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Item does not contain fulltext OBJECTIVE: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL). METHODS: A systematic review was conducted according to the PRISMA guidelines using Ovid MEDLINE, EMBASe, and PubMed databases for studies reporting on outcomes of PPE for symptom relief or QoL. Descriptive statistics were used on pooled patient cohorts. RESULTS: Twenty-three historical cohorts and case series were included, comprising 509 patients. No comparative studies were found. Most malignancies were of colorectal, gynaecological and urological origin. Common indications for PPE were pain, symptomatic fistula, bleeding, malodour, obstruction and pelvic sepsis. The pooled median postoperative morbidity rate was 53.6% (13-100%), the median in-hospital mortality was 6.3% (0-66.7%), and median OS was 14 months (4-40 months). Some symptom relief was reported in a median of 79% (50-100%) of the patients, although the magnitude of effect was poorly measured. Data for QoL measures were inconclusive. Five studies discouraged performing PPE in any patient, while 18 studies concluded that the procedure can be considered in highly selected patients. CONCLUSION: Available evidence on PPE is of low-quality. Morbidity and mortality rates are high with a short median OS interval. While some symptom relief may be afforded by this procedure, evidence for improvement in QoL is limited. A highly selective individualised approach is required to optimise the risk:benefit equation.

We have already reported that a deep eutectic solvent is one of hopeful solvents to obtain an electroplated Fe-based soft magnetic film since the plating process shows high current efficiency. In this paper, we employed glycine as an additive to improve surface roughness and soft magnetic properties of electroplated Fe–Ni films. The coercivity of the Fe-rich films (>70 at.%) prepared from the glycine-used bath showed lower values compared with those for the no-glycine baths. From the evaluations for the surface roughness and the crystal structure of the as-plated Fe75Ni25 films, we considered that the reductions in the coercivity of the Fe-rich films for the glycine-used baths are attributed to the smooth surface and the reduction in the effective crystalline anisotropy by increase in the volume fraction of an amorphous magnetic phase in the film.

It is well-known that a reduction in thicknesses of soft magnetic materials is one of effective methods to reduce an eddy current loss, and soft magnetic thin ribbons are widely used for high-frequency driven electric machines. Typical soft magnetic thin ribbons are produced by rapid quenching methods, and their thicknesses are approximately 20 $\mu \text{m}$ . In present study, we proposed a novel fabrication method of soft magnetic thin ribbons $( using an electroplating method, and evaluated the ac magnetic properties of the thin ribbons.

Recently, we have reported Fe-Ni films electroplated in Deep-Eutectic-Solvent-based plating bath, and confirmed that the DES-based bath shows high current efficiency (> 90 %) [1]. In our previous studies, we did not use any additives for improvement in levelling and brightness of the films. As studies on additives in DES-based baths are not enough, we focus on phenanthroline, which is used as complex agent [2]–[3], as an additive. In this study, we investigated the effect of the phenanthroline compounds to improve surface roughness and soft magnetic properties.

Fe-Ni-Co ternary alloys are attractive soft magnetic materials, and we have reported a flux gate sensor with an electroplated Fe-Ni-Co film [1]. For improvement in robustness of the sensor output against the temperature variation, an increase in Co content of the film are effective since the Curie temperature increases with increasing the Co content. In the present study, we electroplated Fe-Ni-Co films focusing on the Co content, and evaluated the magnetic and the structural properties.

Deep Eutectic Solvents (DES) are expected as a new solution for plating bath. It is well-known that the bath temperature is one of dominant factors to determine film properties such as surface roughness and magnetic properties. In order to investigate the effect of the bath temperature on film properties, we plated Fe 22 Ni 78 films in the DES-based baths with various temperatures.

Recently, we reported magnetic Fe films plated in Deep-Eutectic-Solvent-based plating baths, and clarified that a DES is one of attractive solvents due to high plating rate (approx. $120 \mu \text{m}/\text{h}$ ) and high current efficiency (> 90 %) [1]. In order to further increase the plating rate, we focused on the current density during the plating. In the present study, we investigated the effect of the current density on plating rate, magnetic properties and surface roughness of the Fe film.

