ABSTRACT
BACKGROUND: Plantago lanceolata L. is used in Iraqi folklore medicine to treat injuries, and its extract is prescribed by some herbalists for cancer patients. This research aimed to evaluate the effect of P. lanceolata leaf extract on breast cancer cell lines in vitro and to identify its active compounds. Crystal violet viability assay was used to determine the cytotoxicity of methanolic P. lanceolata leaf extract against various breast cancer cell lines. MCF7, AMJ13, MDAMB, and CAL51 human breast cancer cells were treated with different concentrations of the extract for 72 h. The morphology of the treated cells was examined under a phase-contrast inverted microscope. The clonogenic ability was assessed through a clonogenic assay. High-performance liquid chromatography (HPLC) analysis was performed to measure the concentrations of phenols and flavonoids in the extract. RESULTS: The methanolic P. lanceolata leaf extract significantly inhibited the proliferation of triple-negative CAL51 cells but showed minor effect on the other breast cancer cells. In addition, at high doses, it induced cytopathic morphological changes. The clonogenic assay showed low colony formation in the exposed cells, especially CAL51 cells. Furthermore, HPLC study revealed that the methanolic extract contained important flavonoid glycosides, especially rutin, myricetin quercetin, and kaempferol. CONCLUSIONS: P. lanceolata leaf extract selectively inhibited the proliferation of CAL51 triple-negative breast cancer cells and showed minor effect on the other breast cancer cells types studied. Thus, this study showed P. lanceolata as a possible natural source of selective anti-triple-negative breast cancer drugs.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Plantago/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Flavonoids/analysis , Humans , Phenols/analysis , Plant Extracts/chemistry , Plant Leaves/chemistryABSTRACT
BACKGROUND: The aim of the present study was to evaluate the clinical significance of protein-bound polysaccharide K (PSK) in patients with primary gastric cancer who were being treated with an oral fluoropyrimidine (S-1). METHODS: Clinical reports of 190 gastric cancer patients treated with S-1 chemotherapy, with or without PSK, at Kochi Medical School between 2007 and 2012 were investigated retrospectively to analyze survival. The neutrophil:lymphocyte ratio (NLR) was also evaluated as indicator of the immunoenhancing effect of PSK. RESULTS: Overall survival was significantly longer in patients treated with S-1 + PSK than in those given S-1 alone (hazard ratio for death, 0.608; 95% confidence interval 0.375-0.985; P = 0.041). Furthermore, there was a tendency for changes in the NLR during chemotherapy to be lower in the S-1 + PSK group than in the S-1 group, but the difference did not reach statistical significance (P = 0.054). When patients were divided into groups based on preoperative NLR (i.e. <2.5 and ≥2.5), the mean (±SEM) NLR 1 month after the beginning of chemotherapy in the NLR ≥2.5 subgroup was significantly lower in patients treated with S-1 + PSK rather than S-1 alone (1.7 ± 0.7 vs. 3.3 ± 4.1, respectively; P = 0.043). CONCLUSIONS: Immunochemotherapy using PSK improves the survival of patients with advanced gastric cancer. The NLR may be a useful biomarker for evaluating prognosis in these patients.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphocytes , Neutrophils , Stomach Neoplasms/drug therapy , Adenocarcinoma/blood , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Drug Combinations , Female , Fungal Proteins/administration & dosage , Fungal Proteins/immunology , Humans , Immunotherapy , Kaplan-Meier Estimate , Lymphocyte Count , Male , Middle Aged , Oxonic Acid/administration & dosage , Polysaccharides/administration & dosage , Polysaccharides/immunology , Retrospective Studies , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Survival Rate , Tegafur/administration & dosageABSTRACT
Previously, a specific dietary supplement, selected vegetables (SV), was found to be associated with prolonged survival of stage III and IV non-small cell lung cancer (NSCLC) patients. In this study, several anticancer components in SV were measured; the anticancer activity of SV was assessed using a lung tumor model, line 1 in BALB/c mice. SV was also used in conjunction with conventional therapies by stage IIIB and IV NSCLC patients whose survival and clinical responses were evaluated. A daily portion (283 g) of SV was found to contain 63 mg of inositol hexaphosphate, 4.4 mg of daidzein, 2.6 mg of genistein, and 16 mg of coumestrol. Mouse food containing 5% SV (wt/wt) was associated with a 53-74% inhibition of tumor