Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, ...cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease.
Purpose
Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15–30% of cases, therefore it ...would be useful to assess if pretreatment of
18
F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC.
Methods
Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models.
Results
In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index).
Conclusions
If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.
To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology ...reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (
p
< 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm
2
and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (
p
= 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (
p
= 0.036) in the entire cohort. In the Luminal B/HER2− subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (
p
= 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2− subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.
A drastic amphibian decline has been observed worldwide, which can be attributed (among other factors) to exposure to pollutants. Considering that cadmium corresponds to the most rapidly increasing ...trace metal in the environment, the aim of this work was to evaluate whether the exposure (2 and 16 days) of bullfrog tadpoles to this trace metal, at the concentration currently considered environmentally safe (at 1ppb) in class 1 and 2 waters by the Brazilian Environmental Council, can affect the cardiac performance of these animals. The acute exposure (2 days) of tadpoles to cadmium resulted in a marked bradycardic response, which was correlated with an incomplete cardiac relaxation, without any compensation by improved cardiac twitch force (Fc) or contraction velocity (TPT), nor even by cardiac hypertrophy. Indeed, after 16 days of exposure, the cardiac function of tadpoles became even more depressed due to a marked decrease in Fc, a prolongation of TPT, and also incomplete relaxation (i.e. increases in the ventricle resting tension), without changes in ventricle relative mass. Altogether, the cardiodepressive effects of cadmium (especially after more prolonged exposure periods) impose negative alterations on a tadpole׳s development and also impede adequate homeostatic adjustments to respond appropriately to the exposure to cadmium with increase in energetic demand to counteract the deleterious effects of the xenobiotic. These disturbances can impair tadpoles׳ growth, development and reproduction. It is a fact that allows us to strongly suggest that cadmium concentrations, which are currently considered environmentally safe in Brazil, should be revised.
•The acute exposure of tadpoles to cadmium resulted in a marked bradycardia.•This response was not compensated by any improvement in the inotropism.•After 16 days, the impact became more evident, since the contraction force decreased.•Cardiac imbalances can impair tadpoles’ growth, development and reproduction.•The concentration of cadmium considered safe to Brazilian waters should be revised.
Cancer and blood coagulation Boccaccio, C; Medico, E
Cellular and molecular life sciences : CMLS,
05/2006, Letnik:
63, Številka:
9
Journal Article
Recenzirano
In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or ...inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer.
Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, ...we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation.
Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques.
Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs.
Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.
Dimethyl Disulfide (DMDS), as an EC formulation, was applied via drip-irrigation to control the root-knot nematode Meloidogyne incognita in two trials in protected crops. The trials were carried out ...in Sicily (Italy) during 2012 on melon and on tomato, according to a randomized block design with 4-5 replicates per treatment. The soil of the sites was sandy and naturally severely infested by the nematode. DMDS was applied at the rates of 300, 400, and 500 kg/ha (the last rate only in tomato). The soil was covered with virtually impermeable film (VIF) before fumigation and uncovered 2 weeks later. DMDS treatments were compared with 1,3-dichloropropene (140 L/ha for melon and 180 L/ha for tomato) and a non-treated control. Yield was recorded in all trials. The nematode attack on the roots was evaluated according to the 0-10 Zeck’s scale modified (0 no galls and 10 root system completely deformed by large and numerous galls). In the melon trial, 60 days after transplanting (DAT), both DMDS doses (400 and 300 kg/ha) showed low root gall indices (1.2 and 1.5, respectively), compared to the non-treated control (5.5) and 1,3-dichloropropene (4.2). In the tomato trial 120 DAT, DMDS at 500, 400 and 300 kg/ha showed root gall indices of 2.9, 2.7, and 3.0, respectively, compared to 9.6 of the non-treated control and 3.6 of 1,3-dichloropropene. All nematicidal treatments significantly increased marketable yields of melon and tomato in comparison to non-treated controls. Therefore, DMDS, once registered, could be a new effective solution to control root-knot nematodes in protected crops and because of its favourable ecotoxicologial profile, it could also be considered for IPM programmes of protected crops.
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