A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer.

PURPOSE/OBJECTIVE(S): To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer. MATERIALS/METHODS: We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment. CONCLUSION: Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards.

[Extended thymectomy and intraoperative-intrapleural perfusion hyperthermo-chemotherapy for stage IVa invasive thymoma with myasthenia gravis].

A 37-year-old woman diagnosed with ocular myasthenia gravis was referred to our department. Chest computed tomography (CT) showed anterior mediastinal tumor and right pleural dissemination. Extended thymectomy and right intraoperative-intrapleural perfusion hyperthermo-chemothrapy (IPHC) were performed. Pathological diagnosis was invasive thymoma type B2 and stage IVa based on Masaoka's classification. The post operative course was uneventful. The patient underwent 4 cycles of adjuvant chemotherapy with doxorubicin, cisplatin, vincristine, and cyclophosphamide (ADOC), and is free from recurrence at 12 months postoperatively.

Generation and properties of ascorbic acid-deficient transgenic tobacco cells expressing antisense RNA for L-galactono-1,4-lactone dehydrogenase.

In higher plants, the terminal step of L-ascorbic acid (AsA) biosynthesis is catalyzed by the enzyme L-galactono-1,4-lactone dehydrogenase (EC 1.3.2.3, GalLDH). We generated AsA-deficient transgenic tobacco BY-2 cell lines by antisense expression of the GalLDH cDNA that was amplified from BY-2 cells using PCR. Two transgenic cell-lines, AS1-1 and AS2-2, having a marked expression of antisense RNA were analyzed. Antisense suppression of GalLDH mRNA led to a significant decline in the GalLDH activity. The AsA levels in the transgenic cell lines were found to be 30% lower than the wild-type BY-2 cells. In synchronous cultures, division of AS1-1 and AS2-2 cells was restrained with a concomitant decrease in mitotic index that was probably due to a decline in AsA levels. The rate of cell growth was also found to be less than that of the wild-type cells. Interestingly, there was a significant phenotypic difference between the transgenic and wild-type cells. The calli of AS1-1 and AS2-2 appeared to be sticky and soft. Back extrusion method also showed that AsA-deficient BY-2 callus was rheologically soft. Furthermore, microscopic analysis revealed that AS1-1 and AS2-2 cells were abnormally slender, suggesting a potential for a significant and a uni-axial elongation. Thus, we observed that decline in the AsA levels has an adverse effect on the division, growth and structure of a plant cell.

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

Topical gentian violet for cutaneous infection and nasal carriage with MRSA.

This study describes a potential effect of topical gentian violet on cutaneous infection and nasal carriage with methicillin-resistant Staphylococcus aureus (MRSA). 0.5% gentian violet was used in 28 cases of skin lesions once a day, while a 0.3% solution was applied on the nasal vestibules of nine cases twice a day. The period for eradication in the 28 skin cases was 9.1 +/- 6.0 days. It was 15.3 +/- 9.0 days for the nine nasal lesions. The minimal inhibitory concentration (MIC) of gentian violet against MRSA from the four isolated strains was 0.0225 +/- 0.0096 microg/mL. No adverse reactions occurred throughout the study. It is suggested that gentian violet may be potentially effective against MRSA.

Evaluation of the efficacy of a 3.2% glutaraldehyde product for disinfection of fibreoptic endoscopes with an automatic machine.

The efficacy of 'Cidex Plus' 3.2% alkaline glutaraldehyde was evaluated for the disinfection of fibreoptic endoscopes. The glutaraldehyde concentration in 'Cidex Plus', stored in an automatic machine (Olympus EW-20), remained higher than 2% (2.21%) even after a total of 102 disinfection cycles during 28 consecutive days. The results of the in-vitro study on antimicrobial activity showed that this alkaline glutaraldehyde product had a greater activity against 20 test organisms, including vegetative bacteria, bacterial spores, mycobacteria, and fungi, than 2% glutaraldehyde alone. The presence of 10 or 30% human serum did not appear to affect the activity of glutaraldehyde adversely. Instrument samples made from a variety of materials such as stainless steel, glass, teflon, etc. were not damaged after 168 h of immersion in alkaline glutaraldehyde, although it contained approximately 1.7 times more glutaraldehyde than 2% glutaraldehyde alone. Based on these results, 3.2% alkaline glutaraldehyde is considered to be a more effective disinfectant for fibreoptic endoscopes, with the use of an automatic machine, than 2% glutaraldehyde.

