Craniospinal irradiation using helical tomotherapy: evaluation of acute toxicity and dose distribution.

The purpose of this study was to evaluate acute toxicity of craniospinal irradiation (CSI) using helical tomotherapy (HT) and compare its dose distribution with that of conventional linac-based plans. Twelve patients with various brain tumors were treated with HT-CSI. Median patient age was 14 years (range: 4-37 years). Median CSI dose was 30.6 Gy in 18 fractions (range: 23.4-40 Gy in 13-25 fractions). Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4.0. Before CSI, 11 patients (92%) received neoadjuvant chemotherapy, so acute toxicity was evaluated by comparing patient status before and after CSI. HT-CSI plans were compared with linac-based CSI plans made using Pinnacle(3) planning system in 9 patients. All patients completed planned CSI without interruption. Grade 3 or higher toxicities were leukopenia seen in 11 patients (92%), anorexia in 6 (50%), anemia in 5 (42%), and thrombopenia in 5 (42%). Administration of granulocyte colony-stimulating factor, platelet transfusion and total parenteral nutrition were required in 8 (67%), 5 (42%) and 5 (42%) patients, respectively. HT plans were superior to linac-based plans in terms of homogeneity and conformality in planning target volume (PTV). For most organs at risk (OARs), volumes receiving more than 10 Gy (V10 Gy) or 20 Gy (V20 Gy) were lower in HT plans. However, HT plans significantly increased mean doses to the lung, kidneys and liver, and V5 Gy of 6 OARs including the lung. Despite intensive neoadjuvant chemotherapy, acute toxicity of HT-CSI was acceptable. HT provided better dose distribution in PTV than conventional linac. In most OARs, smaller volumes received >10-20 Gy in HT plans, although larger volumes received 5-10 Gy.

Ringed silicon rubber attachment prevents laparoscopic surgeon's thumb.

BACKGROUND: This investigation, using the nerve conduction study, aimed to quantify the degree of laparoscopic surgeon's thumb, and to evaluate the effect of the ringed silicon rubber attachment (RSRA) developed by the authors. METHODS: For the study, 26 residents or students performed surgical tasks (grasping and dissecting) using both the laparoscopic forceps with RSRA and the conventional instrument. The paresthesia was evaluated with a severity score obtained by interview and measurement of sensory nerve conduction velocity (SCV). RESULTS: The mean severity score was 2.57 +/- 0.58 m/s for the conventional forceps and 1.05 +/- 0.80 m/s for the forceps with RSRA (p < 0.01). For the grasping task with the conventional forceps, the mean SCV was 58.3 +/- 2.81 m/s before and 54.8 +/- 2.83 m/s after the task (p < 0.01), whereas for the dissecting task, the corresponding values were 57.5 +/- 2.46 m/s and 56.1 +/- 2.93 m/s (p < 0.01). For the grasping task with the RSRA, the mean SCV was 57.1 +/- 3.33 m/s before and 55.9 +/- 3.18 m/s after the task (p < 0.01), whereas for the dissecting task, the corresponding values were 55.7 +/- 4.59 m/s and 55.8 +/- 3.50 m/s (nonsignificant difference). CONCLUSIONS: Laparoscopic surgeon's thumb was induced by compression of the lateral digital nerve. The RSRA significantly reduced the degree of paresthesia.

Radiation myelopathy after radioactive iodine therapy for spine metastasis.

A case of radiation myelopathy after radioactive iodine therapy is reported. This is the first report to describe radiation myelopathy after I-131 therapy. A 62-year-old female with spinal metastasis of T10 received I-131 therapy. She presented with radiation myelopathy 34 months after the irradiation. We need to recognize the possibility of this serious complication even in the case of I-131 therapy. There is a risk of radiation myelopathy even after I-131 therapy, especially in cases with spinal cord compression such as this.

Weekly 1 hour paclitaxel infusion in patients with recurrent gynecological tumors: a pilot study.

