Identification of genes required for protection from doxorubicin by a genome-wide screen in Saccharomyces cerevisiae

Anthracyclines are chemotherapeutic agents commonly used to treat a broad range of malignancies. Although effective, these drugs present serious complications, most notably cardiotoxicity. To determine the mechanisms that mediate cytoprotection from doxorubicin, we have screened the collection of Saccharomyces cerevisiae haploid gene deletion mutants. We have identified 71 deletion strains that display varying degrees of hypersensitivity to doxorubicin at a concentration that does not significantly reduce the viability of wild-type cells. Complementation of the doxorubicin-sensitive phenotype of the deletion strains with the wild-type genes proves that the sensitivity of the strain to doxorubicin is due to the gene deletion. The genes that mediate cytoprotection from doxorubicin belong to multiple pathways including DNA repair, RNA metabolism, chromatin remodeling, amino acid metabolism, and heat shock response. In addition, proteins with mitochondrial, osmosensing, vacuolar, and ribosomal functions are also required for protection from doxorubicin. We tested the sensitivity of the deletion strains to other cytotoxic agents, which resulted in different drug-specific sensitive groups. Most of the identified genes have mammalian homologues that participate in conserved pathways. Our data may prove useful to develop strategies aimed at sensitizing tumor cells to doxorubicin as well as protecting cardiac cells from its cytotoxic effects.     

Pancreatoblastoma: a rare tumour accidentally found

A 15-year-old girl, who was previously well, complained of a mass in the abdomen after a minor motor vehicle accident. Physical and radiological investigations revealed a mass in the body of pancreas containing proteinaceous material and multiple nodules in both lobes of liver. Serological investigations for malignancy were normal. Histopathological examination of the resected specimen showed pancreatoblastoma. Pancreatoblastoma is an unusual malignant tumour seen in infants and children although rare cases have also been reported in adults. They are clinicopathologically distinct from adult pancreatic ductal carcinoma. The histogenesis, clinical features and treatment options are discussed along with presentation of the case.     

Management of rectal cancer in pregnant women

We relate 2 cases reports about rectal cancer and pregnancy. This association is rare but is a real problem of management because diagnosis is done latly and it mate have incompatibility between treatments and pregnancy. A medical bibliography has been done, to define the best medical procedure in function of the disease staging and the pregnancy term. It shows that a multi disciplinary decision must be done, which take into consideration the choice of the obstetricals, pediatricians, surgeons, and oncologists, but also the patient's choice.     

Mature cystic teratoma: unusual presentation as anterior neck swelling

The unusual presentation of a mature mediastinal cystic teratoma as an anterior neck swelling in a 29-year-old Malay woman is reported.     

Heterotopic ossification in skeletal muscle metastasis from colonic adenocarcinoma--a case report

Colonic adenocarcinoma metastasising to the skeletal muscle is rare. A-56-yr-old Malay man was diagnosed to have adenocarcinoma of the right colon [Dukes B] for which a right hemicolectomy was performed, followed by radiotherapy and chemotherapy. Five years later the patient presented with a mass in the rectus abdominis muscle. The serum carcinoembryonic antigen was 71 ng/Ml. The mass was resected. Gross and microscopical examination showed multiple deposits of mucin-secreting adenocarcinoma with prominent heterotopic ossification in the stroma. The exact pathogenesis and significance of heterotopic ossification is not clear, but bone morphogenetic proteins may play an important role.