Since the tumor thrombus in the main portal vein appears in the terminal stage of hepatocellular carcinoma (HCC), any attempt to remove it surgically is thought to be impractical as the malignancy itself cannot be entirely removed. During the past 5 years, we have performed tumor thrombectomy combined with hepatectomy in 29 of 298 patients with HCC. This combined therapy was initially decided upon as an emergency measure to prevent impending rupture of esophageal varices, rather than to improve patient survival. Since portal flow was obtained after removal of thrombi, this condition enabled transcatheter arterial embolization (TAE) and/or percutaneous ethanol injection therapy (PEIT). Although improved patient survival was not the primary goal of the emergency operation and there was an operative mortality of 11%, half of the other patients in the present series had unexpectedly high survival rates of 1 year (52.2%), 2 years (23.2%), and 3 years (11.6%), which were significantly higher than in patients not undergoing operation (n = 22).

Aged↗

PubMedDate not supplied

Inhibitory effect of bestatin on the growth of human lymphocytes.

Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes.

Aminopeptidases↗

PubMedDate not supplied

Signal pathway involved in increased expression of neutral endopeptidase 24.11 by gonadotropin releasing hormone in choriocarcinoma cells.

Neutral endopeptidase 24.11 (NEP) is known to regulate cellular functions by degrading several bioactive peptides, such as gonadotropin-releasing hormone (GnRH). The present study was performed to clarify the mechanisms of NEP expression by GnRH in human choriocarcinoma (BeWo) cells. GnRH increased NEP expression and enzyme activity in a dose- and time-dependent manner in BeWo cells. The phosphorylation levels of protein kinase C (PKC) delta, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1 and 2) were enhanced after 10 min exposure of 10(-6)m GnRH. The effect of GnRH on both NEP expression and enzyme activity was completely inhibited by inhibitors of PKC, PKC delta, and p38MAPK. Cell number was reduced by 54.4 per cent of the control by culture with 10(-6)m GnRH for 24 h. However, phosphoramidon, a NEP specific inhibitor, inhibited antiproliferative effect of GnRH and reverted to the control level. In conclusion, GnRH induces NEP expression by PKC delta and p38MAPK, and increased NEP expression may be involved in antiproliferative effect in BeWo cells.

Adult↗

PubMedDate not supplied

Neoadjuvant chemotherapy for FIGO stage III or IV ovarian cancer: Survival benefit and prognostic factors.

The survival benefit of neoadjuvant chemotherapy (NAC) was assessed in patients with FIGO stage III or IV ovarian cancer, and the prognostic value of various therapeutic factors was determined. In patients treated for stage III or IV ovarian malignancies at the Department of Obstetrics and Gynecology of Nagoya University or related institutions between 1987 and 1996, 119 had a histologic diagnosis of serous cystadenocarcinoma. For this group, the long-term outcome was compared between 96 patients receiving conventional adjuvant chemotherapy following standard surgery and 23 patients treated with NAC, both followed by a second cytoreductive surgery. In a total of 29 patients with all histologic types of malignancy, the tumor response to NAC and survival were analyzed on the basis of histology, chemotherapy regimen, residual tumor size after the second cytoreductive operation, and the dose intensity of cisplatin. The long-term outcome (5-year survival rate) was better in patients treated with conventional adjuvant chemotherapy than in patients receiving NAC, although the difference was not significant. Overall survival did not differ significantly in relation to tumor histology or chemotherapy regimen. With respect to residual tumor size after the second surgery, patients with a residual tumor < or = 2 cm in diameter had a significantly better prognosis than those with a residual tumor >2 cm. A better prognosis was also associated with a higher dose intensity of cisplatin, and patients treated at >or = 18 mg/m(2)/week survived significantly longer than those receiving <18 mg/m(2)/week.

Adult↗

PubMedDate not supplied

Prognostic importance of vascular endothelial growth factor and its receptors in the uterine sarcoma.

Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P= 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P= 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.

Adult↗

PubMedDate not supplied

Usefulness of granulocyte colony-stimulating factor on neutropenia in patients of invasive mole and choriocarcinoma.

The effect of human granulocyte colony stimulating factor (hG-CSF) was investigated on the proliferation of choriocarcinoma cells in vitro. No growth-stimulating effect was observed. Then, 22 patients with invasive mole and 9 patients with choriocarcinoma who received combination chemotherapy were treated with hG-CSF when white blood cell counts decreased below 2,000/mm3. The duration of neutropenia was reduced significantly by 3-4 days with the use of hG-CSF. No side effects were observed. These results indicate safety and usefulness of hG-CSF as an adjunct to chemotherapy in the treatment of gestational trophoblastic disease.

Adult↗

PubMedDate not supplied

Partial review of immunotherapeutic pharmacology in stem cell transplantation.

In two separate lymphoma populations, we examined immune reconstitution following high dose chemotherapy (HDT) and bone marrow transplantation (BMT). In the first study we followed immune reconstitution for one year after HDT and BMT. In the second study we examined the ability of the orally active immunomodulator, Bestatin to augment immune reconstitution following HDT and BMT. The studies on immune reconstitution following HDT and BMT were undertaken in a cohort of non-Hodgkin's lymphoma (NHL) patients (n = 35) and examined the peripheral blood (PB) leukocyte subsets and their in vitro functions. Our results demonstrate that monocyte and natural killer (NK) cell engraftment occurred more rapidly then did T cell reconstitution. We also observed a significant decrease in the CD4:CD8 ratio post-transplantation as compared to normal PB donors due to a decrease in CD4+ cells. In addition, following HDT and BMT, measures of T cell function (phytohemagglutinin [PHA] mitogenesis) and T helper cell activity (pokeweed mitogen [PWM] mitogenesis) were consistently depressed as compared to cells from normal PB. Further, we demonstrate a correlation between the loss of T cell function and the frequency of circulating monocytes, suggesting a cause-effect relationship. Despite the dysfunction in T cells following HDT and BMT, immune-modulating agents can still augment the immune function. One such drug is Bestatin (ubenimex), an inhibitor of aminopeptidase (AP) that binds to CD13 on macrophage/monocytes. To examine its immune modulatory activity after HDT and BMT, a dose finding (10, 30, 90 and 180 mg/day) phase Ib trial was conducted with 30 Hodgkin's disease (HD) and NHL patients who received no drug (control), or Bestatin daily for 60 days following BMT. In these studies, Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on two consecutive days. These studies revealed that Bestatin significantly increased the PHA and PWM responses in a dose-dependent manner. Flow cytometric analysis revealed a significant increase in NK cells (CD56+), B cells (CD19+), as well as the CD4:CD8 cell ratio. The latter observation was associated largely with a depression in the percent of CD8+ T cells as opposed to an increase in CD4+ T cells. We conclude that despite the peripheral tolerance observed following HDT and BMT, Bestatin could significantly increase some, but not all, immune surrogates.

Adjuvants, Immunologic↗