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At least 883 records · Page 49Linked to original sources
PubMed2001

The synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice.

We have evaluated two synthetic epothilone analogues lacking the 12,13-epoxide functionality, 12,13-desoxyepothilone B (dEpoB), and 12,13-desoxyepothilone F (dEpoF). The concentrations required for 50% growth inhibition (IC(50)) for a variety of anticancer agents were measured in CCRF-CEM/VBL1000 cells (2,048-fold resistance to vinblastine). By using dEpoB, dEpoF, aza-EpoB, and paclitaxel, the IC(50) values were 0.029, 0.092, 2.99, and 5.17 microM, respectively. These values represent 4-, 33.5-, 1,423- and 3,133-fold resistance, respectively, when compared with the corresponding IC(50) in the parent [nonmultiple drug-resistant (MDR)] CCRF-CEM cells. We then produced MDR human lung carcinoma A549 cells by continuous exposure of the tumor cells to sublethal concentrations of dEpoB (1.8 yr), vinblastine (1.2 yr), and paclitaxel (1.8 yr). This continued exposure led to the development of 2.1-, 4,848-, and 2,553-fold resistance to each drug, respectively. The therapeutic effect of dEpoB and paclitaxel was also compared in vivo in a mouse model by using various tumor xenografts. dEpoB is much more effective in reducing tumor sizes in all MDR tumors tested. Analysis of dEpoF, an analog possessing greater aqueous solubility than dEpoB, showed curative effects similar to dEpoB against K562, CCRF-CEM, and MX-1 xenografts. These results indicate that dEpoB and dEpoF are efficacious antitumor agents with both a broad chemotherapeutic spectrum and wide safety margins.

Animals↗
PubMed1998

Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel.

The epothilones are naturally occurring, cytotoxic macrolides that function through a paclitaxel (Taxol)-like mechanism. Although structurally dissimilar, both classes of molecules lead to the arrest of cell division and eventual cell death by stabilizing cellular microtubule assemblies. The epothilones differ in their ability to retain activity against multidrug-resistant (MDR) cell lines and tumors where paclitaxel fails. In the current account, we focus on the relationship between epothilone and paclitaxel in the context of tumors with multiple drug resistance. The epothilone analogue Z-12,13-desoxyepothilone B (dEpoB) is >35,000-fold more potent than paclitaxel in inhibiting cell growth in the MDR DC-3F/ADX cell line. Various formulations, routes, and schedules of i.v. administration of dEpoB have been tested in nude mice. Slow infusion with a Cremophor-ethanol vehicle proved to be the most beneficial in increasing efficacy and decreasing toxicity. Although dEpoB performed similarly to paclitaxel in sensitive tumors xenografts (MX-1 human mammary and HT-29 colon tumor), its effects were clearly superior against MDR tumors. When dEpoB was administered to nude mice bearing our MDR human lymphoblastic T cell leukemia (CCRF-CEM/paclitaxel), dEpoB demonstrated a full curative effect. For human mammary adenocarcinoma MCF-7/Adr cells refractory to paclitaxel, dEpoB reduced the established tumors, markedly suppressed tumor growth, and surpassed other commonly used chemotherapy drugs such as adriamycin, vinblastine, and etoposide in beneficial effects.

Animals↗
PubMed2001

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 +/- 0.9), when given in the dose of 10-50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.

Acetic Acid↗
PubMed1994

The structure of Yalom's Curative Factors Scale.

Factor analysis was used to evaluate the short form of Yalom's Curative Factors Scale with data from 372 participants in the 1986 American Group Psychotherapy Association Institute Groups. With the data randomly assigned to three subgroups, results showed 10 scale items loading on three factors across all three subgroups. When the data was organized into two self-selected subgroups corresponding to the two Institute group categories, factor analyses showed the first factor to be consistent with the previous analyses, but other factors showed differences interpreted to be characteristic of the two groups' modalities. The study suggests a framework for understanding the concept of therapeutic factors and how they work together.

Adult↗
PubMed2004

Maternal resources, proximity of services, and curative care of boys and girls in Minya, Egypt 1995-97.

