Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis.

Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.

Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.

BACKGROUND: The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. METHODS: One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. RESULTS: One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. CONCLUSION: Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.

Bone mineral density and parathyroid function in patients on maintenance hemodialysis.

BACKGROUND: The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details. METHODS: In a cross-sectional design, data from 270 patients (age 55 ± 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D. RESULTS: Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the "low PTH" group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the "target range" (100-300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = -0.255, -0.278 and -0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the "low PTH" group. CONCLUSIONS: Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.

The prognostic role of clinical, morphological and molecular markers in oral squamous cell tumors.

Despite of considerable advances in the diagnostic and therapeutic possibilities, the prognosis of epithelial tumors in the oral cavity is still very poor. A knowledge of the prognostic factors at the beginning of treatment is therefore indispensable for determination of the appropriate therapy for the given patient. These factors may be linked to the patient (e.g. age, sex, general condition and immunological parameters) or to the tumor localization. A survey of the literature reveals that the TNM stage, the grade, the mode of invasion and the depth of the tumor infiltration are generally the most important factors influencing the fate of the patient. The prognosis depends primarily on the clinicopathological parameters, though even if they are known, it is not possible to screen out those patients who are at particular risk of a relapse. During the past 10 years, study of the DNA content distribution, the proliferation markers and certain oncogenes has come into the focus of attention; great interest is also shown in the extracellular matrix components and the metalloproteinases, which play key roles in the invasion and metastasis formation.

Characterization of germination with physical parameters: correlation of relative mass and density as an indicator function of the germination of European Turkey oak acorn.

During germination of European Turkey oak acorn (Quercus cerris L.), a linear relationship was established between mass and density. Water take-up induced by osmotic pressure of imbibition was established to be independent of the volume of the acorn. Development of the germinating acorn can be characterized by its physical parameters of relative mass (the mass of the germinating acorn divided by its mass at the beginning of germination) and density. Linear correlation between the increment of relative mass and the decrease in density reveals an important property of the germinating acorn, namely that the slopes of the straight lines fitted to the data pairs of relative mass and density can statistically be considered as a constant. On the basis of this finding, the germinating acorns having the same values of relative mass and density can be grouped into the same developmental stage.

Resection and replacement of the carotid artery in metastatic head and neck cancer: literature review and case report.

Metastases of advanced tumours of the oral cavity sometimes affect the cervical segments of the carotid arteries. The situation is worse in the 5-10% of cases in which the metastasis involves the common or internal carotid to such an extent that resection and replacement of the artery become necessary. Following clinical, CT/NM, and angiographic examinations, a surgical plan for the resection and reconstruction of the affected vascular segment is formulated. In preparing a treatment plan, emphasis must be placed on the expected quality of life, and careful consideration must be given to the extent of the operation.A survey of the international literature reveals that the reported mean 1-year complaint free survival rate after resection and reconstruction varies between 0 and 44%. In our experience, the wall of the carotid vessels is very resistant to tumour invasion in a large majority of patients. When radical surgery and reconstruction are carried out in the same session, does this increase the long-term cure rate and lengthen patient survival? A number of authors agree that radical interventions do not alter the survival indices significantly, but may improve the quality of life and regional control of the disease. The controversy over this topic is illustrated by means of a case report.

Malignant myoepithelioma. Clinicopathological and immunohistochemical characteristics.

A malignant myoepithelioma arising in the submucosal accessory glands of the oral cavity of a 23-year-old woman is reported. The patient was very young compared to the cases in the literature, and the tumour had an unusual vestibular location. A false diagnosis of pleomorphic adenoma had been made by fine needle aspiration biopsy. The surgery comprised a wide tumour excision, but neck dissection was not indicated. The final histologic diagnosis was malignant myoepithelioma. Immunohistochemically putative myoepithelial markers were highly expressed.

Structure and drug release of lamellar liquid crystals containing glycerol.

Lamellar lyotropic liquid crystalline (LLC) systems are thermodynamically stable, optically isotropic systems, which are formed with low energy input. New possibilities for the development of controlled drug delivery systems are inherent in these systems due to their stability and special skin-similarly structure. The present aim was to formulate multicomponent LLC systems with a relatively low surfactant content, composed of materials official in the European Pharmacopoeia 4th. Polarizing light microscopic examination of the samples was carried out, together with TEM observation of replicas produced by freeze-fractured technique for the purpose of demonstrating the presence of lamellar LC domains. Our LLC samples contained: Brij 96 (poly-oxyethylene-10-oleyl ether) with water, liquid petrolatum (LP) and glycerol in a given concentration range. The interlamellar repeated distance (d(L)) confirming the existence of a regular structure was determined by means of X-ray diffraction. The d(L) and G'values of the samples changed according to a maximum curve with increasing glycerol concentration up to 40% (w/w). A prolonged drug release was observed in case of the very water-soluble ephedrine hydrochloride and the same phenomena was observed in the case of tenoxicam, which is practically insoluble in water.

Quadruple cancer, including triple cancers in the head and neck region.

Multiple primary tumors are not rare: they are encountered in 3-5% of malignant tumors. They are particularly frequent in the head and neck [20]. They are most often met with secondary malignant tumors; triple tumors occur in only 0.5%, quadruple tumors in 0.3% of malignant tumors. The possibility of developing a second metachronous cancer 5 years after undergoing treatment of the initial head and neck cancer is approximately 22%. Multiple metachronous tumors often appear 3-4 years after the observation of the primary tumor, or even after 5-10 years in the case of laryngeal tumors. The frequency of multiple primary tumors in the head and neck region supports the "field cancerization" theory, according to which the inducing agents (primarily smoking and alcohol consumption) can initiate the tumorous degeneration at a number of sites in the oropharyngeal region. The authors report on a case in whom surgery for bladder tumor was followed 101 months later by tumor development in the region of the head and neck: 3 such tumors were treated within a period of 21 months. The histologic result on the bladder tumor was transitiocellular carcinoma, while the latter ones were squamous cell carcinomas. Three of the tumors were treated effectively (no local recurrence or metastasis developed), but the fourth led to the death of the patient. The literature on multiple tumors of the head and neck is reviewed, and possible etiologic factors are discussed. It is pointed out that, besides primary and secondary prevention, close observation of these patients is required, repeated panendoscopy of the upper aerodigestive tract and genetic examinations are recommended.