Treatment of acute lymphoblastic leukemia in the elderly: an evaluation of interferon alpha given as a single agent after complete remission

Although interferon (IFN) has been used in elderly patients with acute lymphoblastic leukemia (ALL), the benefits from IFN therapy have not been properly assessed, especially as it was given combined with other cytotoxic drugs, which obscured the role of IFN if any. In 1997, we started a study aimed at improving our previous results in elderly patients with ALL and at assessing the therapeutic role of IFN in this disease. Fifty-eight patients with ALL, aged 55-81 years (median: 64.9 years), were randomly allocated to treatment with vindesine or vincristine during induction. After a first consolidation course, IFN was administered as a single agent for three months together with cranial radiotherapy. Chemotherapy was then resumed with a second consolidation course and maintenance. A complete remission (CR) was obtained in 58% of patients (CI: 45-71%), significantly less than in our previous study which included IFN combined with chemotherapy during maintenance (CR: 85%, CI:70-94%, p = 0.007). Overall survival (median: 289 vs 434 days in the previous study, p = 0.01) and disease-free survival (median: 146 vs 427 days, p = 0.009) were also inferior in the present study. In particular, the pattern of relapses over time suggested that the 3 month IFN treatment phase with no additional chemotherapy might have contributed to the comparatively poor outcome of this cohort. In addition, vindesine given during induction did not prove less neurotoxic than vincristine, did not improve the CR rate, and had no impact on survival. In conclusion, although similar to published studies in elderly patients with ALL, this study is inferior to our previous one. INF, given as a single drug, has a modest role if any in the treatment of older persons with ALL.     

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Etoposide, a topoisomerase II inhibitor widely used in cancer therapy, is suspected of inducing secondary tumors and affecting the genetic constitution of germ cells. A better understanding of the potential heritable risk of etoposide is needed to provide sound genetic counseling to cancer patients treated with this drug in their reproductive years. We used a mouse model to investigate the effects of clinical doses of etoposide on the induction of chromosomal abnormalities in spermatocytes and their transmission to zygotes by using a combination of chromosome painting and 4',6-diamidino-2-phenylindole staining. High frequencies of chromosomal aberrations were detected in spermatocytes within 64 h after treatment when over 30% of the metaphases analyzed had structural aberrations (P < 0.01). Significant increases in the percentages of zygotic metaphases with structural aberrations were found only for matings that sampled treated pachytene (28-fold, P < 0.0001) and preleptotene spermatocytes (13-fold, P < 0.001). Etoposide induced mostly acentric fragments and deletions, types of aberrations expected to result in embryonic lethality, because they represent loss of genetic material. Chromosomal exchanges were rare. Etoposide treatment of pachytene cells induced aneuploidy in both spermatocytes (18-fold, P < 0.01) and zygotes (8-fold, P < 0.05). We know of no other report of an agent for which paternal exposure leads to an increased incidence of aneuploidy in the offspring. Thus, we found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny. This finding suggests that individuals who undergo chemotherapy with etoposide may be at a higher risk for abnormal reproductive outcomes especially within the 2 months after chemotherapy.     

The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle

Placement of the division site at midcell in Escherichia coli requires the MinE protein. MinE acts by imparting topological specificity to the MinCD division inhibitor, preventing the inhibitor from acting at the midcell site while permitting it to block division at other unwanted sites along the length of the cell. It was previously shown that MinE assembled into a ring structure that appeared to be localized near midcell, apparently explaining the ability of MinE to specifically counteract MinCD at midcell. We report here that the MinE ring is not fixed in position near midcell but is a dynamic structure that undergoes a repetitive cycle of movement first to one cell pole and then to the opposite pole. Taken together with studies of the dynamic behavior of the MinD protein, the results suggest that the topological specificity of division site placement may not involve a localized action of MinE to counteract the MinCD division inhibitor at midcell but rather the ability of MinE to move the division inhibitor away from midcell and to the cell poles.     

