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At least 469 records · Page 26Linked to original sources
PubMed2006

Phase I/II study of docetaxel, ifosfamide, and doxorubicin in advanced, recurrent, or metastatic soft tissue sarcoma (STS).

BACKGROUND: Based on reports of the efficacy of docetaxel (T) in STS, we undertook a phase I/II trial to determine the response rate (RR), dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of addition of T to doxorubicin (A) and ifosfamide (I) in advanced STS. METHODS: Patients with advanced, recurrent, or metastatic STS, without prior chemotherapy, were enrolled in a dose escalation trial. Dose levels: I-A 40 mg/m(2); I 4.0 gm/m(2); T 40 mg/m(2), II-A 50; I 5.0; T 50, III-A 60; I 6.0; T 60, and IV-A 75; I 7.5; T 75. MTD was defined as the dose producing DLTs in >or=2 of 3-6 patients treated. RESULTS: 21 patients were accrued. Median age: 55 (28-78) years. HISTOLOGY: leiomyosarcoma 10, spindle cell sarcoma 3, synovial sarcoma 2, angiosarcoma 1, fibrous histiocytoma 1, epitheliod hemangio-endothelioma 1, and 3 not specified. MTD was level III (A 60, I 6.0, and T 60). DLT was myelosuppression. All grade 4 toxicities were hematologic. Patients received median 2 cycles (range 2-9). Eight patients (38%) achieved partial response (PR). PR occurred after six cycles in 5 patients. 18 patients died. Median overall survival: 17 months (95% CI, 9.1-33.6 months). CONCLUSIONS: The recommended Phase II dose of this combination is level III: A 60 mg/m(2), I 6.0 g/m(2), T 60 mg/m(2), with mesna and granulocyte-colony stimulating factor. The RR is similar to that of AI in other trials, but the survival is better than anticipated.

Adult↗
PubMed1998

A dominant role for non-MHC gene effects in susceptibility to cyclosporin A (CsA)-induced autoimmunity.

Lethally irradiated LEW rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period develop a graft-versus-host-like disease upon withdrawal of CsA. This T cell-mediated autoimmune disease is referred to as CsA-induced autoimmunity (CsA-AI). CsA-AI-susceptible LEW rats and resistant BN rats differ greatly in the composition of their peripheral T cell compartment. To dissect the role of MHC and non-MHC genes in the development of peripheral T cell subsets in combination with susceptibility to CsA-AI the respective MHC congenic strains (LEW-1N and BN-1L) were examined for their T cell subsets and for their ability to develop CsA-AI. In this study we show that the Th1/Th2-like cell ratio as well as susceptibility to CsA-AI are under control of the non-MHC genes. This suggests that the Th1/Th2-like cell ratio is a critical determinant for development of CsA-AI. Alternatively, resistance can be attributed to lack of target organ susceptibility due to the absence of the target autoantigen in resistant rat strains. This interpretation is rejected, since both BN as well as BN-1L rats consistently develop the characteristic macroscopic and microscopic signs of CsA-AI upon adoptive transfer with autoreactive LEW-1N and LEW T cells, respectively. Therefore, it can be concluded that the non-MHC genes encode for immune deviation and thereby determine susceptibility or resistance to CsA-AI.

Adoptive Transfer↗
PubMed2004

Allergic contact dermatitis to white petrolatum.

White petrolatum is known for its nonsensitizing and nonirritating properties. Only a few cases of allergic contact dermatitis to white petrolatum have been reported. Although it is a rare event, the finding of contact sensitization to white petrolatum raises the potential problem of its usage of common topical agents or vehicles for patch testing. We herein report a case of allergic contact dermatitis to white petrolatum.

Allergens↗
PubMed2001

Isolation and in vivo and in vitro antifungal activity of phenylacetic acid and sodium phenylacetate from Streptomyces humidus.

The antifungal substances SH-1 and SH-2 were isolated from Streptomyces humidus strain S5-55 cultures by various purification procedures and identified as phenylacetic acid and sodium phenylacetate, respectively, based on the nuclear magnetic resonance, electron ionization mass spectral, and inductively coupled plasma mass spectral data. SH-1 and SH-2 completely inhibited the growth of Pythium ultimum, Phytophthora capsici, Rhizoctonia solani, Saccharomyces cerevisiae, and Pseudomonas syringae pv. syringae at concentrations from 10 to 50 microg/ml. The two compounds were as effective as the commercial fungicide metalaxyl in inhibiting spore germination and hyphal growth of P. capsici. However, the in vivo control efficacies of the two antifungal compounds against P. capsici infection on pepper plants were similar to those of H(3)PO(3) and fosetyl-AI but less than that of metalaxyl.

