Non-alcoholic steatohepatitis occurring in a patient with T-lymphoblastic lymphoma during chemotherapy including prednisolone.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Keiichi Kondo
Publications and source records attributed to Keiichi Kondo.
Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping.
Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor-associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG(1) mAb that recognizes a sialylated sugar chain, designated as KL-6, classified in 'Cluster 9 (MUC1)'. Using the anti-KL-6 mAb, we investigated antitumor effects of anti-MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti-KL-6 mAb induced capping of MUC1 and facilitated E-cadherin-mediated cell-cell interaction in the breast cancer cell lines YMB-S and ZR-75-1S, which proliferate in suspension culture without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of lymphokine-activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell-cell interactions, leading to inhibition of tumor proliferation due to cell-cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells.
Animals↗
Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis.
OBJECTIVE: Circulating levels of KL-6, a high MW glycoprotein (MUC1 mucin), are elevated in a majority of patients with a number of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). However, KL-6 levels vary from patient to patient. The aim of the present study was to determine whether the serum KL-6 level at the time of diagnosis predicts prognosis in IPF. METHODS: The relationship between clinical variables and prognosis in 27 patients with IPF were analysed retrospectively. The diagnosis was made by histological examination (n = 16) or on clinical findings including high-resolution CT scanning (n = 11). All patients were followed up for at least 3 years. Variables such as age, FVC%, PaO(2) at rest, initial LDH level, C-reactive protein and KL-6 were used for analysis. RESULTS: At the cut-off level determined by receiver operating characteristic curves, LDH and KL-6 showed a significant correlation with the patient's prognosis by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of prognosis. The patients were categorized by their serum KL-6 levels (as above or below the cut-off level of 1000 U/mL) and their survival estimated using the Kaplan-Meier method. The difference in median survival between the two groups was significant. The median survival of patients with low KL-6 was more than 36 months, whereas that of patients with high KL-6 was only 18 months. CONCLUSION: These results suggest that initial evaluation of serum KL-6 level can predict survival in patients with IPF.
Antigens, Neoplasm↗
Effect of imatinib mesylate combined with granulocyte colony-stimulating factor on leukaemic blast cells derived from advanced-stage chronic myelogenous leukaemia patients.
Neutropenia is a severe adverse effect that can occur when treating patients with imatinib mesylate for advanced-stage chronic myelogenous leukaemia (CML). Therefore, we evaluated in vitro the combined effect of imatinib and granulocyte colony-stimulating factor (G-CSF) on proliferation and apoptosis of Bcr-Abl-expressing leukaemic cells to infer the safety of G-CSF administration. In KU812 and K562 cell lines, G-CSF neither stimulated their proliferation nor abolished the suppressive effect of imatinib. However, it stimulated the proliferation of blast cells in 2 out of the 5 cases with advanced-stage CML. These in vitro studies appear to provide data for the decision of G-CSF administration in combination with imatinib in the treatment of neutropenic patients with advanced-stage CML.
Antineoplastic Agents↗
Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein.
Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an allele-specific manner. The best documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and hence target for destruction, the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type 2C VHL disease), in contrast to classical VHL disease, appear to be normal with respect to HIF regulation. Using a simple method for identifying proteins that are differentially secreted by isogenic cell line pairs, we confirmed that the HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells. In addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression and secretion of clusterin, which does not behave like a HIF target. Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohistochemistry. Therefore, clusterin is a secreted marker for a HIF-independent pVHL function that might be especially important in pheochromocytoma development.
Adrenal Gland Neoplasms↗
[A case of seminoma with a low level positive of serum hCG (human chorionic gonadotropin) beta considered as false positive hCGbeta].
