Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

The effect of triethylene thiophosphoramide (Thio-TEPA), an alkylating agent structurally related to nitrogen mustard, has been described in 39 cases of very advanced ovarian carcinoma. Of the 39 cases treated, 21 had been previously treated and 18 were new cases. In the 39 cases, 42 cycles were evaluable (table 1). 8 cases showed a varying degree of improvement. Marked regression of growth and improvement of symptoms (regression exceeding 50%) was achieved in 7 cases (table 1). Regression of less than 50 % was achieved in 1 case (table 1). The clinical regression is only temporary. A high percentage of cases had side-effects. Of the 42 evaluable, 29 (69%) had one or more side-effects; particularly 28 showed leukopenia, 11 trombocytopenia, 13 anemia and 3 oral or gastrointestinal toxicity (table 2). In conclusion the therapeutic value of Thio-TEPA in ovarian cancer is small. A review of the literature has not shown that other drugs offer longer survival. The control of advanced disease can reasonably be more optimistic when randomized, prospective, clinical trials are performed. A plan for investigation in this direction is in preparation.

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Bioinformatic and Experimental Analysis Reveals Knockdown of KIF15 Promotes Cell Apoptosis via Activating Crosstalk of Multi-Pathways in Ovarian Cancer

10.21203/rs.3.rs-72091/v1 ◽

2020 ◽

Author(s):

Xinwei Sun ◽

Mengyue Chen ◽

Bin Liao ◽

Zhiqing Liang

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Poor Prognosis ◽

Early Stage ◽

Experimental Methods ◽

Therapeutic Strategies ◽

Tumor Formation ◽

Fundamental Feature ◽

Therapeutic Value

Abstract Background: Ovarian cancer (OC) is the most lethal malignancy of females worldwide. Unlimited proliferation is a fundamental feature of OC cells. The genes associated with cell proliferation are potential histopathological biomarkers and targets of anti-tumor therapeutic strategies. In the present study, we aimed to identify proliferation-associated biomarkers with potential prognostic, diagnostic, and therapeutic value and reveal the underlying molecular mechanism of the candidate gene involved in OC by a combination of bioinformatic and experimental methods.Results: KIF15 was upregulated in early-stage OC tissues and could predict poor prognosis of patients of Stage I and II. The knockdown of KIF15 significantly inhibited cell proliferation, tumor formation, and growth as well as promoted apoptosis of OC cells. A combination of experimental and bioinformatic analyses revealed KIF15 knockdown promoted cell apoptosis via activating crosstalk of multi-pathways in OC.Conclusion: In this study, KIF15, an early-stage prognostic gene, was identified as a potential histopathological biomarker and therapeutic target of OC.

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Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1111/j.1600-0412.1992.tb00006.x ◽

1992 ◽

Vol 71 ◽

pp. 39-54 ◽

Cited By ~ 6

Author(s):

John A. Holt ◽

Anton Scharl ◽

Stig Kullander ◽

Matthias W. Beckmann

Keyword(s):

Ovarian Cancer ◽

Steroid Hormones ◽

Therapeutic Value

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Efficacy Evaluation Of Albumin-Bound Paclitaxel Combined With Carboplatin As Neoadjuvant Chemotherapy For Primary Epithelial Ovarian Cancer

10.21203/rs.3.rs-117727/v1 ◽

2020 ◽

Author(s):

Huan Wang ◽

Yimin Han

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Operation Time ◽

Efficacy Evaluation ◽

Total Incidence ◽

Total Hospital Stay ◽

Therapeutic Value ◽

Primary Epithelial Ovarian Cancer ◽

Medical University

Abstract Background: This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as a neoadjuvant chemotherapy regimen for primary epithelial ovarian cancer. Methods: Seventy-six patients with advanced primary epithelial ovarian cancer admitted for treatment at the Third Affiliated Hospital of Harbin Medical University from January 2015 to August 2020 were retrospectively selected. All patients underwent surgery after two courses of neoadjuvant chemotherapy with a combination of paclitaxel and carboplatin. Among the patients included for study, 34 were in the Nab-TC program and 42 in the TC program. Results: After two courses of chemotherapy, the ORR value was 52.38% in the TC group and 58.82% in the Nab-TC group (P=0.355). The CA125 value of the Nab-TC group decreased by 88.28% and that of the TC group by 86.99% (P=0.358). Overall operation time, intraoperative blood loss and postoperative hospital time of patients in the Nab-TC group were lower (P>0.05) and length of total hospital stay was significantly lower (P<0.05) relative to the TC group. Moreover, incidence of bone marrow suppression, abnormal liver function, arrhythmia and hyperglycemia in the Nab-TC group were lower (P>0.05) and total incidence of nausea and vomiting as well as grade III and IV stages were significantly lower (P<0. 05) than those in the TC group. However, the frequency of acral numbness in Nab-TC group was higher compared to the TC group (P<0.05). Conclusion: The efficacy of the Nab-TC regimen as neoadjuvant chemotherapy for advanced primary epithelial ovarian cancer was equivalent to that of the TC regimen, along with a lower incidence of adverse reactions, supporting its therapeutic value in the clinic.

