Adipose stromal cells promote the transition of colorectal cancer cells toward a mesenchymal-like phenotype

Colon cancer progression is among the risks that increase with obesity. We have recently unveiled the molecular mechanism by which adipose tissue-released molecules, HGF and IL-6, make colorectal cancer (CRC) cells acquiring mesenchymal traits. Targeting of adipose-derived factors abrogate the metastatic potential of CRC stem cells (CR-CSCs) in obese patients

Editorial: Lipid alterations in cancer development, resistance and recurrence

Lipids, as well as proteins and nucleic acids, are essential for mammalian cellular biology, as they play critical roles in cellular membrane architecture, in intra- and intercellular signaling, and as fundamental energy storage. These molecular mechanisms are particularly pronounced in the context of tumors, where neoplastic cells must adapt to changes in the microenvironment, characterized by inadequate vascularization, nutrient deprivation, extracellular matrix accumulation resulting from stroma cell recruitment including immune cell infiltration, and the expansion of cancer-associated fibroblasts (CAFs)

Colorectal cancer defeating? Challenge accepted!

Colorectal tumours are actually considered as aberrant organs, within it is possible to notice a different stage of cell growth and differentiation. Their origin is reported to arise from a subpopulation of tumour cells endowed with, just like the healthy stem cells, self-renewal and aberrant multi-lineage differentiation capacity likely to be called colorectal cancer stem cells (CCSCs). Cancer stem cells (CSCs) fate, since their origin, reflects the influences from their microenvironment (or niche) both in the maintenance of stemness, in promoting their differentiation, and in inducing epithelial-mesenchymal transition, responsible of CSCs dissemination and subsequent formation of metastatic lesions. The tumour cells heterogeneity and their immuno-response resistance nowadays probably responsible of the failure of the conventional therapies, make this research field an open issue. Even more importantly, our increasing understanding of the cellular and molecular mechanisms that regulate CSC quiescence and cell cycle regulation, self-renewal, chemotaxis and resistance to cytotoxic agents, is expected to eventually result in tailor-made therapies with a significant impact on the morbidity and overall survival of colorectal cancer patients

The miRNA Contribution in Adipocyte Maturation

Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs

Role of Type I and II interferons in colorectal cancer and melanoma

Cancer can be considered an aberrant organ with a hierarchical composition of different cell populations. The tumor microenvironment, including the immune cells and related cytokines, is crucial during all the steps of tumor development. In particular, type I and II interferons (IFNs) are involved in a plethora of mechanisms that regulate immune responses in cancer, thus balancing immune escape versus immune surveillance. IFNs are involved in both the direct and indirect regulation of cancer cell proliferation and metastatic potential. The mutational background of genes involved in IFNs signaling could serve as a prognostic biomarker and a powerful tool to screen cancer patients eligible for checkpoint blocking therapies. We herewith describe the latest findings regarding the contribution of IFNs in colorectal cancer and melanoma by researching their dual role as either tumor promoter or suppressor, in diverse tumor types, and microenvironmental context. We are reporting the most innovative and promising approaches of IFN-based therapies that have achieved considerable outcomes in clinical oncology practice and explain the possible mechanisms responsible for their failure

A Case-Control Comparison of Surgical and Functional Outcomes of Robotic-Assisted Spleen-Preserving Left Side Pancreatectomy versus Pure Laparoscopy

Aim During left-sided spleen-preserving pancreatectomy (SPLP), limitations of laparoscopy may require spleen sacrifice or conversion to maintain patient safety. The objective of our study is to compare surgical and functional outcomes of robot-assisted and pure laparoscopic SPLP in patients with benign or borderline lesions of the body/tail of the pancreas. Patients and methods This was a case-matched study: fifteen patients who had robotic SPLP (R-SPLP) were matched with 15 comparable patients who had pure laparoscopic SPLP (L-SPLP). The peri-operative variables (conversion rate, amount of bleeding, operation time, length of hospital stay, complications, mortality and readmission) as well as the spleen preservation rate were compared between the two groups, The European Organisation for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) specific questionnaires were used in each arm after at least 1 year of follow up in order to evaluate quality of life (QoL). Results No R-SPLP was converted to conventional laparoscopy, hand-assisted laparoscopy, or open surgery whereas L-SPLP had a conversion rate of 13.3% (p=n.s.); also fistula formation (20% vs. 46%; p=n.s.) was higher in the laparoscopic group although not statistically significant. Mean operative time (220 vs. 279 min; p=0.027) was shorter and the spleen-preserving rate (fail/ success, 0/15 vs. 4/11; p=0.03) of R-SPLP was significantly better compared to L-SPLP. Moreover, length of hospital stay was significantly shorter in the R-SPLP group compared to the L-SPLP group (6.5 vs. 8.8 days; p=0.04). Post-operative high grade surgical complications occurred only in one L-SPLP patient (0% vs. 6.6%; p=n.s.). Quality of life scores were not significantly different between the two groups. Conclusions R-SPLP could provide an increased chance for spleen preservation and faster surgical procedure. Furthermore, fistula formation and conversion rate seem to be lower, reducing the length of the hospital stay. Our case matched study confirmed the potential peri-operative benefits of robotic assistance in this setting, however these benefits did not translate into a better quality of life at least one year post-operatively

