Biomedical subjects

Yukinori Kurokawa

Publications and source records attributed to Yukinori Kurokawa.

10 recordsLinked to original sources

PubMed2026

A multicenter phase II trial of ramucirumab plus irinotecan for early recurrence of gastric cancer during or after adjuvant chemotherapy with docetaxel plus S-1 therapy: the RAMIEL trial (OGSG1901).

BACKGROUND: There is currently no established chemotherapy regimen for early recurrence of pathological stage III gastric cancer (GC) following adjuvant chemotherapy with docetaxel plus S-1 (DS) after D2 gastrectomy. We aimed to evaluate the efficacy and safety of ramucirumab plus irinotecan in patients with GC who experienced early recurrence during or within 6 months after DS adjuvant chemotherapy. METHODS: This prospective, open-label, multicenter phase II trial enrolled eligible patients treated at 25 centers of the Osaka Gastrointestinal Cancer Chemotherapy Study Group in Japan. Patients received ramucirumab (8 mg/kg) and irinotecan (150 mg/m2) every 2 weeks. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. The sample size was set at 40 based on a threshold median OS of 7 months and an expected median OS of 11 months, with a one-sided alpha error of 0.05 and a power of 0.80. RESULTS: Between November 2019 and July 2023, 43 patients were enrolled, and 39 were included in the analysis after excluding three ineligible patients and one who did not initiate protocol treatment. The median OS was 15.9 months (95% CI: 8.8-42.0; p = 0.003). The median PFS was 5.5 months (95% CI: 3.9-8.1), and the ORR was 38.5%. Grade  ≥ 3 adverse events, including neutropenia (25.6%) and hypertension (25.6%), were observed in more than 20% of patients. CONCLUSION: Ramucirumab plus irinotecan demonstrated promising efficacy and manageable toxicity in patients with early recurrence of GC following adjuvant DS therapy. TRIAL REGISTRATION: This study was prospectively registered in the Japan Registry of Clinical Trials (jRCTs05119071, October 6, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs051190071 ).

Docetaxel↗

PubMed2006

Influence of overweight on surgical complications for gastric cancer: results from a randomized control trial comparing D2 and extended para-aortic D3 lymphadenectomy (JCOG9501).

BACKGROUND: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. METHODS: We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). RESULTS: Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. CONCLUSIONS: Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.

Aged↗

PubMed2006

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site.

Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.

Aged↗

PubMed2006

Central genetic alterations common to all HCV-positive, HBV-positive and non-B, non-C hepatocellular carcinoma: a new approach to identify novel tumor markers.

Hepatocellular carcinoma (HCC) is a common malignancy, but the prognosis remains poor due to the lack of sensitive diagnostic markers. To gain insight into the central molecular features common to all types of HCC, and to identify novel diagnostic markers or therapeutic targets for HCC, we performed a gene expression profiling analysis using a high throughput RT-PCR system. After examining the mRNA expression of 3,072 genes in 204 (119 tumor and 85 non-tumor) liver samples, we identified differential gene expression between the HCV group (n=80), HBV group (n=19) and non-B, non-C group (n=20) with a principal component analysis and a correlation spectrum analysis. After selection of genes differentially expressed between tumor and non-tumor tissues (p<0.01) within each HCC group, a total of 51 differentially expressed genes (23 upregulated and 28 downregulated genes) were found to be common to the three HCC groups. Gene Ontology grouping analysis revealed that genes with functions related to cell proliferation or differentiation and genes encoding extracellular proteins were found to be significantly enriched in these 51 common genes. Using an atelocollagen-based cell transfection array for functional analysis of eight upregulated genes, five (CANX, FAM34A, PVRL2, LAMR1, and GBA) significantly inhibited cellular apoptosis by two independent assays. In conclusion, we identified 51 differentially expressed genes, common to all HCC types. Among these genes, there was a high incidence of anti-apoptotic activity. This combination approach with the advanced statistical methods and the bioinformatical analysis may be useful for finding novel molecular targets for diagnosis and therapy.

Apoptosis↗

PubMed2005

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Aged↗

PubMed2004

Molecular prediction of response to 5-fluorouracil and interferon-alpha combination chemotherapy in advanced hepatocellular carcinoma.

