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Biomedical subjects

T Horai

Publications and source records attributed to T Horai.

At least 19 recordsLinked to original sources

Gefitinib treatment affects androgen levels in non-small-cell lung cancer patients.

Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR, HER1/ErbB1) tyrosine kinase, has been shown to have clinical activity against non-small-cell lung cancers (NSCLCs), especially in women nonsmokers with adenocarcinomas. The aim of the present study was to clarify the relationship between androgen levels and gefitinib treatment in patients with advanced NSCLCs. Sera from 67 cases (36 men and 31 women) were obtained pretreatment and during treatment with gefitinib monotherapy (days 14-18) for examination of testosterone, dehydroepiandrosterone sulphate (DHEA), and dehydroepiandrosterone sulphate (DHEAS) levels. Testosterone and DHEA during treatment were significantly lower than the pretreatment values in both women and men, and the DHEAS levels during treatment were also significantly lowered in women. Gefitinib treatment significantly suppressed androgen levels, especially in women who had no smoking history. In addition, hormone levels in women responding to gefitinib were significantly lower during the treatment than in women who did not respond. Gefitinib-associated decrease in serum androgen levels may play a role in its clinical efficacy.

Adult↗

Low-cost soft-copy display accuracy in the detection of pulmonary nodules by single-exposure dual-energy subtraction: comparison with hard-copy viewing.

This study endeavored to clarify the usefulness of single-exposure dual-energy subtraction computed radiography (CR) of the chest and the ability of soft-copy images to detect low-contrast simulated pulmonary nodules. Conventional and bone-subtracted CR images of 25 chest phantom image sets with a low-contrast nylon nodule and 25 without a nodule were interpreted by 12 observers (6 radiologists, 6 chest physicians) who rated each on a continuous confidence scale and marked the position of the nodule if one was present. Hard-copy images were 7 x 7-inch laser-printed CR films, and soft-copy images were displayed on a 21-inch noninterlaced color CRT monitor with an optimized dynamic range. Soft-copy images were adjusted to the same size as hard-copy images and were viewed under darkened illumination in the reading room. No significant differences were found between hard- and soft-copy images. In conclusion, the soft-copy images were found to be useful in detecting low-contrast simulated pulmonary nodules.

Humans↗

Clinical value of pleural lavage cytological positivity in lung cancer patients without intraoperative malignant pleuritis. Recurrent pattern based on semiquantitative analysis of tumor cells in pleural lavage.

OBJECTIVES: We recently developed pleural lavage cytology for lung cancer patients without intraoperative signs of malignant pleuritis (Ann Surg Oncol, 4: 409, 1997). We analyzed recurrent patterns in pleural lavage cytology-positive lung cancer patients without intraoperative signs of malignant pleuritis based on semiquantitative evaluation of tumor cell clusters in pleural lavage solution. METHODS: Between December 1987 and December 1998, pleural lavage cytology-positive results after thoracotomy were obtained in 97 cases of lung cancer despite the lack of evidence of malignant pleuritis. Based on semiquantitative evaluation of the mean number of tumor cell clusters per slide in pleural lavage solution, patients were classified as Type I, in whom the mean number of clusters was < 1; Type II, in whom clusters numbered 1-10; and Type III, in whom clusters exceeded 10. RESULTS: Type I patients numbered 37, Type II 40, and Type III 20. By September 1999, pleural recurrence had occurred in 17 patients (18%)--2(5%) Type I, 4 (10%) Type II, and 11 (55%) Type III. The incidence of pleural recurrence was significantly higher for Type III patients, i.e., 5 of 11 Type III patients with pleural recurrence showed no sign of distant metastasis. In contrast, the main recurrent patterns in the other 2 groups were extrathoracic, nodal, and/or intrapulmonary. CONCLUSIONS: The semiquantitative evaluation of tumor cell clusters in pleural lavage cytology-positive patients provided useful information on postoperative recurrence. Since Type III patients are at high-risk for pleural recurrence, postoperative therapy targeting local control should be conducted in such patients.

Adult↗

Primary primitive neuroectodermal tumor of the lung: report of two cases.

