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Biomedical subjects

I Kawase

Publications and source records attributed to I Kawase.

At least 37 records · Page 2Linked to original sources

[Prognostic significance of alterations in telomeric repeat length in patients with pathological stage I-II non-small cell lung cancer].

UNLABELLED: The purpose of this study was to evaluate the correlation between alteration in telomere length and prognosis in patients with pathological stage I-II non-small cell lung cancer. We measured telomeric repeat length and telomerase activity by use of southern blot analysis of terminal restriction fragments and a non-radioactive ELISA-based assay, respectively. RESULTS: Alterations in TRF lengths were present in 17(29.8%) of 57 patients. Patients with altered TRF length had significantly shorter survival than did patients without (P = 0.0051). In multivariate analysis, only alteration in TRF length independently correlated with shortened survival (P = 0.0033).

Adult↗

[Analysis of the factors involving in the success or failure of home infusion therapy (HIT)].

A survey was conducted from April through September, 1997, of 24 hospitalized terminal lung cancer patients connected to IVH and CSC, for whom the possibility of release from hospital was considered, and of their families. A comparative survey was made between patients who accepted HIT and those who did not. No difference was found between the groups by age, sex, or disease stage, nor was there a difference in physical symptoms such as pain and respiratory difficulty. However, the percentage of patients who were told the name of their disease was significantly higher in the group switched to HIT, 3 of whom were even given prognoses. There was no difference in the percentage of patients who lived with their families, although there was a higher percentage in the HIT group whose spouses also lived with the family. Nineteen of the 24 patients wished to return home, but 8 of those patients were not released from hospital for such reasons as the patient not wanting to be a burden on his or her family or the family's lack of ability to provide care. It was found that important factors in urging home care for the terminal cancer patient were whether or not the patient was told the name of his or her disease, and whether or not the patient lived with a healthy spouse.

Aged↗

Transcutaneous needle biopsy of the lung.

PURPOSE: To evaluate the usefulness of transcutaneous needle biopsy (TCNB). MATERIAL AND METHODS: From May 1988 to December 1994, we performed TCNB under fluoroscopic control in 408 patients with mass lesions of the peripheral lung. The Surecut needle (1.5 mm) was selected mainly because of its ability to obtain specimens large enough for histological examination. Of the 408 patients, 286 had had previous bronchofiberscopic examinations but no definite diagnosis had been reached. RESULTS: A definite diagnosis was obtained by TCNB in 305 (74.7%) of 408 cases (251 malignant neoplasms, 54 benign lesions). In malignant neoplasms, the pathological diagnosis based on cytology and histology together was more reliable than that based on cytology alone. Although the complications of this procedure (such as pneumothorax) were within the range of acceptability, care should be taken to avoid air embolism and the seeding of cancer cells along the needle tract. CONCLUSION: TCNB with the Surecut needle is a useful procedure with relatively low risk.

Biopsy, Needle↗

Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts.

We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.

Animals↗

[Home infusion therapy for cancer patients at a near-terminal stage--analysis of cases who died at home].

To improve the quality of life in cancer patients at a near-terminal stage, we assisted patients to stay home using a system for home infusion therapy (HIT) established at Osaka Prefectural Habikino Hospital in 1994. From April in 1995 to April in 1996, 25 patients were treated at home using the HIT system for longer than 7 days. Thirteen out of 25 patients still stayed at home even at a terminal stage and died in their residences. There was no difference either in the mean age or in the HIT duration between 13 patients who died at home and the remaining 12 patients who were readmitted to their hospitals before death. However, 47% of the patients who died at home had been told their diagnoses by doctors and realized their own prognoses, while only 17% of the patients who died in the hospital knew their diagnoses and prognoses. Seventy-seven percent of the patients who died at home were given home oxygen therapy (HOT), against 33% of the patients who died in the hospital. Furthermore, the patients who died at home were given more intensive care than the patients who died in the hospital, because the former had a larger family than the latter. In conclusion, HIT at a near-terminal stage and death at home may be more readily accepted by patients who know their diagnoses and prognoses and have a large family.

