Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

2009 ◽  
Vol 101 (03) ◽  
pp. 541-546 ◽  
Author(s):  
Andreas Scorilas ◽  
Sonia Markakis ◽  
Diane Kowalski ◽  
Robert L. Camp ◽  
Eleftherios P. Diamandis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Evaluation of the prognostic significance of human kallikrein 8 protein expression levels in advanced ovarian cancer by using automated quantitative protein analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5581-5581
Author(s):  
P. Kountourakis ◽  
A. Psyrri ◽  
A. Scorilas ◽  
S. Markakis ◽  
D. Kowalski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Expression Levels ◽  
Response To Chemotherapy

5581 Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 8 (hkl8) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Materials and Methods: A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of kallikrein 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time of the cohort was 34.35 months. One hundred twenty six of 150 cases had sufficient tissue for AQUA analysis. There was association between tumor mask hk8 protein expression levels and clinicopathological variables including grade (p=0.0011), residual disease (p=0.0063),clinical response to chemotherapy (p=0.0346). In univariate survival analysis there was a correlation between hk8 tumor mask expression and 5 years progression-free survival. Low hk8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterized prognostic variables, tumor hkl8 expression level retained its prognostic significance for disease free survival (95%CI: 0.341–1.027, p=0.0468). Conclusions: Human Kallikrein 8 is an adverse prognostic factor in patients with ovarian cancer.The possibilities that hK8 may be suitable candidate as diagnostic, prognostic marker and therapeutic target merit further investigation. No significant financial relationships to disclose.

scholarly journals Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

2020 ◽  
Vol 35 (4) ◽  
pp. 20-27 ◽  
Author(s):  
Enrico Potenza ◽  
Giulia Parpinel ◽  
Maria E. Laudani ◽  
Chiara Macchi ◽  
Luca Fuso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Value ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Ca 125 ◽  
Free Survival ◽  
The Third ◽  
Response To Chemotherapy

Introduction: At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. Methods: We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016–2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Results: Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). Conclusions: We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

scholarly journals Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1013
Author(s):  
Chara Papadaki ◽  
Stavroula Manolakou ◽  
Eleni Lagoudaki ◽  
Spyros Pontikakis ◽  
Despo Ierodiakonou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Protein Expression ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Protein Levels ◽  
Low Expression

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

scholarly journals Successful treatment of advanced ovarian cancer with anlotinib: a case report

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097682
Author(s):  
Ping Zhang ◽  
Liangliang Ma ◽  
Xiaojie Wang ◽  
Ruijie Zhang ◽  
Yuting Dong
Keyword(s):  
Ovarian Cancer ◽  
Mild Hypertension ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Inhibit Tumor Growth ◽  
Free Survival ◽  
Multiple Line ◽  
Serum Ca125

Ovarian cancer remains the most lethal gynecological malignant tumor, with relapse occurring in approximately 70% of advanced cases. Anlotinib is an oral small-molecule multi-targeted tyrosine kinase inhibitor that can resist neoangiogenesis and inhibit tumor growth. Previous research demonstrated clinical antitumor activity of anlotinib in various cancers. We report the case of an elderly woman with advanced ovarian cancer who received anlotinib after failure of multiple-line chemotherapy. A partial response was observed after six cycles of anlotinib monotherapy, with a reduction in the size of the metastases and significantly decreased serum CA125 levels from 1832.7 U/mL to 118.7 U/mL. She continued to take anlotinib, with a progression-free survival time of more than 4 months. Only mild hypertension was observed during the treatment. Anlotinib monotherapy may be a novel therapeutic option for patients with advanced ovarian cancer.

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Survival ◽  
Stable Disease ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Second Look

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
Author(s):  
Andreas du Bois ◽  
Anne Floquet ◽  
Jae-Weon Kim ◽  
Joern Rau ◽  
Josep M. del Campo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).

Poly-(ADP-ribose) polymerase inhibitors: paradigm shift in the first-line treatment of newly diagnosed advanced ovarian cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 721-727
Author(s):  
Fady Gh Haddad ◽  
Elias Karam ◽  
Elissar Moujaess ◽  
Hampig Raphael Kourie
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Excision Repair ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
First Line ◽  
Free Survival ◽  
Base Excision ◽  
Breast Cancer Gene

Debulking surgery associated with chemotherapy represent the backbone of ovarian cancer therapy. Adding bevacizumab has improved survival. Recently, PARP inhibitors were added in the first line as maintenance treatment for the patients who achieve a complete or partial response. These drugs act by blocking the activity of the PARP enzyme responsible for base-excision repair, and have shown positive responses when used for tumors lacking homologous recombination. Olaparib, niraparib and veliparib were evaluated and showed an increase in the duration of progression-free survival: 22.1 months (hazard ratio [HR] = 0.59), 13.8 (HR = 0.62) and 23.5 (HR = 0.68) with olaparib, niraparib and veliparib, respectively. This review describes the benefit of PARP inhibitors as maintenance therapy and discusses the efficacy according to breast cancer gene and homologous recombination status.

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