growth rate. Fourteen of the 18 patients who ingested SV daily for 2-46 months were included in the analyses; none showed evidence of toxicity. The first lead case remained tumor free for > 133 months; the second case showed complete regression of multiple brain lesions after using SV and radiotherapy. The median survival time of the remaining 12 patients was 33.5 months, and one-year survival was > 70%. The median survival time of the 16 "intent-to-treat" patients (including ineligible patients) was 20 months, and one-year survival was 55%. The Karnofsky performance status of eligible patients was 55 +/- 13 at entry but improved to 92 +/- 9 after use of SV for five months or longer (p < 0.01). Five patients had stable lesions for 30, 30, 20, 12, and 2 months; two of them, whose primary tumor was resected, used SV alone and demonstrated an objective response of their metastatic tumors. In addition to the two lead cases, eight patients had no new metastases after using SV. Three patients had complete regression of brain metastases after using radiotherapy and SV. In this study, daily ingestion of SV was associated with objective responses, prolonged survival, and attenuation of the normal pattern of progression of stage IIIB and IV NSCLC. A large randomized phase III clinical trial is needed to confirm the results observed in this pilot study.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diet therapy , Dietary Supplements , Lung Neoplasms/diet therapy , Vegetables/chemistry , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Coumestrol/administration & dosage , Disease Models, Animal , Female , Genistein/administration & dosage , Humans , Isoflavones/administration & dosage , Karnofsky Performance Status , Lung Neoplasms/mortality , Male , Mice , Mice, Inbred BALB C , Middle Aged , Neoplasm Staging , Nutritive Value , Phytic Acid/administration & dosage , Pilot Projects , Survival Analysis , Time FactorsABSTRACT
The oxidative burst has been suggested to be a primary event responsible for triggering the cascade of defense responses in various plant species against infection with avirulent pathogens or pathogen-derived elicitors. The molecular mechanisms of rapid production of active oxygen species (AOS), however, are not well known. We isolated homologs of gp91 phox, a plasma membrane protein of the neutrophil NADPH oxidase, from a potato cDNA library. Molecular cloning of the cDNA showed that there are two isogenes, designated StrbohA and StrbohB, respectively. The RNA gel blot analyses showed that StrbohA was constitutively expressed at a low level, whereas StrbohB was induced by hyphal wall components (HWC elicitor) from Phytophthora infestans in potato tubers. Treatment of potato tubers with HWC elicitor caused a rapid but weak transient accumulation of H2O2 (phase I), followed by a massive oxidative burst 6 to 9 h after treatment (phase II). Diphenylene iodonium (DPI), an inhibitor of the neutrophil NADPH oxidase, blocked both bursts, whereas pretreatment of the protein synthesis inhibitor cycloheximide with the tuber abolished only the second burst. These results suggest that the expression of StrbohA and StrbohB contributes to phase I and II bursts, respectively. The same is true for arachidonic acid, a lipid component of P. infestans-stimulated biphasic oxidative burst, whereas an endogenous signaling molecule, salicylic acid, only induced a weak phase II burst. Both molecules induced the StrbohB expression, which is in agreement with the second burst. To characterize the signal transduction pathway leading to the oxidative burst, we examined the role of protein phosphorylation in HWC-stimulated StrbohB gene expression. K252a and staurosporine, two protein kinase inhibitors, blocked the transcript accumulation. Two inhibitors of extracellular Ca2+ movement, however, did not abolish the transcript accumulation of StrbohB, suggesting that certain calcium-independent protein kinases are involved in the process of StrbohB gene expression. Additionally, we examined a causal relationship between the oxidative burst and expression of defense genes induced by the HWC elicitor. The transcript accumulation of genes related to sesquiterpenoid phytoalexin synthesis (lubimin and rishitin) and phenylpropanoid pathway was inhibited slightly by the DPI treatment, suggesting that the oxidative burst is not essential to activate these genes. Interestingly, the concomitant presence of DPI with the elicitor resulted in an increase in lubimin accumulation and a decrease in rishitin accumulation. Because it is known that lubimin is metabolized into rishitin via oxylubimin, we propose that AOS mediates the synthesis of rishitin from lubimin.
