S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration

It has been previously shown that S100A2 is down-regulated in tumor cells and can be considered a tumor suppressor. We have recently shown that this down-regulation can be observed particularly in epithelial tissue, where S100A2 expression decreases remarkably in tumors as compared with normal specimens. In the present paper we investigate whether S100A2 could play a tumor-suppressor role in certain epithelial tissues by acting at the cell migration level. To this end, we made use of five in vitro human head and neck squamous cell carcinoma lines in which we characterized S100A2 expression at both RNA and protein level. To characterize the influence of S100A2 on cell kinetic and cell motility features, we used two complementary approaches involving specific antisense oligonucleotides and the addition of S100A2 to the culture media. The different expression analyses gave a coherent demonstration of the fact that the FADU and the RPMI-2650 cell lines exhibit high and low levels of S100A2 expression, respectively. Antisense oligonucleotides (in FADU) and extracellular treatments (in RPMI) showed that, for these two models, S100A2 had a clear inhibitory influence on cell motility while modifying the cell kinetic parameters only slightly. These effects seem to be related, at least in part, to a modification in the polymerization/depolymerization dynamics of the actin microfilamentary cytoskeleton. Furthermore, we found evidence of the presence of the receptor for advanced glycation end-products (RAGE) in RPMI cells, which may act as a receptor for extracellular S100A2. The present study therefore presents experimentally based evidence showing that S100A2 could play a tumor-suppressor role in certain epithelial tissues by restraining cell migration features, at least in the case of head and neck squamous cell carcinomas.     

13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy

Chronic allograft nephropathy is characterized by chronic inflammation and fibrosis. Because retinoids exhibit anti-proliferative, anti-inflammatory, and anti-fibrotic functions, the effects of low and high doses of 13-cis-retinoic acid (13cRA) were studied in a chronic Fisher344-->Lewis transplantation model. In 13cRA animals, independent of dose (2 or 20 mg/kg body weight/day) and start (0 or 14 days after transplantation) of 13cRA administration, serum creatinine was significantly lower and chronic rejection damage was dramatically reduced, including subendothelial fibrosis of preglomerular vessels and chronic tubulointerstitial damage. The number of infiltrating mononuclear cells and their proliferative activity were significantly diminished. The mRNA expression of chemokines (MCP-1/CCL2, MIP-1alpha/CCL3, IP-10/CXCL10, RANTES/CCL5) and proteins associated with fibrosis (plasminogen activator inhibitor-1, transforming growth factor-beta1, and collagens I and III) were strikingly lower in treated allografts. In vitro, activated peritoneal macrophages of 13cRA-treated rats showed a pronounced decrease in protein secretion of inflammatory cytokines (eg, tumor necrosis factor-alpha, interleukin-6). The suppression of the proinflammatory chemokine RANTES/CCL5 x 13cRA in fibroblasts could be mapped to a promoter module comprising IRF-1 and nuclear factor-kappaB binding elements, but direct binding of retinoid receptors to promoter elements could be excluded. In summary, 13cRA acted as a potent immunosuppressive and anti-fibrotic agent able to prevent and inhibit progression of chronic allograft nephropathy.     

Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.     

Complex open elbow fracture Gustilo-Anderson type IIIB treated with the primary elbow arthroplasty: A case report

Total elbow arthroplasty as a treatment option for open elbow fracture is relatively rare described. We reported a 39 years old polytrauma patient with complex open elbow fracture (Gustilo-Anderson type IIIB). The patient presented with large soft tissues defect on dorsal part of the left elbow, ulnar palsy due to the irreparable loss of the ulnar nerve, distal triceps loss due to the complete loss of the olecranon, loss of both humeral condyles with collateral ligaments and complex elbow instability. Only few similar cases have been published. Reconstructive surgery included repetitive radical debridement, irrigation, vacuum assisted closure system therapy, external fixation, coverage of the soft tissue defect with fascia ecutaneous flap from the forearm. Four months after the injury, total elbow arthroplasty with autologous bone graft (from the proximal radius) inserted in the ulnar component, was performed. At 3 years postoperatively, the patient is able to perform an active flexion from 0 to 110 with full pronosupination. Only passive extension is allowed. The ulnar neuropathy is persistent. Patient has no signs of infection or loosening of the prosthesis.     

