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New Treatment Modalities (new + treatment_modality)
Selected AbstractsTreatment of alcoholic liver diseaseLIVER TRANSPLANTATION, Issue S2 2007Christopher Paul Day Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with corticosteroids. Despite the importance of reactive oxygen species in the pathophysiology of ALD and ASH, antioxidants provide no benefit in the treatment of patients with ASH. Proinflammatory cytokines are important in the pathophysiology of ALD and might mediate most of the inflammatory aspects of these disorders. New treatment modalities in ASH might involve antagonism of proinflammatory cytokines such as tumor necrosis factor (TNF) by specific antibodies or other TNF-interfering treatment strategies. Propylthiouracil and S-adenosyl methionine may be beneficial to patients with alcoholic cirrhosis, but both require further randomized, controlled trials before their use can be recommended. Liver transplantation is an effective therapy for patients with advanced alcoholic cirrhosis who have not recovered after a period of abstinence. Liver Transpt 13: S69,S75. 2007. © 2007 AASLD. [source] New treatment modalities for granuloma facialeBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2003E. Ludwig Summary Granuloma faciale (GF) is a rare, chronic skin disorder in which numerous treatment modalities have been used without any consistent long-term effect. We report three cases of GF, two of which were successfully treated with the Laserscope potassium-titanyl-phosphate 532-nm laser within 2 weeks and one with topical tacrolimus ointment 0·1%. Our observations suggest that these new treatment modalities for GF, which we report here for the first time, can provide effective and non-invasive treatment for this disease. [source] Cancer of the esophagus and gastric cardia: recent advances,DISEASES OF THE ESOPHAGUS, Issue 1 2004G. N. J. Tytgat SUMMARY., Esophageal cancer and cancer of the gastric cardia, in particular adenocarcinomas, have shown a rapid and largely unexplained increase in incidence in many developed countries around the world. These diseases have a poor prognosis and current therapies have a modest impact on survival. This review presents recent advances in the epidemiology, etiology, diagnosis, staging, prevention and treatment of resectable and advanced disease. Although significant progress has been made in these areas of research and patient management over the past years, prognosis for most patients diagnosed with esophageal cancer or cancer of the gastric cardia remains poor. New diagnostic procedures, improved surgical procedures, combined treatment modalities and new treatment modalities are being evaluated and may be expected to contribute to improved patient outcomes and better palliation of symptoms in the future. [source] High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican populationHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2004Adriana Báez PhD Abstract Background. Recent evidence has accumulated suggesting that human papillomavirus (HPV) plays a role in the development of head and neck squamous cell carcinoma (HNSCC). HPV16 is the most common of the HPV subtypes associated with oral and laryngeal malignancies. This study estimated the prevalence of HPV16 DNA in Puerto Rican patients with HNSCC. Methods. DNA was extracted from frozen tissue of 118 HNSCCs. Genomic DNA was screened for the presence of HPV16 DNA with E6-specific and E7-specific primers. Results. HPV16 was detected in tumor tissue of 52 patients (44%) with HNSCC. The oropharynx had a slightly higher incidence of HPV16 DNA. Fifteen of 66 patients with HPV16-negative HNSCC later had recurrences. Positivity for HPV16 was independent of the tumor grade, tumor stage, nodal status, and tobacco or alcohol use. The 3-year survival rate was higher in HPV16-positive patients than in HPV16-negative patients (36% vs 21%). Conclusions. Our findings suggest that HPV16 may play a role in the etiology of a subgroup of HNSCC in Puerto Ricans. Overall survival times of the HPV16-positive patients were not significantly different from those of HPV16-negative patients. Increasing our understanding of the role of HPV16 in the etiology of HNSCC might facilitate the development of new treatment modalities for this subgroup of HNSCC. © 2004 Wiley Periodicals, Inc. Head Neck26: 778,784, 2004 [source] Blockage of the neurokinin 1 receptor and capsaicin-induced ablation of the enteric afferent nerves protect SCID mice against T-cell-induced chronic colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2009Monika Gad PhD Abstract Background: The neurotransmitter substance P (SP) released by, and the transient receptor potential vanilloid (TRPV1), expressed by afferent nerves, have been implicated in mucosal neuro-immune-regulation. To test if enteric afferent nerves are of importance for the development of chronic colitis, we examined antagonists for the high-affinity neurokinin 1 (NK-1) SP receptor and the TRPV1 receptor agonist capsaicin in a T-cell transfer model for chronic colitis. Methods: Chronic colitis was induced in SCID mice