Antifungal Agents↗
PubMed1998

Spontaneous apoptosis in ovarian cancer: an unfavorable prognostic factor.

Apoptosis and cell proliferation play important roles in the cellular response to chemotherapy, and may have prognostic value. The percentage of apoptotic cells [apoptotic index (AI)] was evaluated in ovarian carcinomas of 25 patients by the terminal desoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique. All patients were surgically treated and received postoperatively chemotherapy consisting of cytoxan and cisplatin or carboplatin. As a marker of proliferation the mRNA expression of histone H3 in tumor tissue was determined. In addition, tumor vascularity was assessed by immunohistochemistry and factor VIII. Patients with high AI had significantly shorter survival times (p=0. 0001) or recurrence-free intervals (p=0.004) than patients with low AI. No significant relationship was found between AI and histone H3 mRNA expression, however, an inverse correlation of AI with microvessel density was detected. Tumors with high AI had significantly lower microvessel count than tumors with low AI (p=0. 002). The obtained data suggest that AI can be predictive of treatment outcome in ovarian cancer.

Antineoplastic Agents↗
PubMed1998

Synthesis of some novel pyrazole derivatives as potential antiinflammatory agents with minimum ulcerogenic activity.

Two novel isomeric series, N-substituted-5-amino-4-(3,4-dimethoxyphenyl)-3-hydroxy-1 H-pyrazole-1-carboxamides (or thiocarboxamides) 6a-e, 7a, b and N-substituted-3-amino-4-(3,4-dimethoxyphenyl)-5-hydroxy-1 H-pyrazole-1-carboxamides or (thiocarboxamides) 9a-c were synthesized. Moreover, the pyrazolo-[1,5-a]-1,3,5-triazine derivative 8 was also prepared. The new compounds were tested biologically for their in vivo antiinflammatory activity (AI) against carrageenan-induced rat paw oedema. All the investigated compounds exhibited significant AI activity in the range of 23-65%. The most potent compounds were further evaluated for their ulcerogenic liability and acute toxicity. They were found to be less toxic and nearly devoid of ulcerogenic activity as compared to phenylbutazone and indometacin.

Animals↗
PubMed2003

Prevention and therapy of fungal infection in severe acute pancreatitis: A prospective clinical study.

AIM: To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP). METHODS: Seventy patients with SAP admitted from Jan. 1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were compared. RESULTS: The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16% vs 30%, P<0.05 and 9% vs 30%, P<0.01, respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole group. CONCLUSION: Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with SAP. But once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective.

Acute Disease↗
PubMed2000

Hygienic aspects of storage and use of semen for artificial insemination.

The artificial insemination (AI) industry has developed over the last 50 years to the extent that it is used in almost every country in the world. One of the main factors contributing to its success is the confidence of the farmers that germplasm is not associated with pathogens, so that AI can be performed without risks. This has been achieved as a result of a considerable amount of research based on sound scientific data that has identified the major risk pathogens. A summary of these studies, given in this section, shows that despite the large number of agents that could be transmitted via the semen, there are cost-effective means to prevent such hazards. One of the basic rules is that the males should be housed in strictly protected semen collection centres (SCCs). Such centres should be approved by the veterinary authorities based upon specific criteria, which include special housing and operating specifications. This also includes specific means of monitoring the health of individual males through regular clinical examinations, assessment of semen and testings for various diseases. Two new challenges can now be identified, one relevant to so-called emerging diseases the impact of which on the status of the semen donors should always be assessed, and the second, relates to endangered genetic resources which may become extinct without active conservation programmes. The experience gained by the AI industry over the last 50 years should help to solve those problems. Currently, the use of semen derived from approved SCCs warrants their disease-free status.

Animal Diseases↗
PubMed1991

Role of postreplication repair in transformation of human fibroblasts to anchorage independence.

