Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor-stroma ratio in colon cancer.

BACKGROUND: The TNM (tumor-node-metastasis) Evaluation Committee of Union for International Cancer Control (UICC) and College of American Pathologists (CAP) recommended to prospectively validate the cost-effective and robust tumor-stroma ratio (TSR) as an independent prognostic parameter, since high intratumor stromal percentages have previously predicted poor patient-related outcomes. PATIENTS AND METHODS: The 'Uniform Noting for International application of Tumor-stroma ratio as Easy Diagnostic tool' (UNITED) study enrolled patients in 27 participating centers in 12 countries worldwide. The TSR, categorized as stroma-high (>50%) or stroma-low (≤50%), was scored through standardized microscopic assessment by certified pathologists, and effect on disease-free survival (DFS) was evaluated with 3-year median follow-up. Secondary endpoints were benefit assessment of adjuvant chemotherapy (ACT) and overall survival (OS). RESULTS: A total of 1537 patients were included, with 1388 eligible stage II/III patients curatively operated between 2015 and 2021. DFS was significantly shorter in stroma-high (n = 428) than in stroma-low patients (n = 960) (3-year rates 70% versus 83%; P < 0.001). In multivariate analysis, TSR remained an independent prognosticator for DFS (P < 0.001, hazard ratio 1.49, 95% confidence interval 1.17-1.90). As secondary outcome, DFS was also worse in stage II and III stroma-high patients despite adjuvant treatment (3-year rates stage II 73% versus 92% and stage III 66% versus 80%; P = 0.008 and P = 0.011, respectively). In stage II patients not receiving ACT (n = 322), the TSR outperformed the American Society of Clinical Oncology (ASCO) criteria in identifying patients at risk of events (event rate 21% versus 9%), with a higher discriminatory 3-year DFS rate (stroma-high 80% versus ASCO high risk 91%). A trend toward worse 5-year OS in stroma-high was noticeable (74% versus 83% stroma-low; P = 0.102). CONCLUSION: The multicenter UNITED study unequivocally validates the TSR as an independent prognosticator, confirming worse outcomes in stroma-high patients. The TSR improved current selection criteria for patients at risk of events, and stroma-high patients potentially experienced chemotherapy resistance. TSR implementation in pathology diagnostics and international guidelines is highly recommended as aid in personalized treatment.

Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons.

Tropomyosin-related kinase (Trk) receptors modulate neuronal structure and function both during development and in the mature nervous system. Interestingly, TrkB and TrkC are expressed as full-length and as truncated splice variants. The cellular function of the kinase-lacking isoforms remains so far unclear. We investigated the role of the truncated receptor TrkB.T1 in the hippocampus of transgenic mice overexpressing this splice variant by analyzing both neuronal structure and function. We observed an impairment in activity-dependent synaptic plasticity as indicated by deficits in long-term potentiation and long-term depression in acute hippocampal slices of transgenic TrkB.T1 mice. In addition, dendritic complexity and spine density were significantly altered in TrkB.T1-overexpressing CA1 neurons. We found that the effect of TrkB.T1 overexpression differs between subgroups of CA1 neurons. Remarkably, overexpression of p75(NTR) and its activation by chemical induction of long-term depression in slice cultures rescued the TrkB.T1-dependent morphological alterations specifically in one of the two subgroups observed. These findings suggest that the TrkB.T1 and p75(NTR) receptor signaling systems might be cross-linked. Our findings demonstrate that TrkB.T1 regulates the function and the structure of mature pyramidal neurons. In addition, we showed that the ratio of expression levels of p75(NTR) and TrkB.T1 plays an important role in modulating dendritic architecture and synaptic plasticity in the adult rodent hippocampus, and, indeed, that the endogenous expression patterns of both receptors change reciprocally over time. We therefore propose a new function of TrkB.T1 as being dominant-negative to p75(NTR).

Improved sealant retention with bonding agents: a clinical study of two-bottle and single-bottle systems.

Recent in vitro work and a short clinical study suggest that adding a bonding agent layer between sealant and saliva-contaminated enamel allows for adequate bond strength and retention of resin sealants and may improve success of all sealant applications. This five-year clinical study scored 617 occlusal and 441 buccal/lingual molar sealants, with use of a split-mouth design, with half receiving sealant alone and half bonding agent plus sealant. Treatment effects and potential risk factors for sealant failure were tested by means of a Cox regression model. Three bonding agent groups were analyzed for treatment effect: Tenure primer, Scotchbond Multi-Purpose, and 3 single-bottle dentin bonding agents as a third group. The single-bottle group was successful in reducing risk of sealant failure, with a hazard ratio (HR) of 0.53 (p = 0.014) for occlusal and 0.35 (p = 0.006) for buccal/lingual sealants. Scotchbond was detrimental to occlusal sealant success, with a HR of 2.96 (p = 0.0003). Tenure primer was neutral, showing HRs close to 1.0. Variables that affected success differed between occlusal and buccal/lingual sealants, suggesting that failures on these two surfaces may be dependent upon differing factors. Early eruption stage was a significant risk factor for both surfaces (HR = 2.91, p = 0.00001, occlusal; and HR = 1.52, p = 0.015, buccal/lingual). Behavior (HR = 1.96, p = 0.0007), salivary problems (HR = 1.73, p = 0.002), and visually apparent variations in enamel (HR = 1.51, p = 0.018) were significant risk factors for occlusal sealants only. In addition to completing detailed analyses of risk factors for sealant survival, this study shows that single-bottle bonding agents protect sealant survival, yielding half the usual risk of failure for occlusal sealants and one-third the risk of failure for buccal/lingual sealants.

