Subject(s)
Cyclophosphamide/adverse effects , Cytomegalovirus Infections/drug therapy , Cytomegalovirus , Immunosuppressive Agents/adverse effects , Stomach Ulcer/virology , Cyclophosphamide/therapeutic use , Dermatomyositis/complications , Dermatomyositis/drug therapy , Female , Ganciclovir/therapeutic use , Gastroscopy , Humans , Immunosuppressive Agents/therapeutic use , Middle Aged , Steroids/therapeutic use , Stomach Ulcer/complications , Stomach Ulcer/pathologySubject(s)
Adenocarcinoma/pathology , Intussusception/diagnostic imaging , Peutz-Jeghers Syndrome/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/complications , Adult , Female , Hemorrhage/etiology , Humans , Intussusception/complications , Peutz-Jeghers Syndrome/complications , Tomography, X-Ray Computed , Uterine Cervical Neoplasms/complicationsSubject(s)
Crohn Disease/complications , Ileal Diseases/diagnostic imaging , Intestinal Perforation/diagnostic imaging , Pneumoperitoneum/diagnostic imaging , Radiography, Thoracic , Supine Position , Adult , Crohn Disease/diagnostic imaging , Humans , Ileal Diseases/etiology , Intestinal Perforation/etiology , Male , Pneumoperitoneum/etiologyABSTRACT
Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti-retroviral therapy. HCV-related liver disease is more severe in HIV-infected patients than in non-HIV-infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down-regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin-selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose-dependently repressed HCV replication at low concentrations (IC(50), 9.88 micromol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 micromol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.
Subject(s)
Antiviral Agents/pharmacology , Hepacivirus/drug effects , Interferon-alpha/pharmacology , Nelfinavir/pharmacology , Virus Replication/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Synergism , Genes, Reporter , Humans , Inhibitory Concentration 50 , Luciferases/genetics , Luciferases/metabolismSubject(s)
Crohn Disease/diagnosis , Duodenal Diseases/pathology , Duodenoscopy/methods , Stomach Diseases/pathology , Adult , Cecum/surgery , Crohn Disease/pathology , Crohn Disease/surgery , Duodenal Diseases/diagnosis , Endoscopy, Gastrointestinal/methods , Follow-Up Studies , Humans , Ileum/surgery , Image Enhancement/methods , Indigo Carmine , Intestinal Mucosa/pathology , Laparotomy/methods , Male , Preoperative Care/methods , Risk Assessment , Sensitivity and Specificity , Stomach Diseases/diagnosisSubject(s)
Crohn Disease/diagnostic imaging , Adult , Barium Sulfate , Contrast Media , Humans , Male , RadiographySubject(s)
Crohn Disease/complications , Ileal Diseases/diagnosis , Intestinal Fistula/diagnosis , Urinary Bladder Fistula/diagnosis , Adult , Diagnostic Imaging , Humans , Ileal Diseases/etiology , Ileal Diseases/therapy , Intestinal Fistula/etiology , Intestinal Fistula/therapy , Male , Urinary Bladder Fistula/etiology , Urinary Bladder Fistula/therapySubject(s)
Diphosphonates/adverse effects , Esophagitis/chemically induced , Esophagoscopy , Hematemesis/chemically induced , Administration, Oral , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Diphosphonates/therapeutic use , Esophagitis/diagnosis , Esophagus/drug effects , Esophagus/pathology , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Mucous Membrane/drug effects , Mucous Membrane/pathology , Osteoporosis/chemically induced , Osteoporosis/prevention & controlABSTRACT
The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.