BACKGROUND: Intensifying the dose of paclitaxel given in a weekly schedule is useful towards improving the therapeutic index of paclitaxel in treating a variety of advanced and recurrent malignancies and is suitable for outpatient administration. This pilot study was carried out to evaluate the safety of weekly paclitaxel administration by 1 h infusion in the outpatient setting. METHODS: Eleven patients with recurrent gynecological tumors who had previously been treated with at least one platinum-based chemotherapy regimen participated in the study between May 1999 and March 2000. Paclitaxel was given at a dose of 70 mg/m(2 ) as a 1 h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The 11 patients received a total of 166 cycles of therapy. All patients received 70 mg/m(2 ) doses of paclitaxel without treatment delay. No hypersensitivity reactions were elicited. Grade 3 or 4 leukopenia and neutropenia occurred in 9 and 36% of the patients, respectively. Granulocyte colony-stimulating factor was required for only one patient and no patients experienced febrile neutropenia. Neurotoxicity was the most serious adverse effect and all patients experienced grade 1 or 2 peripheral neuropathy. Grade 1 or 2 myalgias were observed in 45% of the patients. Alopecia was universal. No Grade 3 or higher non-hematological toxicities were observed. CONCLUSION: Weekly 1 h paclitaxel administration is considered safe as a salvage therapy for recurrent gynecological tumors, making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

c-Fos/activator protein-1 transactivates wee1 kinase at G(1)/S to inhibit premature mitosis in antigen-specific Th1 cells.

M-phase promoting factor is a complex of cdc2 and cyclin B that is regulated positively by cdc25 phosphatase and negatively by wee1 kinase. We isolated the wee1 gene promoter and found that it contains one AP-1 binding motif and is directly activated by the immediate early gene product c-Fos at cellular G(1)/S phase. In antigen-specific Th1 cells stimulated by antigen, transactivation of the c-fos and wee1 kinase genes occurred sequentially at G(1)/S, and the substrate of wee1 kinase, cdc2-Tyr15, was subsequently phosphorylated at late G(1)/S. Under prolonged expression of the c-fos gene, however, the amount of wee1 kinase was increased and its target cdc2 molecule was constitutively phosphorylated on its tyrosine residue, where Th1 cells went into aberrant mitosis. Thus, an immediate early gene product, c-Fos/AP-1, directly transactivates the wee1 kinase gene at G(1)/S. The transient increase in c-fos and wee1 kinase genes is likely to be responsible for preventing premature mitosis while the cells remain in the G(1)/S phase of the cell cycle.

Remission of metastatic cervical adenocarcinoma with weekly paclitaxel.

We report the use of paclitaxel in the successful treatment of a patient with recurrent adenocarcinoma of the cervix. Paclitaxel, 70 mg/m2 by 1-h infusion weekly, was administered to a 59-year-old patient with cervical adenocarcinoma showing lung metastasis. She showed partial clinical response after seven cycles, and at the completion of 20 cycles she showed complete response, which was confirmed by chest X-ray and computed tomography scan. Toxicities including neurotoxicity were mild. She showed an objective response to treatment for over 8 months, and she enjoyed a favorable quality of life during and after treatment. Weekly paclitaxel was very well tolerated, yet was effective for recurrent cervical adenocarcinoma.

Initial induction and subsequent reduction of alpha(2u)-globulin in urine and serum of mature male rats after repeated intraperitoneal injections of (anti)estrogen.

The influence of sex (anti)hormones on expression of alpha(2u)-globulin (a2uG) is complex and has not been sufficiently detailed. In order to assess the specificity of sex (anti)hormone action on a2uG expression and the utility of this approach as a sensitive screening method, mature male rats were given daily intraperitoneal injections of 17beta-estradiol (E2), dihydrotestosterone (DHT), tamoxifen (TX) and flutamide (FL) for 5 consecutive days. They were employed as representatives of estrogen, androgen, antiestrogen and antiandrogen categories, respectively. Urinary a2uG was specifically altered with E2 (1 microg/kg/day) and TX (50 mg/kg/day), but not by DHT (1 mg/kg/day) or FL (50 mg/kg/day). E2 and TX temporarily increased urinary a2uG on days 1 or 2, and days 2-4, respectively, followed by a return to the control level, and then a decrease with E2. The reduction in urinary a2uG on day 6 was more pronounced than the drop in serum a2uG. Serum hormone levels, and liver and testis weights were not remarkably altered with any treatment. Another strong xenoestrogen, diethylstilbestrol, also significantly reduced urinary and serum a2uG at 1 mg/kg/day on day 6. However, the other xenoestrogens (100 mg/kg/day of bisphenol A, nonylphenol, and dichlorodiphenyltrichloroethane, and 10 mg/kg/day of dieldrin) and phytoestrogens (10 mg/kg/day of genistein and daidzein) were without any appreciable influence. The results indicate that urinary a2uG is a sensitive indicator of estrogen action in mature male rats, with two different responses, initial induction and subsequent reduction.

