Ribosome Display and Selection of Human Anti-Placental Growth Factor scFv Derived from Ovarian Cancer Patients

The purpose of the study was to determine vascular endothelial growth factor (VEGF) concentrations in ascites from ovarian cancer and to correlate these data with VEGF expression in ovarian tumors, serum VEGF concentrations, and clinicopathologic characteristics. Ascites, serum, and tumor tissue from 65 ovarian carcinomas and eight borderline tumors were collected. VEGF concentration in peritoneal fluids and sera was determined using enzyme immunoassay. VEGF tumor expression was evaluated immunohistochemically. Significantly higher VEGF concentrations were found in ascites from malignant tumors (median, 2575 pg mL−1) compared with borderline tumors (median 181.9 pg mL−1) and benign peritoneal fluid (184.5 pg mL−1). Both VEGF ascites concentration and tumor expression correlated with advanced tumor stages and ascites volume. Elevated VEGF ascites levels were negatively correlated to patient survival. No differences between VEGF serum levels could be observed between ovarian cancer patients and patients with benign cysts. This study showed for the first time the clinical significance of elevated VEGF ascites level in ovarian carcinomas. VEGF is expressed by ovarian tumor cells and locally released in the malignant peritoneal fluid but is not increased in the serum of preoperative ovarian cancer patients. The enhanced VEGF level support novel therapeutic perspectives by VEGF inhibition.

Download Full-text

Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients

Scientific Reports ◽

10.1038/s41598-019-54116-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Kentaro Sugino ◽

Ryo Tamura ◽

Hirofumi Nakaoka ◽

Nozomi Yachida ◽

Manako Yamaguchi ◽

...

Keyword(s):

Ovarian Cancer ◽

Homologous Recombination ◽

Cancer Patients ◽

Somatic Mutations ◽

Clear Cell ◽

Gene Mutations ◽

Parp Inhibitors ◽

Low Grade ◽

Mmr Genes ◽

Selection Of

AbstractWe explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.

Download Full-text

Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer

Journal of Oncology ◽

10.1155/2010/257058 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 40

Author(s):

Marie-Claude Beauchamp ◽

Amber Yasmeen ◽

Ariane Knafo ◽

Walter H. Gotlieb

Keyword(s):

Ovarian Cancer ◽

Growth Factor ◽

Early Detection ◽

Cancer Patients ◽

Signs And Symptoms ◽

Advanced Stage ◽

Insulin Growth Factor ◽

Therapeutic Modalities ◽

Growth Factor Pathways

Ovarian cancer is the most lethal of all gynecological malignancies, due in part to the diagnosis at an advanced stage caused by the lack of specific signs and symptoms and the absence of reliable tests for screening and early detection. Most patients will respond initially to treatment but about 70% of them will suffer a recurrence. Therefore, new therapeutic modalities are urgently needed to overcome chemoresistance observed in ovarian cancer patients. Evidence accumulates suggesting that the insulin/insulin growth factor (IGF) pathways could act as a good therapeutic target in several cancers, including ovarian cancer. In this paper, we will focus on the role of insulin/IGF in ovarian cancer tumorigenesis and treatment.

Download Full-text

A Significance of Insulin-like Growth Factors (IGFs) and Insulin-like Growth Factor Binding Proteins (IGFBPs) in Ascites of Ovarian Cancer Patients

Korean Journal of Gynecologic Oncology and Colposcopy ◽

10.3802/kjgoc.1998.9.1.44 ◽

1998 ◽

Vol 9 (1) ◽

pp. 44

Author(s):

Ki Heon Lee ◽

Kyung Tai Kim ◽

Youn Yeoung Hwang

Keyword(s):

Ovarian Cancer ◽

Growth Factors ◽

Growth Factor ◽

Cancer Patients ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Insulin Like Growth Factors

Download Full-text

Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2

Cellular Physiology and Biochemistry ◽

10.1159/000438635 ◽

2016 ◽

Vol 38 (1) ◽

pp. 351-358 ◽

Cited By ~ 10

Author(s):

Ning Song ◽

Hao Liu ◽

Xiaoxin Ma ◽

Shulan Zhang

Keyword(s):

Ovarian Cancer ◽

Growth Factor ◽

Western Blot ◽

Cell Invasion ◽

Placental Growth Factor ◽

Strongly Correlated ◽

Jnk Signaling ◽

P38 Inhibitor ◽

Protein Levels ◽

Cell Invasiveness

Background/Aims: The aggressive manner of ovarian cancer (OVC) cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF) promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

Download Full-text