Two cases of primitive neuroectodermal tumor of the lung are reported. The first case is a 41-year-old man with a tumor in the left upper lung, and the second case is a 30-year-old woman with a tumor in the right lower lung. In both cases, the tumors originated in the lung but not in the chest wall. No distant metastasis was detected. In case 1, transcutaneous fine-needle biopsy (TCNB) revealed small round cell proliferation, although bronchoscopic examination showed no abnormal findings. Both the expression of Mic2 protein and t(11;22)(q24;q12) translocation were proved in the tumor cells. The tumor cells were positive for periodic acid-Schiff (PAS), neuron-specific enolase (NSE), and vimentin, but negative for Leu7, chromogranin A, and pro-gastrin-releasing peptide (ProGRP). In case 2, bronchoscopic examination showed only compressive change in right lower lobe bronchi. TCNB revealed small round tumor cells expressing Mic2 protein. The tumor cells were negative for leukocyte common antigen, S100 protein, pankeratin, chromogranin A, and desmin, but weakly positive for NSE and moderately positive for Ki-67 (MIB1). Both patients were successfully treated by the combination of surgical resection and chemotherapy, and are alive with no sign of recurrence for approximately 22 months in case 1 and 16 months in case 2.

12E7 Antigen↗

Detection of bone marrow metastases of small cell lung cancer with magnetic resonance imaging: early diagnosis before destruction of osseous structure and implications for staging.

Small cell lung cancer (SCLC) frequently metastasizes to bone and bone marrow. Skeletal scintigraphy and bone marrow cytology or biopsy, are incorporated into the staging procedures to examine these organs. However, skeletal scintigraphy is not highly specific to metastases, and only one or two bone marrow sites can be examined by cytology or biopsy. We have already reported that magnetic resonance imaging (MRI) could improve the sensitivity in detecting bone marrow metastases. The result of the bone marrow MRI was an independent prognostic factor of SCLC patients [9]. In the present study, we analyzed the results of skeletal scintigraphy and bone marrow aspiration with special reference to the results of MRI examination. We also analyzed the relationship between bone marrow lesions and bone lesions. For this purpose, we visualized bone marrow metastases with MRI and determined their anatomical locations and sizes. Approximately half of bone marrow lesions stayed in bone marrow during follow-up period ranging from 57 to 154 days, whereas about half of them were accompanied by hot spots in follow-up skeletal scintigraphy, which indicates the destruction of osseous structure. Additionally, 87.5% of osteolytic changes that newly appeared in skeletal scintigraphy were preceded by adjacent bone marrow lesions. All new lesions that appeared in follow-up skeletal scintigraphy within 3 months after the initial presentation had the preceding bone marrow lesions. These results mean that almost all lesions in skeletal scintigraphy derived from bone marrow metastases. Furthermore, appreciable volume of cancer cells is present in bone marrow before osteolytic changes appear in skeletal scintigraphy.

Adult↗

Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry.

STUDY OBJECTIVES: We performed a clinical trial of laser-induced fluorescence endoscopy (LIFE) for detection of precancerous lesions and cancer including carcinoma in situ (CIS), which are difficult to detect by white-light bronchoscopy. DESIGN: Results with LIFE were compared with the criterion standard, white-light bronchoscopy. The evaluation of these endoscopic results spectrofluorometrically was examined, and pixels of LIFE images composed of digital signals for the intensities of red and green were analyzed. SETTING: Tertiary-level hospital treating referrals and subjects with suspicious results in mass screening. PATIENTS: We examined 65 subjects with suspected lung cancer by both methods, and performed biopsy on 216 lesions. RESULTS: The accuracy of diagnosis by white-light bronchoscopy, with histopathologic results as the standard, was 48.6%. The accuracy by LIFE was 72.7%. The sensitivity of conventional bronchoscopy for detection of severe dysplasia (21 biopsy specimens) or cancer (28 biopsy specimens) was 61.2% and specificity was 85.0%. With results by LIFE added, these values were 89.8% and 78.4%, respectively. Of nine patients with CIS, only LIFE showed one lesion, and only LIFE showed the extent of seven of the lesions. The autofluorescence of eight lesions was measured spectrofluorometrically; normal bronchial tissue, severe dysplasia, and cancerous tissue had spectral differences. The red/green intensity of cancers on histograms of LIFE images generally was greater than the ratios for metaplasia or normal bronchial wall. CONCLUSIONS: Use of both methods should facilitate early detection. Evaluation by spectrofluorometry and analysis of digital signal intensity of results by LIFE make results more objective.

Adult↗

Percutaneous brachytherapy for small-sized non-small cell lung cancer.

A patient with a small-sized pulmonary adenocarcinoma was successfully treated by percutaneous high dose rate interstitial brachytherapy alone. The patient, who had an adenocarcinoma with 12-mm diameter in the lingular lobe of left lung, was judged to be inoperable because of poor pulmonary function due to emphysema and extensive pleural adhesion. The tumor was punctured with a 21-gauge fine applicator needle followed by the introduction of an iridium 192 (192Ir) radioactive source through the applicator needle using a remote afterloader. The tumor was irradiated for 225.1 s in one fraction. The tumor was in the inside of the iso-dose line of 40 Gy. The delivered doses calculated at nine reference points, which were 12.5 mm distant from the center of the tumor, distributed between 19.225 and 32.169 Gy, with a mean of 24.8 Gy. No apparent side effect including pneumothorax and hemoptysis was observed. The tumor shrank and showed no increment of the size for about 2 years.

