Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer.

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

The forgotten art of cold therapeutic properties in cancer: A comprehensive historical guide.

Cold therapy has been used for centuries, from Julius Caesar to Mohandas Gandhi, as a potent therapeutic approach. However, it has been largely forgotten in modern medicine. This review explores the history of cold therapy and its potential application as a therapeutic strategy against various diseases, including cancer. We examine the different techniques of cold exposure and the use of other therapeutical approaches, such as cryoablation, cryotherapy, cryoimmunotherapy, cryothalectomy, and delivery of cryogen agents. While clinical trials using cold therapy for cancer treatment are still limited, recent research shows promising results in experimental animal cancer models. This area of research is becoming increasingly significant and warrants further investigation.

A mechanistic view of the use of cold temperature in the treatment of cancer.

In their latest article, Seki and colleagues investigate the potential role of cold as a therapeutical option to treat various cancer types, including even clinically untreatable cancers such as pancreatic cancers. The authors suggest that cold exposure may have a tumor-suppressive effect mediated by the activation of brown adipose tissue (BAT), in charge of dissipating heat through non-shivering thermogenesis. In this regard, circulating blood glucose is decreased, restricting the tumor glucose uptake, which is redistributed, favoring BAT uptake to fuel thermogenesis.1.

Detection of chromosome instability by interphase FISH in mouse and human tissues.

Chromosomal instability (CIN), a type of genomic instability, favors changes in chromosome number and structure and it is associated with the progression and initiation of multiple diseases, including cancer. Therefore, CIN identification and analysis represents a useful tool for cancer diagnosis and treatment. Here, we report an optimized molecular cytogenetic protocol to detect CIN in formalin-fixed, paraffin-embedded mouse and human tissues, using fluorescent in situ hybridization to visualize and quantify chromosomal alterations such as amplifications, deletions, and translocations. For complete information on the generation and use of this protocol, please refer to Brandt et al. (2018).

Diet, Microbiota, and Colorectal Cancer.

The intestinal epithelium is a very dynamic tissue under a high regenerative pressure, which makes it susceptible to malignant transformation. Proper integration of various cell signaling pathways and a balanced cross talk between different cell types composing the organ are required to maintain intestinal homeostasis. Dysregulation of this balance can lead to colorectal cancer (CRC). Here, we review important insights into molecular and cellular mechanisms of CRC. We discuss how perturbation in complex regulatory networks, including the Wnt, Notch, BMP, and Hedgehog pathways; and how variations in inflammatory signaling, nutrients, and microbiota can affect intestinal homeostasis contributing to the malignant transformation of intestinal cells.

mTORC1 Inactivation Promotes Colitis-Induced Colorectal Cancer but Protects from APC Loss-Dependent Tumorigenesis.

Dietary habits that can induce inflammatory bowel disease (IBD) are major colorectal cancer (CRC) risk factors, but mechanisms linking nutrients, IBD, and CRC are unknown. Using human data and mouse models, we show that mTORC1 inactivation-induced chromosomal instability impairs intestinal crypt proliferation and regeneration, CDK4/6 dependently. This triggers interleukin (IL)-6-associated reparative inflammation, inducing crypt hyper-proliferation, wound healing, and CRC. Blocking IL-6 signaling or reactivating mTORC1 reduces inflammation-induced CRC, so mTORC1 activation suppresses tumorigenesis in IBD. Conversely, mTORC1 inactivation is beneficial in APC loss-dependent CRC. Thus, IL-6 blockers or protein-rich-diet-linked mTORC1 activation may prevent IBD-associated CRC. However, abolishing mTORC1 can mitigate CRC in predisposed patients with APC mutations. Our work reveals mTORC1 oncogenic and tumor-suppressive roles in intestinal epithelium and avenues to optimized and personalized therapeutic regimens for CRC.