Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin

The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.     

Model-driven integration using existing models

Models can describe business transactions in terms of business entities and help automate some systems integration tasks. The joint action model describes a new business transaction motivating systems integration.     

Wireless network coding in slotted aloha with two-hop unbalanced traffic

This paper deals with two representative unbalanced traffic cases for two-hop wireless relay access systems employing network coding and a slotted ALOHA protocol. Network coding is a recent and highly regarded technology for capacity enhancement with multiple unicast and multisource multicast networks. We have analyzed the performance of network coding on a two-hop wireless relay access system employing the slotted ALOHA under a balanced bidirectional traffic. The relay nodes will generally undergo this unbalanced multidirectional traffic but the impact of this unbalanced traffic on network coding has not been analyzed. This paper provides closed-form expressions for the throughput and packet delay for two-hop unbalanced bidirectional traffic cases both with and without network coding even if the buffers on nodes are unsaturated. The analytical results are mainly derived by solving queueing systems for the buffer behavior at the relay node. The results show that the transmission probability of the relay node is a design parameter that is crucial to maximizing the achievable throughput of wireless network coding in slotted ALOHA on two-hop unbalanced traffic cases. Furthermore, we show that the throughput is enhanced even if the traffic at the relay node is unbalanced.     

Effects of Plant Vascular Architecture on Aboveground–Belowground-Induced Responses to Foliar and Root Herbivores on <Emphasis Type="Italic">Nicotiana tabacum</Emphasis>

Herbivores induce systemic changes in plant traits, and the strength of these induced responses is often associated with the degree of vascular connectivity that links damaged and undamaged plant tissues. Although this phenomenon is known to occur aboveground in leaves, it is unknown whether or not leaf–root induction similarly follows the vascular architecture of plants. To test for this possibility, we manipulated foliar and root herbivory on tobacco (Nicotiana tabacum) by the leaf-chewing insect Spodoptera exigua and the root-galling nematode Meloidogyne incognita. Subsequent changes in secondary chemistry (alkaloids and phenolics) were measured in leaves and roots that were orthostichous (vertically aligned) and nonorthostichous (opposite) from the herbivore-damaged tissues. Aboveground caterpillar herbivory elicited stronger secondary chemical responses in orthostichous compared with nonorthostichous plant tissues, although the magnitude of this difference was greater in leaves than roots. However, belowground nematode herbivory did not affect the secondary chemistry of tobacco leaves, despite inducing strong local responses in roots. Thus, plant vascular architecture can mediate the magnitude of systemic induction in roots as well as in leaves, with stronger responses in tissues that are more closely aligned. As a result, herbivores that co-occur on the same sector of plant (both aboveground and belowground) may be more likely to affect one another via induced responses than herbivores that occur on plant tissues sharing fewer resources. Miscellaneous  Robert F. Denno, deceased     

Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.     

The ratio of reduced glutathione/oxidized glutathione is maintained in the liver during short-term hepatic hypoxia

Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.     

Prognostic significance of bone metastases in patients with metastatic prostate cancer

BACKGROUND: The distribution of bone metastases on a bone scan has not been duly considered when assessing the prognosis of metastatic prostate cancer. METHODS: The medical records of 76 patients with newly diagnosed, untreated metastatic prostate cancer were reviewed. According to the distribution of bone metastases on the initial bone scan, we divided the patients into three groups: Group I (having bone metastases exclusively within the pelvis and the lumbar spine), Group II (having bone metastases exclusively outside these bones), and Group III (having bone metastases in both areas). RESULTS: Among the responders to androgen deprivation, those in Group I survived significantly longer than did those in Groups II or III. Because the extent of the disease and the distribution of histologic differentiation in Groups I and II were similar, the results indicate that the presence of bone metastases outside the pelvis and the lumbar spine is predictive of short survival time. This prediction was not possible when the extent of disease (EOD) grading system was used. CONCLUSION: The distribution of bone metastases on the initial bone scan should be considered as a variable for the prognostic stratification of patients with metastatic prostate cancer.     

Modified constant modulus algorithm for digital signal processingadaptive antennas with microwave analog beamforming

This paper proposes a novel algorithm, called modified constant modulus algorithm (M-CMA), which is able to give adaptability to microwave beamforming phased array antennas. Since microwave analog beamformers basically require much fewer RF devices than digital beamformers, microwave analog beamformers based on M-CMA, that is, adaptive microwave beamformers, can be cheaply fabricated. Therefore, they are very suitable for mobile communication systems where both miniaturization and low cost are required for the mobile terminals. M-CMA obtains a gradient vector by a combination of analytical calculation and perturbation of the microwave beamforming control voltage. Though M-CMA is implemented with a digital signal processor, M-CMA controls the microwave analog beamformer by utilizing the gradient vector. The microwave analog beamformer based on M-CMA is analyzed to have the following characteristics: (1) the beamformer can point its main beam to the desired direction in additive white Gaussian noise (AWGN) channels; (2) although the beamformer may possibly fail in ill solutions in cochannel interference (CCI) channels, M-CMA can converge to the optimum solution when the desired direction is roughly a priori known     

Combination chemotherapy of continuous infusion 5-fluorouracil and daily low-dose cisplatin in advanced gastrointestinal and lung adenocarcinoma

Continuous intravenous infusion (c.v.i.) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 45 patients with advanced and recurrent unresected colorectal, lung, gastric and pancreatic adenocarcinoma. 5-FU was given at a dose of 320 mg/m2/day, c.v.i. for 4 weeks, and CDDP between 3.5 to 7 mg/m2/day, infused for one hour five times a week for 4 weeks. Patients received 1 to 3 cycles of treatment (average 1.5 cycle). Pancreatic cancer cases needed longer treatment periods (2.25 cycles). The response rate of colorectal cancer cases was 57.7% (15/26), pancreas cancer 40%, gastric cancer 62.5%, and lung cancer 66.7%. The overall response rate was 57.8%. No severe side effects occurred in any of these cases. These data indicate that this combination 5-FU + daily low-dose CDDP chemotherapy is effective in the treatment of advanced gastrointestinal and lung adenocarcinoma.     

Lack of survival benefit of extended lymph node dissection for ductal adenocarcinoma of the head of the pancreas: retrospective multi-institutional analysis in Japan

It has not been established that extended lymph node resection is necessary for ductal adenocarcinoma of the head of the pancreas. According to the general rules for the study of pancreatic cancer, a multiinstitutional, retrospective clinical study was undertaken to investigate the efficiency of extended lymph node dissection for this malignancy. Altogether 501 patients underwent resection of the pancreas between 1991 and 1994 at 77 medical facilities; the surgical procedures, staging, lymph node dissection, curability, and survival rate were analyzed retrospectively. Eighteen of the patients died within 30 postoperative days, leaving 483 patients to be studied. The resection was curative microscopically in 94 patients, resulting in a 3-year survival of 29%. Macroscopically curative resection resulted in a 3-year survival of 14%; noncurative resection produced a 3-year survival of 6%. Although extended lymph node dissection was performed on 38 patients in stage I, 42 patients in stage II, 206 patients in stage III, and 1 patient in stage IV, there was no improvement in survival when the results were compared to those seen after standard or palliative lymph node dissection. The extent of lymph node dissection has not affected the prognosis for ductal adenocarcinoma of the head of the pancreas at any stage of the course of the disease. Excessive lymph node dissection in advanced cases does not necessarily lead to a favorable prognosis. The patients who undergo a radical operation with an adequate lymph node dissection have longer survivals.