Despite declines in the risk of dying among children in Egypt, girls' excess mortality in early childhood persists. Using data from a representative sample of children in Minya, Egypt, I assess whether maternal resources, marital household structure, and proximity of services influence disparities by sex in curative care. The results show that boys visit any source of care marginally more often than girls. Among children who receive care, boys more often receive private care. Higher maternal education has no effect on the relative odds of private care, whereas maternal residence with marital relatives reduces the odds that girls receive private care. Having a public clinic in the neighbourhood, at which private services may be offered, increases girls' odds of receiving private care. Higher and more equitable levels of care-seeking at public and private services of higher quality may reduce differences in the survival of boys and girls in a highly sex-stratified setting.

Child↗
PubMed2002

Curative therapy of advanced essential thrombocythemia or polycythemia vera by hemopoietic stem cell transplantation.

Twenty-five patients with advanced essential thrombocythemia (ET; n = 13) or polycythemia vera (PV; n = 12) received hemopoietic stem cell transplants (HSCT) at the Fred Hutchinson Cancer Research Center. In most cases the indication to perform an HSCT was myelofibrosis with splenomegaly and peripheral blood cytopenias or the development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients were 18-60 (median 43) years old with intervals from diagnosis to HSCT of 8-348 (median 168) months. All but five patients had been treated with cytotoxic agents, and nine patients were splenectomized before transplant. Conditioning was performed with chemotherapy only or chemotherapy plus total body irradiation regimens followed by the infusion of either marrow (n = 19) or peripheral blood stem cells (n = 6) from related (n = 16) or unrelated (n = 9) donors. All evaluable patients showed sustained neutrophil engraftment. Nine patients (seven with AML/MDS, two with myelofibrosis) died of transplant-related complications, and 16 are surviving, 14 of them in continuous unmaintained remission. With a median follow-up of 41 (range 5-116) months after transplant, survival at 3 years is 64%. These data provide evidence that HSCT can be a curative treatment for patients with advanced PV and ET.

Adolescent↗
PubMed1999

Antibacterial action of extracts of Clinopodium vulgare L. curative plant.

Clinopodium vulgare L. is one of the curative plants used in Bulgarian folk medicine, mainly during wars for the purposes of healing wounds. The antibacterial activity was studied based on its phytochemical properties. By colony forming unit (CFU)/ml values obtained in different intervals after inoculation of 5% extracts of Clinopodium vulgare L. in ethanol and propylene glycol, it has been proved that the plant showed a very strong action on bacteria. The effects of this action are on gram-positive and gram-negative microorganisms and also on isolated microorganisms at laboratory conditions from significant urocultures with multiple resistance. These results are very important as a basis for searching possibilities for utilizing the antibacterial properties of this plant pharmaceutically.

Anti-Bacterial Agents↗
PubMed1956

An experimental analysis of the curative action of penicillin in acute bacterial infections. I. The relationship of bacterial growth rates to the antimicrobial effect of penicillin.

Three strains of pneumococcus (types I and III), equally sensitive to penicillin, have been shown to be killed by the antibiotic in vitro when grown either in enriched beef infusion broth or in a thin serous exudate. Killing of the bacteria resulted promptly when the penicillin was added during the logarithmic phase of growth but failed to occur if addition of the antibiotic was delayed until the later "stationary" growth phase. In analogous experiments with thick purulent exudates from established subcutaneous abscesses, the pneumococci failed to grow rapidly, and added penicillin exerted only a relatively slow bactericidal effect. The relevance of these in vitro observations to the curative action of penicillin was demonstrated in a systematic histologic study of the antimicrobial effect of the drug in experimental (type I) pneumococcal pneumonia. Evidence was obtained that at least two distinct processes are involved. The first, the direct bactericidal effect of the penicillin itself, was shown to operate in the outer edema zone of the spreading pneumonic lesion where the micro-organisms multiply rapidly in the thin serous exudate. The second, which predominates in the older more central portions of the lesion, was demonstrated to depend upon destruction of the pneumococci by phagocytosis. Here the bacteria, having presumably reached a relatively stationary phase of growth in the alveolar exudate, are resistant to the bactericidal action of the penicillin but are readily destroyed by the phagocytes.