Successful treatment of two patients with recurrent endometrial cancer by weekly paclitaxel.

OBJECTIVE: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Paclitaxel (70 mg/m(2) by 1-h infusion weekly) was administered to two patients with recurrent endometrial cancer of the lung. RESULTS: After 5 cycles, both patients with platinum-resistant disease achieved clinical partial responses confirmed by computed tomography (CT) scan. The serum CA125 levels of case 1 decreased to cut-off level. The response duration of both patients was 4 months. The toxicity was acceptable and probably less pronounced than that characterize of the standard tri-weekly schedules. CONCLUSION: Although conclusions regarding survival are premature, weekly paclitaxel might offer better quality of life during treatment.

Antibodies to calcium channel and synaptotagmin in Lambert-Eaton myasthenic syndrome.

In the Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disease that is often associated with lung cancer and characterized by reduced quantal release of acetylcholine from the motor nerve terminal, our studies to search for the target of LEMS antibodies have brought the voltage-gated calcium channel (VGCC) into relief. Among multiple types of VGCCs, the P/Q-type was highly recognized by LEMS antibodies. Using synthetic peptides or recombinant proteins as antigens, the study specified the S5-S6 linker regions in 3 of 4 domains as immunodominant sites in the molecular structure of P/Q-type VGCC alpha1 subunit. Synaptotagmin, one of the functionally VGCC-associated synaptic proteins, was also found to be an immunogen in the pathogenesis of LEMS.

Recombinant calcium channel is recognized by Lambert-Eaton myasthenic syndrome antibodies.

The authors studied sera from 36 patients with Lambert-Eaton myasthenic syndrome (LEMS) by immunoblots using the recombinant protein derived from the DNA sequence encoding for the domain III S5-S6 linker of the P/Q-type voltage-gated calcium channel al subunit. The results of 18 patients were positive for antibodies to this recombinant protein. The results of 2 of 10 patients with lung cancer without LEMS were also positive.

Lambert-Eaton myasthenic syndrome as an autoimmune calcium-channelopathy.

Lambert-Eaton myasthenic syndrome (LEMS), often associated with small cell lung carcinoma (SCLC), is a disease of neuromuscular transmission in which antibodies directed against voltage-gated calcium channel (VGCC) in the motor nerve terminal play a crucial role in causing a deficient quantal release of acetylcholine. We focused attention on the P/Q-type VGCC, against which a majority of LEMS patients carry the specific antibody. Since the P/Q-type VGCC expresses in SCLC, the motor nerve terminal and SCLC may share a common VGCC antigen. In search for antigenic sites at the molecular level, We employed peptides or recombinant protein corresponding to the S5-S6 linker of each of four domains forming the alpha 1A subunit and tested their antigenicity. As the result, we specified the domain II, III and IV as immunodominant sites by the induction of an immune-mediated animal model of LEMS and the assay for antibodies in LEMS patients. Also, by use of peptides or recombinant protein corresponding to the synaptotagmin I, we found that in this VGCC-associated protein, the segment which exposes extracellularly during exocytosis can be antigenic for LEMS.

An approach to identify new genes in autoimmune diseases: lessons from rheumatoid arthritis.

We have searched the human genome for genes that predispose to rheumatoid arthritis using fluorescence-based microsatellite marker analysis and affected sib-pair linkage studies. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DX1232, have been assigned, which we call RA1, RA2 and RA3 for rheumatoid arthritis disease loci. We are now assigning the death receptor 3 as a candidate gene for RA1, and the truncated form of Dbl proto-oncogene, which does not contain the 23rd and 24th exons, as disease gene for RA3. Microsatellite marker analyses seem to be promising and new genes are now being identified by reference to sequence tag sites.

