Suppression methods of radon emanation from phosphorus fertiliser and diatomaceous earth.

The present paper shows methods to suppress radon emanation from artificial porous materials such as phosphorous fertiliser or diatomaceous earth with a small amount of radium. The basic concept of suppression is making the radon emanation mechanism 'null', which comes from the fact that recoil is the main mechanism of radon emanation at room temperature. Nullifying may be done through removal of water in the pore volume by heating and through removal of pores by melting or filling with sulphur. These radon emanation suppression methods were tried for phosphorous fertiliser and diatomaceous earth with a small amount of radium. The melting method was the most effective of all. Sustainability of these methods was also studied. The melting method was the most sustainable. The heating method was also sustainable for diatomaceous earth in spite of a long-term immersion in water.

Emergence of morphological order in the network formation of Physarum polycephalum.

Emergence in a system appears through the interaction of its components, giving rise to higher order or complexity in the system. We tested for the presence of emergent properties in a biological system using the simplest biological entity of a unicellular organism; the plasmodium of Physarum polycephalum, a giant unicellular amoeboid organism that forms a network-like tubular structure connecting its food sources. We let two plasmodium networks within a single cell interact with each other, and observed how the intracellular interaction affected the morphologenesis of the plasmodium networks. We found that the two networks developed homologous morphology. We further discuss the presence of autonomous and emergent properties in homologous network formation.

Neoadjuvant chemoradiotherapy followed by esophagectomy for initially resectable squamous cell carcinoma of the esophagus with multiple lymph node metastasis.

Neoadjuvant chemoradiotherapy (CRT) was expected to improve surgical curability and prognosis for advanced esophageal cancer. However, the clinical efficacy of neoadjuvant CRT followed by esophagectomy with three-field lymphadenectomy (3FL) for initially resectable esophageal squamous cell carcinoma (SCC) remains unclear. Since 1998, we have defined the status of metastases to five or more nodes, or nodal metastases present in all three fields as multiple lymph node metastasis, which was previously shown to be associated with poor prognosis. Between 1998 and 2002, 83 patients with initially resectable esophageal SCC were prospectively allocated into two groups, according to the clinical status of nodal metastasis. Nineteen patients clinically accompanied by multiple lymph node metastasis initially underwent neoadjuvant CRT followed by curative esophagectomy with 3FL (CRT group). The other 64 patients clinically without multiple lymph node metastasis immediately received curative esophagectomy with 3FL (control group). Although the overall morbidity rate was significantly higher in the CRT group, no in-hospital death occurred in either group. Patients without pathologic multiple lymph node metastasis in the CRT group showed a significantly better disease-free survival rate than either patients pathologically with multiple lymph node metastasis in the control group or those in the CRT group. However, the differences in the overall survival rate among the groups were not significant. Thus, the significant survival benefit by neoadjuvant CRT in addition to esophagectomy with 3FL was not confirmed, although it may have been advantageous, without increase in mortality, to at least some patients who responded well to neoadjuvant CRT. Therefore, neoadjuvant CRT can be an initial treatment of choice for resectable esophageal SCC clinically with multiple lymph node metastasis. The prediction of response to CRT and the development of alternative treatment for hematogenous recurrence could achieve a further survival benefit of this trimodality treatment.

Prospective randomized study of open versus laparoscopy-assisted distal gastrectomy with extraperigastric lymph node dissection for early gastric cancer.

BACKGROUND: Laparoscopy-assisted surgery with extraperigastric lymph node dissection for gastric cancers has been described, but the clinical benefits of these surgeries still are unclear. Short-term clinical outcomes were compared between laparoscopy-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy (ODG) for early gastric cancer in a prospective randomized fashion. METHODS: For this study, 28 patients with early gastric cancers in the lower half of the stomach were randomly assigned to either LADG (n = 4) or ODG (n = 14). Postoperative pain, levels of acute inflammatory responses, and pathologic evaluation of the operative specimens were compared. RESULTS: The LADG group required a significantly shorter period of postoperative epidural anesthesia, showed significantly lower levels of serum interleukin-6 and C-reactive protein, and had no major postsurgery complications. Pathologic examinations showed that surgery was equally radical in the two groups. CONCLUSION: The findings show that LADG with extraperigastric lymph node dissection is a safe and less invasive alternative to the open procedure.

Does incineration turn infectious waste aseptic?

Incineration of infectious waste is considered to be biologically safe. We performed basic experiments to confirm that bacillus spores are killed by incineration in a muffle furnace. Biological samples containing 10(6) spores of Bacillus stearothermophilus were placed in stainless steel Petri dishes and then into hot furnaces. The furnace temperature and duration of incineration were 300 degrees C for 15 min, 300 degrees C for 30 min, 500 degrees C for 15 min, 500 degrees C for 30 min and 1100 degrees C for 3 min. We confirmed that all spores of B. stearothermophilus were killed at each of these settings. The effect of incineration seems to be equivalent to that of sterilization, based on the satisfactory sterilization assurance level of 10(-6).

Prognostic value of preoperative serum immunosuppressive acidic protein in patients with esophageal squamous cell carcinoma.

Immunosuppressive acidic protein (IAP) is a potent biological marker of immunological surveillance in patients with malignant tumors. The aim of this study was to analyze the clinicopathologic significance of IAP in patients with esophageal carcinoma. Preoperative serum IAP concentration was measured by enzyme-linked immunosorbent assay in 115 patients with primary esophageal squamous cell carcinomas. The associations between clinicopathologic factors, C-reactive protein (CRP) values and IAP concentration were determined. Prognostic values were determined by multivariate analysis using Cox's proportional hazards model. The IAP concentration is significantly higher in patients with stage II-IV cancers than in those with stage I cancer. Significant differences in IAP concentration were observed depending upon tumor size, tumor depth, lymph node status and CRP values. A high IAP concentration, more than 500 micro g/mL, was an independent prognostic factor. Thus, a high IAP concentration is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Prognostic significance of the number of metastatic lymph nodes in early gastric cancer.