Anti-Bacterial Agents↗
PubMed1956

An experimental analysis of the curative action of penicillin in acute bacterial infections. II. The role of phagocytic cells in the process of recovery.

Type I pneumococci injected into the leg muscles of otherwise normal mice reached a maximum total population of approximately 10(6) organisms. In mice rendered severely leucopenic by previous irradiation the maximum bacterial counts recorded were of the order of 10(9). Since the lesions in the latter animals were relatively acellular, the thousandfold difference in the two experiments represented a rough measure of the antibacterial action of the leucocytic exudate. The suppressive effect of the leucocytic exudate was shown by histologie studies to involve phagocytosis. The ingestion of pneumococci was clearly demonstrable within the first 12 to 18 hours. Accordingly, it was attributed to surface phagocytosis. In support of this conclusion was the finding that type III pneumococci reached a significantly higher total population in the myositis lesions than did type I. The type III strain used had been previously shown to be resistant to surface phagocytosis during active growth, whereas the type I strain was known to be susceptible throughout its growth phase. Evidence was also presented that the dense leucocytic exudate probably caused in addition a significant degree of bacteriostasis. When penicillin therapy was begun 9 hours after inoculation, the pneumococci were cleared from the lesions with equal rapidity regardless of the presence or absence of leucocytic exudate. At this early stage the pneumococci were multiplying rapidly in the lesions of both the irradiated and unirradiated mice and therefore were promptly killed by the direct action of the penicillin. When the start of treatment was delayed, however, until 24 hours after inoculation, the bacteria in both sets of lesions had already reached their maximum counts and therefore were presumably resistant to the bactericidal effect of the antibiotic. Under such circumstances the destruction of the bacteria was found to be significantly less prompt in the acellular lesions than in those with a normal cellular exudate. It is concluded from these findings that, in established pneumococcal myositis in mice, the curative effect of penicillin is due, not to the bactericidal action of the antibiotic alone, but rather to the combined effect of the drug and the cellular defenses of the host. The same conclusion also appears to be applicable to analogous acute infections in man, particularly when they are sufficiently advanced to be definitively diagnosed.

Animals↗
PubMed1949

The effect of the size of the inoculum and the age of the infection on the curative dose of penicillin in experimental infections with streptococci, pneumococci, and Treponema pallidum.

The amount of penicillin which suffices to abort pneumococcal and streptococcal infections in white mice and rabbits, as well as syphilitic infection in rabbits, has been shown to increase markedly with the number of organisms inoculated. The curative dose increases also with the age of the infection, presumably owing to the interim increase in the number of organisms in the nfected host. The necessity for the larger doses of penicillin is attributed to the longer itime for which effectively bactericidal concentrations of penicillin must then be provided in order to kill the larger number of organisms.

Animals↗
PubMed2002

Mitogens for curative therapy of HIV-1 infections; an update.

The curative objectives of administering mitogens in conjunction with HAART have been to initiate killer reactions against HIV-1, replenish CD4 cells, rejuvenate CD8 cells, stimulate effective immune reactions against malignancies, generate tolerated immune responses against conventional and opportunistic infections, resist treatment-evading tactics of HIV mutations, and reconstitute both immune and hematopoietic competences. With recent observations that these aims might be thwarted by sequestration of HIV-1 infection in memory cells residing in the circulation, lymph nodes, and spleen as well as in various other sites not readily accessible to eradication, stronger emphasis should be focused primarily on mitogen-induced blockage of HIV-1 entry into CD4 cells. Equally important would be the mitogen panactivation of any cells sequestering virions and proviruses, thereby forcing them out of the latent G0 phase and exposing them to destruction by HAART and the immune responses. While the currently best established mitogens for HIV-1 therapy, PHA-L4 and PWM, might be successfully applied independently or in tandem, other mitogens may be found suitable for evaluation.