Calcium channel peptide can cause an autoimmune-mediated model of Lambert-Eaton myasthenic syndrome in rats.

The Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular transmission characterized by the reduced quantal release of acetylcholine from the motor nerve terminal, wherein the P/Q-type of voltage-gated calcium channel (VGCC) and is attacked by a majority of LEMS antibodies. Using the molecular structure of the alpha1 subunit (consisting of 4 domains) of the P/Q-type VGCC as a reference, we synthesized the extracellular region (S5-S6 linker) of the domain III, known as the segment which plays an important role in channel functions. Six of the ten Lewis rats immunized with this synthetic peptide conjugated with carrier protein showed moderate weakness (grade 1 in a 3-graded scale, for myasthenic weakness in experimental animals) and a reduction in acetylcholine quantum content of end-plate potentials. Antipeptide antibodies raised in test rats reacted with omega-conotoxin MVIIC-sensitive cerebellar extract (P/Q-type VGCC) and the domain III peptide inhibited the binding of rat antibodies to VGCCs. Our findings suggest the identification of one of the potential epitopes of LEMS antibodies.

[Trends in comprehensive treatment for gynecologic malignancies].

Advances in many areas, including oncology-epidemiology, chemotherapy, diagnosis, surgery, radiology, and clinical research have all had a positive impact on the treatment of gynecologic malignancies, so that today we have achieved an improved quality of life concomitant with increased survival rates in patients. The improvements in therapy for gynecologic malignancies have been in diagnostic procedures, such as tumor markers, molecular biologic methods, and image analysis. Considerable progress has been made in surgical management, from focal excision of primary lesions to minimal debulking surgery after the initial chemotherapy for advanced cancer. Chemotherapy has advanced markedly after the introduction of cisplatin, and various regimens or anticancer drug-analogs of cisplatin, camptotesin, and paclitaxel have been introduced. In recent years, the quality of life of patients with malignancies has been one of the most important factors in treatment. Intensive and combination therapies will be put to greater use for gynecologic malignancy in the future.

Detection of ALMB-toxin in the larval body of Myrmeleon bore by anti-N-terminus peptide antibodies.

Antibodies were raised against a synthetic antigen carrying the N-terminus peptide of ALMB-toxin, which had been isolated from the antlion, Myrmeleon bore, that exhibited high specificity to the toxin. Analyses with the antibodies showed the toxin to be present mainly at the larval stage and localized in a region from the thorax to abdomen of the larval body.

Solitary splenic recurrence of ovarian cancer: case report and review of the literature.

We report a rare case of solitary recurrence of ovarian cancer in the spleen which developed 4 years after initial treatment. Only six cases have been reported in the literature and all were serous carcinoma. Our patient had a splenectomy without any complications but developed a liver metastasis 10 months after splenectomy.

Structure-activity Relationship for the Insect Antifeedant Activity of Benzofuran Derivatives.

Coumaran (2,3-dihydrobenzofuran), a secondary metabolite of Cyperus nipponicus, inhibits the feeding of polyphagous insects. This secondary metabolite is regarded as one of the defensive systems of the Cyperaceae. A number of naturally occurring benzofurans that differ in their substitution pattern and oxidation state have been investigated for their ability to inhibit insect feeding by a bioassay with the common cutworm (Spodoptera litura F. Noctuidae) that applies the leaf disk method. The evaluation of the antifeedant activity of each test compound used the ED50 value based on the dose-response curve that was calculated with the probit method. The 2,3-dihydrobenzofuran derivative, 7-acetyl-4,6-dimethoxy-2-isopropenyl-2,3-dihydrobenzofuran, had an ED50 value of 1.3 µg (5.4×10(-9) mol)/cm(2) against the common cutworm. The introduction of methoxy and acetyl groups increased the insect antifeedant activity. Furthermore, the insect antifeedant activity increased with decreasing lipophilicity of the test compounds.