Subject(s)
Membrane Glycoproteins/genetics , NADH, NADPH Oxidoreductases/genetics , NADPH Oxidases , Phytophthora/pathogenicity , Plant Proteins/genetics , Solanum tuberosum/genetics , Amino Acid Sequence , Arachidonic Acid/pharmacology , Calcium/metabolism , Cell Respiration , Cell Wall/physiology , Humans , Immunity, Innate , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/classification , Membrane Glycoproteins/metabolism , Molecular Sequence Data , NADH, NADPH Oxidoreductases/classification , NADPH Oxidase 2 , Phylogeny , Phytophthora/classification , Plant Proteins/classification , Plant Proteins/metabolism , Salicylic Acid/pharmacology , Sequence Homology , Signal Transduction , Solanum tuberosum/metabolism , Solanum tuberosum/microbiologyABSTRACT
Soybean soluble polysaccharides (SSPS) extracted from soybean cotyledons have a pectin-like structure. The core polysaccharides after treatments with four kinds of hemicellulases and a pectinase contained approximately equal numbers of L-rhamnose and D-galacturonate residues, suggesting the presence of the rhamnogalacturonan (RG) I structure consisting of the diglycosyl repeating unit, -4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-. The lengths of RG chains were calculated as approximately 15, 28, and 100 diglycosyl repeats. The RG components linked to each other by intervention of galacturonan (GN) chains, constituting the backbone of SSPS. All arabinose residues, which constitute 21% of total SSPS sugars, were found to be in side chains from RG regions, and this was also true for galactose residues, which constitute 50% of total sugars. Of arabinose residues, 94% are present as alpha-1,3- or alpha-1,5-arabinans, and 89% of galactose residues were present as beta-1,4-galactans. Galactan chains are modified with arabinose, xylose, fucose, and glucose at the sites close to the RG regions.
Subject(s)
Glycine max/chemistry , Polysaccharides/chemistry , Arabinose/analysis , Carbohydrate Conformation , Carbohydrate Sequence , Chromatography, Gel , Chromatography, Ion Exchange , Galactose/analysis , Glycoside Hydrolases/chemistry , Molecular Sequence Data , Pectins/analysis , Polygalacturonase/chemistry , Polysaccharides/isolation & purification , Rhamnose/analysisABSTRACT
PURPOSE: Treatment for benign prostatic hyperplasia (BPH), including minimally invasive therapy, can impair the quality of life. We prospectively determined the impact of 4 different interventional therapies on quality of life and sexual function. MATERIALS AND METHODS: A total of 173 patients were prospectively evaluated between February 1995 and August 1997. Treatment modalities consisted of standard transurethral resection of the prostate in 55 cases, transurethral microwave thermotherapy in 34, interstitial laser coagulation of the prostate in 42 and transurethral needle ablation in 42. Disease specific quality of life was assessed using the International Prostate Symptom Score quality of life assessment index and BPH impact index. In addition, a self-reporting questionnaire was completed before and 3 months after treatment to determine the impact on sexual function. RESULTS: All 4 treatment groups showed significant improvement in the symptom score, International Prostate Symptom Score quality of life assessment score and BPH impact index score. Satisfaction with treatment was highest in patients treated with transurethral resection or laser coagulation. A mild to moderate decrease in erectile function was noted in 26.5%, 18.2%, 18.4% and 20.0% of the transurethral resection, microwave thermotherapy, laser coagulation and needle ablation groups, respectively, but there was no significant difference of mean pretreatment and posttreatment erectile function or libido scores in any group. Ejaculation loss or severe decrease in ejaculate volume was reported by 48.6%, 28.1%, 21.6% and 24.3% of the patients, respectively. Interestingly, 20 of the 44 patients (45. 5%) with loss of ejaculation or severe decrease in ejaculate reported deterioration of the sex life, while only 2 (3.6%) of the 56 without any change in ejaculate volume reported such deterioration. The association of ejaculatory dysfunction with an adverse impact on sexual activity was highly significant (p <0.0001). CONCLUSIONS: Significant improvement in quality of life could be achieved with the present assessed interventional therapies. There was no significant change in sexual desire or erectile function with these therapies. Posttreatment sexual dysfunction appears to be mainly related to impaired ejaculatory function. Urologists should provide proper counseling regarding the possibility of this complication even in patients receiving minimally invasive treatment.