Animals↗
PubMed2003

Curative potential of foremost mitogen applications.

This paper is presented as a sequel to the Mitogen Information Summaries article, representing a condensation of salient features involved with facilitating the curative potential of the more important mitogen applications. Following is a resumé of the critical attributes of mitogen therapy relative to the management of malignant tumors: (1) An inherent capability to recognize and destroy mutated or damaged tissues without altering those that are normal; (2) The capacity to induce global immunostimulation by the nonspecific activation of CD4+/- and CD8+/- cells with balanced production of a variety of cytokines able to stimulate B cell, NK cell, and macrophage pathways, at the same time augmenting myeloproliferation; (3) The ability to afford protection and accelerated recovery from the immunosuppressive and myelosuppressive effects of tumors, infections, GvH reactions, and autoimmune states along with the surgery, irradiation, chemotherapeutic agents, antibiotics, and suppressive factors used in their management; (4) Berke's in vitro data from the lectin-dependent cellular cytotoxicity (LDCC) system showing that systemic administration of mitogens such as PHA-L4 should indeed prove destructive to virtually any type of malignancy, leaving normal tissues undamaged; and (5) The potential of these activities to reconstitute the immune competence so vital to lasting cures. The potential role of L4 immunotherapy for infections may be defined by the following criteria: those, including drug-resistant infections, not satisfactorily treatable otherwise; those in which a rapid response is essential; those that are subclinical, latent, recurrent, chronic, persistent, highly lethal, or opportunistic; those in patients with impaired immune responses; and most importantly, those that are not likely to be adversely affected by immunostimulation. Certain paths of administration such as the intralesional (for granulomas), intrapleural (for pleurisy, empyema), and intraperitoneal (for peritonitis) routes might be tested as supplements to intravenous administration in treating infections using dosages comparable to tumor therapy. Intradermal or dermal applications might be used alone for localized viral or fungal skin lesions. The comparative advantages of each mitogen are listed as follows: PHA-L4, longest experience and most complete, including use in humans; Fraction IV PHA, nonagglutinating, otherwise comparable to L4; PWM, nonagglutinating in the broad mitogenic range, high potency that reduces dosage requirements, noncommercial product preferable for experimental studies and for potential advancement to human use.

Animals↗
PubMed2005

Curative antitumor immune response is optimal with tumor irradiation followed by genetic induction of major histocompatibility complex class I and class II molecules and suppression of Ii protein.

Transfecting genes into tumors, to upregulate major histocompatibility complex (MHC) class I and class II molecules and inhibit MHC class II associated invariant chain (Ii), induces a potent anti-tumor immune response when preceded by tumor irradiation, in murine RM-9 prostate carcinoma. The transfected genes are cDNA plasmids for interferon-gamma (pIFN-gamma), MHC class II transactivator (pCIITA), an Ii reverse gene construct (pIi-RGC), and a subtherapeutic dose of adjuvant IL-2 (pIL-2). Responding mice rejected challenge with parental tumor and demonstrated tumor-specific cytotoxic T lymphocytes (CTLs). We have extended our investigation to determine the relative roles of each one of the four plasmids pIFN-gamma, pCIITA, pIi-RGC, and pIL-2 in conjunction with radiation for the induction of a curative immune response. Upregulation of MHC class I with pIFN-gamma or class II with pCIITA, separately, does not lead to a complete response even if supplemented with pIL-2 or pIi-RGC. An optimal and specific antitumor response is achieved in more than 50% of the mice when, after tumor irradiation, tumor cells are converted in situ to a MHC class I+/class II+/Ii- phenotype with pIFN-gamma, pCIITA, pIi-RGC, and pIL-2. We demonstrate further that both CD4+ helper T cells and CD8+ cytotoxic T cells are essential for induction of an antitumor response because in vivo depletion of either subset abrogates the response. The radiation contributes to the gene therapy by causing tumor debulking and increasing the permeability of tumors to infiltration of inflammatory cells.

Animals↗
PubMed2005

Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders.

