Effect of p63 expression on survival in oral squamous cell carcinoma

BACKGROUND: P63 is the protein codified by p63 gene, a p53 gene homolog, known for its pivotal role in cell cycle regulation, and involved in the tumor differentiation. Aims of the present study were to assess the frequency and pattern of p63 protein expression in oral squamous cell carcinoma (OSCC) in relation to the main tumour characteristics and to verify whether p63 can be considered a marker of prognosis in patients with OSCC. MATERIAL AND METHODS: In a retrospective study, a cohort of 64 OSCC patients was investigated for p63 protein expression and its cellular localization by immunohistochemistry (monoclonal mouse anti-human p63 protein-clone 4A4). After grouping by p63 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. RESULTS: The overall frequency of p63 overexpressed was of 57.8 percent. Various p63 staining patterns were observed according to G score, with a significant correlation between p63 overexpression and the lowest G score (P < 0.0001). No statistically significant difference was found between p63 pattern expression and age, sex, staging. OSCC patients with p63 overexpressed were found to have a poorer survival rate with respect to OSCCs with a normal pattern of expression (P = 0.024). CONCLUSIONS: On the basis of these results, it is possible to suggest p63 pattern expression as a reliable indicator of histological grading and an early marker of poor prognosis.     

Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat

Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of α-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.     

Adrenal surgery in the pediatric population

Adrenal tumors in children may be benign or malignant. In addition, both benign and malignant tumors may be hormonally active, leading to hypertension, metabolic crises, and endocrinopathies. These tumors may be found incidentally or secondary to signs and symptoms of the aforementioned disorders. Both a metabolic and a radiographic work-up are required before treatment of an adrenal tumor. The primary therapy for most adrenal lesions is surgical, though some are treated medically or require chemotherapy before excision. Laparoscopy has become the surgical approach of choice in both adult and pediatric patients with localized disease. Open surgical approaches remain necessary in patients with extensive locally invasive or metastatic disease.     

Mid-region parathyroid hormone-related protein (PTHrP) binds chromatin of MDA-MB231 breast cancer cells and isolated oligonucleotides “in vitro”

We have previously shown that PTHrP(38–94)-amide restrains growth and invasion “in vitro”, causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated “in vivo”. PTHrP(38–94)-amide contains the domain implicated in the nuclear import of PTHrP. Although the nucleus was identified as a destination for mid-region PTHrP, evidence for direct DNA-binding capability is lacking to date. Here, we examined the localization of PTHrP(38–94)-amide within MDA-MB231 cells and within metaphase spread preparations and characterized its DNA-binding properties, employing a combination of immunocytochemical, cytogenetic, “whole genome”/conventional PCR, EMSA and DNase footprinting techniques. The results obtained: (i) show that PTHrP(38–94)-amide gains access to the nuclear compartment of MDA-MB231 cell; (ii) demonstrate that PTHrP(38–94)-amide is a DNA-binding peptide; and, (iii) represent the first data to date on the potential molecular targets in both cellular chromatin and isolated oligonucleotides “in vitro”.     

Lubricin immunohistochemical expression in human temporomandibular joint disc with internal derangement

J Oral Pathol Med (2011) 40 : 587–592 Lubricin is a chondroprotective, mucinous glycoprotein which contribute to joint lubrication, especially to boundary lubrication and maintains joint integrity. The present investigation aimed to study the immunolocalization of lubricin in TMJ discs from patients affected by anterior disc displacement with reduction (ADDwR) ADDwoR. Eighteen TMJ displaced disc affected by ADDwoR were processed immunohistochemically, with a polyclonal anti‐lubricin antibody, used at 1:50 working dilution. The percentage of lubricin immunopositive cells (extent score = ES) and the extent of lubricin staining of the disc extracellular matrix (ECM), were evaluated. Each sample was scored for histopathological changes. Percentage of immunostained surface disc cells was the same (ES = 4) in both control and ADDwOR cells, being this data not statistically significant (P < 0.05). In pathological specimens the percentages of lubricin‐stained cells was very high with an ES of 4 respect to control specimen, and this difference was statistically significant different (P > 0.05). The extracellular matrix (ECM) of discs at the disc surfaces of both pathological and normal specimens was very heavily stained (++++). Both the ES and ECM staining were not statistically correlated to the TMJ degeneration score according to the Spearman’s rank correlation coefficient. According to our findings, a longstanding TMJ disc injury, affects lubricin expression in the TMJ disc tissue and not its surfaces, moreover, lubricin immunostaining is not correlated to TMJ disc histopathological changes.     