Administration, Cutaneous↗

Involvement of small GTPases Rho and Rac in the invasion of rat ascites hepatoma cells.

Lysophosphatidic acid (LPA) triggers the invasion of a mesothelial cell monolayer by rat ascites hepatoma (MM1) cells. LPA also induces rapid morphological changes of MM1 cells, cell surface blebbing and pseudopodia formation. Pseudopodia formation is tightly correlated with cellular invasiveness. Clostridium Botulinum C3 exoenzyme and genistein abrogated the formation of blebs and pseudopodia together with the inhibition of invasion, indicating that GTPase Rho and certain tyrosine kinases are involved in both processes. MM1 cells expressing constitutively active Rho exhibited the invasion and the formation of blebs and pseudopodia in the absence of LPA. In contrast, MM1 cells expressing constitutively active Rac were not invasive in the absence of LPA, but were invasive in the presence of LPA. Their morphological response to LPA was almost the same as that of parental MM1 cells. Expression of dominant negative Rac suppressed the invasiveness to approximately 3% of that of parental MM1 cells, together with the inhibition of pseudopodia formation. Thus, Rho and Rac are cooperatively involved in both the invasion and the related morphological changes of MM1 cells. Rho activation is sufficient both for the induction of invasion and the morphological changes leading to the invasion, whereas Rac activation is necessary but not sufficient by itself. We propose that Rho activation is not mediated by Rac but the cooperation of both GTPases is essential to trigger the invasive behavior of MM1 cells.

Animals↗

Successful removal of a primitive neuroectodermal tumor in the lung with gross extension into the left atrium.

We report here the successful multi-model treatment of a 31-year-old female demonstrating a primitive neuroectodermal tumor originating in the lower lobe of the right lung with gross extension into the left atrium via the inferior pulmonary vein. The tumor was markedly reduced by combination chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, and ifosfamide. The residual tumor was completely removed through a combined left atrial resection and right middle and lower lobectomy, using a percutaneous cardiopulmonary support system.

Adult↗

Comparison of computed tomography and pathologic examination for evaluation of response of primary lung cancer to neoadjuvant therapy.

Twenty-four patients (nine with squamous cell carcinoma, 14 with adenocarcinoma, and one with large cell carcinoma) underwent neoadjuvant therapy followed by surgical resection. The authors studied changes in tumor size, shape, and contrast enhancement on computed tomography (CT), and compared them with results of pathologic examination of surgical specimens. The size of tumors on CT was evaluated according to the criteria of the World Health Organization. Surgical specimens were evaluated histologically on the basis of the area of viable cancer cells. Of 14 patients considered to have a partial response on the basis of World Health Organization criteria, five had pathologic changes of complete response. After therapy, the residual tumors in these five patients showed irregular shapes with concave tumor margins on CT images and no enhancement. The authors found that CT size criteria tended to underestimate the therapeutic effect demonstrated by pathologic examination. On the basis of these results, the authors propose three CT criteria for complete response: 1) more than 50% size reduction, 2) a change in tumor morphologic features from round or oval to irregular after neoadjuvant therapy, and 3) disappearance of contrast enhancement.

Adenocarcinoma↗

Expression of cathepsin B in small cell lung carcinoma cells in relation to in vitro invasiveness.

Cathepsin B expression and its relation to in vitro invasiveness were investigated in small cell lung carcinoma cells (OC-10 cells). A subclone derived from OC-10 cells (10N) was similar to the parental cells both in growth pattern and morphology. However, the in vitro invasive capacity of OC-10 cells was 4 times higher than that of 10N cells. Cathepsin B activities in the plasma membrane fraction and spent medium of OC-10 cells were 2-fold higher than those of 10N cells. The invasiveness of OC-10 cells was markedly blocked by the addition of cysteine proteinase inhibitors, E-64C or leupeptin, while treatment of 10N cells with 2% (v/v) DMSO resulted in a 2-fold increment both in invasive capacity and cathepsin B activity. Immunoblot analysis demonstrated that the intensity of the cathepsin B band from OC-10 or 10N cells was not remarkably different regardless of DMSO treatment. Although no significant correlation was observed between the biochemical activity and protein of cathepsin B, in vitro invasive capacity of OC-10 cells strongly correlated with cathepsin B activity. These results suggest that cathepsin B plays an important role in the invasiveness of human small cell lung carcinoma cells.