Fe-Ni alloy films were electroplated in DES-based plating baths with various primary amines, and we investigated the effect of the primary amines on the magnetic and the structural properties of the films. The primary amines of ammonium sulfamate, DL-α-alanine and L-glutamic acid reduced the coercivity and the surface roughness of the Fe-rich films (Fe > 70 at.%), and the reduction tendencies of the coercivity and the roughness show good agreement with the result of our previous study on another primary amine of glycine. From the results for the TEM observation, we found that the texture of the Fe-rich film is clearly different from that for the Fe-poor one (Fe < 30 at.%), and we concluded that the primary amines are effective additives for the Fe-rich films electroplated in the DES-based plating baths., AIP Advances, 8(5), 056106; 2018

The hedgehog (Hh) signaling pathway has been reported to be associated with the growth of pancreatic cancer, but its role in the invasive phenotype is poorly understood. Therefore, we investigated the role of the Hh pathway in pancreatic cancer cell invasiveness using a Matrigel invasion assay. Blockade of the Hh pathway by cyclopamine inhibited pancreatic cancer cell invasion in association with a decreased expression of matrix metalloproteinase (MMP)-9. By contrast, activation of the Hh pathway by the addition of exogenous Sonic hedgehog increased cell invasion and MMP-9 expression. Stable transfection of pancreatic cancer cells with Gli1 increased their invasiveness, which was associated with activation of MMP-9. We also showed that inhibition of MMP-9 by small interfering RNA blocked the increased invasiveness of Gli1-transfected cells. Furthermore, inhibition of Gli1 by small interfering RNA suppressed the invasiveness and MMP-9 expression of pancreatic cancer cells. Taken together, these findings suggest that members of the Hh pathway, especially Gli1, play an important role in the invasiveness of pancreatic cancer cells through the regulation of MMP-9 expression. (Cancer Sci 2008; 99: 1377–1384)

Background & Aims: Colorectal cancers are resistant to conventional chemotherapeutic treatments, including taxanes. γ-Secretase is a multimeric membrane protein complex responsible for the intramembrane proteolysis of various type I transmembrane proteins, including amyloid β-precursor protein and Notch. γ-Secretase inhibitors have attracted increasing interest as anticancer drugs because of their ability to inhibit Notch signaling. However, the therapeutic usefulness of γ-secretase inhibitors against colorectal cancers remains unclear. Methods: The effects of γ-secretase inhibitors on growth and apoptosis induced by various chemotherapeutic agents in colon cancer cells were evaluated using Hoechst 33342 staining, colony formation assay, and cell cycle analysis. The effect of γ-secretase inhibitors on taxane-induced mitotic arrest was evaluated using the cyclin B1–associated histone H1 kinase assay and MPM-2 reactivity. The involvement of Notch signaling was evaluated by the silencing of Notch/CBF1 signaling by RNA interference. Results: γ-Secretase inhibitors enhanced taxane-induced mitotic arrest and apoptosis of colon cancer cells both in vitro and in vivo, although γ-secretase inhibitors alone did not affect growth and apoptosis of colon cancer cells. We also showed that this effect by γ-secretase inhibitors was restricted to taxanes and colon cancer cells. Silencing of Notch/CBF1 signaling failed to affect paclitaxel-induced mitotic arrest and apoptosis. Conclusions: These data suggest that γ-secretase inhibitors could be a new therapeutic modality for overcoming resistance to taxanes in colorectal cancers.

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-κB (NF-κB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-κB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-κB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-κB by inflammatory stimuli, including interleukin-1β, tumor necrosis factor-α, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-κB. NF-κB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-κB suppressed the enhanced cell proliferation. Our data suggest that NF-κB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-κB activation in part through Shh overexpression. (Cancer Res 2006; 66(14): 7041-9)

Background: Early events in the progression of 90% of sporadic colorectal cancers depend on constitutive activation of Wnt signalling. Recent data also indicate a close association between the Hedgehog (Hh) and Wnt pathways in colonic epithelial cell differentiation. Aims: To investigate whether expression of Gli1, a transactivator of Hh signalling, can suppress Wnt signalling and inhibit proliferation of human colorectal cancer cells. Methods: Gli1 and nuclear β-catenin expression were examined in a series of 40 human colorectal cancers by immunohistochemistry. We quantified Gli1 and nuclear β-catenin staining as markers of Hh and Wnt pathway activation, respectively. Two human colon cancer cell lines, SW480 and HCT116, with mutations in APC and β-catenin, respectively, were used. The effects of Gli1 overexpression on Wnt transcriptional activity, β-catenin subcellular distribution, and proliferation in these cells were analysed. Results: Nuclear accumulation of β-catenin and the Gli1 staining level were inversely associated in the 40 human colorectal cancers. Wnt transcriptional activity was reduced in Gli1 transfected cells. These effects were observed even in Gli1 transfected cells cotransfected with mutated β-catenin. Furthermore, nuclear accumulation of β-catenin was diminished compared with that in empty vector transfected cells, and downregulated transcription of c-Myc was observed in Gli1 transfected cells. Proliferation of Gli1 transfected cells was also significantly suppressed compared with that in empty vector transfected cells. Conclusions: Our data suggest that Gli1 plays an inhibitory role in the development of colorectal cancer involving Wnt signalling, even in cases with the stabilising mutation of β-catenin.