Subject(s)
Diathermy , Laser Coagulation , Prostatic Hyperplasia/therapy , Quality of Life , Transurethral Resection of Prostate , Aged , Aged, 80 and over , Ejaculation , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Helicobacter pylori can produce a persistent infection in the human stomach, where chronic and active inflammation, including the infiltration of phagocytes such as neutrophils and monocytes, is induced. H. pylori may have a defense system against the antimicrobial actions of phagocytes. We studied the defense mechanism of H. pylori against host-derived peroxynitrite (ONOO(-)), a bactericidal metabolite of nitric oxide, focusing on the role of H. pylori urease, which produces CO(2) and NH(3) from urea and is known to be an essential factor for colonization. The viability of H. pylori decreased in a time-dependent manner with continuous exposure to 1 microM ONOO(-), i.e., 0.2% of the initial bacteria remained after a 5-min treatment without urea. The bactericidal action of ONOO(-) against H. pylori was significantly attenuated by the addition of 10 mM urea, the substrate for urease, whereas ONOO(-)-induced killing of a urease-deficient mutant of H. pylori or Campylobacter jejuni, another microaerophilic bacterium lacking urease, was not affected by the addition of urea. Such a protective effect of urea was potentiated by supplementation with exogenous urease, and it was almost completely nullified by 10 microM flurofamide, a specific inhibitor of urease. The bactericidal action of ONOO(-) was also suppressed by the addition of 20 mM NaHCO(3) but not by the addition of 20 mM NH(3). In addition, the nitration of L-tyrosine of H. pylori after treatment with ONOO(-) was significantly reduced by the addition of urea or NaHCO(3), as assessed by high-performance liquid chromatography with electrochemical detection. These results suggest that H. pylori-associated urease functions to produce a potent ONOO(-) scavenger, CO(2)/HCO(3)(-), that defends the bacteria from ONOO(-) cytotoxicity. The protective effect of urease may thus facilitate sustained bacterial colonization in the infected gastric mucosa.
Subject(s)
Helicobacter pylori/drug effects , Nitrates/pharmacology , Urease/metabolism , Ammonia/pharmacology , Anti-Bacterial Agents/pharmacology , Carbon Dioxide/metabolism , Drug Interactions , Helicobacter pylori/enzymology , Helicobacter pylori/pathogenicity , Microbial Sensitivity Tests , Oxidants/pharmacology , Sodium Bicarbonate/pharmacology , Tyrosine/analogs & derivatives , Tyrosine/metabolism , Urea/metabolism , Urease/antagonists & inhibitorsABSTRACT
Zaldaride maleate (ZAL), a calmodulin inhibitor, that ameliorates secretory diarrhea in rodents, has a racemic structure. In this study, we compared the antidiarrheal and antisecretory effects of ZAL and its optical isomers, R(-)-isomer and S(+)-isomer, in rats. In Ussing chamber experiments, the inhibitory action of ZAL on acetylcholine-induced ion transport in the rat colonic mucosa was equipotent for both optical isomers, with IC50 values of approximately 3--4 micromol/l. In castor-oil-induced diarrhea, ZAL and its S(+)-isomer inhibited the incidence of diarrhea, whereas the R(-)-isomer had no effect. In 16,16-dimethyl prostaglandin E2-induced diarrhea, ZAL, the S(+)-isomer and the R(-)-isomer significantly ameliorated diarrhea at doses of 30, 10 and 30 mg/kg (p.o.), respectively; the ED50 values were 25, 10 and above 30 mg/kg (p.o.), respectively. The pharmacokinetic parameters after administration of 30 mg/kg (p.o.) of each compound were as follows: ZAL (Cmax: 378 ng/ml, AUC0-12: 1650 ng-h/ml); S(+)-isomer (Cmax: 565 ng/ml, AUC0-12: 2230 ng-h/ml) and R(-)-isomer (Cmax: 271 ng/ml, AUC0-12: 613 ng-h/ml) (mean, N=4). In conclusion, despite the fact that the antisecretory actions of ZAL and its optical isomers are the same, the antidiarrheal actions of ZAL and its S(+)-isomer are more potent than that of the R(-)-isomer. The antidiarrheal actions of ZAL and its optical isomers may be related to plasma levels.