Carcinoma, Small Cell↗

Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer.

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P = 0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P = 0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.

Bone Marrow Neoplasms↗

NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model.

We investigated the effects of NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on bone metastasis of human breast cancer, MDA-231 cells. Tumor cells (2 x 10(5) cells in 0.2 ml of phosphate-buffered saline; PBS) were injected through the diaphragm into the left ventricle of the heart of laparotomized nude mice (male 5-week-old ICR-nu/nu). L-NAME (2 mg/mouse/injection in 0.1 ml of PBS) was given intraperitoneally to mice 6 h and 3 h before and immediately, 3 h, 6 h, 18 h and 21 h after the intracardiac injection of tumor cells. As a control, 0.1 ml of PBS was injected instead of L-NAME. The effect of NG-nitro-D-arginine-methyl ester (D-NAME; 2 mg/mouse/injection), an inactive analogue of L-NAME, was also investigated to evaluate the specificity of L-NAME action. Radiographical examination 31 days after the tumor-cell injection showed that the incidence and number of osteolytic bone metastases and the number of bones with metastasis in L-NAME-treated mice were significantly reduced compared with those in PBS-treated mice (P < 0.05). The differences between PBS-treated and D-NAME-treated mice were not significant. Our findings suggest that specific and appropriate NOS inhibitors may represent a new pharmacological approach to therapy for cancer patients at risk of developing osteolytic bone metastases.

Animals↗

Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements.

Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its utility for gene therapy was examined by the treatment of either c-, L- or N-myc-overexpressing the small cell lung cancer (SCLC) cell line with ganciclovir (GCV). The chloramphenicol acetyltransferase assay demonstrated that the overexpression of any myc genes activated transcription from the CAT gene depending on the Myc-Max binding sites. The transduction of the HSV-TK gene ligated with the CACGTG core rendered all three SCLC lines to be more sensitive to GCV than parental ones in vitro. In addition, the growth of c- or L-myc-overexpressing SCLC cells containing the hybrid HSV-TK gene were significantly suppressed by GCV in vivo. When parental SCLC cells were mixed with HSV-TK-expressing tumor cells at a ratio of 1:3, GCV treatment inhibited tumor growth by 90% compared with parental cells only, indicating the existence of the "bystander effect." These data suggest that the CACGTG-driven HSV-TK gene may be useful for the treatment of SCLC overexpressing any type of myc family oncogenes.

Antimetabolites, Antineoplastic↗

Hemispheric asymmetry of event-related potentials in a patient with callosal disconnection syndrome: a comparison of auditory, visual and somatosensory modalities.

To investigate whether callosal lesions affect the distribution of event-related potentials (ERP) between the two hemispheres and whether hemispheric ERP distribution differs among sensory modalities, a patient with interhemispheric disconnection syndrome and 47 controls were subjected to an oddball paradigm. High (target) and low tone bursts for auditory, red (target) and green lights for visual and electrical stimuli delivered to the index (target) or fifth finger for somatosensory ERPs were presented to the unilateral ear, visual field and hand, respectively. The subjects were instructed to press a button with the hand on the stimulated side. The results showed that the hemispheric asymmetry of the patient's auditory ERPs was not significantly different from that of the controls, regardless of which ear was stimulated. In contrast, the visual and somatosensory ERPs showed a delay of the P3 latency and an attenuation of the N1-P2 and N2-P3 amplitude over the hemisphere ipsilateral to the stimulus, regardless of the stimulated side. These findings suggest that the source of P3 generation is relatively lateralized to the hemisphere contralateral to the stimulus, and that the callosal transfer of visual and somatosensory information is involved in the P3 generation in the hemisphere ipsilateral to the stimulus.

Acoustic Stimulation↗

[Relationship between intraoperative pleural lavage cytology and recurrence in pleural cavity after resection of lung metastasis from colorectal cancer].

Seventeen patients with lung metastases from colorectal cancer underwent intraoperative pleural lavage cytology immediately after thoracotomy from August 1988 to December 1994. Patients with pleural effusion and/or dissemination were excluded. The median followup period was 34 months (range 3-52 months). Of the 17 patients, 13 were cytologically negative (76%, group A) and 4 were positive (24% group B). Recurrence rate in the pleural cavity was 25% (1/4) in group B and 0% (0/13) in group A. The three-year survival rate was 0% in group B and 78% in group A, respectively. These results indicate that intraoperative pleural lavage cytology is useful in the assessment of prognosis, and locoregional therapy should be considered for cytology positive group.

Colorectal Neoplasms↗