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Biomedical subjects

M Higashiyama

Publications and source records attributed to M Higashiyama.

At least 109 records · Page 6Linked to original sources

[Development of new in vitro chemosensitivity test using collagen gel droplet embedded culture and its clinical usefulness].

We developed a new in vitro assay for chemosensitivity test using collagen gel droplet embedded culture and image analysis. In this in vitro assay, we successfully minimized the cancer cell number required for culture to approximately 3-10 x 10(3) cells for each 30 microliters collagen gel droplet, obtained the sufficient growth of cancer cells using serum-free medium while suppressing the growth of fibroblastic cells, and measured the volume of cancer cells by eliminating the contaminating fibroblastic cells by an image processing technique. Anticancer effects of the in vitro assay showed a very good correlation with those of in vivo nude mouse assay using human cancer cell lines. The success rates of the in vitro assay for 141 surgical specimens of primary lung cancers and for 65 of primary breast cancers were 89 and 80%, respectively. The accumulated in vitro assay response rates of MMC, CDDP, VDS and VP-16 for primary lung cancers and of MMC, 5-FU and ADR for primary breast cancers were similar to the respective clinical response rates. These results suggest that this in vitro chemosensitivity test may be practically useful for clinical applications.

Animals↗

[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↗

[Combined resection of the descending aorta for lung cancer with aortic invasion].

Four lung cancer patients underwent left pneumonectomy combined with resection of the descending aorta. Their tumors arose from the superior segment (S6) of the left lower lobe and directly invaded the aorta. Their angles of contact with descending aorta were more than 130 degrees. There were two squamous cell carcinoma, and one each of large cell carcinoma, and adenosquamous carcinoma. In Case 1, the defect of the descending aorta was closed by patch graft using simple aortic cross-clamping. In the other three patients, the aorta was replaced by a 5-7 cm long woven Dacron tube graft under temporary bypass using Anthron tube. Their postoperative courses were uneventful. Although the follow-up period is too short at present, two cases (3 and 4) have been alive without recurrence for five and two months, respectively. The induction chemotherapy followed by extended surgery (Case 4) may become a feasible treatment modality to overcome the poor prognosis in patients with advanced lung cancer invading to the great vessels.

Adenocarcinoma↗

[A case of pulmonary tumorlet with tuberculoma misdiagnosed as small cell lung carcinoma by transbronchial lung biopsy].

A 59-year-old woman was picked up by chest X-ray findings. Her CT scan film showed a tumor shadow in the upper lobe of the left lung, and by transbronchial lung biopsy, she was diagnosed as a small cell lung carcinoma. Lobectomy was performed, but the lesion was diagnosed as tuberculoma by frozen section. Furthermore, on postoperative histological examination, a minute lesion of tumorlet, which was histologically identical to that preoperatively detected by transbronchial lung biopsy was found in the adjacent tissues of the tuberculoma. Pulmonary tumorlet is clinically a rare lesion, but the diagnosis and treatment for small-sized tumor or tumor-like lesion may be carefully done, taking into account the existence or co-existence of tumorlet lesion.

Biopsy↗

Surgery for brain metastases from nonsmall cell lung carcinomas and tissue cultures from the resected specimens.

Between 1978 and 1989, 44 patients underwent 44 thoracotomies and 55 craniotomies for nonsmall cell lung carcinoma (NSCLC) and its brain metastases. Patients ages ranged from 20 to 75 years. There were no intraoperative mortalities. The 2-, 3-, and 5-year survival rates following the initial craniotomy were 23%, 10%, and 10%, respectively. Patient survival did not differ with respect to solitary or multiple metastases or the sequence of surgery for primary lesion and brain metastases. Moreover, there was no significant difference in survival between patients treated by surgery alone and those receiving surgery followed by whole brain radiotherapy. After 1985, in vitro tissue culture was attempted using freshly resected specimens of brain metastases obtained from 30 consecutive cases. Of those specimens, nine (30%) were successfully established as permanent cell lines. Eight of those cell lines revealed DNA-aneuploid pattern on flow cytometric analysis. The remaining cell line was not analyzed. Karyotype analysis was also performed in eight of nine established cell lines. Two adenocarcinoma cell lines showed the presence of +3p- chromosome, and three showed +7q- chromosome as recurrent chromosomal abnormalities. These findings provide new evidence concerning the presence of 3p- and/or 7q- marker chromosomes in certain adenocarcinoma cell lines established from brain metastases. The prognosis was poorer in the group with in vitro tumor growth than that in the group showing no in vitro tumor growth. These cell lines established from brain metastases may be useful materials not only for studying the biological characteristics and chemo-sensitivity testing, but also for estimating prognoses after resection of brain metastases.