The tuberculosis pandemic today: routes of transmission and new target groups

Tuberculosis, a disease that has been with us since the dawn of time, shows little sign of disappearing. Declines in death rates observed for several centuries prior to 1960 have been reversed in recent decades. This is in spite of the fact that efficient means of controlling the disease have been available during this period. This article reviews experience in 3 communities: among the Inuit, who live in the region of the North Pole; in the Beijing Municipality in the People's Republic of China; and in a socially isolated community in South Africa. In the first 2 communities, dramatic declines in the burden of disease have been observed: in the Inuit community, this occurred after substantial intervention; in the Beijing Municipality it was done with limited resources. The third community in South Africa illustrates an alarming trend, with tuberculosis being seen in a variety of locations but in the absence of external agents such as HIV infection. Clearly we need to refocus our efforts to control this disease, making use of the new tools that are rapidly becoming available. This must be done without delay, before influences such as HIV infection put the possibility of control completely out of reach.     

Significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment

BACKGROUND/AIMS: To evaluate clinical significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment. METHODOLOGY: By using the color Doppler velocity profile technique, preoperative portal hemodynamic status was assessed in 29 patients with hepatocellular carcinoma treated surgically, including 15 segmentectomies, 6 hemihepatectomies and 8 transarterial chemoembolizations. Forty-six normal volunteers were taken as control. Comparison of preoperative portal hemodynamics between patients recovering from operation smoothly (tolerant subgroup) and those with major complications or death (intolerant subgroup) was done, and discriminant analysis was employed to identify the cut-off value for significant parameters that maximally separate the tolerant subgroup from the intolerant subgroup. RESULTS: In the portal trunk, CSVmax (maximum cross-sectional mean velocity) was significantly lower in the hepatocellular carcinoma group compared with the normal group (P < 0.01); flow volume was not obviously different between the two groups; congestion index was markedly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the splenic vein, CSVmax and congestion index was not obviously different between the hepatocellular carcinoma and the normal groups; flow volume was significantly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the hepatocellular carcinomas, twenty-three patients recovered smoothly from the operation and the remaining 6 had severe complications or death. Tolerant subgroup had a significantly higher preoperative CSVmax and flow volume and lower congestion index of the portal trunk compared with the intolerant subgroup (all P < 0.01). Discriminant analysis revealed that portal trunk CSVmax > 13.50 cm/s and flow volume > 12.13 mL/min/kg could predict tolerance for surgery, with an accuracy of 82.7% and 89.7%, respectively. CONCLUSIONS: The results suggest that preoperative portal hemodynamic status in hepatocellular carcinomas had a close correlation with hepatic functional reserve, and CSVmax and flow volume of portal trunk might become valuable predictive parameters.     

Electrochemical therapy--comparison with other local treatment methods on rat model

BACKGROUND/AIMS: Electrochemical therapy is an alternative to treat hepatoma. We compare this method with the other local injection methods on rat liver. METHODOLOGY: Five groups of Wister rats (24 in each) were anaesthetized. Electrochemical therapy was set under direct current, 6 volts, electrodes were 0.5 cm apart, 0.5 cm deep into exposed parenchyma for 10 min. Local injection was done with 50 microL of 95% alcohol, 30 microL of 20% acetic acid, 30 microL of 35% hydrochloric acid, and 30 microL of 20% sodium hydroxide via a 27-gauge needle under direct vision into each rat. Rats and their livers were examined postmortem on day 1, 3, 7 and 14. RESULTS: In electrochemical therapy, the treated area showed coagulation necrosis and without blood cells on day 1; then the margin became blurred. Mononuclear cell infiltration, reperfusion and fibrous band formation were prominent from day 3 through day 14. In local injection groups, the necrosis is quite irregular and unpredictable. The regeneration went under similar process. CONCLUSIONS: To destroy tissue locally, electrochemical therapy is unique for its predictability in destructive area and the recovery process and is as effective as the other injection methods. Therefore, it has great potential for hepatoma treatment.     

Differentially expressed genes in hepatocellular carcinoma induced by woodchuck hepatitis B virus in mice

INTRODUCTIONHepatocellular carcinoma(HCC)is one of the major causes of death in the word.The mechanism of carcinogenesis is unknown,although it is widely accepted that HBV and HCV are clsely related to liver cancer[1-5[1-5].Previously,a variety of studies have described the differences in gene expression which distinguished tumor from nontumor[6-11].Cloning of the genes,especially the genes associated with HBV and HCV,is still very important to account for the development of liver cancer.