Wine consumption and renal diseases: new perspectives

Investigations into the relation between wine consumption and kidney disease have been limited. Patients with chronic renal failure show accelerated atherosclerotic damage and, considering the well-known protective effect of wine on the cardiovascular system, moderate wine consumption might be advantageous. Oxidative stress and endothelial dysfunction, which are inter-related, play a role in the pathophysiology of many renal diseases, including acute and chronic renal failure. Ethanol and non-alcoholic wine components, especially polyphenols, influence oxidative balance and endothelial function. Although long-term alcohol abuse has been associated with many renal alterations in humans, in experimental studies wine polyphenols enhanced kidney antioxidant defenses, exerted protective effects against renal ischemia/reperfusion injury, and inhibited apoptosis of mesangial cells. Moreover, in diabetic patients the administration of moderate amounts of red wine and a polyphenol-enriched diet slowed the progression of diabetic nephropathy. Moreover, the unfavorable effect of ethanol on blood pressure control seems to be counterbalanced by polyphenol protective effects. There is convincing evidence of a beneficial effect of controlled wine consumption patients with renal disease, but controlled clinical trials are needed to confirm this hypothesis.     

Expression of Interleukin-1 and temporomandibular disorder: Contemporary review of the literature

Objective: Temporomandibular disorders (TMD) are a group of conditions affecting the temporomandibular joint (TMJ), leading to jaw dysfunction, joint and muscle pain, and a decrease in quality of life. A communication network of pro- and anti-inflammatory mediators called cytokines maintains the homeostasis of the TMJ. This review will focus on the Interleukin (IL) family of cytokines, which have been quantified in TMJ synovial fluids in a variety of studies. IL-1α and IL-1β have pro-inflammatory effects, while the endogenous receptor antagonist (IL-1RA) inhibits the pro-inflammatory effects of IL-1.

Methods: A literature search (2006–2016) to identify eligible studies was completed using the PubMed database. Studies identified used saline irrigation to quantify cytokine profiles in synovial fluid of healthy and/or dysfunctional joints.

Results: The initial search yielded 111 articles, 5 of which met the inclusion criteria after inter-reviewer discussion.

Conclusions: Articles that compared IL-1 concentrations in TMD vs. control groups found significant differences.     

Current Status of Robot-Assisted Partial Nephrectomy

The incidence of incidentally diagnosed small renal masses is rising. Although open partial nephrectomy (OPN) remains the reference standard for clinically localized renal lesions, growing experience with minimally invasive PN has demonstrated equivalent oncologic efficacy and improved short-term perioperative outcomes compared to open techniques. Compared to the technically demanding laparoscopic PN (LPN), robotic PN (RPN) overcomes a number of the technical hurdles of LPN with a shorter learning curve, and now has emerged as an attractive minimally invasive treatment option for amenable tumors. Although experience with RPN has been limited to date, early series have demonstrated short-term oncologic outcomes comparable to OPN and equivalent perioperative outcomes to LPN (all ≤ level III evidence). Although prospective evidence would be ideal, clinical trial comparisons with LPN and OPN will be fraught with accrual challenges and are not expected in the near future. This review summarizes the advantages and indications for a robotic approach, operative principles and emerging technologies, early functional and oncologic outcomes, and expected future advances of RPN for localized renal tumors.     

Longitudinal changes in social functioning in mildly disabled patients with relapsing–remitting multiple sclerosis receiving subcutaneous interferon β-1a: results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study (II)

Purpose

To report longitudinal changes in and explore the influence of cognition on social functioning in mildly disabled patients with relapsing?Cremitting multiple sclerosis (RRMS).

Methods

Italian patients (18?C50?years) with RRMS and Expanded Disability Status Scale (EDSS) score ??4.0 were assigned to interferon ??-1a, 44 or 22???g subcutaneously three times weekly, and underwent annual assessments for social functioning (Environmental Status Scale [ESS]) over 3?years.

Results

Baseline total ESS score did not differ between patients with and without cognitive impairment (P?=?0.505). Total ESS score remained low (<2.0) and stable over 3?years in the whole study population, but worsened slightly when assessed by assigned treatment or treatment and baseline cognitive status (both P?=?0.004), driven mostly by changes in the ??transportation?? and ??financial/economic status?? subscales. The strongest independent predictor of worsening ESS score was baseline EDSS score. Test?Cretest analyses confirmed that total ESS score and most subscales changed little over 3?years.

Conclusion

ESS scores remained low and changed minimally over 3?years, reflecting the mild physical disability and good cognitive performance in this patient population. Determining the influence of cognitive function and treatment on longitudinal changes in social functioning requires further studies.