Richhouston7363

CCRL2 belongs to the G protein-coupled receptor family and is one of the three chemerin receptors. It is considered as a non-signaling receptor, presenting chemerin to cells expressing the functional chemerin receptor ChemR23/CMKLR1 and possibly GPR1. In the present work, we investigate the role played by CCRL2 in mouse cancer models. Loss of function of Ccrl2 accelerated the development of papillomas in a chemical model of skin carcinogenesis (DMBA/TPA), whereas the growth of B16 and LLC tumor cell grafts was delayed. Delayed tumor growth was also observed when B16 and LLC cells overexpress CCRL2, while knockout of Ccrl2 in tumor cells reversed the consequences of Ccrl2 knockout in the host. The phenotypes associated with CCRL2 gain or loss of function were largely abrogated by knocking out the chemerin or Cmklr1 genes. Cells harboring CCRL2 could concentrate bioactive chemerin and promote the activation of CMKLR1-expressing cells. A reduction of neoangiogenesis was observed in tumor grafts expressing CCRL2, mimicking the phenotype of chemerin-expressing tumors. This study demonstrates that CCRL2 shares functional similarities with the family of atypical chemokine receptors (ACKRs). Its expression by tumor cells can significantly tune the effects of the chemerin/CMKLR1 system and act as a negative regulator of tumorigenesis.Endogenous acetaldehyde production from the metabolism of ingested alcohol exposes hematopoietic progenitor cells to increased genotoxic risk. To develop possible therapeutic strategies to prevent or reverse alcohol abuse effects, it would be critical to determine the temporal progression of acute ethanol toxicity on progenitor cell numbers and proliferative status. We followed the variation of the cell proliferation rate in bone marrow and spleen in response to acute ethanol intoxication in the MITO-Luc mouse, in which NF-Y-dependent cell proliferation can be assessed in vivo by non-invasive bioluminescent imaging. One week after ethanol administration, bioluminescent signals in bone marrow and spleen decreased below the level corresponding to physiological proliferation, and they progressively resumed to pre-treatment values in approximately 4 weeks. Boosting acetaldehyde catabolism by administration of an aldehyde dehydrogenase activity activator or administration of polyphenols with antioxidant activity partially restored bone marrow cells' physiological proliferation. These results indicate that in this mouse model, bioluminescent alteration reflects the reduction of the physiological proliferation rate of bone marrow progenitor cells due to the toxic effect of aldehydes generated by alcohol oxidation. In summary, this study presents a novel view of the impact of acute alcohol intake on bone marrow cell proliferation in vivo.To describe and evaluate outcomes of Gamma Knife radiosurgery (GK) for the treatment of pituitary tumors over the past twenty years, a systematic review and meta-analysis according to PRISMA statement was performed. Articles counting more than 30 patients were included. A weighted random effects models was used to calculate pooled outcome estimates. From 459 abstract reviews, 52 retrospective studies were included. Among them, 18 reported on non-functioning pituitary adenomas (NFPA), 13 on growth hormone (GH)-secreting adenomas, six on adrenocorticotropic hormone (ACTH)-secreting adenomas, four on prolactin hormone (PRL)-secreting adenomas, and 11 on craniopharyngiomas. Overall tumor control and five-year progression free survival (PFS) estimate after one GK procedure for NFPA was 93% (95% CI 89-97%) and 95% (95% CI 91-99%), respectively. In case of secreting pituitary adenomas, overall remission (cure without need for medication) estimates were 45% (95% CI 35-54%) for GH-secreting adenomas, 64% (95% CI 0.52-0.75%) for ACTH-secreting adenomas and 34% (95% CI 19-48%) for PRL-secreting adenomas. Entinostat purchase The pooled analysis for overall tumor control and five-year PFS estimate after GK for craniopharyngioma was 74% (95% CI 67-81%) and 70% (95% CI 64-76%), respectively. This meta-analysis confirms and quantifies safety and effectiveness of GK for pituitary tumors.This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, ing to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).Wire-guided localisation (WGL) has been the gold-standard for localising non-palpable breast lesions before excision. Due to its drawbacks, various wireless alternatives have been developed, including LOCalizer™, which is based on radio-frequency identification (RFID) technology. In this systematic review, we consulted EMBASE, Medline and PubMed databases using appropriate search terms regarding the use of RFID technology in the localisation of occult breast lesions. Retrospective and prospective studies were included if they quoted the number of patients, rate of successful placement, retrieval rate, margin positivity rate and the re-excision rate. In addition, studies comparing RFID to WGL were also included and analysed