Krebswissenschaft und -therapie

Epigenetic has become, in recent years, in a very important process in the control of several pathologies, including cancer. DNA methylation has been described in numerous studies as crucial for differentiation control, cell proliferation and invasion in cancer. Pancreas ductal adenocarcinoma is one of the most deadly diseases of our society; its complexity and variability have become one of the medical challenges of this decade. Combining the potential of epigenetic with the high mortality and the limited knowledge of pancreatic ductal adenocarcinoma origin, may result in new approaches for diagnosis, treatment and monitoring, crucial in this pathology. For this purpose, we analyzed genes involved in different cellular processes (GSTP1, p16, RASFF1A, RARβ2, CyclinD2, HIN-1, SOCS1, TIMP3, DAPK and TWIST1) in 61 cases of pancreatic ductal adenocarcinoma. A first approach led us to analyze the Src pathway, never studied in this sense, as crucial in the development of this pathology. Clusters for clinicopathological characteristics and epigenetic profiles were obtained. The high degree of methylation of these adenocarcinomas, and the statistical relationship between Src pathway methylation and clinicopathological profile, has been postulated, for the first time. These results show the importance of this pathway in pancreatic disease, opening a new challenge for research and therapy.

Background: Non-small cell lung cancer is the most common cause of death from cancer in the world. Here we demonstrate the effect of 5-aza-2’-deoxycytidine (5-dAza), which is one of the most promising anticancer drugs, on the growth and metabolism of mouse (KLN205) and human non-small cell lung cancer-derived (hNSCLC) cells.

Results: In both cell lines we observed reduction of the cells viability and rate of their proliferation after 5-dAza treatment. These changes correlated with the lowering of ATP synthesis and lactate release from cells and with overproduction of reactive oxygen species. 5-dAza-treatment of lung cancer cells also induced a decrease of mitochondrial membrane potential and damage of mitochondrial network. These changes were partially reversed by rotenone treatment which also facilitated the cells survival. Proteomic analysis revealed that the demethylation affected the abundance of proteins associated to energy metabolism, especially those of tricarboxylic acid cycle (TCA) and oxidative phosphorylation metabolism (OXPHOS).

Conclusion: Taken together, our work provide evidence that the mechanism of the toxic effect of 5-dAza basically relies on the alteration of mitochondrial function via dysregulation of proteins involved in TCA and OXPHOS.

Cancer of the large intestine is approximately 15% of all malignant cancer of the word. In the study of sections of normal epithelial mucosa of the colon revealed that the contours of the cell membrane is precise, well-defined microvilli in size from 5 × 10 to 10 × 10 nm. The adenocarcinoma cell of the large intestine has the morphological changes of the cell membrane. In the cell membrane in contrast to normal epithelial cells of the mucous membrane of the colon appear pores and the degree of change in this indicator may be different.

Background: Head and neck sarcomas are very rare tumors, accounting less than 1% from all malignancies of this region. They represent a heterogeneous group of tumors with distinct prognostic features. There have been significant improvements in characterizing these sarcomas using traditional morphologic assessments and immunohistochemical analysis, but treatment management is still a big challenge. Prognostic factors are essentially tumor grade, margin status and tumor size. Surgery remains the mainstay of treatment, despite the anatomic constraints, followed by radiation therapy.

Aim: to show the rarity of the head and neck localization, and describe epidemiologic, clinico-radiological, histological features, treatment management and the evolution of these tumors.

Methods: It is a retrospective descriptive study conducted in the department of medical oncology at Hassan II University Hospital between January 2007 and December 2011, including all patients with histologically proven melanoma of the anorectal area.

Results: 10 cases were collected, that represented 7 % from all sarcomas reported at the study period. Five men and 5 women, the mean age was 34 years (range: 17-65years). Local imaging was performed by MRI in six cases and CT scan in 4 cases. It had showed locally advanced disease in 7 cases and among them 6 patients had a metastatic disease at the staging. Lung was the site of predilection of metastases. Histological analysis with the support of immunohisto-chemestry showed diverse histological subtypes. For the 3 cases with localized stages, the mainstay treatment was based on surgery followed by radiation therapy in one case with unclear margins. For metastatic stages, first line of chemotherapy was mainly based on: doxorubicin, ifosfamide, and cisplatine for osteosarcoma. Evolution was marked by disease controlee and remission in 2 patients who underwent surgery with clear margins. Unfortunately by recurrence in patient operated with unclear margins and by rapid progression for metastatic stages leading to death.

Conclusion: Adult head and neck sarcomas are very rare tumors with poor prognosis, high aggressiveness and rate of recurrence. They are frequently diagnosed at advanced stages. Treatment management is still a big challenge given to the difficulty of surgery and modest response to chemotherapy.