Cellular capacity for postreplication repair (PRR) and sensitivity to transformation to anchorage independence (AI) were quantified in normal foreskin and xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo(a)pyrene-diol-epoxide I (BPDE-I). PRR is defined here as a collection of pathways that facilitate the replication of DNA damaged by genotoxic agents. It is recognized biochemically as the process by which nascent DNA grows longer than the average distance between two lesions in the DNA template. PRR refers more directly to the elimination of gaps in the daughter-strand DNA by mechanisms which remain to be determined for human cells, but which may include translesion replication and recombination. PRR was measured in diploid human fibroblasts by analysis of the dose kinetics for inhibition of DNA strand growth in carcinogen-treated cells. Logarithmically growing foreskin fibroblasts (NHF1) displayed D0 values of 4.3 J/m2 and 0.14 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. XP variant cells (CRL1162) exhibited corresponding D0 values of 1.5 J/m2 and 0.16 microM. The increased sensitivity to inhibition of DNA replication by UV in these XP variant fibroblasts (2.9-fold greater than normal) was mirrored by an enhanced frequency of transformation to AI. XP variant fibroblasts (CRL1162) were 3.2 times more sensitive to transformation to AI by UV than were the normal foreskin fibroblasts. As predicted by the PRR studies, both cell types exhibited similar frequencies of AI colonies induced by BPDE-I. Apparent thresholds were observed for induction of AI by UV (normal fibroblasts, 2.7 J/m2; XP variant fibroblasts, 0.3 J/m2) and BPDE-I (both, 0.05 microM). Doses of UV and BPDE-I above these thresholds produced proportional increases in the inhibition of DNA replication in operating replicons and in the induced frequency of anchorage-independent colonies. At doses of UV and BPDE-I that produced the same degree of inhibition of DNA strand growth, BPDE-I induced a greater number of cells capable of anchorage-independent growth than did UV in both normal and XP variant fibroblasts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1997

Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.

Adult↗
PubMed2026

Precision Medicine in Transfusion-Dependent and Non-Transfusion-Dependent &#x3b2;-Thalassemia: Toward Personalized Diagnosis and Therapy.

&#x3b2;-thalassemia comprises a clinically heterogeneous group of disorders in which anemia severity, transfusion exposure, iron loading, and organ complications vary widely among individuals. This structured narrative review summarizes practical applications of precision medicine in transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), with explicit attention to which strategies apply to each clinical category. Literature indexed in PubMed and Scopus from 2000 to 2025 was reviewed using terms related to thalassemia, precision medicine, magnetic resonance imaging (MRI), chelation tailoring, next-generation sequencing (NGS), fetal hemoglobin (HbF) modifiers, luspatercept, mitapivat, hepcidin, gene therapy, gene editing, and artificial intelligence (AI). Evidence was synthesized descriptively because interventions, outcomes, and populations were heterogeneous, and no pooled meta-analysis was performed. In TDT, precision care is centered on individualized transfusion planning, extended red-cell antigen matching, MRI-guided cardiac and hepatic iron monitoring, organ-directed chelation intensification, and selection of disease-modifying or curative approaches. In NTDT, precision care emphasizes accurate phenotype classification, MRI liver iron concentration, because serum ferritin may underestimate iron burden, selective chelation, surveillance for NTDT-specific complications, and individualized use of agents that improve anemia. Personalized chelation should include deferiprone, either alone or in combination, when cardiac iron is increased. Comprehensive molecular diagnosis should include HBB together with HBA1 and HBA2 assessment, while secondary and tertiary modifiers help explain phenotypic variability and complication risk. Hepcidin and growth differentiation factor 15 (GDF-15) are discussed as investigational biomarkers; transferrin saturation is not recommended for routine iron-overload assessment in thalassemia. AI currently has its strongest role in screening and diagnosis, whereas risk-stratification models remain exploratory. Equitable implementation requires standardized TDT/NTDT pathways, regional MRI and genomics access, longitudinal registries, and multidisciplinary interpretation.

Humans↗
PubMed1997

Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs.