To clarify the significance of the expression of pyrimidine nucleoside phosphorylase (PyNPase) mRNA as a predictive factor for the prognosis of patients with oesophageal carcinoma, the PyNPase mRNA in the tumours and normal tissues from 55 resected cases of oesophageal carcinoma was examined by a reverse transcription polymerase chain reaction (RT-PCR). As a result, a positive correlation was observed between the tumour/normal (T/N) ratio of the expression of PyNPase mRNA by RT-PCR and that of the enzyme activity of PyNPase based on the findings of an enzyme linked immunosolvent assay (r = 0.594, P = 0.009). The T/N ratio of the expression of PyNPase mRNA was significantly higher in the cases with lymph vessel invasion (P = 0.013), lymph node metastasis (P = 0.0016), and an advanced stage of the disease (P = 0.021) than those without these factors. The patients with a higher T/N ratio of PyNPase mRNA showed significantly worse prognosis than those with a lower T/N ratio (P = 0.023 with log-rank tests). A multivariate analysis for the cumulative survival rates revealed that a high T/N ratio of the expression of PyNPase mRNA was independently related to a poor prognosis. These findings suggested that the determination of PyNPase mRNA by RT-PCR thus appears to be a new useful parameter for identifying both a poor prognosis and a highly malignant potential of oesophageal carcinoma. © 1999 Cancer Research Campaign

Tissue inhibitor of metalloproteinase (TIMP) has been reported to inhibit tumour invasion through an inactivation of matrix metalloproteinase (MMP) both in vitro and in vivo. Among the TIMP family, TIMP-1 possesses not only proteinase inhibitory activity but also a growth-promoting function. However, the significance of the expression of TIMP-1 in human gastric carcinoma tissue has yet to be clarified. In 50 examined cases of gastric carcinoma, 44 (88%) cases showed a higher expression of TIMP-1 mRNA in the biopsy samples from the tumour tissue (T) than in the biopsy samples from the corresponding normal tissue (N), as determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In a multivariate analysis, the T/N ratio of TIMP-1 mRNA was found to be an independent factor influencing the depth of tumour invasion and was the second most important factor in determining the prognosis of patients. As RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of the TIMP-1 expression in biopsy specimens by RT-PCR may thus provide useful preoperative information on tumour aggressiveness. Images Figure 1 Figure 2 Figure 4

A non-linear seismic response analysis method for 2-D saturated soil-structure system with an absorbing boundary is presented. According to the 3-D strain space multimechanism model for the cyclic mobility of sandy soil, a constitutive expression for the plane strain condition is first given. Next, based on Biot's two-phase mixture theory, the finite element equations of motion for a saturated soil structure system with an absorbing boundary during earthquake loadings are derived. A simulation of the shaking table test is performed by applying the proposed constitutive model. The effectiveness of the absorbing boundary is examined for the 2-D non-linear finite element models subjected to random inputs. Finally, a numerical seismic response analysis for a typical saturated soil-structure system is performed as an application of the proposed method.

The cyclic mobility behaviour of sand by the three-dimensional (3-D) strain space multimechanism model based on the micromechanics of granular material is investigated. The constitutive properties are characterized by the volumetric and shear mechanisms for the initial isotropic soil. The 3-D shear mechanism is decomposed into a number of microscopic plane-strain shear mechanisms in various orientations, each of which in turn consists of a number of microscopic simple shear mechanisms. Using an appropriate summation of mechanisms, the total deformation behaviour can be obtained by evaluating contributions from each mechanism. Based on the some assumptions, the dilatancy model proposed by Iai et al.1 is extended from the two-dimensional (2-D) space to the 3-D space. Comparisons of theoretically predicted results are made with experimental measurements.

Recent studies have shown that microsatellite instability (MSI) play an important role in the development of various types of cancer. To clarify the clinicopathologic significance of MSI in colorectal carcinoma (CRC), the presence of MSI was examined in 54 Japanese cases of CRC using the polymerase chain reaction-based method. The incidence of MSI in CRC cases was 13 out of 54 cases (24%). CRC with MSI also showed a significant tendency not to have lymph node metastasis (P

Deflagration-to-detonation transition (DDT) using flame jets was experimentally studied to improve performance of pulse detonation engines. The detonation tube has a total length of 7350 mm and an inner diameter of 50 mm. Three types of flame jets were arranged by changing configuration of sub-chamber: two flame jets colliding at the tube center (counter type), two flame jets forming a swirl inside the detonation tube (offset type), and one flame jet supplied in the axis direction of the detonation tube (conventional type). Test gas was a stoichiometric acetylene-air mixture. The experimental results show that the shortest DDT time is provided by a swirling flame jet emanating in the oblique direction to the tube axis. The DDT time decreases with increase in the orifice diameter and length of the sub-chamber. It was also found that DDT distance is not significantly affected by types of the flame jets and slightly decreases with decrease in length of the sub-chamber.

