Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study

2020 ◽  
Author(s):  
M Klar ◽  
H Machida ◽  
B.H Grubbs ◽  
S Matsuzaki ◽  
L.D Roman ◽  
...  
2020 ◽  
Vol 157 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Koji Matsuo ◽  
Hiroko Machida ◽  
Brendan H. Grubbs ◽  
Shinya Matsuzaki ◽  
Maximilian Klar ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3727
Author(s):  
Dafne Jacome Sanz ◽  
Juuli Raivola ◽  
Hanna Karvonen ◽  
Mariliina Arjama ◽  
Harlan Barker ◽  
...  

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.


2021 ◽  
Vol 160 (1) ◽  
pp. 206-213
Author(s):  
Andra Nica ◽  
Ji Young Jennifer Lee ◽  
Nicole Look Hong ◽  
Taymaa May

1998 ◽  
Vol 16 (2) ◽  
pp. 397-404 ◽  
Author(s):  
O T Jóhannsson ◽  
J Ranstam ◽  
A Borg ◽  
H Olsson

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.


2004 ◽  
Vol 43 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Hans O. Thulesius ◽  
Anna C. Lindgren ◽  
Håkan L. Olsson ◽  
Anders Håkansson

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