Ovarian cancer ranks fifth in cancer related deaths for women in USA. The high mortality rate associated with ovarian cancer is due to diagnosis at later stages of disease and the high recurrence rate of 60-80%. Recurrent ovarian cancers are more likely to present as multidrug resistance (MDR) leading to unfavorable response from 2 and 3 line chemotherapy. Nanoemulsions (NEs) are emerging as an attractive drug delivery system to overcome MDR challenges. NEs can also minimize exposure of therapeutic cargo to normal tissues potentially reducing side effects. In >80% of ovarian cancers, Folate Receptor-α (FR-α) is expressed at 10- to 100-fold higher levels than on non-pathological tissues. Therefore, folate (FA) is being evaluated as an active targeting moiety for FR-α ovarian cancer. To improve therapeutic outcome with reduced toxicity, we developed NMI-500, a FA targeted gadolinium (Gd) annotated NE loaded with docetaxel (DTX). NMI-500 has been developed as theranostic agents as Gd will enable physician to acquire real time pharmacodynamics data on NE + DTX accumulation in target lesions. In present study, characterization for key translational metrics of NMI-500 showed size distribution in range of 120 to 150 nm and zeta potential around -45 mV. Active targeting of FA was evaluated against FR-α KB cells and results demonstrated significant improvement in cell association which was surface ligand density dependent. We found that NMI-500 was able to inhibit tumor growth in a spontaneous transgenic ovarian cancer model with improved safety profile and this growth inhibition could be longitudinally followed by MRI. These results indicate NMI-500 warrants advancement to clinical trials.
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http://dx.doi.org/10.1080/15384047.2017.1395118 | DOI Listing |
Afr J Reprod Health
November 2024
Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin,300060 China.
The objective of this study was to examine the efficacy of the concurrent utilization of estradiol valerate and kuntai capsule (a Chinese herbal preparation) in addressing premature ovarian failure (POF) and its ramifications for ovarian hemodynamics and sex hormone levels. A retrospective study of 104 patients with POF was conducted, dividing them into control (n=50) and observation groups (n=54). The control group received estradiol valerate, while the observation group received estradiol valerate and KunTai capsules over 12 weeks.
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Department Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
Background: Anastomotic leakage (AL) is a major complication in colorectal surgery, particularly following rectal cancer surgery, necessitating effective prevention strategies. The increasing frequency of colorectal resections and anastomoses during cytoreductive surgery (CRS) for peritoneal carcinomatosis further complicates this issue owing to the diverse patient populations with varied tumor distributions and surgical complexities. This study aims to assess and compare AL incidence and associated risk factors across conventional colorectal cancer surgery (CRC), gastrointestinal CRS (GI-CRS), and ovarian CRS (OC-CRS), with a secondary focus on evaluating the role of protective ostomies.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFInt J Clin Oncol
January 2025
Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 2-1-1, Idaidori, Yahaba, Iwate, 028-3695, Japan.
Background: The quality of life (QOL) of ovarian cancer patients is often impaired by refractory ascites. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for refractory ascites, but adverse events, such as fever, are problematic. Several cytokines have been suggested to be responsible for the adverse events, but they have not been investigated in detail.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, 420 Delaware St SE, MMC 609, Minneapolis, MN, 55455, USA.
Within ovarian cancer research, patient-derived xenograft (PDX) models recapitulate histologic features and genomic aberrations found in original tumors. However, conflicting data from published studies have demonstrated significant transcriptional differences between PDXs and original tumors, challenging the fidelity of these models. We employed a quantitative mass spectrometry-based proteomic approach coupled with generation of patient-specific databases using RNA-seq data to investigate the proteogenomic landscape of serially-passaged PDX models established from two patients with distinct subtypes of ovarian cancer.
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