by injection of CD4+CD25, T cells. The importance of NK-1 signaling and TRPV1 expressing afferent nerves for disease development was studied in recipient SCID mice systemically treated with either high-affinity NK-1 receptor antagonists or neurotoxic doses of capsaicin. In addition, we studied the colitis-inducing effect of NK-1 receptor deleted CD4+CD25, T cells. Results: Treatment with the NK-1 receptor antagonist CAM 4092 reduced the severity of colitis, but colitis was induced by NK-1 receptor-deleted T cells, suggesting that SP in colitis targets the recipient mouse cells and not the colitogenic donor T cells. Capsaicin-induced depletion of nociceptive afferent nerves prior to CD4+CD25, T-cell transfer completely inhibited the development of colitis. Conclusions: Our data demonstrate the importance of an intact enteric afferent nerve system and NK-1 signaling in mucosal inflammation and may suggest new treatment modalities for patients suffering from inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2007Anje A. te Velde PhD Abstract Background: Mouse models of inflammatory bowel diseases (IBD) are used to unravel the pathophysiology of IBD and to study new treatment modalities, but their relationship to Crohn's disease (CD) or ulcerative colitis (UC) is speculative. Methods: Using Agilent mouse TOX oligonucleotide microarrays, we analyzed colonic gene expression profiles in three widely used models of experimental colitis. In 2 of the models (TNBS and DSS-induced colitis), exogenous agents induce the colitis. In the third model the colitis is induced after transfer of a T-cell population (CD4+CD45RBhigh T cells) that lacks regulatory cells into an immunodeficient host. Results: Compared with control mice, in DSS, TNBS, and the CD45RB transfer colitis mice, 387, 21, and 582 genes were more than 2-fold upregulated in the intestinal mucosa. Analyses of exclusively shared gene expression profiles between the different models revealed that DSS/transfer colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and TNBS/transfer colitis 1. Seven genes were upregulated in all three models. The CD45RB transfer model expression profile included the most genes that are known to be upregulated in IBD. Of 32 genes that are known to change transcriptional activity in IBD (TNF, IFN -,, Lt,, IL - 6, IL - 16, IL - 18R1, IL - 22, CCR2, 7, CCL2, 3, 4, 5, 7, 11, 17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3,, and Pap, S - 100a8, S - 100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS, 15/32 are upregulated or downregulated in DSS and 30/32 are upregulated or downregulated in the CD45RB transfer colitis. Conclusion: The pattern of gene expression in the CD45RB transfer model most closely reflects altered gene expression in IBD. (Inflamm Bowel Dis 2007) [source] Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial,INTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Ninke Leffers Abstract The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53-SLP) vaccine, twenty patients with recurrent elevation of CA-125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53-SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no , grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN-, producing p53-specific T-cell responses were induced in all patients who received all 4 immunizations as measured by IFN-, ELISPOT. An IFN-, secretion assay showed that vaccine-induced p53-specific T-cells were CD4+, produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53-specific response. P53-specific T-cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53-specific T-cells. As best clinical response, stable disease evaluated by CA-125 levels and CT-scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine-induced immunity. This study shows that the p53-SLP vaccine is safe, well tolerated and induces p53-specific T-cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper-1 polarization and clinical efficacy. © 2009 UICC [source] Regulatory issues in cellular therapiesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S38 2002Adrian P. Gee, Article first published online: 23 APR 200 Cellular and gene therapies offer considerable promise as new treatment modalities. The Food and Drug Administration has been developing strategies to regulate these rapidly evolving fields in a manner that sustains progress and also ensures minimization of potential risks. The death of a patient on a gene therapy study highlighted a number of potential problems that have galvanized the agency to examine their strategy and to review current regulations for gene therapy. Meanwhile, a unified regulatory approach is emerging for cell-based therapies. This stratifies the level of regulation based upon the potential risk to the donor of the cells and the recipient. In this article the history and status of regulation of cellular therapy is briefly reviewed. J. Cell. Biochem. Suppl. 