis deregulation, as a result of environmental toxin action. This is the first report of molecular biomarker linkage with OS for BEN-associated UUTT.

Prognostic Value of Human Epidermal Growth Factor Receptor 2 (Her-2)/neu in Patients With Advanced Ovarian Cancer Treated With Platinum/Paclitaxel as First-Line Chemotherapy: A Retrospective Evaluation of the AGO-OVAR 3 Trial by the AGO OVAR Germany

2009 ◽  
Vol 19 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Jacobus Pfisterer ◽  
Andreas Du Bois ◽  
Eva-Katrin Bentz ◽  
Friedrich Kommoss ◽  
Philipp Harter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Advanced Stage ◽  
First Line ◽  
Her 2 ◽  
Epidermal Growth ◽  
Line Chemotherapy

Objectives:Results on the prognostic value of human epidermal growth factor receptor 2 (HER-2)/neu in ovarian cancer are inconsistent. This exploratory analysis evaluates Her-2/neu as a prognostic factor in a large cohort of patients with advanced-stage ovarian cancer treated with platinum/paclitaxel as first-line chemotherapy within a prospective randomized trial.Methods:Her-2/neu expression was assessed by immunohistochemistry in 359 patients (46%) treated within the AGO-OVAR 3 trial (n = 783). Patients received either cisplatin/paclitaxel or carboplatin/paclitaxel according to the study protocol. Immunohistochemistry results were scored according to the Dako score.Results:Her-2/neu Dako scores of 0 or 1+ was found in 337 patients (94%) and a score of 2+ or 3+ in 22 patients (6%). Her-2/neu overexpression (2+/3+) was associated with a higher International Federation of Gynecology and Obstetrics stage and larger postoperative residual disease. There were no significant differences in response to chemotherapy between the Her-2/neu score subgroups and in progression-free survival time. In a multivariate analysis, the Her-2/neu score had no significant impact on overall survival time.Conclusions:In the present study, Her-2/neu overexpression in patients with advanced-stage ovarian cancer was rare and provided no evidence for a prognostic value of Her-2/neu in patients with advanced ovarian cancer treated with platinum/paclitaxel.

Trastuzumab, Paclitaxel, Carboplatin, and Gemcitabine in Advanced Human Epidermal Growth Factor Receptor-2/neu–Positive Urothelial Carcinoma: Results of a Multicenter Phase II National Cancer Institute Trial

2007 ◽  
Vol 25 (16) ◽  
pp. 2218-2224 ◽  
Author(s):  
Maha H.A. Hussain ◽  
Gary R. MacVicar ◽  
Daniel P. Petrylak ◽  
Rodney L. Dunn ◽  
Ulka Vaishampayan ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Urothelial Carcinoma ◽  
Growth Factor Receptor ◽  
Human Epidermal Growth Factor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Purpose We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. Results Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu–positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu–positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.

Prognostic Significance of Overexpression and Phosphorylation of Epidermal Growth Factor Receptor (EGFR) and the Presence of Truncated EGFRvIII in Locoregionally Advanced Breast Cancer

2007 ◽  
Vol 25 (28) ◽  
pp. 4405-4413 ◽  
Author(s):  
Yago Nieto ◽  
Fatima Nawaz ◽  
Roy B. Jones ◽  
Elizabeth J. Shpall ◽  
Samia Nawaz
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
High Dose ◽  
Egfr Expression ◽  
Her 2 ◽  
Epidermal Growth

Purpose The prognostic value of the epidermal growth factor receptor (EGFR) in breast cancer and more specifically, in patients with locoregionally advanced disease, is still undefined. We hypothesized that EGFR status plays a major prognostic role in this setting, through expression, activation, or the presence of its mutated variant EGFRvIII. Patients and Methods We reviewed tumor samples of 225 patients treated uniformly in prospective trials of high-dose chemotherapy for four to nine positive axillary nodes, ≥ 10 positive nodes, or inflammatory carcinoma, and observed for a median of 9 years (range, 3 to 13 years). We analyzed the effect on outcome of expression of EGFR, phosphorylated EGFR (phospho-EGFR), and EGFRvIII, as studied by immunohistochemistry. Results EGFR expression, phospho-EGFR, and mutated EGFRvIII were detected in 43%, 54%, and 4% of the patients, respectively. EGFR expression correlated with negative hormone receptor status, and was associated with significantly worse relapse-free survival (59% v 79%; P < .001) and overall survival (61% v 81%; P = .001) than no expression. There was no association of phospho-EGFR or EGFRvIII with outcome. Multivariate models confirmed the prognostic effect of EGFR independent of other known prognostic variables in this population. The prognostic value of EGFR was most prominent in the human epidermal growth factor receptor 2 (HER-2) –positive and the estrogen receptor/progesterone receptor–negative subgroups. Conclusion EGFR expression, but not phospho-EGFR or EGFRvIII expression, is an independent adverse prognostic factor in patients with high-risk primary breast cancer, particularly when it is coexpressed with HER-2. Our results suggest the potential benefit of dual EGFR/HER-2 receptor targeting in this setting.

scholarly journals Advances in targeted therapy for esophageal cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yan-Ming Yang ◽  
Pan Hong ◽  
Wen Wen Xu ◽  
Qing-Yu He ◽  
Bin Li
Keyword(s):  
Esophageal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Targeted Therapies ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Immune Checkpoints ◽  
Her 2 ◽  
Epidermal Growth

Abstract Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

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