Subject(s)
Antidiarrheals/therapeutic use , Benzimidazoles/therapeutic use , Diarrhea/drug therapy , Animals , Antidiarrheals/chemistry , Benzimidazoles/chemistry , Castor Oil/adverse effects , Diarrhea/chemically induced , Dinoprostone/adverse effects , Male , Rats , Rats, Sprague-Dawley , StereoisomerismABSTRACT
We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.
Subject(s)
Brain/diagnostic imaging , Cysteine/analogs & derivatives , Lupus Erythematosus, Systemic/diagnostic imaging , Lupus Vasculitis, Central Nervous System/diagnostic imaging , Organotechnetium Compounds , Radiopharmaceuticals , Adult , Cerebellum/diagnostic imaging , Female , Frontal Lobe/diagnostic imaging , Humans , Lupus Vasculitis, Central Nervous System/psychology , Male , Reference Values , Time Factors , Tomography, Emission-Computed, Single-PhotonABSTRACT
BACKGROUND: In spite of the fact that autologous blood is safest for a patient to receive, it is not generally appreciated that adverse reactions during donation and transfusion may occur. This study was conducted to assess the state and the risk of autologous blood transfusion in Japan in 1997. STUDY DESIGN AND METHODS: Results of a nation-wide questionnaire-based survey are presented. The questionnaire assessed the number of autologous blood donations, donation procedures, and the adverse reactions associated with donation, preservation, recombination erythropoietin administration and transfusion. RESULTS: Between November 1996 and October 1997, 10,697,000 ml (or 53,485 units, 200 ml = 1 unit) prestorage blood donation were made by 14,200 patients (averages; 1.9 donations/patient, 753 ml/patient, 398 ml/donation). Of these, 87% were transfused to the patients and the remainder were discarded. Using hemodilution and blood salvage intra- or postoperatively some 2,540,000 ml of blood was collected and > 70% of patient-donors received such blood. Adverse reactions were observed with 1.6% (428/26,905) of donations including 6 angina and 2 asthma attacks. There were 63 (0.2%) problems with 28,705 donations and 117 (0.5%) errors/problems reported for 24,929 units transfused; the most frequent problems were clotting on the units and breakage of the bags during storage. Hypotension using hemodilution (3.7%), coagulation (0.9%) or bacterial contamination (0.4%) using salvage were often observed. A 10-20 ml volume of autologous fresh-frozen plasma was transfused to the wrong recipient. CONCLUSION: Autologous blood transfusion accounts for at least 1.1% (2.8% estimated) of the red cell supply in Japan. Errors and adverse reactions are not infrequent in autologous blood programmes. By introducing systematic safety policies, we will be able to make autologous blood transfusion safer.