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TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02091-6 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xiao Wei ◽

Hua Lou ◽

Dongchen Zhou ◽

Yijuan Jia ◽

Huayi Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Progression ◽

Cross Linking ◽

Matrix Stiffness ◽

Transwell Assay ◽

Primary Tumors ◽

Atomic Force ◽

Therapeutic Value

Abstract Background Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics. Methods Atomic Force Microscope (AFM) was used to measure the Young’s modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry. Results We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. Conclusions These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy.

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Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis

Oncogenesis ◽

10.1038/s41389-021-00339-6 ◽

2021 ◽

Vol 10 (7) ◽

Author(s):

Suresh Chava ◽

Suresh Bugide ◽

Yvonne J. K. Edwards ◽

Romi Gupta

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Metabolic Pathways ◽

Large Scale ◽

Nk Cell ◽

Xenograft Model ◽

Ovarian Cancer Cells ◽

Telomeric Silencing ◽

Mouse Xenograft Model ◽

Cancer Tumor

ABSTRACTOvarian cancer is the leading cause of gynecological malignancy-related deaths. Current therapies for ovarian cancer do not provide meaningful and sustainable clinical benefits, highlighting the need for new therapies. We show that the histone H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) is overexpressed in ovarian cancer and that a higher level of DOT1L expression correlates with shorter progression-free and overall survival (OS). Pharmacological inhibition of DOT1L (EPZ-5676, EPZ004777, and SGC0946) or genetic inhibition of DOT1L attenuates the growth of ovarian cancer cells in cell culture and in a mouse xenograft model of ovarian cancer. Transcriptome-wide mRNA expression profiling shows that DOT1L inhibition results in the downregulation of genes involved in cellular biosynthesis pathways and the upregulation of proapoptotic genes. Consistent with the results of transcriptome analysis, the unbiased large-scale metabolomic analysis showed reduced levels of several metabolites of the amino acid and nucleotide biosynthesis pathways after DOT1L inhibition. DOT1L inhibition also resulted in the upregulation of the NKG2D ligand ULBP1 and subsequent increase in natural killer (NK) cell-mediated ovarian cancer eradication. Collectively, our results demonstrate that DOT1L promotes ovarian cancer tumor growth by regulating apoptotic and metabolic pathways as well as NK cell-mediated eradication of ovarian cancer and identifies DOT1L as a new pharmacological target for ovarian cancer therapy.

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Identification of Novel Biomarkers and Candidate Drug in Ovarian Cancer

Journal of Personalized Medicine ◽

10.3390/jpm11040316 ◽

2021 ◽

Vol 11 (4) ◽

pp. 316

Author(s):

Chia-Jung Li ◽

Li-Te Lin ◽

Pei-Yi Chu ◽

An-Jen Chiang ◽

Hsiao-Wen Tsai ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Tissue ◽

High Expression ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

Kaplan Meier ◽

Candidate Drug ◽

Therapeutic Value ◽

Novel Biomarkers ◽

Low Expression

This paper investigates the expression of the CREB1 gene in ovarian cancer (OV) by deeply excavating the gene information in the multiple databases and the mechanism thereof. In short, we found that the expression of the CREB1 gene in ovarian cancer tissue was significantly higher than that of normal ovarian tissue. Kaplan–Meier survival analysis showed that the overall survival was significantly shorter in patients with high expression of the CREB1 gene than those in patients with low expression of the CREB1 gene, and the prognosis of patients with low expression of the CREB1 gene was better. The CREB1 gene may play a role in the occurrence and development of ovarian cancer by regulating the process of protein. Based on differentially expressed genes, 20 small-molecule drugs that potentially target CREB1 with abnormal expression in OV were obtained from the CMap database. Among these compounds, we found that naloxone has the greatest therapeutic value for OV. The high expression of the CREB1 gene may be an indicator of poor prognosis in ovarian cancer patients. Targeting CREB1 may be a potential tool for the diagnosis and treatment of OV.

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