The effect of prostaglandin F2 alpha (PGF2 alpha) on mammary carcinogens was examined for a new system in female rats, using ethyl methanesulphonate (EMS). The rats were given EMS orally for a period of 12 weeks starting at age 4 weeks. Mammary carcinomas were first detected at the 16th week and were found in all surviving rats at the 32nd week. The concomitant administration of PGF2 alpha for 8 weeks made the development of tumor retarded; i.e., the carcinomas were first detected at the 30th week and final tumor incidence at the 44th week was 61.1%. The incidence of developing mammary carcinomas and multiplicity (number of mammary carcinomas per rat) were significantly lower in PGF2 alpha treated rats than in those given EMS alone. The inhibitory effect of PGF2 alpha on tumor development was apparent when PGF2 alpha was concomitantly given to the rats with EMS at age 4 weeks, while PGF2 alpha injections after oral administration of EMS at age 16 weeks did not significantly retard tumor development. Histologically, no significant difference in morphology was observed between PGF2 alpha-treated and PGF2 alpha-non-treated rats in either the cancerous or noncancerous mammary tissues. The finding demonstrates that PGF2 alpha inhibits the development of EMS-induced mammary carcinomas when given to younger rats, presumably by affecting the hormonal status rather than by direct action on the mammary glands.

The mode of inactivation of cis-diamminedichloroplatinum (II) (DDP) in the bloodstream by sodium thiosulfate (STS) was investigated experimentally and clinically by a bioassay system using the phytohemagglutinin stimulation assay of human peripheral blood mononuclear cells. Active DDP in the plasma of dogs after 3 mg/kg of DDP injection, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. In 6 patients with hepatic malignancies who were treated with hepatic artery infusion of 3 mg/kg DDP and systemic STS, active DDP in the plasma was not detectable in the concurrent presence of STS at molar ratios of more than 500. Severe DDP toxicity in these patients was completely protected. The results indicate that an inactivation of DDP in the bloodstream after DDP injection and, further, an effective protection against DDP toxicity can be achieved by the concurrent presence of STS at molar ratios of more than 500 in the plasma of these patients.

Morphogenic signals like Hedgehog (Hh) and Wnt are reported to play critical roles in the progression of gastric cancer. We aimed to assess the relationship between Hh and Wnt signaling pathways. In 58 gastric cancer specimens, Wnt pathway activation was inversely correlated with Hh pathway activation. When AGS gastric cancer cells, in which Wnt signaling was constitutively active, were used as a target cell line, Gli1 overexpression suppressed Wnt transcriptional activity, nuclear beta-catenin accumulation and proliferation of AGS cells. Knock-down of beta-catenin by siRNA suppressed Wnt pathway activity and proliferation of AGS cells. Our data may provide some clues for the treatment of gastric cancer associated with Wnt signaling activation.

tion has been shown to be effective in the treatment of recurrent chylous effusions. Many embolic agents have been described in the successful occlusion of the thoracic duct. In this study, we evaluate the role and efficacy of using EVOH copolymer (Onyx) in the treatment of traumatic chylous pleural effusions. Background: A retrospective review was performed of consecutive patients with post-operative chylous pleural effusions treated with thoracic duct embolization using EVOH copolymer at a single institution from 2012-2014. Demographic data, surgical history, procedure details, and toxicities were systematically reviewed. Clinical Findings/Procedure Details: 4 patients (M1⁄42) were identified that met inclusion criteria. Median age at treatment was 67. Median follow was 125 days (range 24-246). Two patients had undergone robotic assisted surgery and 2 had undergone open thoracotomy. 3 patients had thoracic duct ligation performed at the time of their initial surgery. Median time from surgery to embolization was 7 days (range 3-15). Daily chest tube drainage range was 150 -2000 ml. All patients underwent bilateral ultrasound guided inguinal nodal lymphangiogram. The thoracic duct was then accessed using a 21 or 22 gauge Chiba needle. A thoracic duct leak was identified in 3 patients. Coils were placed initially in the central duct prior to embolization of the leak limit potential systemic flow. Onyx 34 (ev3 Neurovascular, Irvine, California) was used in 4 patients with additional Onyx 18 in 1 patient for embolization. Volume used was 1-2 ml in all patients. All patients had resolution of the chylous effusion within 1 day of embolization. The subjects were discharged from the hospital between 4-7 days post-procedure. 30 days post-procedure complications included an abdominal wall hematoma in 1 patient who was subsequently started on anticoagulation. No patients developed recurrent chyle leaks during the follow up period. Conclusion and/or Teaching Points: EVOH copolymer is a safe and effective agent for percutaneous thoracic duct embolization. This is the largest reported series to date demonstrating the efficacy of this embolic agent in treating chylous effusions in the post-traumatic setting.