Subject(s)
Blood Specimen Collection/adverse effects , Adolescent , Adult , Aged , Blood Preservation/methods , Blood Preservation/standards , Blood Specimen Collection/methods , Blood Specimen Collection/standards , Blood Transfusion, Autologous/methods , Blood Transfusion, Autologous/standards , Child , Data Collection , Erythropoietin/administration & dosage , Erythropoietin/adverse effects , Humans , Japan , Middle Aged , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effectsABSTRACT
Most solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues or organs, such as extensive angiogenesis and hence hypervasculature, defective vascular architecture, impaired lymphatic drainage/recovery system, and greatly increased production of a number of permeability mediators. The phenomenon now known as the enhanced permeability and retention (EPR) effect for lipid and macromolecular agents has been observed to be universal in solid tumors. Primarily, enhanced vascular permeability will sustain an adequate supply of nutrients and oxygen for rapid tumor growth. The EPR effect also provides a great opportunity for more selective targeting of lipid- or polymer-conjugated anticancer drugs, such as SMANCS and PK-1, to the tumor. In the present review, the basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor. Tumor-specific vascular physiology is also described.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Capillary Permeability , Neoplasms/metabolism , Animals , Antineoplastic Agents/administration & dosage , Humans , Neoplasms/blood supply , Regional Blood FlowABSTRACT
OBJECTIVES: To evaluate the anticancer effects of a lipophilic macromolecular anticancer agent, poly(styrene-co-maleic acid)-conjugated neocarzinostatin (SMANCS), dissolved in a lipid contrast medium (Lipiodol) given via the renal artery to patients with renal cell carcinoma. METHODS: Among 467 patients with renal cell carcinoma treated between April 1984 and March 1993, 191 were treated with SMANCS dissolved in a lipid contrast medium (a 3:2 mixture of Lipiodol F and Lipiodol Ultrafluid; Lpd). Selective arterial infusion of SMANCS/Lpd was performed at a dose of 1.0 or 1. 5 mg/mL. The infusion was repeated at intervals of about 2 weeks or longer, but the doses and the total number of infusions varied among patients, according to results of computed tomography analysis. RESULTS: Statistical analysis was performed for 415 patients who met the criteria of this study. Twenty-six surgical patients with metastases who underwent infusion therapy of SMANCS/Lpd for primary lesions showed 3 and 5-year survival rates of 23.0% and 12.8%, respectively; the rates were 19.3% and 9.7% in 31 patients who did not receive SMANCS infusion therapy. In 125 surgical patients without metastases who underwent SMANCS/Lpd infusion, the 5 and 10-year survival rates were 83.0% and 75.2%, respectively, whereas rates of 84.6% and 78.9% were observed in 199 surgical patients whose median tumor size was significantly smaller, however, than the SMANCS/Lpd infusion group. The maximal tumor diameter at the beginning of treatment was significantly larger (mean diameter 70.8 mm) in the SMANCS/Lpd infusion group than in the noninfusion group (59.1 mm). The survival rate was statistically better for patients with tumors of 100 mm diameter or larger in the SMANCS/Lpd infusion group (P <0.05): 5 and 10-year survival rates were 70.4% and 61.6%, respectively, for the infusion group and 64.6% and 50.9% for the group receiving no drug. In patients with larger tumor (greater than 110 mm), the survival rate at 13 years was 75% in the SMANCS/Lpd infusion group and 0% in the surgery group. CONCLUSIONS: Arterial infusion therapy with SMANCS/Lpd appears to be effective for large renal cell carcinoma without metastases in conjunction with surgery.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Renal Cell/drug therapy , Infusions, Intra-Arterial , Iodized Oil/administration & dosage , Kidney Neoplasms/drug therapy , Maleic Anhydrides/administration & dosage , Polystyrenes/administration & dosage , Zinostatin/analogs & derivatives , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Iodized Oil/adverse effects , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Maleic Anhydrides/adverse effects , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Polystyrenes/adverse effects , Survival Rate , Tomography, X-Ray Computed , Treatment Outcome , Zinostatin/administration & dosage , Zinostatin/adverse effectsABSTRACT
In this study, two females, siblings who exhibited a non-24 h sleep-wake rhythm (non-24 h) at home were observed. However, they showed a delayed sleep phase syndrome (DSPS) immediately after admission to Kurume University Hospital. Melatonin (3 mg) was commenced following chronotherapy and this improved their sleep-wake rhythm. Polysomnography (PSG) showed decreased sleep latency and increased sleep stage. In these cases, the involvement of environmental factors was strongly suggested for the sleep-wake rhythm abnormalities as well as familial factors.
