scholarly journals Role of Circulating Biomarkers in Platinum-Resistant Ovarian Cancer

2021 ◽  
Vol 22 (24) ◽  
pp. 13650
Author(s):  
Carolina Maria Sassu ◽  
Innocenza Palaia ◽  
Serena Maria Boccia ◽  
Giuseppe Caruso ◽  
Giorgia Perniola ◽  
...  

Ovarian cancer (OC) is the second most common cause of death in women with gynecological cancer. Considering the poor prognosis, particularly in the case of platinum-resistant (PtR) disease, a huge effort was made to define new biomarkers able to help physicians in approaching and treating these challenging patients. Currently, most data can be obtained from tumor biopsy samples, but this is not always available and implies a surgical procedure. On the other hand, circulating biomarkers are detected with non-invasive methods, although this might require expensive techniques. Given the fervent hope in their value, here we focused on the most studied circulating biomarkers that could play a role in PtR OC.

2019 ◽  
Author(s):  
Na Li ◽  
Jiao Xiong ◽  
Zhengyu Li

Abstract Background: Homeobox B4 (HOXB4) is associated with the poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains to be determined. Methods:The Cancer Genome Atlas (TCGA) database indicated that high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed through a colony formation, migration, and invasion assay. The effect of HOXB4 on the expression of EMT and cancer stem cell markers was detected. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was performed in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results:Results showed that the expression of HOXB4 was higher in OV tissues than in normal tissues and correlated with the poor prognosis of OV. HOXB4 knockdown suppressed the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the up-regulation of HOXB4 in OV cells. The binding of two DNA motifs through HOXB4 regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in promoting tumor proliferation and metastasis was verified in mice. Further investigation revealed that HOXB4 triggered Snail and Zeb1 expression. Conclusion: Overall, HOXB4 overexpression was remarkably correlated with the poor prognosis of OV. HOXB4 up-regulated DHDDS, which co-contributed to the enhancer proliferation and invasion of OV cells, thus accelerating the malignant progression of OV.


Author(s):  
Marco Petrillo ◽  
Giulio Sozzi ◽  
Margherita Dessole ◽  
Giampiero Capobianco ◽  
Salvatore Dessole ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Shimura ◽  
Seiji Mabuchi ◽  
Naoko Komura ◽  
Eriko Yokoi ◽  
Katsumi Kozasa ◽  
...  

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiang Chen ◽  
Hongyu Li ◽  
Wenda Xu ◽  
Xiaozhong Guo

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.


Pteridines ◽  
2015 ◽  
Vol 26 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Marie Bartouskova ◽  
Bohuslav Melichar ◽  
Beatrice Mohelnikova-Duchonova

AbstractOvarian cancer is the most frequent cause of gynecological cancer-related death. Unfortunately, many patients are diagnosed at an advanced stage and have a poor prognosis. The standard treatment for advanced disease involves maximal cytoreductive surgery and chemotherapy based on platinum compounds and taxanes. Patients presenting at an advanced stage have a higher risk of recurrence. The development of drug resistance currently represents a major obstacle in the systematic treatment and, therefore, the discovery of new anticancer agents and approaches should improve the poor prognosis of these patients. Folate receptor α is overexpressed in epithelial ovarian cancer (EOC), but has limited expression in nonmalignant human tissues. The degree of folate receptor expression corresponds with the stage and grade of the disease. Because of this, folate receptor α seems to be a potential therapeutic target for the treatment of ovarian cancer. Currently, several approaches have been studied to target this protein in ovarian cancer treatment. This review summarizes current knowledge about the potential usage of folate receptors as prognostic and predictive biomarkers as well as their role in the management and targeted therapy of ovarian cancer.


