Clinicopathological characteristics and prognosis of breast cancer patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) can increase the risk of several common cancers, including breast cancer (BC). The purpose of the present study was to investigate the clinicopathological features and prognosis of BC patients with or without T2DM. Seventy-eight patients were diagnosed with T2DM prior to the diagnosis of BC in the Cancer Hospital of Shantou University Medical College (Shantou, China) between 2002 and 2008. A total of 300 BC patients without T2DM were randomly selected as study controls during the same period. The clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) rates of these two groups were compared. Fifty-five BC patients and 133 control patients with T2DM were >50 years old (70.5 and 44.3%, respectively). There were more T2DM BC patients with body mass index (BMI) ≥25 kg/m2 (46.2 vs. 23.3%) and these patients had a higher rate of lymph node involvement (67.9 vs. 55.0%). The DFS of the two groups was 32.1 vs. 22.3%. The OS of the two groups was 24.4 vs. 13.7%. Following adjustment for BMI, tumor-node metastasis stage and stratification of age, the relapse risk of T2DM BC patients was >2-fold higher than that of the control group in the estrogen receptor/progesterone receptor (ER/PR)-positive patients. In Her-2-negative BC patients, the relapse risk of T2DM patients was 2.237-fold higher than that of the non-T2DM patients. In conclusion, T2DM BC patients were significantly older and more likely to be overweight, and had more lymph nodes involvement. T2DM was associated with poor prognosis in ER/PR positive or Her-2-negative BC patients.

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.

An improved model of acetaminophen-induced fulminant hepatic failure in dogs.

We have established an improved model of fulminant hepatic failure in dogs. Buthionine sulfoximine is used to inactivate glutathione synthesis, and small increments of acetaminophen are given intravenously to maintain the plasma level at approximately 200 micrograms/ml for 20 hr. This regimen produces severe liver injury along with many of the features seen in humans with acetaminophen poisoning. The first sign of impending liver failure is hypoglycemia. This occurs about 15 hr into the experiment and requires treatment with a continuous infusion of glucose. Between 15 and 20 hr, serum ALT activity begins to rise, indicating the onset of liver necrosis. Over the following 15 to 20 hr ALT activity continues to rise and is accompanied by an increase in bilirubin, a prolongation of the prothrombin time and the development of fetor hepaticus. Thirty to 48 hr after the initial acetaminophen dose, the animals begin to exhibit symptoms of encephalopathy and progress from lethargy to the inability to maintain posture and then coma, seizures and death. Liver biopsy specimens obtained at several stages throughout the study showed progressive necrosis, ultimately resulting in the complete destruction of zones 2 and 3.

Monoclonal antibody-porphyrin conjugate for head and neck cancer: the possible magic bullet.

Although photodynamic therapy in the treatment of large head and neck cancers showed some initial promise, the results in the final analysis have been somewhat disappointing. Lack of specificity and nonhomogeneous uptake of the porphyrin by the tumor are only some of the problems. The conjugation of a monoclonal antibody (UCD/AB 6.01) with hematoporphyrin derivative that preferentially binds to tumor cells offers promise as a therapeutic agent that will not only improve specificity, but vastly enhances tumor cell kill when exposed to light in its photodynamic range. The application of the monoclonal antibody-hematoporphyrin conjugate (AB:HPD) to A-431 squamous cell carcinoma cells in vitro, followed by exposure to light in the 630 nm range, increases the kill ratio by a factor of 10(5) times. The active tumor cell binding site on the cell surface has been found to be on the microvilli, a site at which a 52 kDa protein that is very similar to keratin 8 is found. The clearance of the conjugate from nude mice who have grown an A-431 tumor shows a retention of AB:HPD of approximately 15% and less than 1% in skin and internal organs when measured at 48 hours. Direct application of AB:HPD to fresh pathology specimens containing human squamous cell carcinomas shows binding exclusively limited to the tumor.