A 32-year-old male consulted a hospital with a complaint of left scrotal swelling. Serum hCGbeta and LDH levels were elevated and computed tomography demonstrated a suspicious small lymphadenopathy in the paraaortic region. Left inguinal orchiectomy was performed. Histological examination demonstrated seminoma. We diagnosed the disease as clinical stage 2A and the patient received 2 courses of chemotherapy with cisplatin, etoposide and bleomycin. After this therapy, the small lymphadenopathy in the paraaortic region did not decrease in size. We considered this lesion a vessel or connective tissue. Although he achieved clinical complete remission and serum LDH level was normalized, the serum hCGbeta level remained low level positive. Urinary hCGbeta level after chemotherapy was below the threshold of detectability. We measured the serum from this patient as well as control sera by two- and four-fold dilution with a diluent comprised of mouse serum as a heterophilic antibody-blocking agent. The serum hCGbeta level of this patient was obviously decreased; in contrast, control sera were decreased in parallel. The serum hCGbeta level of this patient remained low level positive without recurrence for 8 months after chemotherapy. These results strongly suggested that low level of positivity for serum hCGbea in this case was a false positive finding. We consider the measurement of urinary hCGbeta and dilution measurement using a heterophilic antibody-blocking agent to be useful methods of distinguishing false positive findings for serum hCGbeta.
Adult↗
[Propiverine hydrochloride improved correlatively subjective QOL and objective findings in Japanese patients with urinary frequency and/or incontinence].
To investigate how urinary frequency and incontinence affect the patient's subjective quality of life (QOL) and whether an improvement in objective findings by medical treatment affects his/her subjective QOL, a voiding diary using the King's Health Questionnaire (KHQ) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was delivered to patients with urinary frequency and/or incontinence before and after treatment with propiverine hydrochloride for 8 weeks. Sixty-eight patients completed the diary and the questionnaires. Objective symptoms decreased significantly with respect to the mean frequency of urination and to the mean incidence of urinary incontinence. The KHQ and ICIQ-SF scores improved significantly with respect to all domains except personal relationships in the KHQ. In the KHQ, furthermore, a significant correlation was found between decreased incidence of urinary incontinence and improvement in role limitations and between decreased incidence of urinary incontinence and improvement in emotional problems. In the ICIQ-SF, a significant correlation was found between decreased incidence of urinary frequency and subjective improvement in quantity of leakage, between decreased incidence of urinary frequency and improvement in subjective QOL scores, between decreased incidence of urinary frequency and improvement in the total ICIQ-SF score, and between decreased incidence of urinary incontinence and improvement in subjective QOL scores. Thirty-two episodes of adverse reactions were observed. None of them were serious. These results suggest that an improvement in objective symptoms with propiverine hydrochloride favorably improves subjective QOL of the patient, and provide further evidence about the safety and efficacy of propiverine hydrochloride.
Adult↗
Recovery of serum prostate specific antigen value after interruption of antiandrogen therapy with allylestrenol for benign prostatic hyperplasia.
Decrease in serum prostate specific antigen (PSA) concentration is inevitably associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and might mask the presence of prostate cancer or delay its diagnosis. To determine the appropriate timepoint for determination of correct PSA value, we sequentially measured serum PSA and testosterone levels after discontinuation of antiandrogen therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old) with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum testosterone and PSA concentrations were determined before and just after treatment, as well as every month after treatment up to 3 months. After treatment with allylestrenol for 4 months, mean serum testosterone and PSA levels were significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81 +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level recovered to the pretreatment level within 2 months and mean serum testosterone concentration within one month after discontinuation of administration. In conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month washout is adequate for determination of correct PSA value (*: M +/- SD).
Allylestrenol↗
Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small cell lung cancer.
