Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy.

AIMS: HsMAD2 and BubR1 are crucial components of a functional mitotic checkpoint. Recently, impaired mitotic checkpoints or decreased expression of mitotic checkpoint genes have been associated with sensitivity to certain anticancer drugs. The current study aimed to evaluate the association of hsMAD2 and BubR1 with sensitivity to various anticancer drugs in oesophageal squamous cell carcinoma (ESCC) cell lines. We also investigated responses to 5-fluorouracil and cisplatin-based radiochemotherapy in ESCC patients. MATERIALS AND METHODS: HsMAD2 and BubR1 mRNA levels in six ESCC cell lines and 21 ESCC patients were determined by real-time reverse transcription polymerase chain reaction. Responses to 5-fluorouracil, cisplatin, paclitaxel and docetaxel in human oesophageal cancer cell lines, TE1 and TE2, were evaluated by WST-8 colorimetric assay. HsMAD2 and BubR1 levels were compared with clinicopathological characteristics and responses to radiochemotherapy. RESULTS: TE1, with lower hsMAD2 and BubR1, showed greater sensitivity to paclitaxel and docetaxel compared with TE2, with higher hsMAD2 and BubR1. HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01). Tumoral hsMAD2 and BubR1 were significantly decreased after radiochemotherapy (P < 0.01). There was a significantly strong positive association between hsMAD2 and BubR1 in cancer tissue (P < 0.01). Neither clinicopathological characteristics nor the response to radiochemotherapy was associated with hsMAD2 or BubR1. CONCLUSION: The mitotic checkpoint genes, hsMAD2 and BubR1, were co-ordinately overexpressed in ESCC. Low hsMAD2 and BubR1 was associated with sensitivity to paclitaxel and docetaxel. Decreased hsMAD2 and BubR1 after radiochemotherapy may indicate the potential efficacy of taxanes as second-line chemotherapy for recurrent and metastatic oesophageal cancer.

Randomized clinical trial of single- versus multiple-dose antimicrobial prophylaxis in gastric cancer surgery.

BACKGROUND: The optimum duration of antimicrobial prophylaxis in elective gastric cancer surgery is still open to question. This multicentre randomized clinical trial compared a single-dose with a multiple-dose regimen of antimicrobial prophylaxis for prevention of surgical-site infection. METHODS: Between May 2001 and December 2004, 501 patients undergoing elective surgery for gastric cancer in ten centres were allocated randomly to single- or multiple-dose antimicrobial prophylaxis. The primary outcome measure was the incidence of surgical-site infection, analysed by intention to treat. RESULTS: Some 243 patients who received a single dose and 243 who received multiple doses of antibiotics were included in the final analysis. The surgical-site infection rate was 9.5 per cent (23 of 243) and 8.6 per cent (21 of 243) respectively (difference 0.9 (95 per cent confidence interval - 4.3 to 5.9) per cent). Antimicrobial prophylaxis had no major adverse effects. CONCLUSION: The incidence of surgical-site infection in elective gastric cancer surgery was similar with both antibiotic prophylaxis regimens.

Circulating level of hepatocyte growth factor as a useful tumor marker in patients with early-stage gastric carcinoma.

BACKGROUND: Although conventional tumor markers including carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) have been used in gastric cancer patients, clinically useful markers of early gastric cancer have not been identified. The present study was designed to clarify the clinical significance of the circulating level of hepatocyte growth factor (HGF) as a tumor marker, especially in early-stage gastric cancer patients. METHODS: Preoperative serum HGF levels were measured with an enzyme-linked immunosorbent assay in 30 early-stage and 42 advanced-stage gastric cancer patients. RESULTS: The mean value of serum HGF in 72 patients was significantly higher than that in the normal subjects. There was a significant increase in serum HGF levels in both advanced-stage and early-stage patients compared with normal subjects. The positivity rates of HGF in early disease cases were higher than those of CEA and CA19-9. The serum HGF level was significantly higher in patients with vessel invasion than in those without invasion. In smaller early gastric cancers, serum HGF elevation was associated with lymphatic invasion. CONCLUSIONS: The serum HGF level may be a clinically significant tumor marker in patients with early-stage, as well as advanced-stage, gastric cancer. HGF elevation in early-stage patients may help us to predict the risk of lymph node metastasis of early gastric tumors, even of smaller tumor size. HGF may be a useful indicator for appropriate lymphadenectomy in early gastric cancer.

Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product.