Short-term clinical outcomes of robot-assisted intersphincteric resection and low rectal resection with double-stapling technique for cancer: a case-matched study

Background: Intersphincteric resection (ISR) with total mesorectal excision (TME) is an accepted technique for the surgical treatment of very low rectal cancer. Historically it is associated with a higher functional complication rate than the Double Stapling (DS) technique when performed with open or laparoscopic approach. The aim of this study was to compare the surgical, short-term oncologic and functional outcomes of robotic ISR TME (R-ISR-TME) with those of robotic low anterior resection TME with a double stapling technique (R-DS-TME). Methods: Between April 2010 and December 2013, 42 patients underwent robot-assisted rectal resection with TME at our General Surgery Unit, including 10 R-ISR-TME. The outcomes of the R-ISR-TME group were compared with a R-DS-TME group selected using a case-matched methodology. We evaluated the operative, pathological, short-term oncologic results and postoperative sexual, urinary and defecation functions using specific questionnaires. Results: The analyses of the data showed similar results for R-ISR-TME and R-DS-TME regarding the operative, pathological and oncologic results. Focusing on urinary and sexual function, no score values were significantly different at any time between the two groups. The daily frequency of defecation 1 year after surgery was 1.9±0.9 for RISR-TME and 1.8±0.3 for RDS-TME indicating no difference between the two groups. Moreover, there were no significant differences between the two groups in other defecation functions. The mean Wexner score 1 year after surgery was 3.0±1.1 in R-ISR-TME and 2.2±1.0 in R-DS-TME group (p=0.2) and defecation-related quality of life for R-ISR-TME and R-DS-TME was not significantly different (modified fecal incontinence quality of life score: 30.3±19.1 vs 27.5±14.5, respectively; p=0.2). Conclusions: These clinical and functional results suggest that R-ISR-TME could be a good sphincter-preserving surgery for patients with very low rectal cancer. Robotic assistance may overcome some intrinsic limitations of the ISR technique flattening the difference with the DS-TME procedure

FACS-based protocol to assess cytotoxicity and clonogenic potential of colorectal cancer stem cells using a Wnt/β-catenin signaling pathway reporter

Cancer stem cells (CSCs) play a key role in tumor initiation and progression. A real-time tool to evaluate the activation of CSC-specific signaling pathways is crucial for the study of this cancer cell subset. Here, we present a protocol to monitor, in vitro, the activation of Wnt/β-catenin signaling pathway, which is considered a functional biomarker for colorectal CSCs (CR-CSCs). This flow-cytometry-based protocol allows it to isolate CR-CSCs and to evaluate their cytotoxicity upon anti-tumor treatments

Robot-assisted surgery for the radical treatment of deep infiltrating endometriosis with colorectal involvement: short- and mid-term surgical and functional outcomes.

Sexual and urinary dysfunctions are complications in radical treatment of deep infiltrating endometriosis (DIE) with colorectal involvement. The aim of this article is to report the preliminary results of our single-institution experience with robotic treatment of DIE, evaluating intraoperative and postoperative surgical outcomes and focusing on the impact of this surgical approach on autonomic functions such as urogenital preservation and sexual well-being. METHODS: From January 2011 through December 2013, a case series of 10 patients underwent robotic radical treatment of DIE with colorectal resection using the da Vinci System. Surgical data were evaluated, together with perioperative urinary and sexual function as assessed by means of self-administered validated questionnaires. RESULTS: None of the patients reported significant postoperative complications. Questionnaires concerning sexual well-being, urinary function, and impact of symptoms on quality of life demonstrated a slight worsening of all parameters 1 month after surgery, while data were comparable to the preoperative period 1 year after surgery. Dyspareunia was the only exception, as it was significantly improved 12 months after surgery. CONCLUSIONS: Robot-assisted surgery seems to be advantageous in highly complicated procedures where extensive dissection and proper anatomy re-establishment is required, as in DIE with colorectal involvement. Our preliminary results show that robot-assisted surgery could be associated with a low risk of complications and provide good preservation of urinary function and sexual well-being