Metabolic adaptations in cancer stem cells: A key to therapy resistance.

Cancer stem cells (CSCs) are a subset of tumor cells that can initiate and sustain tumor growth and cause recurrence and metastasis. CSCs are particularly resistant to conventional therapies compared to their counterparts, owing greatly to their intrinsic metabolic plasticity. Metabolic plasticity allows CSCs to switch between different energy production and usage pathways based on environmental and extrinsic factors, including conditions imposed by conventional cancer therapies. To cope with nutrient deprivation and therapeutic stress, CSCs can transpose between glycolysis and oxidative phosphorylation (OXPHOS) metabolism. The mechanism behind the metabolic pathway switch in CSCs is not fully understood, however, some evidence suggests that the tumor microenvironment (TME) may play an influential role mediated by its release of signals, such as Wnt/ß-catenin and Notch pathways, as well as a background of hypoxia. Exploring the factors that promote metabolic plasticity in CSCs offers the possibility of eventually developing therapies that may more effectively eliminate the crucial tumor cell subtype and alter the disease course substantially.

A contemporary systematic review of the complications associated with SURGICEL.

BACKGROUND: This review aims to summarize the findings from recent literature (2010-2022) reporting on complications that resulted from the surgical use of SURGICEL for intraoperative hemostasis. METHODS: A literature search was conducted using the MEDLINE (OVID), Embase, and Cochrane Central Register of Controlled Trials - CENTRAL (OVID) databases. The studies were sorted into case reports and other study types for data extraction. Covidence was used for data extraction and statistics were descriptive. RESULTS: Of the total 560 articles screened, 73 papers were selected for a full-text review and 70 studies were included in this review. A total of 7,242 participants were included in the studies (case studies n = 93, others n = 7149). 67/70 of the included studies reported complications when SURGICEL was used intraoperatively. Reported complications included: SURGICEL induced masses (granulomas, abscesses, hematomas, cysts) (n = 25), hemorrhagic complications (n = 12), masses misdiagnosed as tumors, cardiovascular, nervous system, and hepatobiliary complications, pain, and infections. Other complications included: fistulas, erectile dysfunction, chorioamnionitis, swelling, urinary leak, renal failure, and anaphylaxis. CONCLUSIONS: Publications reporting on complications associated with the use of SURGICEL intraoperatively have continued to emerge. Future studies should compare how the types and rates of complications compare between SURGICEL and alternative hemostatic agents.

Distinct mechanisms controlling rough and smooth endoplasmic reticulum contacts with mitochondria.

Gp78 (also known as AMFR), an endoplasmic-reticulum (ER)-associated protein degradation (ERAD) E3 ubiquitin ligase, localizes to mitochondria-associated ER and targets the mitofusin (Mfn1 and Mfn2) mitochondrial fusion proteins for degradation. Gp78 is also the cell surface receptor for autocrine motility factor (AMF), which prevents Gp78-dependent mitofusin degradation. Gp78 ubiquitin ligase activity promotes ER-mitochondria association and ER-mitochondria Ca(2+) coupling, processes that are reversed by AMF. Electron microscopy of HT-1080 fibrosarcoma cancer cells identified both smooth ER (SER; ∼8 nm) and wider (∼50-60 nm) rough ER (RER)-mitochondria contacts. Both short hairpin RNA (shRNA)-mediated knockdown of Gp78 (shGp78) and AMF treatment selectively reduced the extent of RER-mitochondria contacts without impacting on SER--mitochondria contacts. Concomitant small interfering RNA (siRNA)-mediated knockdown of Mfn1 increased SER-mitochondria contacts in both control and shGp78 cells, whereas knockdown of Mfn2 increased RER-mitochondria contacts selectively in shGp78 HT-1080 cells. The mitofusins therefore inhibit ER-mitochondria interaction. Regulation of close SER-mitochondria contacts by Mfn1 and of RER-mitochondria contacts by AMF-sensitive Gp78-mediated degradation of Mfn2 define new mechanisms that regulate ER-mitochondria interactions.