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) is very poor, particularly in patients with tumors that have invaded the major branches of the portal vein. Combination chemotherapy with intra-arterial 5-fluorouracil and subcutaneous interferon-alpha has shown promising results for such advanced HCC, but it is important to develop the ability to accurately predict chemotherapeutic responses. EXPERIMENTAL DESIGN: We analyzed the expression of 3,080 genes using a polymerase chain reaction-based array in 20 HCC patients who were treated with combination chemotherapy after reduction surgery. After unsupervised analyses, a supervised classification method for predicting chemotherapeutic responses was constructed. To minimize the number of predictive genes, we used a random permutation test to select only significant (P < 0.01) genes. A leave-one-out cross-validation confirmed the gene selection. We also prepared an additional 11 cases for validation of predictive performance. RESULTS: Hierarchical clustering analysis and principal component analysis with all 3,080 genes revealed distinct gene expression patterns in responders (those with complete response or partial response) and nonresponders (those with stable disease or progressive disease) to the combination chemotherapy. Using a weighted-voting classification method with either all genes or only significant genes as assessed by permutation testing, the objective responses to treatment were correctly predicted in 17 of 20 cases (accuracy, 85%; positive predictive value, 100%; negative predictive value, 80%). Moreover, patients in the validation dataset could be classified into two distinct prognostic groups using 63 predictive genes. CONCLUSIONS: Molecular analysis of 63 genes can predict the response of patients with advanced HCC and major portal vein tumor thrombi to combination chemotherapy with 5-fluorouracil and interferon-alpha.

Adult↗

PubMed2004

Constrained clusters of gene expression profiles with pathological features.

MOTIVATION: Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features. RESULTS: We present the novel technique of 'itemset constrained clustering' (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as 'tumor' and 'man', or 'except tumor' and 'normal liver function'. In contrast, the k-means method overlooked these clusters.

Algorithms↗

PubMed2004

Molecular-based prediction of early recurrence in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a very poor prognosis, due to the high incidence of tumor recurrence. As the current morphological indicators are often insufficient for therapeutic decisions, we sought to identify additional biologic indicators for early recurrence. METHODS: We analyzed gene expression using a PCR-based array of 3,072 genes in 100 HCC patients. Informative genes predicting early intrahepatic recurrence were selected by random permutation testing, and a weighted voting prediction method was constructed. Following estimation of prediction accuracy, a multivariate Cox analysis was performed. RESULTS: By permutation testing, we selected 92 genes demonstrated distinct expression patterns differing significantly between recurrence cases and recurrence-free cases. Our prediction method, using the 20 top-ranked genes, correctly predicted the early intrahepatic recurrence for 29 of 40 cases within the validation group, and the odds ratio was 6.8 (95%CI 1.7-27.5, P = 0.010). The 2-year recurrence rates in the patients with the good signature and those with the poor signature were 29.4 and 73.9%, respectively. Multivariate Cox analysis revealed that molecular-signature was an independent indicator for recurrence (hazard ratio 3.82, 95%CI 1.44-10.10, P = 0.007). CONCLUSIONS: Our molecular-based prediction method using 20 genes is clinically useful to predict early recurrence of HCC.

Aged↗

PubMed2003

Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene expression profiling study.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) usually develops following chronic liver inflammation caused by hepatitis C or B virus. Through expression profiling in a rare type of HCC, for which the causes are unknown, we sought to find key genes responsible for each step of hepatocarcinogenesis in the absence of viral influence. METHODS: We used 68 non-B, non-C liver tissues (20 HCC, 17 non-tumor, 31 normal liver) for expression profiling with PCR-array carrying 3072 genes known to be expressed in liver tissues. To select the differentially expressed genes, we performed random permutation testing. A weighted voting classification algorithm was used to confirm the reliability of gene selection. We then compared these genes with the results of previous expression profiling studies. RESULTS: A total of 220 differentially expressed genes were selected by random permutation tests. The classification accuracies using these genes were 91.8, 92.0 and 100.0% by a leave-one-out cross-validation, an additional PCR-array dataset and a Stanford DNA microarray dataset, respectively. By comparing our results with previous reports on virus-infected HCC, four genes (ALB, A2M, ECHS1 and IGFBP3) were commonly selected in some studies. CONCLUSIONS: The 220 differentially expressed genes selected by PCR-array are potentially responsible for hepatocarcinogenesis in the absence of viral influence.

Aged↗

PubMed2003

[Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001].

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.

Adolescent↗