PURPOSE: Aminopeptidase N, also known as CD13, has important roles in tumor metastasis and angiogenesis. Its expression in tumor tissue has been reported to be associated with poor prognosis. However, the clinical significance of circulating aminopeptidase N/CD13 in patients with solid tumors is unknown. We previously developed an aminopeptidase N/CD13-specific monoclonal antibody (mAb) MH8-11, which inhibits cell motility and angiogenesis in vitro. The aim of this study was to evaluate the clinical significance of circulating aminopeptidase N/CD13 protein detected by mAb MH8-11 in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We used electrochemiluminescence immunoassay with mAb MH8-11 to determine circulating aminopeptidase N/CD13 levels in 90 healthy volunteers and 90 patients with NSCLC. Circulating aminopeptidase N/CD13 levels were measured in sera taken before treatment and evaluated for a relationship with clinical outcomes. RESULTS: A significant correlation was found between tumor progression and serum aminopeptidase N/CD13 concentrations (r=0.23, P=0.029). High serum aminopeptidase N/CD13 levels (n=17) were associated with advanced stage (P=0.004) or poor performance status (P=0.001). The overall survival rate for patients with high serum aminopeptidase N/CD13 levels (n=17) was significantly less than that of patients with low serum aminopeptidase N/CD13 levels (n=73, P<0.0001). In a multivariate survival analysis in patients with NSCLC, serum aminopeptidase N/CD13 levels had an independent influence on survival (relative risk, 4.1; 95% confidence interval, 1.9-8.8). CONCLUSIONS: Our data suggest that a high level of circulating aminopeptidase N/CD13 at diagnosis is an independent prognostic factor in patients with NSCLC.
Antibodies, Monoclonal↗
Neutropenic enterocolitis in lung cancer: a report of two cases and a review of the literature.
The first patient, a 68-year-old woman, presented neutropenic fever and hemorrhagic diarrhea on the sixth day of a combination chemotherapy of carboplatin and paclitaxel. The second patient, a 30-year-old man, presented neutropenia and diarrhea on the tenth day of the second cycle of a combination chemotherapy of cisplatin and vinorelbine. In both patients, abdominal computed tomography scan showed thickening of the colon wall and pericolic edema, and the ultrasonography revealed echogenic thickening of the colon walls. These findings confirmed the diagnosis of neutropenic enterocolitis. After the treatments, we changed the anticancer drug regimen; and successfully achieved partial responses.
Adenocarcinoma↗
Polymorphism of the MUC1 mucin gene is associated with susceptibility to lung adenocarcinoma and poor prognosis.
MUC1 is a highly glycosylated glycoprotein that is often overexpressed in adenocarcinomas. MUC1 has molecular diversity because of a variable number of tandem repeats (from 25-125 repeats) in the extracellular domain of its core protein. MUC1 plays an important role in facilitating invasion and metastasis of malignant cells, and it also inhibits anti-cancer immune activity against malignant cells. We hypothesize that MUC1 allele length polymorphism (variable number of tandem repeats) is associated with development of lung adenocarcinoma. We evaluated MUC1 gene polymorphism using Southern blot analysis of peripheral blood from patients with non-small cell lung cancer (n=56), patients with benign respiratory disease (n=52), and healthy volunteers (n=52). We found that large MUC1 allele length was significantly associated with lung adenocarcinoma but not with squamous cell carcinoma of the lung. Adenocarcinoma patients with a homozygous large MUC1 genotype had a worse prognosis than patients with a heterozygous (large + small) MUC1 genotype or a homozygous small MUC1 genotype. These results suggest that the large MUC1 allele is associated with susceptibility to lung adenocarcinoma and poor prognosis.
Adenocarcinoma↗
Distal femoral cut perpendicular to the mechanical axis may induce varus instability in flexion in medial osteoarthritic knees with varus deformity in total knee arthroplasty: a pitfall of the navigation system.