Cardiovascular drugs such as antiarrhythmic agents with Vaughan Williams class Ia action have been found to induce a sporadic hypoglycemia. Recent investigation has revealed that these drugs induce insulin secretion from pancreatic beta-cells by inhibiting ATP-sensitive K+ (KATP) channels in a manner similar to sulfonylurea drugs. The mechanism underlying block of KATP channels by antiarrhythmic drugs was different, however, from that of sulfonylureas: firstly, because binding of radioactive glibenclamide could not be inhibited by unlabelled antiarrhythmic agents, and vice versa; secondly, because the two compounds differ in the kinetics and sidedness of drug action-antiarrhythmic drugs act on the channel from the inner surface of the cell membrane, whereas glibenclamide binds through the intramembrane pathway; finally, it was shown that functional KATP channels in beta-cells are composed of two distinct molecules-a sulfonylurea receptor (SUR) and a channel pore-forming subunit, an inwardly-rectifying K channel with two transmembrane regions (Kir6.2). Antiarrhythmic drugs reversibly inhibit the K+ conductance displayed by the Kir6.1 (a putative KATP channel clone)-transfected NIH3T3 cells. Therefore they appear to interact directly with the pore-forming subunit, thereby inhibiting KATP channel currents and exerting an insulinotrophic effect.

3T3 Cells↗
PubMed2006

The impact of tumor progesterone receptor status on optimal adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer: a decision analysis.

BACKGROUND: Emerging data suggest that treatment outcomes with aromatase inhibitors (AIs) and/or tamoxifen may differ for tumors that express both the estrogen receptor (ER) and the progesterone receptor (PR) (ER+/PR+) compared with those that lack PR expression (ER+/PR-). However, the optimal sequencing of AIs and tamoxifen as adjuvant therapy is not known and may differ for biologic subsets of cancers. METHODS: Markov models were used to simulate disease-free survival (DFS) separately among postmenopausal women with ER+/PR+ cancers and women with ER+/PR- cancers. By using risk estimates reported from randomized clinical trials, treatment with 5 years of an AI alone with sequential treatment consisting of tamoxifen with crossover to an AI at 2 years was compared. RESULTS: For women with ER+/PR+ cancers, sequential therapy with tamoxifen followed by crossover to an AI at 2 years yielded modest improvements in 10-year DFS estimates compared with planned AI monotherapy (84.3% vs. 82.2% and 68.8% vs. 64.8% for lymph node-negative and lymph node-positive patients, respectively). However, for women with ER+/PR- cancers, upfront treatment with an AI yielded improved outcomes with 10-year DFS rates of 90.5% and 80.1% for the lymph node-negative and node-positive groups, respectively, compared with 88.2% and 76.1%, respectively, for sequential treatment with tamoxifen followed by an AI. CONCLUSIONS: Modeling estimates suggested that the optimal endocrine treatment strategy may differ based on the biologic features of breast cancer tumors. Patients with ER+/PR+ tumors achieved optimal 10-year DFS estimates with tamoxifen followed by a crossover to AI therapy, whereas patients with ER+/PR- tumors fared best when they initiated treatment with AI.

Age Factors↗
PubMed2006

Cost-utility of adjuvant hormone therapies for breast cancer in post-menopausal women: sequential tamoxifen-exemestane and upfront anastrozole.

BACKGROUND: Adjuvant Anastrozole (ANA) for 5 years and Tamoxifen followed by Exemestane (TAM-EXE) for 2.5 years each have become acceptable alternatives to 5 years of Tamoxifen (TAM) for post-menopausal women with breast cancer. As these newer options are associated with higher drug costs as well as improved outcomes, an economic evaluation was undertaken to compare the cost-utility of ANA and TAM-EXE relative to TAM alone and to each other in terms of cost per quality-adjusted life year (QALY) gained. METHODS: A Markov model was developed to calculate monthly costs and outcomes in a hypothetical cohort of post-menopausal women with early-stage breast cancer. Baseline rates of cancer recurrence and adverse effects with TAM, and hazard ratios associated with ANA and EXE, were derived from the ATAC and IES trials. Patients received hormonal therapy for 5 years and benefit was modeled to persist 5 years beyond treatment. The analysis took a direct payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Canadian dollars. RESULTS: ANA and TAM-EXE were associated with increased costs and QALYs, though the cost-utility of both relative to TAM alone was strongly favourable (<$50,000/QALY). Based on an indirect comparison of ANA and TAM-EXE, using TAM alone as a common comparator, the cost-utility of ANA relative to TAM-EXE appears unfavourable. CONCLUSIONS: Both upfront and sequential AI options were cost-effective alternatives to TAM alone, but TAM-EXE appears to be the economically preferred AI option based on its more favourable cost-utility versus ANA.

Aged↗
PubMed1986

Purification of biologically active apolipoproteins by chromatofocussing.