2021 ◽  

Background Traumatic brain injury (TBI) seriously affects the quality of life of patients. The present study evaluated the role of diffusion tensor imaging (DTI) combined with Neuron-Specific Enolase (NSE) and S100 calcium-binding protein B (S100B) protein in predicting the prognosis of moderate and severe TBI. Methods The TBI patients were divided into moderate TBI (TBIm) and severe TBI (TBIs) groups according to the Glasgow Coma Scale (GCS) after admission. The patients were then divided into good and poor prognosis groups according to the Glasgow Outcome Scale (GOS); moreover, their follow-ups were recorded at 3 and 6 months after injury. This study also included 65 healthy individuals with matched age and gender as the control group. The fractional anisotropy (FA) values of DTI, serum neuron-specific enolase (NSE), and S100B protein levels were detected in this study. The data were analyzed in SPSS software (version 22.0) to evaluate the role of DTI combined with NSE and S100B protein in predicting the prognosis in TBIm and TBIs. Results: After TBI, the FA values of DTI in the TBI group were lower than those in the control group (P<0.05); moreover, the serum NSE and S100B values in the TBI group were higher than those in the control group (P<0.05). In the TBIm patients, the FA values of the corpus callosum in the good prognosis group were higher than that in the poor prognosis group (P<0.05); however, there was no significant difference between the two groups regarding the FA values of the internal capsule and the cerebral peduncle (P>0.05). The serum levels of NSE and S100B in the good prognosis group were significantly lower than those in the poor prognosis group (P<0.05). In the TBIs patients, the FA value of all areas in the good prognosis group was significantly higher than that in the poor prognosis group (P<0.05). However, there was no significant difference between the two prognosis groups regarding the serum levels of NSE and S100B (P>0.05). Conclusion Although DTI combined with NSE and S100B protein can effectively predict the prognosis of patients with moderate and severe TBI in the early stages, various other measures have been used in the studies to predict the prognosis of TBI patients. Accordingly, comparison with other measures is essential in further studies.


2011 ◽  
Author(s):  
Shiying Cui ◽  
Henan Zhao ◽  
Yanfang Ding ◽  
Jinyao Zhao ◽  
Tie Bi ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wen-Xi Tan ◽  
Ge Sun ◽  
Meng-Yuan Shangguan ◽  
Zhi Gui ◽  
Yang Bao ◽  
...  

Abstract Ovarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17097-e17097
Author(s):  
Dolores Gallardo-Rincon ◽  
Antonio Bahena-Gonzalez ◽  
Edgar Montes-Servín ◽  
Elizabeth Montes-Servín ◽  
David Michel-Tello ◽  
...  

e17097 Background: Ovarian cancer (OC) is the first cause of gynecological cancer, and the fifth cause of women cancer-death in US. In Mexico, more than 4,500 new cases of ovarian cancer are diagnosed yearly and it represents the second cause of gynecological cancer mortality. Bevacizumab (BVZ) is an antiangiogenic antibody that has been approved for first-line and recurrence therapy in OC patients. The aim of the study was to evaluate the clinical benefit of BVZ in different lines of treatment in Mexican OC patients. Methods: A total of 94 OC patients treated with BVZ were recruited at the Ovarian Cancer Program of the Instituto Nacional de Cancerología, from February 2012 to September 2018. Clinicopathological characteristics and toxicity was correlated with line of treatment. PFS curves were estimated by the Kaplan–Meier method, while comparisons among groups were analyzed with log-rank or Breslow tests. Results: Most of the patients were stage IIIC (69.1%) with HGSP histology (73.4%). 24 patients (25.5%) received BVZ as first-line treatment before debulking surgery (50% for suboptimal and 45.8% for optimal cytoreduction). 48 patients (51.1%) received BVZ for second-line (72.9% after a platinum-resistant and 27.1% after a platinum-sensitive recurrence) and 22 patients (23.4%) for three or more lines of treatment. Venous thromboembolic events (VTE) were more frequent in multi-treated patients ( P= 0.030). The median PFS was 23.7, 11.7 and 5.8 months for first, second and third or more lines, respectively. Patients with optimal debulking surgery had a better PFS compared with suboptimal and BVZ in first-line patients (24.8 vs 20.9; P= 0.050). Patients with BVZ in second-line who are a platinum-sensitive recurrence had better PFS compared to those with a platinum-resistant disease (15.1 vs 7.6; P= 0.040). Conclusions: OC patients had clinical benefit from treatment with BVZ when used as first-line and first recurrence treatments. The use of BVZ for third or later line treatment has a questionable benefit and is associated with a higher rate of VTE. Also, we highlight that 77% of the patients had the greatest-benefit while 33% had limited-benefit.


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