We herein report a 64-year-old Japanese woman with cystadenocarcinoma of the liver without mesenchymal stroma which had been followed up by imagings for 12 years. A samll round cyst grew from 1 cm to 4 cm in diameter during 10 years. Thereafter, solid components were first detected in the unilocular cystic mass, which showed very rapid growth. Extended right lobectomy with right caudate lobectomy was performed. The histopathological diagnosis was cystadenocarcinoma of the liver without mesenchymal stroma. In this communication, we describe the progressive morphologic changes, shown on imagings, from a benign hepatic cyst to cystadenocarcinoma of the liver without mesenchymal stroma, and we briefly discuss the carcinogenesis of cystadenocarcinoma of the liver.

The MAGE gene is selectively expressed in cancer tissues such as melanoma or gastrointestinal carcinomas, whereas no expression is observed in normal tissues except testis. There are several reports of successful induction of HLA class I-restricted antitumor CTLs using MAGE peptides, and some clinical trials with these immunogenic peptides were reported as effective for some patients with malignant melanoma. However, there are no similar studies in gastrointestinal carcinomas, which are important neoplasms. Autologous dendritic cells (DCs) were generated ex vivo and were pulsed with MAGE-3 peptide, depending on the patient's HLA haplotype (HLA-A2 or A24). Patients were immunized with DC pulsed with MAGE-3 peptide every 3 weeks at four times. Twelve patients with advanced gastrointestinal carcinoma (six stomach, three esophagus, and three colon) were treated, and no toxic side effects were observed. Peptide-specific CTL responses after vaccination were observed in four of eight patients. Improvement in performance status was recognized in four patients. Tumor markers decreased in seven patients. In addition, minor tumor regressions evidenced by imaging studies were seen in three patients. These results suggested that DC vaccination with MAGE-3 peptide is a safe and promising approach in the treatment of gastrointestinal carcinomas.

After a single dose of cisplatin, the ability of peripheral blood mononuclear cells (PBMC) to generate lymphokine-activated killer (LAK) cells was significantly augmented in cancer patients. Based on this clinical finding, the patients with locally advanced esophageal carcinoma were thus treated with a combination of cisplatin and low-dose interleukin-2 (IL-2) in a neoadjuvant setting. Four patients with squamous cell carcinoma of the esophagus (T3 or T4 disease) were preoperatively treated with a regimen consisting of 50 mg/m2 cisplatin on day 1, followed by IL-2 from day 4 through day 8, when the ability of PBMC to generate LAK cells had been shown to be significantly augmented. After two to four courses of the preoperative therapy, one patient achieved a histologic CR, one showed PR and one MR. No severe toxicity was encountered. All patients thereafter underwent surgery. The median survival of these patients was 47.5 months and three of the patients had been disease free for 43 to 62 months after the initiation of the therapy. The combination of cisplatin and low-dose IL-2 administered in a neoadjuvant setting seems to result in an improved survival of locally advanced squamous cell carcinoma of the esophagus.

Measurements of auricles were done about 317 volunteers living in the Saga Prefecture at the age of 50 to 94 years old (71 men and 246 women), from July until November, 1999. 1) A growing tendency was observed in both male and female physiognomic ear length. 2) In contrast, there was no significant increase or decrease in the ear width. 3) A decreasing tendency was observed in the ear index of both male and female volunteers.