Adult↗

p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung.

Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected NSCLC. p21 expression, indicating normal p21 function, was detected in 48 (35.0%) of the 137 patients with curatively resected NSCLC and was detected more frequently in patients with stage I or II disease (40.2%) than in those with stage IIIA disease (22.5%; P = 0.0483). There was no difference in the positive rate between squamous cell carcinoma [SCC; 15 of 48 (31.3%)] and adenocarcinoma [30 of 77 (39.0%)]. For SCC, patients with tumors expressing p21 survived longer than did those with tumors negative for p21 expression; however, the corresponding survival time was not significant for adenocarcinoma. On the other hand, p53 expression, detected in 58 (42.3%) of these patients, did not act as any predictor for prognosis in either SCC or adenocarcinoma. Our findings suggest that the presence of p21 expression is associated with favorable prognosis in SCC and may be useful in obtaining candidates for adjuvant therapies from among patients with SCC.

Adenocarcinoma↗

Pro-gastrin-releasing peptide (31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

Biomarkers, Tumor↗

Determinants of myelosuppression in the treatment of non-small cell lung cancer with cisplatin-containing chemotherapy.

Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and cisplatin (MVP) for inoperable stage III or IV non-small cell lung cancer in a randomized trial. Determinant factors for myelosuppression were evaluated by using univariate analysis and the logistic regression model. Recursive partitioning and amalgamation (RPA) was also used to define patient subgroups frequently suffering from severe bone marrow toxicity. Overall, 33 (25%) of 134 patients experienced at least one episode of grade 4 leukopenia. In univariate analysis, age, body surface area, serum creatinine, and pretreatment hemoglobin concentration were associated with severe leukopenia. A multivariate analysis using the logistic regression method showed that only raised creatinine level was an independent predictor for grade 4 leukopenia (P = 0.049). The RPA model generated three distinct subgroups based on age, body surface area and regimen. The three subgroups were distinguished by the frequency of severe (grade 4) leukopenia (50%, 25%, and 2.4%, respectively) (P < 0.001). Grade 4 leukopenia occurred more frequently in patients in class 3 (age > or = 65 years and treatment with MVP). The RPA model was useful in identifying the risk factors for myelosuppression induced by cisplatin-based chemotherapy, and in defining patient subgroups with elevated risk of toxicity.

Adult↗

[Successful surgical treatment of intraoperative aortic dissection complicating aortic valve replacement].

A 74-year-old man underwent standard aortic valve replacement. The aortotomy was closed by use of strips of Teflon felt because of somewhat friable thin aortic wall. After the termination of cardiopulmonary bypass, aortic cannulation site was carefully sutured enforcing with a piece of pericardium, since some bleeding persisted. The intraoperative diagnosis of acute aortic dissection (Stanford type A) was made with transesophageal echocardiography. Since extension of the dissection toward the aortic root was hardly possible due to the Teflon felt enforced aortotomy closure, further surgical intervention was not considered at this time. Thiry-two hours later after admission to CCU, sudden bleeding through the mediastinal tube prompted the patient back to OR for exploration Bleeding was noted from the posterior wall of the ascending aorta. Ascending aorta and transverse arch were significantly enlarged with notable discoloration. With the aid of extracorporeal circulation and selective cerebral perfusion, the total graft replacement of the ascending aorta and aortic arch was performed. The intimal tear located at the aortic cannulation site. The postoperative course was uneventful. Prompt recognition and appropriate surgical management are necessary to improve patient outcome.

Aged↗

[Coronary reoperation--selection of conduit material and management of stenotic vein graft].