38: 104,112, 2002. © 2002 Wiley-Liss, Inc. [source] Congenital Diaphragmatic Hernia: Update and ReviewJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2001Linda J. Juretschke MSN Newborns with congenital diaphragmatic hernia (CDH) present challenges for the neonatal intensive-care nurse. Although CDH has been a known condition for almost 200 years, the treatment strategy for newborns with CDH has changed during the past decade. Despite these improvements, the mortality rate for this condition remains high. An understanding of the anatomical basis and new treatment modalities for this condition will prepare nurses to care for these newborns. [source] Diabetic neuropathy: therapies on the horizonJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2009Danish Mahmood Abstract Objectives This is a review of emerging interventions from the recent preclinical and clinical literature that demonstrate the potential for effectiveness in the therapy of diabetic neuropathy (DN). DN is the most common complication of diabetes mellitus and up to 50% of patients with type 1 and type 2 forms have some or other form of neuropathy. The pathology of DN is characterized by progressive nerve fibre loss that gives rise to positive and negative clinical signs and symptoms such as pain, paraesthesiae and loss of sensation. Key findings There are very few drugs available to directly treat DN. Those that are clinically indicated provide symptomatic relief but do not repair or reverse underlying nerve damage. However, some agents are in clinical development that may support adult neurons and direct reparative processes after injury stages. Several disease modifying drugs such as aldose reductase inhibitors and protein kinase C inhibitors are in phase III development. Agents on the horizon include neurotrophic factors, growth factors, gene therapy, immunotherapy, poly(ADP-ribose) polymerase inhibitors and non-immunosuppressive immunophilin ligands. Summary Progress has been made toward understanding the biochemical mechanisms leading to diabetic neuropathy, and as a result, new treatment modalities are being explored. The pathogenesis, types and approaches for treating DN together with the newer therapeutic interventions on the horizon are discussed. [source] Angiosarcoma of the scalp: new treatment modalitiesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2001U Wollina [source] A novel method of generating prostate cancer metastases from orthotopic implantsTHE PROSTATE, Issue 2 2003Eva Corey Abstract BACKGROUND Spontaneous metastasis following implantation at the orthotopic site is a highly desired feature in prostate cancer (CaP) models, since it would enable studies of mechanisms associated with tumor cell dissemination. METHODS LuCaP 23.8 and LuCaP 35, hormone-sensitive CaP xenografts that express PSA and the wild-type androgen receptor, were grown orthotopically in SCID mice. When tumor volumes reached ,250,500 mg, primary tumors were removed to allow micrometastases to grow. RESULTS Using this procedure we generated macroscopic metastases (>20 mg) in 71% (LuCaP 23.8) and 100% (LuCaP 35) of animals, respectively. CONCLUSIONS These models may be used to evaluate new treatment modalities and study mechanisms associated with development of metastases. Prostate 56: 110,114, 2003. © 2003 Wiley-Liss, Inc. [source] New treatment modalities for granuloma facialeBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2003E. Ludwig Summary Granuloma faciale (GF) is a rare, chronic skin disorder in which numerous treatment modalities have been used without any consistent long-term effect. We report three cases of GF, two of which were successfully treated with the Laserscope potassium-titanyl-phosphate 532-nm laser within 2 weeks and one with topical tacrolimus ointment 0·1%. Our observations suggest that these new treatment modalities for GF, which we report here for the first time, can provide effective and non-invasive treatment for this disease. [source] Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancerCANCER SCIENCE, Issue 3 2007Sun Lee Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low-oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3,28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9-expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329,333) [source] The economic burden of heart failureCLINICAL CARDIOLOGY, Issue S3 2000J. B. O'Connell M.D. Abstract Heart failure, a major cause of morbidity and mortality among the elderly, is a serious public health problem. As the population ages and the prevalence of heart failure increases, expenditures related to the care of these patients will climb dramatically. As a result, the health care industry must develop strategies to contain this staggering economic burden. Strategies may include adopting approaches for preventing heart failure and implementing new treatment modalities with proven efficacy into large-scale clinical practice. Successful implementation of these strategies will require intensive physician and patient education and development of innovative approaches to fund support services. [source] Itraconazole in the treatment of seborrheic dermatitis: a new treatment modalityINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2004Vahide Baysal MD Background, Due to the high rate of recurrence, seborrheic dermatitis (SD) represents a therapeutic problem. Aim, To