Emerging evidence shows that the efficacy of chemotherapeutic drugs is reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated damage-associated molecular patterns (DAMP, such as CALR exposure, ATP secretion, and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which led to the activation of NF-κB–mediated CCL2 transcription and IkappaB kinase 2–mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced endoplasmic reticulum stress, which triggered protein kinase R–like ER kinase activation and eukaryotic translation initiation factor 2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T-cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer.

Ovarian dermoid cysts, also called mature cystic teratomas (MCTs), account for 69% of ovarian germ cell tumors in young women. The tumors are formed by tissues derived from three germ layers, and sebaceous materials are most commonly seen. The origin of MCTs is widely considered to be the germ cell origin, which completes meiosis I. The clinical symptoms vary widely, but 20% of tumors could be asymptomatic. The diagnosis of MCTs is usually made without difficulty by ultrasound and confirmed by histopathology post-operatively. The imaging findings have a high diagnostic value. The typical characteristics present in the sonographic images, including a dermoid plug or Rokitansky nodule, are considered strong evidence for a teratoma. Although the malignant transformation of MCTs is rare, it can occur in some cases, especially in women of advanced age. The treatment of MCTs depends on the risk of malignancy, the age of the patient, and the patient’s fertility reserve requirement. In this article, we review the epidemiology, clinical symptoms, diagnosis criteria, cellular origin, and treatment of mature cystic teratomas.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.

OBJECTIVE: To compare pelvic floor symptoms, quality of life, and complications in women with symptomatic pelvic organ prolapse (POP) with or without vaginal pessaries in addition to those who do pelvic floor exercises for 12 months. METHODS: This was a parallel-group, single-blind, randomized controlled trial with 12 months of follow-up. Women with symptomatic stage I to stage III POP were randomized to either pelvic floor exercises training (control group) or pelvic floor exercises training and insertion of a vaginal pessary (pessary group). The primary outcome was the change of prolapse symptoms and quality of life by using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaires. Secondary outcomes included bothersome of prolapse symptoms, desired treatment, and any complications. RESULTS: From December 2011 through November 2014, 311 women were screened and 276 were randomized as follows: 137 to the control and 139 to the pessary group. One hundred thirty-two (95.0%) women in the pessary group and 128 (93.4%) in the control group completed the study. The Pelvic Organ Prolapse Distress Inventory of Pelvic Floor Distress Inventory and the Pelvic Organ Prolapse Impact Questionnaire of Pelvic Floor Impact Questionnaire scores decreased in both groups after 12 months, but the mean score differences were higher in the pessary group (Pelvic Organ Prolapse Distress Inventory: −29.7 compared with −4.7, P<.01; Pelvic Organ Prolapse Impact Questionnaire: −29.0 compared with 3.5, P<.01). Complication rates were low and similar in both groups. CONCLUSION: We provided further evidence in nonsurgical treatment for POP. Prolapse symptoms and quality of life were improved in women using a vaginal pessary in addition to pelvic floor exercises. CLINICAL TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics–Clinical Trials Registry, https://www2.ccrb.cuhk.edu.hk/web/?page_id=746, ChiCTR-TRC-11001796.

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.