Angiotensin-converting enzyme (ACE) inhibitory activities and anti-hypertensive activities in spontaneously hypertensive rats (SHR) of 12 kinds of commercial peptides of food additive grade were measured. Four peptide products derived from milk proteins showed strong anti-hypertensive activities (>-18.0 mm Hg). A sample of WE80BG derived from whey proteins showed the strongest anti-hypertensive activity (-21.2 +/- 16.9 mm Hg) with a medium level of ACE inhibitory activity (53.6%), and it was subjected to hydrophobic and gel filtration chromatography. From the low molecular weight fraction, an anti-hypertensive peptide was isolated by using reversed-phase HPLC, and it was found to be a tetrapeptide, alanine-leucine-proline-methionine (Ala-Leu-Pro-Met, ALPM), the origin of which was estimated to be beta-lactoglobulin f 142 to 145. At 8 h after oral administration of ALPM in SHR, systolic blood pressure was significantly decreased (-21.4 +/- 7.8 mm Hg), but the IC50 value (concentration of peptide needed to inhibit 50% of the ACE activity) of ALPM was not so high. We named the Ala-Leu-Pro-Met "beta-lactosin B." This peptide is the second anti-hypertensive peptide found from beta-lactoglobulin. Because WE80BG containing ALPM was also found to show the strongest anti-hypertensive activity (-24.5 +/- 10 mm Hg) at 8 h after oral administration in SHR, WE80BG would be suitable for application to the development of a new food expected to have anti-hypertensive effects.

Profile of monocyte chemoattractant protein-1 circulating levels in gastric cancer patients.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. It acts as an important factor in the cytokine network, which regulates tumor proliferation, whereas the association between serum MCP-1 level and gastric cancer has not yet been clarified. METHODS: The serum concentration of MCP-1 in 76 gastric cancer patients and in 45 normal controls was determined using an immunoradiometric assay. The concentration of MCP-1 in the 47 cancer tissue samples was also determined. RESULTS: The serum concentration of MCP-1 in patients with advanced carcinoma was significantly lower than that in controls. The serum concentration of MCP-1 in patients with advanced carcinoma was significantly lower than that in patients with early carcinoma. The serum concentration of MCP-1 was associated with clinicopathological factors including lymph node metastasis, serosal invasion and histological differentiation of the tumor. In patients who underwent palliative surgery, the serum MCP-1 level significantly decreased postoperatively, whereas in patients who underwent curative surgery the serum MCP-1 level tended to increase. The 4-year survival rate in patients whose serum MCP-1 levels were lower than or equal to the median value was significantly lower than that in patients whose MCP-1 levels were higher than the median value. The tissue concentration of MCP-1 in the cancer tended to decrease in accordance with disease progression. CONCLUSIONS: The serum level of MCP-1 decreased in accord with disease progression, which reflects local consumption in gastric cancer. Serum MCP-1 may be a useful marker that reflects the host's local resistance to the tumor.

[Gastric cancer associated with dermatomyositis accompanied by photoallergy].

A 62-year-old man was admitted to the hospital because of a 5-month history of edematous erythema and itching on the face, upper chest, and upper extremities. The symptoms developed immediately after bathing in the sea. Dermatomyositis associated with photoallergy was diagnosed by skin and muscle biopsy. A search for malignancy revealed Borrmann 3 gastric cancer, and subtotal gastrectomy was performed. He has done well for 3 years and 8 months after the operation, but there has been no remission in the symptoms of dermatomyositis. Dermatomyositis associated with photoallergy has a higher incidence of complications with malignant disease than ordinary dermatomyositis.

[Successful resection of multiple liver metastases from rectal cancer following initial treatment using hepatic arterial infusion chemotherapy and radiotherapy].

A 69-year-old-man was referred to our hospital because of rectal cancer with multiple liver metastases. He was initially treated by hepatic arterial chemotherapy using an infusion reservoir (HACR) and radiotherapy for the rectal cancer. An abdomino-perineal resection and extended left lobectomy of the liver were performed and resulted in a reduction in size of the liver tumor. He was diagnosed as having a recurrent liver metastasis (S7) at 3 months after the operation, and was retreated by HACR in the outpatient clinic. A partial hepatectomy was reperformed at 6 months after the operation. Adjuvant hepatic arterial infusion chemotherapy (HAIC) was performed on an outpatient basis and the patient is doing well without recurrence or relapse. Preoperative arterial chemotherapy for metastatic liver tumor may be of some benefit for certain patients with far advanced colorectal carcinoma.

Delivery of a normal newborn after intensive medical treatment for an acute exacerbation of ulcerative colitis during pregnancy: a case report.

A 28-year-old woman developed an acute exacerbation of chronic ulcerative colitis in the second trimester of pregnancy. She was treated by intensive medical treatment with intravenous prednisolone, betamethasone enema, oral salazosulfapyridine, intravenous ceftazitim, and total parenteral nutrition. The acute relapse subsided after 73 days of the treatment and a normal female newborn weighing 2,208 g was delivered vaginally after 40 weeks' gestation. Our experience showed that the intensive medical therapy did not impair either the course of the pregnancy or the fetal outcome.

Prognostic value of DNA ploidy patterns of colorectal adenocarcinoma: univariate and multivariate analysis.