We have operated upon 30 cases of coronary reoperation during the past 12 years. The mean interval between the two operations was 46 months. The mean follow-up after reoperation was 61 months. The major reasons for reoperation were graft failure from technical problems in early and time-related degeneration in graft and native coronary progression in late cases. We aggressively have replaced the stenotic and obstructed vein graft with the arterial graft at reoperation since 1990. Hypoperfusion syndrome is clinical entity reported secondary to inadequate flow via the internal thoracic artery. For patients with atherosclerotic vein grafts to the LAD, the minimal manipulation of the old vein graft, adding the IMA graft to the LAD and leaving the stenotic vein graft intact appear to be safe and better procedure for long-term results. There were no operative and hospital death. Five and 10 years survival rate were 100% and 90% respectively. Five and 10 years event free rate were 92.1% and 82.9% respectively. The outcome of reoperation was satisfactory.

Adult↗

[Emergent coronary bypass grafting after acute myocardial infarction].

In an attempt to examine various factors affecting the short- and long-term results of emergent coronary bypass graft surgery (ECABG) after an acute myocardial infarction (AMI), all patients undergoing ECABG without associated procedures at our institution from January 1987 to July 1995 were reviewed. Forty eight patients underwent ECABG after AMI. The hospital mortality rate was 20.8%. The charts of these patients were reviewed with regard to sex, age, preoperative shock, location of AMI, type of infarction, coronary anatomy, presence of postinfarction angina, technique of myocardial preservation, use of saphenous vein graft (SVG) alone, time from AMI to operation and short and long-term outcome. Univariate analyses showed that three factors were significantly associated with increased hospital death: preoperative shock (p = 0.001), type of infarction (p = 0.01), use of SVG alone (p = 0.003). Follow-up was 100% complete at a mean time of 36.4 +/- 4.8 months. Of all patients 77.0% were alive at 5 years after operation. Univariate comparison of survival curves and coronary event free curves showed that use of SVG alone was associated with decreased survival (p = 0.0009) and event free (p = 0.02) rates. Patients with non-Q-wave infarction and without cardiogenic shock may undergo ECABG relatively safely at any time. The use of internal thoracic artery at ECABG without cardiogenic shock does not increase hospital mortality and improves both long-term survival and freedom from coronary events.

Adult↗

[Trial of home infusion therapy for near-terminal stage patients with lung cancer].

To improve the quality of life in patients with malignant diseases at the near-terminal stage, we established a system for home infusion therapy (HIT) in Osaka Prefectural Habikino Hospital in 1994. Thirty-three patients were taken care of at home using the HIT system from January, 1995 to May, 1996. Their average age was 70 years old. The duration of HIT varied from 1 to 105 days (mean:25.5 days). Twenty-four cases received parenteral nutrition. The others received agents for brain edema (4 cases), morphine hydrochloride (2 cases), and anti-fungal agents (3 case). Additionally, 63% of these patients required home oxygen therapy (HOT) with HIT. Questionnaires to their families revealed that they were afraid of the progress of the disease in patients and their physical burden became heavier after the start of HIT. However, they were quite satisfied with the results of HIT.

Adolescent↗

Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene.

A carcinoembryonic antigen (CEA)-producing human lung cancer cell line (A549), a nonproducing human lung cancer cell line (CADO-LC9), and a human uterine cervical cancer (HeLa) were transfected with the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by 445 nucleotides upstream from the translational start of CEA gene. Fifty % growth inhibitory concentration of ganciclovir (GCV) was 0.57 micron for HSV-TK-transfected A549; relative sensitivity to GCV was more than 1000 times higher compared to the 50% growth inhibitory concentration of the parental cell line. Both CADO-LC9 and HeLa transfected with HSV-TK were still resistant to GCV. There was no difference in either morphology or doubling time between HSV-TK-transfected and parental clones. Injections (i.p.) of GCV resulted in significant regression of HSV-TK-transfected A549 tumors in nude mice. These data show the possibility of gene therapy using the cell type-specific promoter of CEA gene against CEA-producing adenocarcinoma of the lung.

Adenocarcinoma↗

A frequent deletion of chromosome 5q21 in advanced small cell and non-small cell carcinoma of the lung.

