Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells

Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA-MB-231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin-induced apoptosis, finding that hsp27 protects MDA-MB-231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27-overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIalpha and beta were higher in the controls than the hsp27-overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA-MB-231 cells is associated with altered topo II expression.     

Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma

The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.     

Primary esophageal lymphoepithelioma

Lymphoepitheliomas are extremely rare outside the nasopharynx. Extranasopharyngeal lymphoepithellomas may be located in the stomach or digestive tract, and only one single case of esophageal location has been found in our review. In many cases the tumor is related to Epstein-Barr virus infection. We report a case of undifferentiated carcinoma of the distal third of the esophagus in a 79 year-old man. Pathological examination of the esophagus revealed an undifferentiated carcinoma with lymphold stroma (lymphoepithelioma). In situ hybridization of the neoplastic cells was negative for Epstein-Barr virus. To our knowledge, the present case is the first documented esophageal lymphoepithelioma in Western countries.     

Characterisation with stable isotopes of the presence of a lag phase in the gastric emptying of liquids

Summary Background Gastric emptying of non-nutrient liquids usually lacks the presence of an initial delay phase (lag phase), and so it has been considered to be monoexponential with an initial rapid phase followed by a slower emptying phase. However a lag phase in the gastric emptying of liquids can be found if there is a high caloric density in the liquid meal. Aims of the study To characterise with stable isotopes the presence of a lag phase in the gastric emptying of non-sold meals. Methods Healthy volunteers ingested a low caloric liquid meal (345 KJ/200 mL) (LCLM), a high caloric liquid meal (1135 KJ/180 mL) (HCLM) or a semisolid meal (1403 KJ/500 mL) (SSM). Test meals were labelled with ¹³C-acetate. Breath samples were collected for ^13>CO₂ measurement and data were fitted to a power exponential function. Results Non-solid meals can have different behaviour related to the initial emptying. The presence of a lag phase in the gastric emptying of liquids was not masked by the processing of the tracer previous to its detection in breath. While the LCLM and SSM showed a rapid initial emptying phase (no lag phase), the HCLM has an initial slow emptying phase. The slower gastric emptying of the HCLM compared to the SSM was related to the presence of a lag phase in the gastric emptying of the HCLM. Conclusions The ¹³C-acetate breath test is very accurate to identify and study the lag phase if present of liquid meals.