evaluate the role of oral itraconazole in the treatment of SD. Patients and methods, Thirty-two patients with SD were enrolled in the study. All topical and oral treatments were stopped. The patients applied 1% hydrocortisone cream twice daily for 1 month. In addition, they took itraconazole, 200 mg/day, during the first week of the first month and then hydrocortisone cream was stopped and itraconazole (200 mg/day) was given on the first 2 days of the following 11 months. The patients were followed for 2 months without medicine. The severity score was measured at the initial evaluation, and at the first, 12th, and 14th months. Results, Twenty-eight patients completed the study. There was a statistically significant decrease in the mean severity score at the first, 12th, and 14th months. On the final evaluation at the 12th month, 19 of the 28 patients showed a complete improvement, and three patients showed a slight improvement. Conclusions, This study indicates that itraconazole plays an important role in the treatment of SD. [source] Electroporation-mediated muscarinic M3 receptor gene transfer into rat urinary bladderINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004MASAYUKI OTANI Abstract Background: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene. Methods: Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated. Results: The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum contractile responses of bladder smooth muscle strips significantly increased. Conclusions: These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity. [source] Improved treatment of sudden hearing loss by specific fibrinogen aphaeresisJOURNAL OF CLINICAL APHERESIS, Issue 2 2004Heidrun Ullrich Abstract The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14,16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1,15, 1986; Harris and Sharp, Laryngoscope 100:516,524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41,45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94,100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763,766, 1999; Suckfüll, Lancet 360:1811,1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641,645, 1996; Suckfüll et al., Otol. Neurotol. 23:309,311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1,3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80,100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 ± 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 ± 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen. In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss. J. Clin. Apheresis 19:71,78, 2004. © 2004 Wiley-Liss, Inc. [source] Clinical trial: interferential electric stimulation in functional dyspepsia patients , a prospective randomized studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010S. KÖKLÜ Aliment Pharmacol Ther,31, 961,968 Summary Background, There are several studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with gastroparesis and chronic constipation. Aim, To analyse whether transcutaneous electrical stimulation is an effective procedure in functional dyspepsia patients. Methods, Functional dyspepsia patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Upper gastrointestinal system symptoms were documented at the beginning, during and after the treatment sessions. Results, Patients in therapy (23 cases) and placebo (21 cases) groups were homogeneous with respect to demographic data and upper gastrointestinal system symptoms. In the therapy group, all symptoms other than early satiation improved significantly during and after the treatment sessions, whereas in the placebo group, symptoms including heartburn and vomiting did not change significantly. IFC therapy was superior to placebo with respect to epigastric discomfort, pyrosis, bloating, early satiation and postprandial fullness during the treatment sessions. One month after the treatment sessions, vacuum IFC proved to be superior to placebo with regard to early satiation and heartburn. Conclusions, Vacuum IFC is a non-invasive and effective therapy for functional dyspepsia. Transcutaneous electrical stimulation may represent a new treatment modality for drug-refractory functional dyspepsia patients. [source] Tyrosine kinase inhibitors: From rational design to clinical trialsMEDICINAL RESEARCH REVIEWS, Issue 6 2001Peter Traxler Abstract Protein kinases play a crucial role in signal transduction as well as in cellular proliferation, differentiation, and various regulatory mechanisms. The inhibition of growth related kinases, especially tyrosine kinases, might provide new therapies for diseases such as cancer. The progress made in the crystallization of protein kinases has confirmed that the ATP-binding domain of tyrosine kinases is an attractive target for drug design. Three successful examples of drug design at Novartis using a tyrosine kinase as a molecular target are described. PKI166, a pyrrolo[2,3,- d]pyrimidine derivative, is a dual inhibitor of both the EGFR and the ErbB2 kinases. The compound entered clinical trials in 1999, based on its favorable preclinical profile: potent inhibition of EGF-mediated signalling in cells, in vivo