FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

Angiogenesis and skin carcinomas with skull base invasion: A case-control study

Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome.Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs.Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = 133).Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. (C) 2004 Wiley Periodicals, Inc.

Water sorption enthalpy-entropy compensation based on isotherms of plum skin and pulp

The net isosteric heat and entropy of water sorption were calculated for plum, based on sorption isotherms obtained by the static gravimetric method at different temperatures (20 to 70 degrees C). The Guggenheim-Anderson-deBoer model was applied to the experimental data giving a good agreement between experimental and calculated values. The net isosteric heat of water sorption, estimated by applying Claussius-Clapeyron equation to sorption isotherms, was found to be different for plum skin and pulp, mainly at low moisture contents, and could be well adjusted by an empirical exponential relationship. Plots of enthalpy in contrast to entropy provided the isokinetic temperatures for skin and pulp, indicating an enthalpy-controlled sorption process. Thermodynamic data on water sorption for plums are not found in literature, as opposed to prunes for which the data are abundant.

Chromosome breakpoint distribution in nonmelanoma skin cancers

We have identified chromosome regions that may be sites of genes activated as a result of chromosomal rearrangements observed in 61 of the 86 skin tumors referenced in the literature. The data showed that most of the breakpoints were distributed throughout the genome and some tended to cluster. Highest frequencies of breakpoints were observed in chromosomes with high relative length, except chromosomes 14 and 15 that were more often affected in malignant tumors, despite their size. Our work provides a starting point for more detailed studies that may allow identification of these genes as important keys in the development and progression of skin cancers. (C) Elsevier B.V., 1997.

Immunolocalization of estrogen and progesterone receptors in neuroendocrine tumors of lung, skin, gastrointestinal and female genital tracts

Expression of estrogen (ER) and progesterone (PR) receptors has traditionally been associated with hormone-responsive organs, such as breast, ovary, and endometrium, and carcinomas arising therefrom. More recently, examples of ''unexpected'' ER or PR expression have been reported, particularly in tumors of endocrine tissues, such as thyroid and pancreatic islet cells. We tested the hypothesis that neuroendocrine tumors of various primary and metastatic sites might also express ER or PR or both by performing a retrospective immunohistochemical study in a series of 59 formalin- or mechacarn-fixed neuroendocrine carcinomas of various sites, including lung, skin, gastrointestinal and female genital tracts, and including carcinoid and atypical carcinoid tumors, small cell carcinomas, and Merkel cell carcinomas. We employed the anti-ER monoclonal antibody 1D5 and the anti-PR monoclonal antibody PgR1A6 using standard immunohistochemical techniques after microwave-based heat-induced epitope retrieval. Two of 28 carcinoid tumors demonstrated ER positivity; six of 30 cases were positive for progesterone receptor only. In addition, PR expression was found in one of two cases of atypical carcinoid, in five of 25 cases of small cell carcinoma, and in one of two cases of Merkel cell carcinoma. None of the atypical carcinoids, small cell carcinomas, or Merkel cell carcinomas were ER positive. In most cases, the fraction of tumor cell nuclei that were positive was <50%. These studies add the spectrum of neuroendocrine tumors that can express these hormone receptors. Similar to the pattern previously described in the subsets of meningiomas and islet cell tumors, PR but not ER is detectable in most cases. These results underscore the caution that should be exercised in determining tissue origin of metastatic carcinomas based only on detection of hormone receptors by immunohistochemistry.

Cytogenetic study of neoplastic and nonneoplastic cells of the skin

We describe the cytogenetic study of six neoplastic and eight nonneoplastic skin samples from sun-exposed body sites or sites close to tumors. The cytogenetic findings revealed that chromosome rearrangements are common in sun-exposed normal skin, similar to the situation in cutaneous tumors, and suggest that such karyotypic abnormalities might be indicative of the genetic instability caused by specific mutations and resulting from carcinogenic exposure of the tissue.