separately. Seven studies were included in this systematic review spanning 1151 patients and 1344 tags. The pooled deployment rate was 99.1% and retrieval rate was 100%. Re-excision rate was 13.9%. One complication was identified. Two studies compared RFID with WGL (128 vs. 282 patients respectively). For both techniques the re-excision rate was 15.6% (20/128 vs. 44/282 respectively, p value is 0.995). Based on our review, LOCalizer™ is safe and non-inferior to WGL in terms of successful localisation and re-excision rates. However, further research is required to assess the cost effectiveness of this approach and its impact on the aesthetic outcome compared with WGL and other wire free technologies to better inform decision making in service planning and provision.The iron-chelating drug ciclopirox (CPX) may possess therapeutic potential for cancer treatment, including cervical cancer. As is observed for other chemotherapeutic drugs, CPX can induce senescence or apoptosis in cervical cancer cells which could differently affect their therapy response. The present study aims to gain insights into the determinants which govern the switch between senescence and apoptosis in cervical cancer cells. We performed proteome analyses, proliferation studies by live-cell imaging and colony formation assays, senescence and apoptosis assays, and combination treatments of CPX with inhibitors of oxidative phosphorylation (OXPHOS) or glycolysis. We found that CPX downregulates OXPHOS factors and facilitates the induction of apoptosis under limited glucose availability, an effect which is shared by classical OXPHOS inhibitors. Under increased glucose availability, however, CPX-induced apoptosis is prevented and senescence is induced, an activity which is not exerted by classical OXPHOS inhibitors, but by other iron chelators. Moreover, we show that the combination of CPX with glycolysis inhibitors blocks cervical cancer proliferation in a synergistic manner. Collectively, our results reveal that the phenotypic response of cervical cancer cells towards CPX is strongly dependent on glucose availability, link the pro-apoptotic and pro-senescent activities of CPX to its bifunctionality as an OXPHOS inhibitor and iron chelator, respectively, and provide a rationale for combining CPX with glycolysis inhibitors.miR-27a plays a driver role in rewiring tumor cell metabolism. We searched for new miR-27a targets that could affect mitochondria and identified FOXJ3, an apical factor of mitochondrial biogenesis. We analyzed FOXJ3 levels in an in vitro cell model system that was genetically modified for miR-27a expression and validated it as an miR-27a target. We showed that the miR-27a/FOXJ3 axis down-modulates mitochondrial biogenesis and other key members of the pathway, implying multiple levels of control. As assessed by specific markers, the miR-27a/FOXJ3 axis also dysregulates mitochondrial dynamics, resulting in fewer, short, and punctate organelles. Consistently, in high miR-27a-/low FOXJ3-expressing cells, mitochondria are functionally characterized by lower superoxide production, respiration capacity, and membrane potential, as evaluated by OCR assays and confocal microscopy. The analysis of a mouse xenograft model confirmed FOXJ3 as a target and suggested that the miR-27a/FOXJ3 axis affects mitochondrial abundance in vivo. A survey of the TCGA-COADREAD dataset supported the inverse relationship of FOXJ3 with miR-27a and reinforced cellular component organization or biogenesis as the most affected pathway. The miR-27a/FOXJ3 axis acts as a central hub in regulating mitochondrial homeostasis. Its discovery paves the way for new therapeutic strategies aimed at restraining tumor growth by targeting mitochondrial activities.Pancreatic ductal adenocarcinoma (PDAC) is a treatment-resistant malignancy characterized by a high malignant phenotype including acquired EMT signature and deregulated autophagy. Since we have previously described that the aberrant expression of the mesenchymal FGFR2c and the triggering of the downstream PKCε signaling are involved in epidermal carcinogenesis, the aim of this work has been to assess the contribution of these oncogenic events also in the pancreatic context. Biochemical, molecular and immunofluorescence approaches showed that FGFR2c expression impacts on PDAC cell responsiveness to FGF2 in terms of intracellular signaling activation, upregulation of EMT-related transcription factors and modulation of epithelial and mesenchymal markers compatible with the pathological EMT. Moreover, shut-off via specific protein depletion of PKCε signaling, activated by high expression of FGFR2c resulted in a reversion of EMT profile, as well as in a recovery of the autophagic process. The detailed biochemical analysis of the intracellular signaling indicated that PKCε, bypassing AKT and directly converging on ERK1/2, could be a signaling molecule downstream FGFR2c whose inhibition could be considered as possible effective therapeutic approach in counteracting aggressive phenotype in cancer.