Carcinoma cells activate AMP-activated protein kinase-dependent autophagy as survival response to kaempferol-mediated energetic impairment.

Kaempferol, a dietary cancer chemopreventive polyphenol, has been reported to trigger apoptosis in several tumor histotypes, but the mechanism underlying this phenomenon is not fully understood. Here, we demonstrate that in HeLa cells, kaempferol induces energetic failure due to inhibition of both glucose uptake and Complex I of the mitochondrial respiratory chain. As adaptive response, cells activate autophagy, the occurrence of which was established cytofluorometrically, upon acridine orange staining, and immunochemically, by following the increase of the autolysosome-associated form of the microtubule-associated protein light chain 3 (LC3-II). Autophagy is an early and reversible process occurring as survival mechanisms against apoptosis. Indeed, chemical inhibition of autophagy, by incubations with monensin, wortmannin, 3-methyladenine, or by silencing Atg5, significantly increases the extent of apoptosis, which takes place via the mitochondrial pathway, and shortens the time in which the apoptotic markers are detectable. We also demonstrate that autophagy depends on the early activation of the AMP-activated protein kinase (AMPK)/mTOR-mediated pathway. The overexpression of dominant negative AMPK results in a decrease of autophagic cells, a decrement of LC3-II levels, and a significant increase of apoptosis. Experiments performed with another carcinoma cell line yielded the same results, suggesting for kaempferol a unique mechanism of action

Single-fraction radiotherapy (SFRT) for bone metastases: Patient selection and perspectives

Bone metastases are a frequent and important source of morbidity in cancer patients. Stereotactic body radiation therapy (SBRT) is an established treatment option for local control and pain relief of bone metastases, and it is increasingly used as upfront treatment, postoperative consolidation or salvage treatment after prior RT. However, heterogeneity of dose schedules described in literature represents a severe limitation in the definition of the role of SBRT as a standard of care. No consensus is available on the use of single versus multiple fraction SBRT for bone metastases. Advantages of single-fraction SBRT include shorter overall duration of treatment, absence of inter-fraction uncertainty, improved compliance, theoretical increased efficacy, and lower costs. However, caution has been advised due to reports of severe late toxicities, in particular, vertebral collapse fracture (VCF). The aim of this paper is to review dose fractionation and indications for the management of bone metastases using SBRT

Intestinal Taxa Abundance and Diversity in Inflammatory Bowel Disease Patients: An Analysis including Covariates and Confounders

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn's disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables "age", "eat yogurt at least four days per week" and "eat dairy products at least 4 days per week" as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables "age", "gender", "eat meat at least four days per week" and "eat bread at least 4 days per week" were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour

Is panoramic radiography really a key examination before chemo-radiotherapy treatment for oropharyngeal cancer?

Aim: To evaluate the diagnostic accuracy of panoramic radiography (PAN) for the identification of infectious foci of the tooth and periradicular bone before definitive chemo-radiotherapy treatment for oropharyngeal cancer, using multislice spiral computed tomography (MSCT) imaging as the reference standard. Materials and methods: 50 patients with oropharyngeal cancer who had performed both pre-treatment MSCT and PAN were retrospectively evaluated. Pre-radiotherapy MSCT showed 65 deep caries, 37 root remnants, 143 stage III periodontal diseases, and 77 apical periodontitis, for a total of 322 infectious foci. The same number of healthy teeth (control group) was selected via MSCT to be analysed by PAN. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for PAN images with respect to MSCT imaging were examined. Results: PAN showed sensitivity, negative predictive value, and diagnostic accuracy of 100% for deep caries, root remnants, and stage III periodontal disease, whereas there were 46.8%, 64.7%, and 72.1% apical periodontitis respectively. Conclusions: PAN did not show great diagnostic accuracy in the assessment of apical periodontitis, and therefore maxillofacial MSCT carried out before chemo-radiotherapy treatment should always be examined to identify dental and jaw diseases. Deep caries, root remnants, and stage III periodontal disease were perfectly detected on PAN

Biomarkers in wound drainage fluids of head and neck squamous cell carcinoma patients receiving neck dissection: A pilot study

Aim: In a pilot prospective study, we aimed to test the feasibility and report on the preliminary results on the expression of molecular biomarkers in wound drainage fluids (WDFs) of operated head and neck squamous cell carcinoma (HNSCC) patients. Material and methods: Nineteen patients undergoing primary tumor resection with en-block neck dissection were enrolled. In postoperative days 1–3, the expression of several biomarkers in WDFs was measured using enzyme-linked immunosorbent assay (ELISA) kits and correlated with clinical and histopathologic features. Results: The expression of stromal cell-derived factor 1 (CXCL-12) was significantly increased in WDFs in presence of lymph node metastases, extranodal extension (ENE), and in case of close resection margins. In addition, Osteopontin expression was significantly increased in presence of ENE, whereas transforming growth factor beta (TGF-β) detection was significantly reduced. At multivariate analysis, CXCL-2 levels in both day 1 and 3 post-surgery were the only factor which retained significance in the prediction of close surgical margins (p = 0.028 and 0.025 for day 1 and day 3, respectively). Both CXCL-2 and Ostepontin assays were significantly correlated with ENE (p = 0.018 and 0.035 for day 1; 0.052 and 0.025 for day 3, respectively) whereas TGF- β expression was significant at day 1 only (p = 0.038) Conclusions: Our pilot study showed that WDFs could qualify as a potential source of relevant postoperative information. Further studies are needed to confirm the prognostic impact of CXCL-12, Osteopontin and TGF-β expressed in WDFs on the personalized management of HNSCC

Stereotactic reirradiation for local failure of brain metastases following previous radiosurgery: Systematic review and meta-analysis

Introduction: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN). Methods: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN. Results: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19–30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8–22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %–19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %–19 %] vs 7 %[95 %CI 3 %–12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %–25 %] vs 7%[95 %CI 3 %–13 %], p = 0.004). Conclusions: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS

treatment patterns in elderly patients with locally advanced head and neck squamous cell carcinoma la hnscc results from an eortc led survey

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