An antitumor, branched (1-->3)-beta-D-glucan from a water extract of fruiting bodies of Cryptoporus volvatus.

A water-soluble, (1-->6)-branched (1-->3)-beta-D-glucan (H-3-B) was isolated from a hot-water extract of the fruiting bodies of the fungus, Cryptoporus volvatus (Basidiomycetes). Enzymatic analysis using exo-(1-->3)-beta-D-glucanase and methylation analysis indicated that this polysaccharide has a main chain composed of beta-(1-->3)-linked D-glucopyranosyl residues, and single, beta-(1-->6)-linked D-glucopyranosyl residues attached as side chains to, on average, every fourth sugar residue of the main chain. This structure was confirmed by 13C NMR spectra of the glucan in Me2SO-d6. The weight-average molecular weight (Mw) of H-3-B was determined to be 44.0 x 10(4) by gel permeation chromatography equipped with a low-angle laser-light-scattering photometer. The electron microscopic observations showed that H-3-B and its sonicated sample (S-H-3-B, Mw = 13.7 x 10(4)) can be described as linear worm-like chains. The mass per unit length for native and sonicated H-3-B was determined to be 1750 and 1780 g mol-1 nm-1, respectively, from the contour lengths obtained by electron microscopy and the molecular weights. These values are in good agreement with that expected for the triple stranded structure. A sample denatured in 0.1 M NaOH and subsequently renatured by neutralization showed a mixture of linear and cyclic structures, and larger aggregates with less well-defined morphology. The H-3-B and S-H-3-B had antitumor activity against the Sarcoma 180 tumor.

[Curability of multidisciplinary treatment including combined hyperthermia, radiotherapy and chemotherapy].

Reported are the results in 311 patients who received a multidisciplinary treatment for their cancers, said treatment combining hyperthermia, radiotherapy, and chemtherapy. Of his number, 266 patients were in the advance stage of their disease while another 42 still had localized cancers. According to the criteria of Koyama and Saitoh for evaluating solid tumors that had received chemotherapy, of 298 evaluable patients, 64 showed a complete response (CR), 94 showed a partial response (PR), 89 showed no change (NC), and 57 showed a progressive disease (PD), for an overall response of 53.0% (158 cases). A multidisciplinary treatment combining radiotherapy and hyperthermochemotherapy was used for cases involving localized tumors of the vulva, the skin, the thyroid gland, the prostate gland, the uterus, the rectum, the soft tissue bone, and the ovary, though our treatment regimen could not be continued in cases of tumors involving the stomach, the esophagus, the lung, the mediastinum, the liver, and the pancreas. Our data has shown that a high overall rate of curability was achieved in cases involving the stomach, the bladder, the blood, the skin, the head, and neck, and the esophagus.

Effect of proglumide on rat pancreatic growth.

Proglumide, a glutaramic acid derivative, is a specific competitive inhibitor of gastrin and cholecystokinin (CCK) receptors. As such, it blocks gastrin-stimulated acid secretion, the trophic effect of gastrin, and CCK-stimulated smooth muscle contraction and acinar cell secretion. In the current study we have demonstrated that proglumide (100 mg/kg three times per day) blocks the trophic effect of a low dose of CCK octapeptide (300 ng/kg) given three times a day for 2 days. The same dose of proglumide when given alone for 6 days, however, resulted in a significant stimulation of pancreatic growth. Proglumide had no effect on the trophic response to a high dose of CCK-OP (5 micrograms/kg) administered for either 2 or 6 days. These results indicate that given over a period of several days proglumide behaves like a partial agonist of pancreatic growth.