antitumor activity in several EGFR overexpressing xenograft tumor models in nude mice, long-lasting inhibition of EGF-stimulated EGFR autophosphorylation in tumor tissue, good oral bioavailability in animals, and no prohibitive in vitro and in vivo toxicity findings. The anilino-phthalazine derivative PTK787/ZK222584 (Phase I, co-developed by Schering AG, Berlin) is a potent and selective inhibitor of both the KDR and Flt-1 kinases with interesting anti-angiogenic and pharmacokinetic properties (orally bioavailable). STI571 (GlivecÔ, GleevecÔ), a phenylamino-pyrimidine derivative, is a potent inhibitor of the Abl tyrosine kinase, which is present in 95% of patients with chronic myelogenous leukemia (CML). The compound specifically inhibits proliferation of v-Abl and Bcr-Abl expressing cells (including cells from CML patients) and shows anti-tumor activity as a single agent in animal models at well-tolerated doses. Pharmacologically relevant concentrations are achieved in the plasma of animals (oral administration). Promising data from phase I and II clinical trials in CML patients (98% haematological response rate in Phase I) support the fact that the STI571 represents a new treatment modality for CML. In addition, potent inhibition of the PDGFR and c-Kit tyrosine kinases also indicates its possible clinical use in solid tumors. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 6, 499,512, 2001 [source] Fumaric acid esters therapy: a new treatment modality in pityriasis rubra pilaris?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005Article first published online: 23 FEB 200 No abstract is available for this article. [source] Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactionsCANCER SCIENCE, Issue 8 2007Yoshiki Akatsuka Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versus-leukemia/lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed self-proteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT. (Cancer Sci 2007; 98: 1139,1146) [source] Personalized peptide vaccines: A new therapeutic modality for cancerCANCER SCIENCE, Issue 10 2006Kyogo Itoh Therapeutic cancer vaccines have enjoyed little success so far, although many clinical trials have been conducted. Therefore, the creation of new protocols capable of inducing an objective response is required. We examined two of these protocols in the present review. The first is a personalized protocol to take into account the immunological diversity of cytotoxic T lymphocyte responses among patients. The second is a combination therapy designed to adapt to the presence of major histocompatibility complex (MHC)-loss cancer cells. The objective response rates of our classical (non-personalized) peptide vaccines were 0%, whereas that of personalized vaccines was 11.1% in the total advanced cancers and ,20% in malignant glioma and cervical cancers, respectively. A ,50% decrease in serum prostate-specific antigen (PSA) was seen in 8.7% of advanced hormone refractory prostate cancer patients by personalized vaccination alone, whereas such a decrease was seen in 54% of patients when the personalized vaccination was combined with a low dose of estramustine. Based on these experiences, we propose a personalized peptide vaccine combined with chemotherapy as a new treatment modality for cancers. (Cancer Sci 2006; 97: 970,976) [source] The effect of narrowband ultraviolet B on the expression of matrix metalloproteinase-1, transforming growth factor-,1 and type I collagen in human skin fibroblastsCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2 2007C. P. Choi Summary Background., Ultraviolet (UV) irradiation induces chronic skin diseases, such as skin cancer and photoageing, and the mechanisms of this skin damage are associated with the upregulation of matrix metalloproteinases (MMPs) and decreased collagen synthesis. Narrowband ultraviolet B (NB-UVB) radiation is a relatively new treatment modality for vitiligo and psoriasis. However, the mechanism of NB-UVB action on photoageing is not completely understood. Aims., We investigated the effects of NB-UVB on the expression of MMP-1, transforming growth factor (TGF)-,1 and type I collagen in cultured human skin fibroblasts. Methods., Cultured human fibroblasts were irradiated with either NB-UVB (50,800 mJ/cm2) or broadband UVB (BB-UVB; 25 mJ/cm2). The expression of MMP-1, TGF-,1 and type I collagen mRNA was determined by reverse-transcription PCR. Expression of MMP-1 and TGF-,1 protein was determined by ELISA and that of type I collagen by Western blotting. Results., NB-UVB induced the expression of MMP-1 and reduced the expression of TGF-,1 and type I collagen at the mRNA and protein levels in a dose-dependent manner. The expression of type I collagen protein decreased more after irradiation with 25 mJ/cm2 of BB-UVB than 400 mJ/cm2 of NB-UVB. Conclusions., This study indicates that NB-UVB irradiation reduces type I collagen synthesis in human skin fibroblasts by inhibiting TGF-,1 expression and stimulating the release of MMP-1. It also suggested that the photoageing-related effects of NB-UVB are weaker than those of BB-UVB in vitro. [source] | ||||||||||||||||||||||||||||||||||