Two factors that influence the external rotation angle of the femoral rotational axis in total knee arthroplasty (TKA) were assessed in 40 medial osteoarthritic knees with varus deformity. First, the anatomic configuration of the femur was assessed using standardized radiographs of the patients' lower extremities before TKA. Second, the degree of medial soft tissue release was assessed during TKA. The radiographs showed that the characteristics of the femur were lateral bowing of the shaft and external rotation of the condyle in the coronal plane. Therefore, when the distal femur is cut perpendicular to the mechanical axis, the cut surface may be in too much of a valgus position. Furthermore, some degree of medial soft tissue release was necessary in all knees. Medial soft tissue release rotates the femur externally in extension in the coronal plane, and it rotates the femur externally around the femoral axis in flexion relative to the tibia. A distal femoral cut in too much of a valgus position and medial soft tissue release induces varus instability in flexion in knees with lateral bowing of the femoral shaft. Anatomic variation such as femoral bowing should be considered when a navigation system is used for TKA because the navigation system shows only the mechanical axis.
Aged↗
Expression patterns of sialylated epitope recognized by KL-6 monoclonal antibody in ocular surface epithelium of normals and dry eye patients.
PURPOSE: To determine the association of the KL-6 epitope (sugar moiety) with MUC1 and its distribution on the ocular surface of human non-dry and dry eyes. METHODS: The human ocular surface was examined immunohistochemically and immunoelectron microscopically using monoclonal antibody (mAb) KL-6, which recognize a carbohydrate epitope of MUC1. The expression patterns of KL-6 epitope in corneal and conjunctival cells were examined by impression cytology from 24 non-dry eye volunteers and 43 dry-eye patients. RESULTS: In the cornea, bulbar conjunctiva, and limbus epithelium, mAb KL-6 reacted to the apical cell membrane of superficial cells and the intercellular space of superficial and wing cells. No immune reactivity of mAb KL-6 was observed in the basal plasma membrane of basal epithelial cells. Results of impression cytology indicated that the corneal epithelium of 13 of 24 non-dry eyes was weakly stained by mAb KL-6, whereas 42 of 43 dry eyes showed a mosaic pattern. In non-dry eyes, 19 of 24 bulbar conjunctival epithelia expressed the KL-6 epitope in a honeycomb pattern. In mild (17/19) and moderate (17/17) dry eye conjunctiva, the KL-6 epitope showed a mosaic pattern. However, the expression of KL-6 epitope decreased in severe dry eyes, showing a mosaic pattern in three of seven patients and labeling a few cells weakly in four of seven patients. CONCLUSIONS: These findings suggest that there is an upregulation of the sialylated KL-6 epitope of MUC1 by apical corneal and conjunctival cells in mild and moderate dry eyes. This upregulation may in part alleviate the consequences caused by goblet cell mucin dysfunction in dry eyes. It is noteworthy that the KL-6 epitope is downregulated in the conjunctiva of severe dry eyes, a phenomenon that may be explained in part by the malfunction of conjunctival epithelial cells.
Antibodies, Monoclonal↗
Successful micafungin (FK463) treatment of invasive pulmonary aspergillosis in a patient with acute lymphoblastic leukemia in a phase II study.
We treated a 52-year-old woman with acute lymphoblastic leukemia (ALL) who developed invasive pulmonary aspergillosis (IPA) as a result of neutropenia following remission-induction chemotherapy. Although serological test results, such as those for platelia and pastrex, were all negative and the serum level of beta-D-glucan was low, Aspergillus DNA was detected in blood by the polymerase chain reaction method. A clinically documented diagnosis of IPA was made on the basis of chest x-rays, computed tomography scan findings, and the detection of Aspergillus DNA. Micafungin (FK463), a candin class antifungal agent, was administered at a dose of 75 to 150 mg/day, because other antifungal agents were not effective. The increase in serum concentration of micafungin was dose-dependent and was accompanied by improvement of symptoms and objective findings. Micafungin was effective for the treatment of IPA in this patient with ALL.
Antineoplastic Agents↗
Pulmonary edema in pheochromocytoma.
Explore the source record for details and available documents.
Adrenal Gland Neoplasms↗
Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer.
