A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.     

Immunotherapy for urothelial carcinoma: Metastatic disease and beyond

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.     

Rosmarinus plants: Key farm concepts towards food applications

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.     

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.