We have examined the deletion of the long arm of chromosome 5 (5q) in 59 cases of advanced lung cancer [39 cases of small cell lung cancer (SCLC), 20 cases of non-SCLC] using 12 restriction fragment length polymorphism markers on 5q. Of 59 lung cancer cases, 48 (81%) exhibited deletion at any portion of the 5q locus (loci). Such a high frequency of 5q deletion has not been reported in surgically resectable non-SCLC. One SCLC case showed a 5q deletion only in metastatic sites but not in the primary cancer. These data suggest that the inactivation of putative tumor-suppressor gene(s) on 5q may be a late event in the progression of lung cancer. There was no significant difference in frequency of 5q deletion between SCLC and non-SCLC. Compared to non-SCLC, however, SCLC usually showed widespread deletion on 5q. While the most frequent target region was estimated to be about 3-5 megabases at 5q21 around the adenomatous polyposis coli (APC) gene locus, some cases showed more telomeric deletion (5q33-35), suggesting that there are at least two different tumor-suppressor genes on 5q associated with the progression of lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Development and evaluation of oral reporting system for PACS.

Experimental workstations for oral reporting and synchronized image filing have been developed and evaluated by radiologists and referring physicians. The file media is a 5.25-inch rewritable magneto-optical disk of 600-Mb capacity whose file format is in accordance with the IS&C specification. The results of evaluation tell that this system is superior to other existing methods of the same kind such as transcribing, dictating, handwriting, typewriting and key selections. The most significant advantage of the system is that images and their interpretation are never separated. The first practical application to the teaching file and the teaching conference is contemplated in the Osaka University Hospital. This system is a complete digital system in terms of images, voices and demographic data, so that on-line transmission, off-line communication or filing to any database will be easily realized in a PACS environment. We are developing an integrated system of a speech recognizer connected to this digitized oral system.

Education, Medical↗

Detailed deletion mapping of the short arm of chromosome 3 in small cell and non-small cell carcinoma of the lung.

We constructed a detailed deletion map of the short arm of chromosome 3 (3p) for 55 lung cancer cases by using 17 restriction fragment length polymorphism (RFLP) probes. Initially, we examined 40 small cell lung cancer (SCLC) cases and found three regions of deletion at 3p25-26, 3p21.3 and 3p14-cen, suggesting the possibility of at least three different tumor-suppressor genes on 3p. In order to obtain more detailed deletion area, and to compare the pattern of 3p deletion, we also examined 15 non-small cell lung cancer (NSCLC) cases. Compared to NSCLC cases, most of SCLC cases have widespread deletion on 3p, suggesting multiple tumor-suppressor genes on 3p may be inactivated in this type of cancer. In 3p21.3 area, minimum overlapping area of deletion lays between two probes which are close to each other. These data will be useful to isolate the putative tumor-suppressor genes located on the chromosome 3p.

Carcinoma, Non-Small-Cell Lung↗

Complementary DNA sequence encoding the major neural cell adhesion molecule isoform in a human small cell lung cancer cell line.

The neural cell adhesion molecule (N-CAM), a member of the immunoglobulin gene super-family mediating homophilic cell-cell adhesion in a neuroendocrine system, is preferentially expressed in human small cell lung cancer (SCLC). Immunoprecipitation of a panel of SCLC cell lines by monoclonal antibodies (mAbs) specific for N-CAM detects mainly the 145-kDa isoform. This result was correlated with Northern blotting where a single 6.2-kb mRNA was detected in nine SCLC cell lines. To determine cDNA sequence encoding the N-CAM isoform, we selected several cDNA clones encoding N-CAM isolated from OS2-R, a SCLC cell line established in our laboratory. Based on the analysis of the full-length cDNA obtained from two clones, the sequence of this 145-kDa isoform was shown to be essentially identical to that of the 140-kDa N-CAM isoform of neuroblastoma except for a single base pair changed at position 1620 without changing amino acid encoded.

Amino Acid Sequence↗