Because MAGE-2 gene is expressed in a wide variety of malignant tumors and HLA-A24 is the most common allele in the Japanese population and is also frequently present in Caucasians, the identification of MAGE-2-encoded peptide presented by HLA-A24 is, therefore, considered to be important in order to develop specific immunotherapy for malignant tumors using peptides as a vaccine. By using a MHC-binding assay, eight peptides derived from MAGE-2 were found to bind with sufficient affinity to the HLA-A24 molecule. When the induction of specific cytotoxic T lymphocytes (CTLs) was examined using a simplified method, the highest human lymphocyte antigen (HLA) binder (EYLQLVFGI) in these peptides was able to elicit CTLs from unseparated peripheral blood mononuclear cells in HLA-A24 healthy donors by stimulation with freshly isolated, peptide-pulsed peripheral blood mononuclear cells as antigen-presenting cells and also by using interleukin 7 and keyhole-limpet hemocyanin in a primary culture. The induced CTL could, thus, lyse HLA-A24 tumor cells expressing MAGE-2, as well as the peptide-pulsed target cells, with antigen specificity in a HLA class I-restricted manner. The identification of this peptide may, thus, be of therapeutic value in peptide-based vaccines for the treatment of several types of malignant tumors expressing MAGE-2.

We designed a chemoimmunotherapy regimen with a single dose of mitomycin C (MMC) followed by subsequent OK-432 injections, since the ability of peripheral blood mononuclear cells (PBM) to generate OK-432 activated killer cells had previously been shown to be augmented by MMC in cancer patients. We herein report on a case with far advanced gallbladder carcinoma who demonstrated a remarkable response to this chemoimmunotherapy, and thus underwent a curative resection. A 67 year-old Japanese woman was diagnosed as having gallbladder carcinoma with invasion to the liver and portal vein, as well as obvious lymph node metastasis. Since these findings suggested the tumor to be unresectable at that time, our chemoimmunotherapy regimen with MMC and OK-432 was administered. After four courses of therapy, a computed tomography (CT) scan revealed the disappearance of both tumor invasion to the surrounding organs and lymph node metastasis, which therefore prompted us to attempt a radical tumor resection. The histology of the resected specimen revealed that the majority of cancer cells had been killed by the pre-operative therapy and that only remnants of viable cancer cells were found in a part of the neck of the gallbladder and in 2 regional lymph nodes. This experience thus suggests the effectiveness of our chemoimmunotherapy regimen against gallbladder carcinoma.

The effect of diethyldithiocarbamic acid methyl eater (Me-DDC), a metabolite of disulfiram, on hepatic delta-aminolevulinic acid (ALA) synthetase activity was investigated in male rats. The results obtained were as follows: 1) When rats were given intraperitoneally Me-DDC at the dose levels of 0.0625, 0.125, 0.25 and 0.50 mmol/kg, the activity of ALA synthetase showed a maximum level at a dose of 0.125 mmol/kg. 2) ALA synthetase activity increased rapidly and reached a maximum level in about 2 hr after the intraperitoneal administration of Me-DDC (0.125 mmol/kg). 3) Pretreatment with phenobarbital (an inducer of drug metabolizing enzymes) tended to depress the increase of ALA synthetase caused by Me-DDC, whereas pretreatment with SKF 525-A (an inhibitor of drug metabolizing enzymes) stimulated slightly the Me-DDC-induced increased of the enzyme. 4) The apparent Km value of the enzyme for glycine did not change but the Vmax value increased in Me-DDC-treated rats. 5) Actinomycin D (a potent inhibitor of DNA-dependent synthesis of RNA), when administered to rats before Me-DDC, completely prevented the induction of ALA synthetase caused by the latter compound. 6) Pretreatment with phorone (a glutathion depletor) 4 hr prior to the administration of Me-DDC completely inhibited the Me-DDC-induced increase of ALA synthetase.

We examined the effects of postoperative 5-fluorouracil (5-FU) infusions and oral treatment with 1-hexylcarbamoyl-5-fluorouracil (HCFU) on patients curatively resected for stages II-IV colorectal cancer. The study was prospectively randomized, and 251 (93.3%) of 269 patients were valid candidates for statistical assessment. The inductive regimen for group A included 5-FU 10 mg intravenous (i.v.) injections on days 0, 1, 2, 7, 8 and 9, postoperatively. For maintenance therapy, group A received HCFU 300 mg orally and daily for 52 weeks beginning 2 weeks after surgery. The regimen for group B included only 5-FU injections. The effects of this chemotherapy were also retrospectively analyzed for groups at a high risk for recurrence, stages III-IV, transmural invasion-positive and lymph node metastasis-positive cases. There was no statistical difference in survival time between the groups for 251 eligible cases (p = 0.079). In group A given 5-FU plus HCFU, there was a reduction in the recurrence rate for patients with stages III-IV or lymph node metastasis-positive colorectal cancers (p0.05) and prolongation of the survival time for patients with stage III-IV, transmural invasion-positive or lymph node-positive colorectal cancers (p0.05). Our findings show that the combination of 5-FU infusion and the continuous administration of HCFU is effective in treating patients with surgically resected colorectal cancer who are at high risk for a recurrence.