Subject(s)
Melatonin/administration & dosage , Sleep Deprivation , Sleep Disorders, Circadian Rhythm/genetics , Adolescent , Female , Humans , Polysomnography , Sleep Disorders, Circadian Rhythm/therapy , Treatment OutcomeABSTRACT
Lipid hydroperoxides (LOOH or oxidized oils) are known as unfavorable food components. Molecular details of the fate and mechanisms of LOOH to exert adverse effects in vivo are, however, little understood. In the present study, we demonstrated that LOOH generated alkylperoxyl radical (LOO*) after reaction with various heme compounds such as myoglobin, cytochrome c, hemin, hematin, etc., but little formation of other radical species was noticed such as L* or LO*. It was also shown that LOO* thus formed exhibits cytotoxicity and caused DNA damages including strand breakage and abasic site formation. This highly toxic LOO* is effectively scavenged by hot water extracts of vegetable (soup), flavonoids, polyphenols as well as tocopherols. Another important finding is that crude vegetable oils are rich in potent-LOO* scavenging activity, which exhibits potent anti-oxidant activity as well; whereas highly purified oils are scanty in such components and LOO* scavenging activity. These findings imply that a considerate processing in the refining of oils should be needed to retain such potent endogenous anti-oxidative radical scavenging-components.
Subject(s)
Lipid Peroxides/chemistry , Lipid Peroxides/pharmacology , Plant Oils/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Survival/drug effects , DNA Damage , Food Handling , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Free Radicals , Lipid Peroxides/analysis , Luminescent Measurements , Plasmids/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & developmentABSTRACT
PURPOSE: To describe a method for making morphometric analysis of the pores in the lamina cribrosa with a confocal scanning laser ophthalmoscope (SLO). METHODS: Sixteen consecutive images were acquired with an SLO from the retinal surface to the bottom of the optic disc in +0.25-diopter increments. An He-Ne laser (633 nm) with a 20 degrees field of view was used. The images from each section were processed and combined with the aid of Macintosh software. RESULTS: Eyes with physiological cupping showed uniformly round or nearly round pores, whereas eyes with primary open-angle glaucoma frequently had compressed pores. CONCLUSIONS: In vivo morphometry of the surface of the internal lamina cribrosa can be performed by this technique, which should be useful for evaluating the progression of glaucomatous changes of the optic nerve head.
Subject(s)
Glaucoma, Open-Angle/pathology , Lasers , Ophthalmoscopy , Optic Disk/pathology , Optic Nerve/pathology , Optic Neuropathy, Ischemic/pathology , Humans , Image Processing, Computer-Assisted , Models, Biological , Observer Variation , Reproducibility of Results , Video RecordingABSTRACT
We recently reported that alkylperoxyl radical (ROO(*)) enhanced carcinogenesis in rats treated with carcinogen (Sawa et al. Cancer Epidemiol. Biomarkers Prev. 1998, 7, 1007-1012), and the tumor promoting action of ROO(*) could be reduced by addition of hot-water extracts of vegetables (Maeda et al. Jpn. J. Cancer Res. 1992, 83, 923-928). Here we described the ROO(*)-scavenging activity of flavonoids and nonflavonoid phenolics and their role in anti-tumor-promoter effects. A model molecular species, ROO(*), was generated from tert-butyl hydroperoxide (t-BuOOH) and heme iron, and the scavenging of t-BuOO(*) was determined by (a) bioassay based on the bactericidal action of ROO(*), (b) luminol-enhanced chemiluminescence, and (c) electron spin resonance. Of 17 authentic plant phenolics tested, 9 compounds (including rutin, chlorogenic acid, vanillin, vanillic acid, neohesperidin, gallic acid, shikimic acid, rhamnetin, and kaempferol) showed remarkably high ROO(*)-scavenging activity. Some of them were detected and quantified in hot-water extracts of mung bean sprouts, used as the model vegetable, and their contents increased after germination, which paralleled very well to the ROO(*)-scavenging capacity of the vegetable extracts. Thus, a diet rich in these radical scavengers would reduce the cancer-promoting action of ROO(*). Consequently, the carcinogenic potentials of oxygen-related radicals may be suppressed.