Diagnosis and therapy of injuries of the lamina fibrocartilaginea of the hand (palmar plate)

Authors studied a frequent injury of the finger joints. The anatomy, the mechanism of the injuries, the diagnostic possibilities of the lamina fibrocartilaginea ("palmar plate") and of the palmar ligaments of the joints are described. In the diagnosis a special significance is attached to the stressed and tangential X-ray pictures. They take the part of the conservative treatment of the injury. In cases of dislocations, that cannot be reduced, of open "palmar plate" injuries and of major hyperextension and dislocations of the broken bone scale, operative treatment is thought necessary. In the treatment of the injuries of the "palmar plate" of the PIP joint they use the so called rein method, that keeps the palmar cartilaginous joint capsule, torn at the injury, on its original place, it enables however the active joint movements, the gymnastics and hinders this way the development of the joint contracture.     

Hirntumor und Kopfschmerz

Methods

The possible association of brain tumour with headache was investigated in 100 patients seen for brain surgery. Preoperatively, 43 patients suffered from headache. These patients were thoroughly questioned about the nature of their pain. Investigation included the McGill Pain Questionnaire.

Results

In only 11 of the patients was headache the primary symptom of a brain tumour. Pain intensity was found to be lower in patients with brain tumour then in those with extracranial tumours or headache of other origins. Female subjects, patients under 50 years of age and those with elevated intracranial pressure experienced more intensive pain. Diurnal variation in pain intensity was observed in 60% of patients with headache. There was no evidence, however, of an association with elevated intracranial pressure.

Conclusions

Our investigations yielded new information concerning the epidemology of headache accompanying brain tumours. Headache is not an early cardinal symptom of brain tumours, as was generally believed earlier. With the help of the McGill Pain Questionnaire a fine quantitative and qualitative characterization of headache of different origins could be made. The connection between tumour localization and pain lateralization, as well as the possible mechanisms of intracranial pain projection was extensively analysed. The interpretations of the results are at best hypotheses and they do not help determine why more than half of the patients with brain tumour did not experience headache.     

DNA histogram typing and DNA index measurements in 508 invasive breast carcinomas from fine-needle aspirates and imprint smears as opposed to formalin-fixed paraffin-embedded tissues

Morphometric, i.e. nuclear area (NA), and densitometric, i.e. nuclear DNA content, features were characterized in a series of 508 invasive ductal breast carcinomas. The specimens analyzed were from three distinct sources, i.e. fresh material (252 fine-needle aspirates as opposed to 147 imprint smears) immediately fixed in EFA fixative as opposed to archive material, i.e. 109 formalin-fixed paraffin-embedded tumours that were subsequently deparaffinized. Morphonuclear parameters were computed on Feulgen-stained nuclei by means of a cell image processor. Our results show that the development of nuclear size and DNA content in function of anatomopathological grading is approximately the same for specimens of breast cancer provided by FNAs, imprint smears and formalin-fixed paraffin-embedded tissues. However, in these latter instances it seems that part of the morphometric information is slightly modified in relation to the information obtained from fresh material directly fixed in EFA for cytophotometric analysis. The greatest discriminatory power of the morphometric parameters was obtained in relation to the FNAs. Lastly, in the present study we come out in favor of the idea that henceforth it would be preferable to express results concerning nuclear DNA content as DNA histogram types rather than in terms of DNA indices.     

Interaction of aluminum with biomolecules - any relevance to Alzheimer's disease?

The possible involvement of aluminum in Alzheimer's disease (AD) is discussed focusing, on the one hand, on a critical review of the analytical results concerning the brain aluminum content of AD patients, and on the other hand, on the in vitro interactions of AI(III) with biologically relevant potential AI(III) binders occurring in intracellular and/or extracellular fluids. The biomolecules considered are such as amino acids, organic and inorganic phosphates, nucleotides, catecholamines and transferrin. It is quite clear from the results that definition of the actual AI(III) species present in the biological systems is essentially important in any studies of the neurotoxic role of aluminum.     

Falloposcopy after prostaglandin treatment of tubal pregnancy

We report on a tubal pregnancy treated with prostaglandin F₂ locally. Falloposcopy two years afterwards showed multiple, non obstructive adhesions of the tubal epithelium.