To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

Adult↗
PubMed1993

Ethanol and hydrazine sulfate induced chronic hepatic injury in rats: the curative effect of administration of glucogenic amino acids.

There is a widespread belief that when ethanol is fed to rats for a long time, it produces only fatty degeneration without necrosis or fibrosis. In this study, hydrazine sulfate, an inhibitor of low Km ALDH and gluconeogenetic enzymes, was fed with ethanol to rats, and produced more serious pathological changes compared with those found in Lieber's model. Male Sprague-Dawley rats were fed with a low fat liquid diet as a basal diet with ethanol (4%, w/v) and hydrazine sulfate for 4 weeks. At the end of the experiment, plasma aminotransferase levels were found to be elevated. Histological examination showed not only fatty degeneration but also pericellular fibrosis. Therefore, we have evaluated the curative effect of glucogenic amino acids, alanine and glutamine, on this hepatic injury model and found them to be partially protective.

Alanine Transaminase↗
PubMed2005

MiGenes: a searchable interspecies database of mitochondrial proteins curated using gene ontology annotation.

MOTIVATION: There has been an explosion of interest in the role of mitochondria in programmed cell death and other fundamental pathological processes underlying the development of human diseases. Nevertheless, the inventory of mitochondrial proteins encoded in the nuclear genome remains incomplete, providing an impediment to mitochondrial research at the interface with systems biology. We created the MiGenes database to further define the scope of the mitochondrial proteome in humans and model organisms including mice, rats, flies and worms as well as budding and fission yeasts. MiGenes is intended to stimulate mitochondrial research using model organisms. SUMMARY: MiGenes is a large-scale relational database that is automatically updated to keep pace with advances in mitochondrial proteomics and is curated to assure that the designation of proteins as mitochondrial reflects gene ontology (GO) annotations supported by high-quality evidence codes. A set of postulates is proposed to help define which proteins are authentic components of mitochondria. MiGenes incorporates >1160 new GO annotations to human, mouse and rat protein records, 370 of which represent the first GO annotation reflecting a mitochondrial localization. MiGenes employs a flexible search interface that permits batchwise accession number searches to support high-throughput proteomic studies. A web interface is provided to permit members of the mitochondrial research community to suggest modifications in protein annotations or mitochondrial status.

Animals↗
PubMed2006

ORegAnno: an open access database and curation system for literature-derived promoters, transcription factor binding sites and regulatory variation.

MOTIVATION: Our understanding of gene regulation is currently limited by our ability to collectively synthesize and catalogue transcriptional regulatory elements stored in scientific literature. Over the past decade, this task has become increasingly challenging as the accrual of biologically validated regulatory sequences has accelerated. To meet this challenge, novel community-based approaches to regulatory element annotation are required. SUMMARY: Here, we present the Open Regulatory Annotation (ORegAnno) database as a dynamic collection of literature-curated regulatory regions, transcription factor binding sites and regulatory mutations (polymorphisms and haplotypes). ORegAnno has been designed to manage the submission, indexing and validation of new annotations from users worldwide. Submissions to ORegAnno are immediately cross-referenced to EnsEMBL, dbSNP, Entrez Gene, the NCBI Taxonomy database and PubMed, where appropriate. AVAILABILITY: ORegAnno is available directly through MySQL, Web services, and online at http://www.oreganno.org. All software is licensed under the Lesser GNU Public License (LGPL).

Binding Sites↗
PubMed1991

Protective and curative effects of rifampicin in Acanthamoeba meningitis of the mouse.

BALB/c mice inoculated nasally with Acanthamoeba culbertsoni, resulting in amebic encephalitis and death 3-7 days, were treated with rifampicin prophylactically (daily for 2 days with 75 and 100 mg/kg) and after infection (daily for 5 days with doses of 10-100 mg/kg). Prophylactic treatment resulted in full protection against infection, as assessed by absence of symptoms of central nervous system malfunction and negative brain culture 10 days after inoculation. Curative treatment was effective at the same doses; however, at doses of 10, 25, and 50 mg/kg, only two of six animals were free of symptoms and infection.

Acanthamoeba↗