Chromatofocussing has been used to isolate homogeneous apolipoproteins (apo) from human very-low-density lipoproteins and high-density lipoproteins with protein recovery of 70%. The inclusion of sulfhydryl-reducing agent (dithiothreitol) was required during solubilization of the lipoproteins (following delipidation) to achieve reproducible elution profiles. Removal of polyvalent buffers from apoproteins was rapidly accomplished on small columns of hydroxylapatite. The biological activity of purified apo AI and apo CII was confirmed by assessment of their ability to activate lecithin:cholesterol acyltransferase or lipoprotein lipase, respectively. Functional properties of isolated apo E were assessed by in vitro interaction with the low-density lipoprotein receptor expressed by cultured fibroblasts. Apolipoproteins purified by this rapid procedure exhibit identical physical, chemical and biological properties to those purified by other, more tedious techniques.

Animals↗
PubMed2003

Cytotoxic and antimalarial beta-carboline alkaloids from the roots of Eurycoma longifolia.

Three new [n-pentyl beta-carboline-1-propionate (1), 5-hydroxymethyl-9-methoxycanthin-6-one (2), and 1-hydroxy-9-methoxycanthin-6-one (3)] and 19 known beta-carboline alkaloids were isolated from the roots of Eurycoma longifolia. The new structures were determined by comprehensive analyses of their 1D and 2D NMR and mass spectral data and by chemical transformation. These compounds were screened for in vitro cytotoxic and antimalarial activities, and 9-methoxycanthin-6-one (4) and canthin-6-one (5) demonstrated significant cytotoxicity against human lung cancer (A-549) and human breast cancer (MCF-7) cell lines.

Alkaloids↗
PubMed2003

Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney.

Recent studies have indicated that urotensin II (UII), a cyclic peptide, is vasoactive and may be involved in cardiovascular dysfunctions. It remains unknown, however, whether UII plays a role in the control of renal vascular tone and tubular function. In the present study, a continuous infusion of synthetic human UII (hUII) into the renal artery (RA) in anesthetized rats was found to increase renal blood flow (RBF) and urinary water and sodium excretion (UV and UNaV) in a dose-dependent manner. At a dose of 20 ng. kg-1. min-1, it increased RBF by 20% and UV and UNaV by 94 and 109%, respectively. Nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) completely abolished hUII-induced increases in RBF and water/sodium excretion. In isolated, pressurized, and phenylephrine-precontracted small RA with internal diameter of approximately 200 microm, hUII produced a concentration-dependent vasodilation with a maximal response of 55% at 1.5 microM. l-NAME significantly blocked this hUII-induced vasodilation by 60%. In denuded RA, hUII had neither vasodilator nor vasoconstrictor effect. With the use of 4,5-diaminofluorescein diacetate-based fluorescence imaging analysis of NO levels, hUII (1 microM) was shown to double the NO levels within the endothelium of freshly dissected small RA, and l-NAME blocked this UII-induced production of endothelial NO. These results indicate that UII produces vasodilator and natriuretic effects in the kidney and that UII-induced vasodilation is associated with increased endothelial NO in the RA.

Animals↗
PubMed2005

Prescription pattern of aromatase inhibitors in the adjuvant setting in Germany--final results of a survey among german breast cancer specialists.

INTRODUCTION: The prescription practice of adjuvant therapy with aromatase inhibitors (AI) in Germany is not known, also considering that approval is still limited or awaited. We conducted a survey among breast specialists of the German Society of Senology. METHOD: A standardized questionnaire and the latest abstracts of the 3 trials were sent out to 1,223 members, responses were anonymized. All questions were to be answered with respect to the patients' national health insurance (NHS) or private health insurance (PHS) status. RESULTS: Questionnaire were predominantly completed by gynecologists (82.4%). In all, >16,000 breast cancer patients had been treated in 2003. A total of 69.4% of physicians initiated adjuvant AI in up to 25% of NHS patients, 5.6% treated >50% of patients. However, 10.3% of physicians treated >50% of their PHS patients with an AI. Under the hypothesis of an unrestricted label for AI, 44.5% of physicians would treat >50% patients. The switch to an AI after 2-3 years of tamoxifen was chosen in 22% for NHS patients and in 36% of PHS patients. Continuing an AI after 5 years of tamoxifen was favored. in 26% of NHS and 35% of PHS patients. CONCLUSION: Tamoxifen as the previous gold standard is being replaced by AI; a dramatic change in treatment pattern is expected with less restricted approval.

Antineoplastic Agents↗