Past, Present, and Future of Serum Tumor Markers in Management of Ovarian Cancer: A Guide for the Radiologist.

The ability to accurately detect early ovarian cancer and subsequently monitor treatment response is essential to improving survival for patients with ovarian malignancies. Several serum tumor markers (STMs)-including cancer antigen 125 (CA-125), human epididymis protein 4 (HE4), cancer antigen 19-9 (CA 19-9), and carcinoembryonic antigen (CEA)-have been used as a noninvasive method of identifying ovarian cancer in conjunction with imaging. Although current guidelines do not recommend use of STMs as screening tools for ovarian cancer, these markers have clinical utility in both diagnosis and surveillance for women with ovarian cancer. CA-125 is the most commonly used STM; its level may be elevated in several types of ovarian cancer, including epithelial cell tumors, carcinosarcoma, teratomas, and secondary ovarian malignancies. An elevated level of CA 19-9 is associated with clear cell tumors, teratomas, and secondary malignancies. CEA is most commonly associated with mucinous ovarian cancers. Finally, HE4 is being increasingly used to identify certain subtypes of epithelial ovarian cancers, particularly serous and endometrioid tumors. Diagnosis of ovarian cancers relies on a combination of CA-125 levels and US findings, which include a large adnexal mass or high-risk features, including septa and increased vascularity. CT is preferred for staging and is used along with PET and STM monitoring for surveillance. Increasingly, MRI is being used to characterize ovarian lesions that are indeterminate at US or CT. The future of STM testing involves development of "liquid biopsies," in which plasma samples are analyzed for evidence of tumors, including circulating tumor DNA or tumor cells and tumor micro-RNA. When combined with traditional imaging techniques, liquid biopsies may lead to earlier diagnosis and improved survival. An invited commentary by Shinagare is available online. ©RSNA, 2021.

Overview of systemic treatment in recurrent and advanced cervical cancer: a primer for radiologists.

Imaging has a central role in surveillance of cervical cancer, guiding decision on when to initiate treatment for recurrent disease and to guide management in advanced cervical cancer. Due to the increased availability of pelvic radiation therapy, the rate of atypical presentation of recurrent disease has increased. Simultaneously, the array of systemic therapies now available for advanced cervical cancer has considerably expanded in the last few years, with therapies now available in mid and low-income countries. While pelvic recurrences are amenable of loco-regional treatment, recurrent disease may present with metastases to the thoracoabdominal organs, lymph nodes, bones, skin and brain, for which systemic treatment represent the standard of care. Besides combined chemotherapy regimens, alternative chemotherapies, biosimilars and immune checkpoint inhibitors are now available, each associated with a definite pattern of response and toxicity. In this review, after describing the typical and atypical presentations of recurrent and advanced cervical carcinoma on cross-sectional imaging, we will discuss systemic treatment for recurrent or advanced disease and their associated radiographic sequelae, in light of the newly available therapies.

The Secretome of Hydrogel-Coembedded Endothelial Progenitor Cells and Mesenchymal Stem Cells Instructs Macrophage Polarization in Endotoxemia.

UNLABELLED: : We previously reported the delivery of endothelial progenitor cells (EPCs) embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during acute kidney injury (AKI) and promotes angiogenesis. We attempted to further ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem cells (MSCs), while examining their paracrine influence on cytokine/chemokine release and proinflammatory macrophages. A live/dead assay determined whether EPC-MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral ligation). Cytokine/chemokine release from embedded stem cells was examined, including effects on macrophage polarization and release of proinflammatory molecules. EPC-MSC coculturing improved stem cell viability during LPS exposure, an effect augmented by MSC hypoxic preconditioning. The delivery of coembedded EPCs with hypoxic preconditioned MSCs to AKI mice demonstrated additive improvement (compared with EPC delivery alone) in medullary RBF and proteinuria, with comparable effects on serum creatinine, MAP, and angiogenesis. Exposure of proinflammatory M1 macrophages to EPC-MSC conditioned medium changed their polarization to anti-inflammatory M2. Incubation of coembedded EPCs-MSCs with macrophages altered their release of cytokines/chemokines, including enhanced release of anti-inflammatory interleukin (IL)-4 and IL-10. EPC-MSC delivery to endotoxemic mice elevated the levels of circulating M2 macrophages and reduced the circulating cytokines/chemokines. In conclusion, coembedding EPCs-MSCs improved their resistance to stress, impelled macrophage polarization from M1 to M2 while altering their cytokine/chemokines release, reduced circulating cytokines/chemokines, and improved renal and vascular function when MSCs were hypoxically preconditioned. SIGNIFICANCE: This report provides insight into a new therapeutic approach for treatment of sepsis and provides a new and improved strategy using hydrogels for the delivery of stem cells to treat sepsis and, potentially, other injuries and/or diseases. The delivery of two different stem cell lines (endothelial progenitor cells and mesenchymal stem cells; delivered alone and together) embedded in a protective bioengineered scaffolding (hydrogel) offers many therapeutic benefits for the treatment of sepsis. This study shows how hydrogel-delivered stem cells elicit their effects and how hydrogel embedding enhances the therapeutic efficacy of delivered stem cells. Hydrogel-delivered stem cells influence the components of the overactive immune system during sepsis and work to counterbalance the release of many proinflammatory and prodamage substances from immune cells, thereby improving the associated vascular and kidney damage.