Effects of catechins on human blood platelet aggregation and lipid peroxidation.

The activity of catechins was studied for inhibitory activity in human blood platelets. Platelet aggregation and peroxidation were evaluated in platelet rich plasma (PRP) obtained from samples of healthy volunteers. Human blood platelets were submitted to stimulation with 300 microM arachidonic acid, 3 microM adenosine diphospate (ADP) and 6 microM epinephrine. Treatment with (200 microg/mL) catechin or epicatechin was sufficient to exhibit a potent inhibitory effect of the three agents. The inhibitory effect was dose dependent at concentrations of 20-200 microg/mL. Using malondialdehyde (MDA) as an index of total lipid peroxidation capacity, decreased production of MDA of the platelets treated with catechin or epicatechin after stimulation by arachidonic acid was observed. These findings suggest that catechins protect platelets from peroxidative stress and their aggregation.

Incidence of oral complications and application of a preventive protocol in children with acute leukemia.

This prospective, controlled study was designed to assess the effectiveness of a preventive oral protocol in children receiving antineoplastic treatment for acute lymphoblastic leukemia (ALL). During a 13-month period, 96 children from one to 16 years of age with a diagnosis of ALL were evaluated. When the study was initiated, 60 patients already undergoing chemotherapy received palliative treatment for complications (Group I). Thirty-six children (Group II) with newly diagnosed ALL received a daily preventive protocol consisting of: (1) elimination of bacterial plaque; (2) application of a mouthwash with a non-alcoholic solution of chlorhexidine 0.12% and (3) topical application of iodopovidone, followed by "swish and swallow" with nystatin 500,000 units. Children in both groups were examined every 7 to 14 days by our pediatric dentistry team. We found a significant improvement in oral hygiene (p = 0.001) and a significant decrease in the incidence of mucositis grade 2 (p = 0.0013) and oral candidiasis (p = 0.009) in the Group II children. These findings show that the systematic application of a preventive protocol significantly reduces the incidence of oral complications. The results of this study identify a need to include a pediatric dentist in a multidisciplinary team which provides oral care for cancer patients.

Adhesion of a compomer to dental structures.

The objective of this study was to evaluate the bond strength of a compomer to dental enamel, dentin, and cementum. Flat surfaces of these tissues were obtained from recently extracted human teeth. The different substrates were either treated with PSA (a primer and adhesive) or acid etched (35% phosphoric acid gel) and treated with PSA. Cylindrical specimens of compomer were then bonded to the substrates. Shear bond strength was determined after a 24-hour immersion in 37 degrees C water. Significant differences were found between both treatments on enamel, while none were found on dentin or cementum. The use of acid etchant on enamel as a surface-conditioning step previous to priming with PSA allowed a better bond between Dyract compomer and that substrate; acid etching was not particularly needed on dentin and cementum.

Barcoll hardness of resin-modified glass-ionomer cements and a compomer.

The objective of this study was to evaluate the influence of several factors on the hardness of resin-modified glass-ionomer cements (hybrid ionomers) and polyacid-modified resin composites (compomers). Disk-shaped specimens were prepared from the following materials: Vitremer, Fuji II LC, Photac-Fil, and Dyract. Three specimens of each product were irradiated with a light-curing device and three were not. Barcoll hardness was determined on both sides of the specimen 10 minutes after irradiation and after 48 hours of immersion in 37 degrees C water. A factorial design was used to evaluate the factors that influenced the results. The Dyract group that was not light cured was not included in the analysis because the product did not harden under this circumstance. Analysis of variance revealed a significant effect of material, time, and specimen side when light curing was carried out. The use or nonuse of light curing was also significant. For some hybrid ionomers (e.g., Photac-Fil), light curing is a more essential step than for others to obtain adequate hardness values.

Shear bond strength of adhesive composite systems to human dentin.

This study was carried out to evaluate the following adhesive systems under different conditions from the point of view of the bond strength that is obtained on dentin: Scotchbond Multipurpose, 3M: Denthesive II, Kulzer; Optibond, Kerr with techniques # 1 and 5; and A.R.T. Bond. Coltene. Composite resin (Z100, 3M) cylindrical specimens were bonded to flat dentin surfaces and the adhesive strength was determined under shear. No significant differences were found between the group in which products were used with a separate step of dentin demineralization and the group in which this step is not recommended or was omitted. It can be concluded that the use of dentin acid treatment as a separate step is not necessarily required for high composite bond strength even when it could represent a convenient clinical step to prepare enamel surfaces simultaneously.

[Carcinoembryonic antigen in serum and tissue of benign and cancerous breast lesions]. / L'antigène carcino-embryonnaire (ACE) Sérique et tissulaire dans les lésions bénignes et canceréuses du sein.

The tissular CEA was studied with the immunoperoxidase method and the circulating CEA with the enzyme immunoassay (EIA), using peroxidase-coupled antibodies. 51 cases of mammary cancers as well as 33 benign lesions were examined in order to study a possible correlation between the frequency of CEA-positive tissues and CEA-positive sera in the same patient. It has been confirmed that CEA-positive tumors can be accompanied by low or negative CEA serum levels. An attempt was made to analyze the stage and the histologic type of lesions in comparison to the positivity and the increase of CEA.