As the basis for the application of MAGE antigens to therapeutic use, the induction of peptide-specific CTLs has been investigated by the stimulation of peripheral blood mononuclear cells (PBMCs) with antigenic peptides derived from MAGE genes. However, the cross-reactivity of the peptide-induced CTLs to the target cells endogenously presenting the MAGE epitope, especially in cancer patients, remains controversial, despite the use of complicated manipulations. Because we recently developed a new simplified method to induce peptide-specific CTLs that killed MAGE expressing tumor cells from the PBMCs of a healthy donor, we examined the induction of specific CTLs by stimulation of PBMCs with HLA-A2-restricted MAGE-3 peptide in HLA-A2(+) cancer patients whose tumors expressed MAGE-3 by using the simple method. The CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells and by using interleukin 7 and keyhole limpet hemocyanin for the primary culture. All CTLs induced from the PBMCs of four cancer patients tested could thus lyse the HLA-A2 target cells pulsed with the peptide, and moreover, two of the CTLs were also able to kill HLA-A2 tumor cells expressing MAGE-3 in a HLA class I and A2-restricted manner. Therefore, these findings seem to indicate that HLA-A2-restricted MAGE-3 peptide may be potentially useful for specific immunotherapy in cancer patients.

Influence of an intake of the riboflavin that exerts upon osteogenesis in this research, was examined by a nutritional methods. It search the condition of femur in rats they reared and given three type riboflavin dosage, namely, sufficient riboflavin, few deficient riboflavin and administered sufficient after few deficient riboflavin. As a result, an influence of riboflavin dosage was not recognized about each of the body weight, food intake, and weight and length of femur. In other words, a deficiency symptom was not observed seemingly in the rat that given riboflavin deficiency diet. Also, the calcium contents in the femur decreased significantly by the deficiency of riboflavin. And, the low value was shown the even in the rat that administered sufficient fibroflavin later. Furthermore, even breaking force of the femur decreased by the deficiency of riboflavin.

Background L-myc polymorphism has been documented to be a representative genetic trait which is related an individual's susceptibility to several cancers. However, there have been no reports concerning any significant association between susceptibility to gastric cancer and L-myc polymorphism. Methods The distribution of L-myc polymorphism in 61 patients with gastric cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 107 healthy control subjects. Results There was a significant difference in the distribution of both genotypes (P = 0·024) and allele frequencies (P = 0·026) between the two groups. The relative risk of gastric cancer for genotypes with the shorter (S) allele was 3·09 compared with the longer (L) allele homozygote. No significant correlation with clinicopathological features of the cancers except for prognosis was found. The patients with SS genotypes had a worse prognosis than those with LL or LS genotypes (P = 0·029). Conclusion L-myc polymorphism may be significant in an individual's susceptibility to gastric cancer in Japan, and may be a useful marker for identifying patients at high risk of developing gastric cancer.

It is important to detect genes that may be good prognostic markers for colon cancer patients. With this in mind, we identified the motility related protein-1 (MRP1/CD9) gene in human colon tissues. The aim of this study was to clarify the significance of MRP1/CD9 gene expression in human colon cancers. We performed the differential mRNA display technique between tumor/normal paired samples of the colon and identified MRP1/CD9. Eighty-two surgical specimens of primary colorectal cancer were analyzed by means of reverse transcription-PCR for the MRP1/CD9 gene. Its expression status and clinicopathological variables were analyzed univariately and multivariately. The MRP1/ CD9 mRNA expression was positive in 56 cases and negative in 26 cases. The MRP1/CD9 negative cases showed a significantly higher frequency of venous-vessel invasion and liver metastasis, or a worse prognosis than the MRP1/CD9 positive cases (P0.05). Multivariate analysis with the Cox regression model disclosed that MRP1/CD9 expression was an independent prognostic factor distinct from the lymph node status. The findings imply that the study of MRP1/CD9 expression may be useful for predicting prognosis of patients with colorectal cancer.

The 12 members of the human melanoma antigen-encoding (MAGE) gene family encode tumor-specific peptide antigens. Some antigens coded by the MAGE genes are potentially useful for cancer-specific immunotherapy. However, little information on the expression of these genes in human colon carcinomas is available. We investigated the expression of 10 of the 12 genes in human colon tissue.Eighty pairs of tumor and normal tissue samples from the human colon were studied by means of reverse transcription-polymerase chain reaction.None of the genes was expressed in the 80 control samples of normal tissue. On the other hand, expression was recognized in tumor samples, ranging from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver metastasis was significantly higher in cases with tumor samples that expressed MAGE-3 than in those that did not express this gene. This tendency was not observed for other members of the MAGE gene family. No significant differences were observed in the other clinicopathologic factors between any MAGE-positive and -negative tumor cases.The MAGE genes were exclusively expressed in carcinoma tissues and not in normal tissues of the colon. The finding that nearly 90% of tumors expressed at least one MAGE gene indicates the possible clinical use of this gene for both immunotherapy and molecular diagnosis.

