A combination of unnatural phosphatidyl acceptor and tandem electrospray ionization mass spectrometry for tracing phospholipase D activity.

Phospholipase D (PLD) is a biocatalyst in the synthesis of bioactive compounds and a key enzyme in a variety of biological signal transductions. A combination of unnatural phosphatidyl acceptor, N,N,N-triethyl-N-2-hydroxyethylammonium bromide 6, as a substrate for PLD, and tandem electrospray ionization mass spectrometry (ESI MS) was found to provide information as to whether a given phospholipid serves as a substrate for the PLD-catalyzed reaction. Thus 2-(13'-hydroperoxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 1, and its degradation products 2-(13'-oxo-octadecadienoyl)-1-palmitoylglycerophosphocholine 9 and 2-(13'-hydroxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 11, in a mixture were found to be a substrate of the PLD-catalyzed transphosphatidylation. The sensitivity of this method was exemplified by the observation that PLD activity in cabbage leaves was detected using a small amount of crude crushed leaves with little pretreatment. This simple method can be used in screening for PLD activity and searching for inhibitors of the enzyme from various natural sources.

Synthesis of novel conjugates of tetraoxane endoperoxide with bis(quaternary ammonium salts).

Novel water-soluble conjugates of 1,2,4,5-tetraoxane bis(quaternary ammonium salts) were synthesized in a relatively stable crystalline form via four steps starting from methyltrioxorhenium-catalyzed endo-peroxidation of ethyl 4-oxocyclohexanecarboxylate with hydrogen peroxide in hexafluoro-2-propanol. The assay for the in vitro toxicity of water-soluble tetraoxanes 5a-5d to malaria parasites indicate that they were inactive against the Plasmodium falciparum FCR-3 strain.

Complete remission by chemotherapy in stage IE-IIE primary gastric lymphoma.

BACKGROUND/AIMS: There are many controversies regarding the treatment for primary gastric non-Hodgkin's lymphoma (PGL). We hypothesized that preoperative chemotherapy and extensive surgery would improve patient survival in the treatment of early stage patients with PGL. METHODOLOGY: Between 1997 and 2001, we prospectively evaluated 10 patients with stage IE and IIE PGL. The histological diagnoses were established by endoscopic biopsies in all cases. All patients received preoperative chemotherapy, i.e. CHOP or MACOP-B. Upon the completion of chemotherapy, the extensive surgery including total gastrectomy, splenectomy, cholecystectomy, and paraaortic lymphadenectomy were performed. The response rates of preoperative chemotherapy and overall survival were analyzed. RESULTS: All patients were still alive with no signs of recurrence with a median follow-up of 86 months (range, 40 to 102 months) after surgery. In all patients, microscopic examinations did not reveal residual lymphoma cells in the resected stomach or lymph nodes. Chemotherapy-related preoperative complications such as perforation or intestinal bleeding did not occur in any of the cases. Postoperative complications developed in 30% (3/10) of patients and consisted of 2 pancreatic fistulas, 3 intra-abdominal abscesses, and 1 anastomotic leak. CONCLUSIONS: Primary chemotherapy alone without surgery may produce complete remission in Stage IE-IIE PGL.

Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer.

PURPOSE: This retrospective study evaluated the effects of neoadjuvant chemotherapy in advanced gastric cancer. METHODS: Between 2002 and 2005, we treated 14 patients with advanced gastric cancer (involvement of more than five nodes or tumor invasion into pancreas) and 25 patients with Stage III gastric cancer. The group of 14 patients with advanced gastric cancer received combination chemotherapy with S-1 and cis-diamminedichloroplatinum (CDDP) as a neoadjuvant chemotherapy (NAC). This regimen was repeated every 5 weeks for a total of 2-5 cycles. The 25 patients with Stage III gastric cancer was carried surgery alone (SA). All patients underwent extensive surgery, including gastrectomy, and D2 lymphadenectomy. The rate of response and overall survival in the two groups were compared. RESULTS: All patients of NAC group completed the planned regimens of chemotherapy and surgery. Patients of the NAC group had a response rate of 78.6% (95% confidence interval 57.1-100.0%). The most common adverse effect was leukocytopenia (42.9%). However, only four patients (28.6%) had upper Grade 2 leukocytopenia, and all recovered promptly. Postoperative complications were not significant differentiated between NAC and SA group of patients (7.2 vs. 4.0%). Patients in the NAC group had a significantly better survival than those in the SA group (P = 0.03). The median survival has not been reached after 26.9 months of median follow-up for patients in the NAC group. 1-, 2-, and 3-year survival rates were 92.3, 92.3, and 61.5%, respectively. NAC was identified as an independent prognostic factor in all patients (P = 0.018). CONCLUSION: Neoadjuvant chemotherapy with TS-1 + CDDP improves the survival in patients with advanced gastric cancer.

Complete cure of metastatic gastric cancer treated with combination chemotherapy using S-1.

A 65-year-old man had gastric cancer with liver and lung metastases, and received three cycles of FLEP (5-fluorouracil, leucovorin, etoposide, cisplatin) chemotherapy on June, 2001. The primary lesion became scar ulceration and adenocarcinoma tissue was recognized by biopsy pathologically. The lung metastases and lymph node metastases disappeared. The metastatic liver lesion decreased more than 95% in size and was judged partial response. Thereafter he received only oral administration of 100mg S-1 (70mg/m2). The metastatic liver lesion was shown to have disappeared on CT of the abdomen and was judged complete response, on June, 2002. Since then, he was receiving S-1 and continued to be complete response for two and half years until June, 2004. The clinical trial of S-1 as an adjuvant therapy for patients with advanced gastric cancer, who underwent curative resection, is ongoing in a multicenter study. Although the outcome is still unknown, the effect of S-1 for adjuvant chemotherapy may be also promising. We think that S-1 is useful as an adjuvant therapy and maintenance therapy of prior treatment including surgical resection.

FLEP chemotherapy for alpha-fetoprotein-producing gastric cancer.

OBJECTIVE: This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer. METHODS: Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test. RESULTS: Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor. CONCLUSION: FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging.

[A case report of colon cancer with liver and lung metastases responding to combination chemotherapy with l-LV, 5-fluorouracil and CPT-11].

A 58-year-old man who had colon cancer with liver and multiple lung metastases underwent ileocecal resection on May 10, 2002. MTT assay of 5-FU and CPT-11 was performed with resected material, with both medicines accepted for sensitivity. On June 4, he received combination chemotherapy with CPT-11 + 5-FU/l-LV. The liver metastasis disappeared and was judged CR from a CT of the abdomen. Almost all the multiple lung metastases had disappeared or were decreased in size. They were therefore judged NC from a CT of the chest. Moreover, CEA and CA19-9 decreased to within normal limits. While he was receiving bimonthly chemotherapy with only CPT-11 as a maintenance therapy, liver and lung metastases did not change. Combination chemotherapy with CPT-11 + 5-FU/l-LV is effective. The anticancer drug sensitivity examination is only one index, however. Considering adverse effects and medical costs, individualized therapy based on the sensitivity test for anticancer drugs should be performed.