We conducted a clinical pharmacological evaluation of paclitaxel/carboplatin combination in Japanese patients with non-small cell lung cancer. The purpose of this study was to identify the optimal dose of this combination and to investigate the relationships between the pharmacokinetic profiles of these 2 drugs, serum thrombopoietin (TPO) kinetics and the platelet-sparing effect. Patients received paclitaxel at 180-225 mg/m(2) by intravenous infusion over 3 h, followed by carboplatin at a target area under the concentration-time curve (AUC) of 6 mg/ml x min as a 1-h infusion. Serum paclitaxel, free platinum and TPO concentrations were measured using high-performance liquid chromatography, atomic absorption spectrometry and a double-sandwich enzyme-linked immunosorbent assay, respectively. Thirteen patients were enrolled. Neutropenia was the most frequent hematological toxicity and was significantly related to the time for which paclitaxel concentrations remained above 0.05 micro mol/ml. The prominent non-hematological toxicities were myalgia and sensory-dominant neuropathy. In this study, platelet and serum TPO kinetics were clearly different from those in our previous study of single-agent carboplatin (21). The platelet counts at the nadir were significantly higher (p<0.0001) in patients treated with paclitaxel/carboplatin combination (161,000+/-38,000/ micro l) compared with single-agent carboplatin (92,000+/-28,000/ micro l). The early increase in TPO (the percentage increase in TPO at day 4) was significantly greater (p=0.0345) in patients treated with paclitaxel/carboplatin combination (57.8+/-44.5%) compared with single-agent carboplatin (21.3+/-34.1%). The recommended doses are paclitaxel 210 mg/m(2) and carboplatin at an AUC of 6 mg/ml x min every 3 weeks. The observed platelet-sparing effect of the paclitaxel/carboplatin might be related to the early increase in circulating TPO levels, although the precise mechanism remains to be elucidated.
Adenocarcinoma↗
Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth.
Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is linked to the development of hereditary (VHL-associated) and sporadic clear-cell renal carcinomas as well as other abnormalities. The VHL gene product, pVHL, is part of an E3 ubiquitin ligase complex that targets the alpha subunits of the heterodimeric transcription factor HIF (hypoxia-inducible factor) for degradation in the presence of oxygen. Here we report that a HIF2alpha variant lacking both of its two prolyl hydroxylation/pVHL-binding sites prevents tumor inhibition by pVHL in a DNA-binding dependent manner. Conversely, downregulation of HIF2alpha with short hairpin RNAs is sufficient to suppress tumor formation by pVHL-defective renal carcinoma cells. These results establish that tumor suppression by pVHL is linked to regulation of HIF target genes.
Adenocarcinoma, Clear Cell↗
Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor.
Loss of the von Hippel-Lindau gene (VHL) expression ca-uses deregulation of contact inhibition of cell growth, which might be one of the bases of the tumor suppressor function of VHL. Here we show that this function of the VHL gene product (pVHL) depends on cell autonomous events. To identify the target gene of pVHL, which is directly involved in the contact inhibition, we compared the gene expression profile between VHL-deficient renal carcinoma 786-O cells and those infected with an adenovirus vector encoding VHL. In addition to known pVHL-regulated genes, such as vascular endothelial growth factor and carbonic anhydrase, we found cyclinD1 as a new target of pVHL at a high cell density. In VHL-expressing cells (VHL (+) cells), the cyclinD1 mRNA expression level diminishes at a high cell density, while it remains at a relatively high level in VHL-deficient cells (VHL (-) cells). The cyclinD1 expression level was also abnormally high in VHL (-) cells at a high cell density. Consequently, the phosporylation level of the retinoblastoma (Rb) protein remained high in these cells, whereas there was no phosporylated Rb in VHL (+) cells under the contact inhibition. The abnormal expression of cyclinD1 at a high cell density was observed even in VHL (+) cells under the hypoxic state. Moreover, ectopic expression of a HIF mutant resistant to pVHL-mediated proteolysis causes the abnormal cyclinD1 expression in VHL (+) cells. Taken together, these observations indicate that VHL is required for the downregulation of cyclinD1 at a high cell density through HIF.
Carbonic Anhydrases↗