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Francesco Tarantini,1 Luisa Anelli,1 Giuseppe Ingravallo,1 Immacolata Attolico,1 Antonella Zagaria,1 Antonella Russo Rossi,1 Lucia Lospalluti,2 Tamara Bufano,2 Giovanni Zanframundo,2 Eugenio Maiorano,1 Giorgina Specchia,1 Francesco Albano11Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari “Aldo Moro”, Bari, Italy; 2Department of Biomedical Sciences and Clinical Oncology, Dermatology Section, University of Bari “Aldo Moro”, Bari, ItalyCorrespondence: Francesco AlbanoDepartment of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari “Aldo Moro”, P.zza G. Cesare, 11, Bari 70124, ItalyTel +39 080 547 8031Email francesco.albano@uniba.itPurpose: In our work we sought to define the prevalence rates of cutaneous events during dasatinib therapy in chronic myeloid leukemia (CML) patients and to investigate the clinical and pathological characteristics of these reactions.Patients and methods: In our institution, 67 CML patients were treated with dasatinib. it was given as first line treatment in 26 (39%) and subsequent treatment in 41 (61%) CML patients. Flow cytometry analysis of peripheral blood and cutaneous biopsy was done on all CML patients with dermatological lesions appearing during dasatinib treatment.Results: Among 67 CML patients, 4 (5.9%) showed skin lesions during dasatinib treatment. The cutaneous manifestations were not generalized but mainly located on the back, abdomen, thorax or leg regions. The patients did not show peripheral lymphocytosis at the time when skin lesions appeared. Overall, histological analysis showed that the skin lesions were characterized by a mild perivascular small CD8+ T lymphocytes infiltrate with minimal epidermotropism.Conclusion: The unusual T cytotoxic cutaneous infiltrate demonstrated in our CML cases could be the expression of a dasatinib-promoted lymphocyte expansion. However, the heterogeneity of the dermatologic manifestations reported in our CML patients could also be related to unknown factors specific to each CML patient. Our work highlights the finding that skin lesions may be associated with dasatinib treatment and that they should not be confused with viral or bacterial infections but rather interpreted as the clinical expression of lymphocytosis promoted by this TKI.Keywords: inhibitor tyrosine kinase, skin lesions, chronic myeloid leukemia, CD8+ lymphocytes, dasatinib

Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38α/β kinases. We report that p38α is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38α activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38α as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38α pathway in the treatment of colorectal cancer.Cell Death and Differentiation (2007) 14, 693–702. doi:10.1038/sj.cdd.4402076; published online 8 December 2006 [ABSTRACT FROM AUTHOR]

A case study based on a 16-year-old boy having mastocytosis is presented.

Abstract Background Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. Methods The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: 30 weeks). Results No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). Conclusion De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.