Subject(s)
Anticarcinogenic Agents/chemistry , Flavonoids/chemistry , Free Radical Scavengers/chemistry , Phenols/chemistry , Vegetables/chemistry , Electron Spin Resonance Spectroscopy , Fabaceae/chemistry , Plants, MedicinalABSTRACT
We assessed the effects of dietary arginine supplementation on protein turnover and organ protein synthesis in burned rats. Male Wistar rats weighing about 200 g underwent catheter jejunostomy and received scald burns covering 30% of the whole-body surface area. Animals were divided into a control group (n = 9) and an arginine group (n = 9) and continuously received total enteral nutrition for 7 d (250 kcal.kg-1.d-1, 1.72 gN.kg-1.d-1). Changes in body weight, plasma total protein, plasma albumin, urinary excretion of polyamines, nitrogen balance, whole-body protein kinetics, and tissue protein synthesis rates were determined. Whole-body protein kinetics and tissue fractional protein synthetic rates (Ks, percent/d) were estimated using a 24-h constant enteral infusion of 15N glycine on the last day. The changes in body weight were not different between the control and arginine groups. The urinary excretion of polyamines was higher in the arginine group than in the control group (P < 0.01). Burned rats enterally fed arginine-supplemented diet yielded significantly greater cumulative and daily nitrogen balance on days 3 and 5 than those fed a control diet (cumulative, P < 0.05; day 3, P < 0.01; day 5, P < 0.01). Whole-body protein turnover rate was significantly elevated in the arginine group as compared to that in the control group (P < 0.05). The Ks of rectus abdominis muscles were significantly increased in the arginine group in comparison to the control group (P < 0.01). We have shown that dietary arginine supplementation improved protein anabolism and attenuated muscle protein catabolism after thermal injury.
Subject(s)
Arginine/administration & dosage , Burns/diet therapy , Burns/metabolism , Proteins/metabolism , Animals , Biogenic Polyamines/urine , Body Weight , Burns/pathology , Diet , Kinetics , Male , Nitrogen/metabolism , Organ Size , Protein Biosynthesis , Rats , Rats, WistarABSTRACT
The effects of Qing Fei Tang (Sei-hai To in Japanese), a Chinese traditional medical mixture, on aspiration pneumonia were studied using mice inoculated with both Streptococcus pneumoniae and gastric juice as aspiration pneumoniae models. Daily (4 weeks) oral usage of Qing Fei Tang before inoculation reduced remarkably the mortality rate of mice. In this aspiration pneumonia model, xanthine oxidase (XO) activity in the lung tissues was elevated, but this elevation was remarkably decreased by use of Qing Fei Tang. These results suggest that Qing Fei Tang pretreatment can reduce oxygen radical production in inflammed lungs and may reduce the mortality for aspiration pneumonia.
Subject(s)
Antioxidants/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Aspiration/drug therapy , Animals , Colony Count, Microbial , Humans , Leukocyte Count , Lung/enzymology , Male , Mice , Neutrophils , Pneumonia, Aspiration/enzymology , Pneumonia, Aspiration/mortality , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Streptococcus pneumoniae/isolation & purification , Superoxide Dismutase/pharmacology , Xanthine Oxidase/metabolismABSTRACT
PURPOSE: We describe a method for the morphometric analysis of the pores in the lamina cribrosa using a confocal scanning laser ophthalmoscope (SLO: Rodenstock company, Germany). METHODS: Four eyes with glaucoma and four eyes with non-glaucoma patients were examined. Sixteen consecutive images were acquired from the surface of the retina to the bottom of the optic disc excavation with +0.25 diopter increments by a He-Ne laser (633 nm) under 20 degree field of view. The images from each section were processed and combined with the aid of Macintosh software. RESULTS: Eyes with physiological cupping showed uniformly round or elliptical pores, whereas compressed and elongated pores were frequently encountered in eyes with primary open angle glaucoma (POAG). CONCLUSION: The technique described allows, in vivo morphometry of the surface of the internal lamina cribrosa and was considered to be useful to evaluate glaucomatous progression.