Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by ...downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer.
Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA.
Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model.
Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.
Oesophageal atresia van Lennep, Marinde; Singendonk, Maartje M J; Dall'Oglio, Luigi ...
Nature reviews. Disease primers,
04/2019, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut. EA commonly occurs with a tracheo-oesophageal ...fistula (TEF). Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA. Although several studies have revealed signalling pathways and genes potentially involved in the development of EA, our understanding of the pathophysiology of EA lags behind the improvements in surgical and clinical care of patients born with this anomaly. EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF. Survival is now ~90% in those born with EA with severe associated anomalies and even higher in those born with EA alone. Despite these achievements, long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common and lead to decreased quality of life. Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair and often underlie these complications and comorbidities. The implementation of several new diagnostic and screening tools in clinical care, including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing and disease-specific quality of life questionnaires now provide better insight into these problems and may contribute to better long-term outcomes in the future.
Topical cosmetic agents may play a role in the management of facial seborrheic dermatitis by reducing inflammation and scale production. Advanced digital photography, equipped with technology able to ...provide a detailed evaluation of red skin components corresponding to vascular flare (erythema-directed digital photography), is a useful tool for evaluation of erythema in patients affected by inflammatory dermatoses. The aim of this study was to assess the efficacy and safety of a new cosmetic topical gel containing piroctone olamine, lactoferrin, glycero-phospho-inositol, and Aloe vera for the treatment of facial seborrheic dermatitis by clinical and advanced digital photography evaluation.
An open-label, prospective, clinical trial was conducted on 25 patients with mild to moderate facial seborrheic dermatitis. Subjects were instructed to apply the gel twice daily for 45 days. The clinical efficacy was evaluated by measuring at baseline, at day 15 and 45 the degree of desquamation (by clinical examination) and erythema (by digital photography technology via VISIA-CR™ system equipped with RBX™), using a 5-point severity scale, and pruritus (by subject-completed Visual Analogue Scale; scale from 0 to 100 mm). Finally, at baseline and at the end of the study, IGA (Investigator Global Assessment) was performed using a 5-point severity scale (from 0 = worsening to 4 = excellent response).
At the end of treatment, a significant reduction (P<0.001) of all considered parameters was observed. Moreover, an excellent response (>80% improvement) was recorded in 47.9% of patients, with no case of worsening. No signs of local intolerance were documented.
The tested cosmetic topical gel was effective in treating mild to moderate seborrheic dermatitis of the face. Erythema-directed digital photography may represent a noteworthy tool for the therapeutic monitoring of facial seborrheic dermatitis and an important adjunct aid in the dermatologic clinical practice.
E-cadherin and beta-catenin are adhesion molecules responsible for the maintenance of normal epithelial cell phenotype. A disturbance in epithelial cell adhesion, which leads to a more invasive and ...metastatic phenotype, is a hallmark of tumor progression. Several immunohistochemical studies have reported a strong correlation between loss of their expression to higher stage and grade in prostate carcinoma, but their influence in metastatic process is not yet known. The aim of this study is to verify the role of adhesion molecules in the progression of prostate cancer (PC), assessing the expression of E-cadherin and beta-catenin in bone metastasis.
Twenty-eight bone metastases of prostate carcinoma were submitted to immunohistochemistry analysis for E-cadherin and beta-catenin expression. In 6 patients, we were able to assess the expression of the adhesion molecules in the primary tumors and their respective metastases. The definition of normal expression for both antibodies was strong and diffuse expression in more than 70% of tumor cells.
In bone metastases, there was loss of expression of E-cadherin and beta-catenin in 86% and 82%, respectively. Among the primary tumors, E-cadherin and beta-catenin expression was normal in 83% and 50% cases, respectively. Considering the 6 patients with paired primary and bone metastasis, we found loss of expression for both E-cadherin and beta-catenin in most of the cases.
Comparing primary PC and its metastasis, we showed persistent loss of E-cadherin and beta-catenin expression. This phenomenon may be related to metastatic potential in PC, because we have shown underexpression for E-cadherin and beta-catenin in 86% and 82% of bone metastases.
A central pillar of modern weed control is the discovery of new herbicides which are nontoxic to humans and the environment and which have low application dosage. The natural products found in plants ...and microorganisms are well suited in this context because they are generally nontoxic and have a wide variety of biological activities. In this work, Diaporthe phaseolorum (Dp), Penicillium simplicissimum (Ps) and Trichoderma spirale (Ts) (methanolic extracts) were evaluated as photosynthesis and plant growth inhibitors in Senna occidentalis and Ipomoea grandifolia. The most significant results were observed for Ts and Dp in S. occidentalis and I. grandifolia, respectively. Ts reduced PI
(abs)
, ET
0
/CS
0
, PHI(E
0
) and PSI
0
parameters by 64, 28, 40 and 38%, respectively, indicating a reduction on electron transport efficiency. Additionally, Ts decreased shoot length by 9%, affecting the plant growth. Dp reduced PI
(abs)
, ET
0
/CS
0
and PHI(E
0
) parameters by 50, 20, 26 and 22%, respectively, revealing the inhibition competency on PSII acceptor site. Furthermore, Dp decreased by 50% the shoot length on germination assay. Thus, the phytotoxic behaviors based on endophytic fungal extracts may serve as a valuable tool in the further development of a bioherbicide since natural products represent an interesting alternative to replace commercial herbicides.
Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether ...the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy.
Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence.
236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7.
Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.
Videodermatoscopy is a non-invasive technique that allows in vivo skin observation at high magnifications.
The goal of this study was to determine if videodermatoscopy enhances diagnostic capability ...beyond standard clinical observation in three series of patients: one group of patients with overt alopecia areata (AA), one with overt androgenetic alopecia (AGA), and one with hair loss with no apparent diagnostic features.
The first group consisted of 200 patients affected by acute (140 patients) and chronic (60 patients) AA, and the second group of 100 patients affected by AGA. In both groups, the clinical diagnosis was confirmed by pull tests and trichograms. The third group consisted of 50 patients with clinically undifferentiated hair loss. In all groups, videodermatoscopy was performed at magnifications ranging from 20x to 600x.
In acute AA (n = 140), three videodermatoscopy patterns were identified, characterized by: (i). 'exclamation point' and/or 'cadaveric' hairs (n = 62); (ii). 'vellus' hairs, in some cases with increased proximal shaft thickness and pigmentation (n = 38); and (iii). coexistence of all the features from (i). and (ii). n = 40. In chronic AA (n = 60), in those cases who were recently converted to chronic form from acute AA (n = 35), videodermatoscopy showed a scalp skin that appeared smooth and thin, with evident follicular openings. In cases of long-standing chronic AA (n = 25), hair follicle openings appeared to be obstructed by keratotic plugs. However, whether the two follicular patterns were related to disease duration or to some unknown factors is unclear. In some patients with chronic AA, videodermatoscopy also revealed hair regrowth, which appeared either as homogeneous, indicating early disease remission (upright 'vellus' hairs), or as sparse, thin, and twisted vellus hairs that were usually lost in a few weeks time. In AGA patients, videodermatoscopy observation allowed an accurate assessment of the ratios of miniaturized to normal hairs, a finding that was interpreted as a prognostic feature. Interestingly, videodermatoscopy clearly demonstrated the hair abnormalities corresponding to both diseases in those patients with concomitant causes of hair loss, as we observed in five patients simultaneously affected by AA and AGA. In the third group, videodermatoscopy allowed identification of early or minimal forms of AA (n = 20), AGA with mild hair loss of the centro-parietal area of the scalp (n = 20), and scarring alopecia (n = 10).
The results indicate that videodermatoscopy represents a very useful tool in the evaluation of hair loss, both for differential diagnosis (especially in early, transitional and mild forms) and for prognostic evaluation. It allows rapid, detailed, and non-invasive observation of the scalp skin and hair, and it provides high-resolution quality imaging.
(a) To externally validate the Crippa and colleagues' nomograms combining PSA, percentage of positive biopsy cores (PPBC) and biopsy Gleason score to predict organ-confined disease (OCD) in a ...contemporary sample of patients treated at a tertiary teaching institution. (b) To adjust such variables, resulting in predictive nomograms for OCD and seminal vesicle invasion (SVI): the USP nomograms.
The accuracy of Crippa and colleagues' nomograms for OCD prediction was examined in 1002 men submitted to radical prostatectomy between 2005 and 2010 at the University of São Paulo (USP). ROC-derived area under the curve (AUC) and Brier scores were used to assess the discriminant properties of nomograms for OCD. Nomograms performance was explored graphically with LOESS smoothing plots. Furthermore, univariate analysis and logistic regression models targeted OCD and SVI. Variables consisted of PSA, PPBC, biopsy Gleason score and clinical stage. The resulted predictive nomograms for OCD and SVI were internally validated with bootstrapping and the same abovementioned procedures.
Crippa and colleagues' nomograms for OCD showed ROC AUC = 0.68 (CI: 0.65-0.70), Brier score = 0.17 and overestimation in LOESS plots. USP nomograms for OCDand SVI showed ROC AUC of 0.73 (CI: 0.70-0.76) and 0.77 (CI: 0.73-0.79), respectively, and Brier scores of 0.16 and 0.08, respectively. The LOESS plots showed excellent calibration for OCD and underestimation for SVI.
Crippa and colleagues' nomograms showed moderate discrimination and considerable OCD overestimation. USP nomograms showed good discrimination for OCD and SVI, as well as excellent calibration for OCD and SVI underestimation.
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