Carrying out a somatotype comparison of both, by using data of anthropometry of Hawaii-born Japanese Children (Hawaii-Children) and Amami-born Japanese Children (Amami-Children) that were carried out in 1977-78 a study with regard to the determination of obesity was carried out. The result that compared a somatotype was as follows. 1. The height of hawaii-Children was almost higher than that of Amami-Children. 2. A body weight was almost the same. 3. Trunk length of Amami-Children was longer than that of Hawaii-Children. 4. Lower limb length of Hawaii-Children was bigger than that of Amami-Children a little. 5. The letio of Rohrer index of Amami-Children was greater than that of Hawaii-Children. Therefore, it is determined that Amami-Children were obesity even from Hawaii-Children. when obesity index is judged from the ratio of the height to body weight. As for skin-fold thicknesses (amount of subcutaneous fat), Hawaii-Children is showing a high value more always than Amami-Children and Hawaii-Children is obesity obviously. Although the measurement result of Rohrer index and skin-fold thicknesses are contradicting this cause is because it differs with both trunk length and Lower limb length. Considering those result, it became obvious that a obesity index calculated from the height and body weight does not show fat volume inside a body precisely. The measurement of amount of subcutaneous fat needs to be carried out to check real obesity. Also, it is important to carry out the measurement of trunk length and Lower limb length in addition to the height and a body weight at least, to know a obesity.

Extract and measure the scapular every part from the fetus that was carried into Saga medical college, the data was processed statistically. Also, the morphological characteristic of scapula of the fetus was clarified by image processing that a computer is used. The result was as follows. A scapular morphological length and also height become big in proportion to the height of fetus. Index of height-length of a fetus was big compared with adult, this trend is remarkable especially in a early stage of development of a fetus. Spinal axis angle of a fetus was also bigger than that of adult and it remarkable differ from an anthropoid very small ane. In general, the scapular shape of a fetus was short length with wide-spreading side and this form resembles to scapula of Jomon period people. The width of cartilage part tend to decrease as ossification progress fast width-wise with growth. However, area of cartilage part tend to become big, because the growth of a cartilage part is going fast lengthwise.

The filter-paper-disk method was employed for measuring the threshold values of four basic taste on lingua-tip with 308 healthy females aged 20-79. Taste substance were sequentially diluted with distilluted water (30 stages from 80.0 g/dl for sucrose, 30 stages from 30.0 g/dl for NaCl, 30 stages from 8.0 g/dl for sodium tartrate, 30 stages from 4.0 g/dl for HCl quinine). The result was as follows. A sensibility of gustation decreased rapidly in accordance with aging. A decrease of bitterness sensibility was most remarkably with aging, succeeded sourness, sweetness, saltyness. Also, a decrease of a gustation sensibility is beginning in early twenties, especially the sensitivity to a sweetness and sour taste decreased conspicuously from twenties to thirties.

MAGE genes code tumor antigens that are recognized by cytolytic T lymphocytes and have been shown to be expressed in various malignant tumors. However, there is still little information on the expression of the MAGE gene family except for reports of MAGE-1 and -3. In this study, we therefore investigated the expression of MAGE-4, -6, -8, -9, -10, -11 and -12, as well as MAGE-1, -2 and -3 in both cell lines and surgical samples of gastric carcinoma, using reverse transcriptionPCR. Of the investigated 11 cell lines, MAGE-4, -6, -8, -9, -10, -11 and -12 were detected in 8 (73%), 6 (55%), 2 (18%), 59 (44%), 6 (55%), 4 (36%), and 7 (64%), respectively. No expression of these genes was seen in any of the 54 samples of normal gastric tissue. In contrast, the tumor tissue samples were found to express MAGE-4, -6, -8, -9, -10, -11, and -12 in 18 (33%), 13 (24%), 6 (11%), 10 (19%), 5 (9%), 13 (24%), and 10 (19%), respectively. Forty-four (82%) of 54 gastric tumors expressed at least one of these genes. No significant correlation was observed between the expression of MAGE genes and any specific clinicopathological factors. These results may hopefully prove to be useful in developing strategies for tumor-specific immunotherapy of gastric carcinoma using MAGE gene products.