ABSTRACT
Functional dyspepsia (FD) is a constellation of epigastric symptoms originating in the gastroduodenal region without organic and metabolic cause. However, similar confounding symptoms can also appear in patients with gallbladder (GB) dyskinesia. Therefore, symptoms of GB dyskinesia may be mistaken for FD. We aimed to identify GB dyskinesia as a cause of FD symptoms compatible with the Rome IV criteria and the need for an evaluation of GB function in patients with FD symptoms.We investigated information of patients with FD symptoms who underwent a quantitative Tc-diisoproyl iminodiacetic acid cholescintigraphy (DISIDA scan) through electronic medical records, and GB dyskinesia was judged to be the cause of the FD symptoms if the symptoms disappeared as GB function normalized on the follow-up DISIA scan in patient with decreased GB function on the initial DISIDA scan.A total of 275 patients underwent a DISIDA scan. Eighteen patients of them had FD symptoms compatible with the Rome IV criteria. Three were lost after undergoing a DISIDA scan. Eight had normal GB function, and the other 7 had decreased GB function on the initial DISIDA scan. In 4 of the 7 patients with GB dyskinesia, FD symptoms disappeared as GB function normalized. As a result, GB dyskinesia was the cause of the symptoms in 4 of 18 patients with FD symptoms compatible with the Rome IV criteria.It is necessary to evaluate GB function in patients with refractory FD symptoms because the symptoms can be caused by GB dyskinesia.
Subject(s)
Biliary Dyskinesia/diagnosis , Adult , Biliary Dyskinesia/diagnostic imaging , Diagnosis, Differential , Dyspepsia/diagnosis , Female , Humans , Male , Middle Aged , Radionuclide Imaging , Retrospective StudiesABSTRACT
UNLABELLED: Background : The impact of the RECIST 1.1 on the selection of target lesions and assessment of tumor response was not evaluated in patients with advanced NSCLC who received cytotoxic chemotherapy. METHODS: We reviewed medical records of patients with advanced NSCLC who received first-line chemotherapy between January 2004 and December 2013 and compared the selection of target lesions and tumor responses using the two RECIST versions. RESULTS: A total of 88 patients who had at least one target lesion according to the RECIST 1.0 were included in the study. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0. When adopting the RECIST 1.1 instead of the RECIST 1.0, 40 patients (45.4%) showed a decrease in the number of target lesions. Three patients no longer had target lesion because of the new lymph node (LN) criteria of the RECIST 1.1. Tumor responses showed a high level of concordance between the RECIST 1.0 and RECIST 1.1, with a kappa value of 0.912. Four patients (4.5%) showed disagreement of tumor responses between the two criteria, which were all due to the change of the LN criteria. CONCLUSION: The RECIST 1.1 showed a high level of concordance with the RECIST 1.0 in the assessment of tumor response in advanced NSCLC patients treated with cytotoxic chemotherapy. The new LN criteria were the major cause of the reduction of target lesions and reclassification of the tumor response.
ABSTRACT
BACKGROUND: The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients. METHODS: We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1). RESULTS: A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0). CONCLUSIONS: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice.
ABSTRACT
PURPOSE: Platinum-based doublet chemotherapy has a major role in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The weekly fractionated administration of cisplatin for patients with NSCLC has been shown to be active. Irinotecan and carboplatin are effective against NSCLC and demonstrated synergism with non-cross-resistance in preclinical studies. We conducted a phase II study of weekly combination of carboplatin and irinotecan as first-line chemotherapy for patients with advanced NSCLC. METHODS: From March 2009 to November 2011, 24 patients who were diagnosed with inoperable or metastatic NSCLC were enrolled. Treatment consisted of carboplatin at an AUC 2.5 mg/mL/min over 30-min intravenous infusion and irinotecan 65 mg/m(2) over 90-min intravenous infusion on day 1 and day 8, respectively. The treatment was repeated every 3 weeks. RESULTS: One patient (4.2 %) achieved complete response, and seven (29.2 %) showed partial response. Overall response rate was 33.3 %, with median response duration of 4.55 months. Nine patients had stable disease, and disease control rate was 70.8 %. With median follow-up of 12.8 months, median progression-free survival was 4.5 months (95 % CI 1.8-7.2), and median overall survival was 15.5 months (95 % CI 6.9-24.1). Major toxicity was myelosuppression. Grade 3-4 neutropenia and thrombocytopenia occurred in 50 and 20.8 % of patients, respectively. Two patients experienced febrile neutropenia. Non-hematologic toxicities were generally mild. One patient suffered grade 4 diarrhea, and one treatment-related death due to pneumonia was occurred. CONCLUSION: The weekly combination of carboplatin and irinotecan showed favorable activity and manageable toxicity profiles in chemo-naïve patients with advanced NSCLC. Our results suggest that this regimen can be a reasonable chemotherapeutic option for patients with advanced NSCLC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Irinotecan , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm StagingABSTRACT
A gene (acas) designated as alpha-amylase was cloned from Arthrobacter chlorophenolicus A6. The multiple amino acid sequence analysis and functional expression of acas revealed that this gene really encoded an amylosucrase (ASase) instead of alpha-amylase. In fact, the recombinant enzyme exhibited typical ASase activity by showing both sucrose hydrolysis and glucosyltransferase activities. The purified enzyme has a molecular mass of 72 kDa and exhibits optimal hydrolysis activity at 45 degrees C and a pH of 8.0. The analysis of the oligomeric state of ACAS with gel permeation chromatography revealed that the ACAS existed as a monomer.
Subject(s)
Arthrobacter/enzymology , Bacterial Proteins/biosynthesis , Glucosyltransferases/biosynthesis , Recombinant Proteins/metabolism , Amino Acid Sequence , Arthrobacter/genetics , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Escherichia coli/enzymology , Escherichia coli/genetics , Glucosyltransferases/genetics , Glucosyltransferases/isolation & purification , Molecular Sequence Data , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Sequence Alignment , Sucrose/metabolismABSTRACT
Amylomaltase, or 4-α-glucanotransferase (EC 2.4.1.25), is involved in glycogen and maltooligosaccharide metabolism in microorganisms, catalyzing both the hydrolysis and transfer of an α-1,4-oligosacchraride to other sugar molecules. In this study, we determined the crystal structure of amylomaltase from Thermus brockianus at a resolution of 2.3 Å and conducted a biochemical study to understand the detailed mechanism for its activity. Careful comparison with previous amylomaltase structures showed a pattern of conformational flexibility in the 250s loop with higher B-factor. Amylomaltase from T. brockianus exhibited a high transglycosylation factor for glucose and a lower value for maltose. Mutation of Gln256 resulted in increased K(m) for maltotriose and a sharp decrease of the transglycosylation factor for maltose, suggesting the involvement of Gln 256 in substrate binding between subsites +1 and +2. Mutation of Phe251 resulted in significantly lower glucose production but increased maltose production from maltopentose substrates, showing an altered substrate-binding affinity. The mutational data suggest the conformational flexibility of the loop may be involved in substrate binding in the GH77 family. Here, we present an action model of the 250s loop providing the molecular basis for the involvement of residues Phe251, Gln256, and Trp258 in the hydrolysis and transglycosylation activities in amylomaltase.