BACKGROUND: The prognostic value of the number of metastatic lymph nodes in early gastric cancer has not been evaluated much, although the significance of metastatic lymph nodes is defined by the location of positive nodes, according to the JRSGC for gastric cancer. METHODS: The postoperative courses of 305 early gastric cancer patients who had undergone D2-extended lymphadenectomy were followed up for a median of 108 months to evaluate the significance of the number of metastatic lymph nodes on recurrence of the disease. RESULTS: Recurrence of gastric cancer was more frequently observed in submucosal cancer than in mucosal cancer. All patients but one who revealed recurrence had nodal metastasis at the time of surgery. In cases with 1-3 metastatic lymph nodes, no patient had revealed any sign of recurrence; however, in cases with 4 or more metastatic lymph nodes, 6 of 7 patients died of recurrent disease. There were 3 cases of bone metastases, 2 of peritoneal dissemination, and 1 each of both recurrent diseases. CONCLUSIONS: These data suggest that in n-positive cases, in which there are 4 or more metastatic lymph nodes, there is a high probability of recurrence of early gastric cancer, and especially of hematogenic metastasis.

Electroporation-mediated transfer of cytokine genes into human esophageal tumors produces anti-tumor effects in mice.

Electroporation facilitates transfer of chemicals or plasmid DNA from extracellular milieu into cells by increasing the permeability of the cell membrane. Delivery of electric pulses to established tumors thereby can improve the susceptibility of tumors to an anti-cancer agent administered. We examined whether electroporation-mediated transfer of cytokine genes into solid tumors could produce anti-tumor effects in the tumor-bearing mice. Plasmid DNA containing cytokine genes were injected into human esophageal T.Tn tumors developed in nude mice and electric pulses were then delivered. Administration of murine GM-CSF or human IL-2 gene followed by electroporation significantly suppressed the subsequent growth of T.Tn tumors and prolonged the survival of the inoculated mice. In contrast, electroporation-mediated introduction of a control gene, human GM-CSF gene, whose products do not bind to murine GM-CSF receptors, did not achieve any anti-tumor effects. In vivo transfection of cytokine genes with electroporation could be a possible therapeutic strategy for established solid tumors.

Copper metabolism after living donor liver transplantation for hepatic failure of Wilson's disease from a gene mutated donor.

There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship. Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation. The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father. The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR. Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene. Serum ceruloplasmin level was sufficient in the donor. The right hepatic lobe graft was transplanted to the recipient. Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion. However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms. We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism. After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient.

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS: S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The patients who achieved a partial or complete response to chemoradiotherapy showed significantly less S-VEGF than those patients who were nonresponders (P = 0.018). A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus.

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer.

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer.

Preclinical study of adenoviral p53 gene therapy for esophageal cancer.

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.

Long-term outcomes of immunosuppressed renal transplant recipients with malignancies.

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor.

Bmx tyrosine kinase has a redundant function downstream of angiopoietin and vascular endothelial growth factor receptors in arterial endothelium.

The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this study, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta-galactosidase substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.

Successful surgical treatment of renal cell carcinoma in a transplanted kidney from a cadaveric donor: report of a case.

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence.

Effects of high ELF magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free DNA mismatch repair.

Environmental electromagnetic fields have been implicated in human cancers. We examined whether high extremely low frequency (ELF) AC magnetic fields could affect DNA synthesis, transcription or repair, using in vitro model systems with defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The efficiency of mutS dependent mismatch repair with human cell extracts was also not affected by the magnetic field exposure. The results suggest that the core processes related to the transmission of genetic information are stable under high ELF magnetic fields.

Combinatory anti-tumor effects of electroporation-mediated chemotherapy and wild-type p53 gene transfer to human esophageal cancer cells.

Delivery of electric pulses to an established solid tumor augments the permeability of cell membrane and increases the susceptibility of tumors to an anti-cancer agent that is administered in the vicinity of tumors. Forced expression of the wild-type p53 gene in tumor cells that have non-functional p53 gene(s) can also enhance their sensitivity to a DNA-damaging agent. To investigate the feasibility of electroporation-mediated therapy for cancer, electric pulses were delivered to human esophageal tumors developed in nude mice after they received an anti-cancer agent and/or plasmid DNA containing the wild-type p53 gene. The growth of esophageal tumors was suppressed with electroporation-mediated chemotherapy compared with the treatment with an anti-cancer agent or electroporation alone. Intratumoral injection of the wild-type p53 gene into p53-mutated esophageal tumors followed by electroporation also inhibited tumor growth. When mice were administered with the wild-type p53 gene and an anti-cancer agent, subsequent electroporation produced a synergistic therapeutic effect. Combinatory transfer of plasmid DNA and a pharmacological agent by electroporation is thereby a possible therapeutic strategy for the treatment of solid tumors.

Gene therapy for cancer.

The basic strategies for gene therapy that have been explored include immunogene therapy such as cytokine gene transfer, selective prodrug activation, so-called suicide genes, transfer of a tumor suppressor gene, and inhibition of activated oncogenes by antisense mechanisms. Many therapeutic protocols have so far been registered in the office of the Recombinant DNA Advisory Committee, NIH, as of June 1999. Regarding the basic research in gene therapy, we planned a clinical application of gene therapy for an esophageal cancer patient at our institution. We review herein the present status of gene therapy for cancer overseas, and describe a protocol of clinical trials for gene therapy for esophageal cancer at our institution.