BACKGROUND/AIM: The prognostic significance of DNA ploidy patterns of colorectal cancer has not yet been settled. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after curative resection. METHODS: DNA ploidy patterns of 140 colorectal adenocarcinomas were determined by DNA flow cytometry, and the prognostic significance of DNA ploidy patterns was evaluated by univariate as well as multivariate analysis. RESULTS: DNA ploidy patterns were diploid in 75 (53.6%) and aneuploid in 65 patients (46.4%). DNA ploidy patterns did not correlate with any of conventional prognostic variables. Univariate analysis disclosed that Dukes B2, C1, and C2 stages of the disease (p < 0.01), positive nodal metastases (p < 0.01), invasion through the intestinal wall (p < 0.01), and poor tumor differentiation (p < 0.05) were associated with worsened survival, but no correlation was found between DNA patterns and survival of patients. Multivariate analysis disclosed that tumor penetration through the bowel wall was associated with poorer survival of patients but the DNA ploidy pattern had no prognostic significance. CONCLUSIONS: A significant prognostic variable for patients after curative resection of colorectal adenocarcinoma was penetration of tumor through the bowel wall but not DNA ploidy patterns.

Capacity of high-density lipoprotein for donating apolipoproteins to fat particles in hypertriglyceridemia induced by fat infusion.

Acquisition of apolipoproteins C-II (apoCII) and C-III (apoCIII) is essential for the regulation of intravascular metabolism of fat particles (exoTG). This study was undertaken to investigate whether the capacity of high-density lipoprotein (HDL) for donating apoCII and apoCIII is influenced by the concentration of triglycerides (TGs) in plasma. A fat emulsion was infused into six male volunteers at a rate of 0.5 g TG.kg-1.h-1 (priming dose) for 30 min. For the following 160 min, fat was infused a fat emulsion was infused into the same subjects at a rate of 0.3 g.kg-1.h-1 for 160 min after the administration of the priming dose of fat emulsion for 30 min (experiment 2). The plasma TG concentrations and the amounts of apoCII and apoCIII in exo TG and HDL were monitored. The concentration of TG in the plasma stabilized at approximately 500 mg/dl in experiment 1, whereas it continued to increase to 815 +/- 42 mg/dl at 160 min after the start of the infusion of the fat emulsion in experiment 2. In experiment 1, the amount of both apoCII and apoCIII began to increase in exoTG and to decrease in HDL after the initiation of fat infusion. These changes in the distribution of apoC stabilized while the TG concentration remained at a plateau value. However, in experiment 2, the amount of apoC in exoTG did not increase further in response to the additional rise in plasma TG level. These results suggest that there is a relative lack of apoC that can be donated by HDL, depending on the quantitative balance between exoTG and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfer of apolipoproteins between plasma lipoproteins and exogenous lipid particles after repeated bolus injections or during a continuous infusion of fat emulsion.

Recent studies on the metabolism of artificial lipid particles in a fat emulsion (exo TG) revealed that exo TG acquired apolipoproteins in vivo and in vitro. In particular, apolipoproteins C-II and C-III (apo C-II and apo C-III) are rapidly transferred from high-density lipoprotein (HDL) to exo TG, and return to HDL after the hydrolysis of exo TG. The present study was undertaken to examine whether the movement of apo C-II and apo C-III between HDL and exo TG is influenced by a prior injection of fat emulsion. Two experiments were undertaken. In experiment 1, six male volunteers received three bolus injections of a fat emulsion at a dose of 0.1 g of TG/kg with intervals of 90 min between injections. In experiment 2, the plasma concentrations of triglycerides were maintained at approximately 500 mg/dl for 160 min by the continuous infusion of exo TG. Levels of apo C-II and apo C-III, and the elimination rate of exo TG were followed in each test. In experiment 1, the movement of apolipoproteins between exo TG and HDL was unchanged between the first, second, and third bolus. The elimination rate of exo TG after the third bolus was higher than that after the first bolus. In experiment 2, after the administration of exo TG, the levels of C apolipoproteins in the fraction of HDL began to decrease, and those in the fraction of very-low-density lipoprotein that contained exo TG began to increase. When the concentrations of triglycerides in plasma reached a plateau, the distribution of C apolipoproteins in the lipoprotein fraction also stabilized.(ABSTRACT TRUNCATED AT 250 WORDS)

[Flow cytometry DNA analysis of a gastric cancer before and after intra-arterial anticancer chemotherapy--report of a case].

Flow cytometric DNA analysis has been performed on tumor tissue obtained by endoscopic biopsy before and after intraarterial infusion of ADM and 5Fu. The patient was a 74-year-old woman with a gastric cancer with an involvement of a para-aortic and cervical lymph nodes. Histological examination revealed a poorly differentiated adenocarcinoma, and flow cytometric DNA analysis disclosed that the DNA ploidy (DNA index) did not differ before and after intraarterial infusion of ADM and 5Fu. The fraction of the tumor cells in the S + G2.M phase of the cell cycle however, decreased from 56% to 44% with anticancer chemotherapy. A flow cytometric DNA analysis, using biopsied samples of tumor tissue, was found to be a useful tool for monitoring the effect of anti-cancer chemotherapy for solid tumors.

Apolipoprotein C-II modifications associated with an infusion of artificial lipid particles.

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.