Adult↗

Differential expression of transforming growth factor-alpha (TGF-alpha) and EGF receptor in transitional area of psoriatic epidermis.

We investigated the localization of TGF-alpha and EGF receptor in psoriatic plaques, especially the clinically-determined transitional zone from uninvolved to involved psoriatic skin by immunohistochemistry. TGF-alpha was not increased in the transitional area compared with normal epidermis. It started to increase within the edge of psoriatic plaques. In contrast, EGF receptor increased up to the suprabasal layers even in the uninvolved skin adjacent to psoriatic plaques, compared with normal epidermis. Slight epidermal hyperplasia was also observed in the clinically-determined transitional area. This result suggests that the increase of EGF receptor precedes that of TGF-alpha in psoriatic plaque formation.

Epidermis↗

Detection of anti-desmocollins I and II autoantibodies in two cases of Hallopeau type pemphigus vegetans by immunoblot analysis.

Pemphigus foliaceus (PF) sera react with a 150 kDa antigen, desmoglein (DG), while pemphigus vulgaris (PV) sera react with a 130 kDa PV antigen. Recent molecular cloning studies have revealed that both DG and PV antigen are members of the cadherin family of cell adhesion molecules and that PV antigen shows very high homology to DG. We have recently noticed that other desmosoal cadherin molecules, desmocollins I and II (DC I/II), are also recognized by some pemphigus antibodies. In the present study we report two cases of Hallopeau type pemphigus vegetans. Immunoblot study revealed that the sera of these cases reacted not only with the PV antigen but also with both DG (PF antigen) and DC I/II. Although the significance of these findings is not known at present, further studies for the antigen profile for more Hallopeau type pemphigus vegetans patients may unravel the pathogenesis of this rare type of pemphigus.

Adult↗

Prognostic significance of pS2 protein expression in pulmonary adenocarcinoma.

In the present study, pS2 protein expression in pulmonary adenocarcinoma was investigated on paraffin-embedded sections obtained from 170 patients. 28 (16%) patients showed varying degrees of pS2 protein expression in the cytoplasm of tumour cells, as detected by immunohistochemical staining with anti-pS2 protein antibody. There was a significant association between pS2 protein expression and larger tumour size, and the acinar or bronchiolo-alveolar subtype. However, no significant correlations between pS2 protein status and the other clinicopathological factors, i.e. T-factor, N-factor, stage and histological differentiation, were shown. In contrast to breast cancer, patients with pS2-positive pulmonary adenocarcinomas had a significantly worse prognosis than those with pS2-negative pulmonary adenocarcinomas; this was true for stage I patients, as well as for all patients. Multivariate analysis showed that pS2 protein expression was a discriminating variable in overall survival. These findings suggest that pS2 protein status is a possible prognostic indicator in pulmonary adenocarcinoma.

Adenocarcinoma↗

Differentiation of a Ewing's sarcoma cell line towards neural and mesenchymal cell lineages.

Two different pathways of differentiation were investigated in Ewing's sarcoma (ES) cell line, designated CADO-ES1, which has been established in our laboratory. This cell line was induced to differentiate and display a neural phenotype when treated with dibutyryl cyclic adenosine monophosphate or when cultured in serum-free medium (HB101). In these in vitro differentiation studies, two different phenotypes were demonstrated by light and electron microscopy. One phenotype, present in a major portion of the cell population, had long neurites in which microtubules were ultrastructurally demonstrated. The other one, present in a minor portion of the cell population, consisted of flat cells with many short processes. After differentiation in serum-free medium, tumorigenicity in nude mice or colony-forming efficiency in soft agar was strongly depressed. In the cells, N-myc, c-fos and c-src genes were not amplified, and although c-myc was amplified by up to 2-fold, depending on the culture conditions, this appeared to be unrelated to the changes of phenotype. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue.

Animals↗

Surgical treatment of brain metastases of lung cancer: retrospective analysis of 89 cases.

The records of 89 patients who underwent surgery for solitary or multiple parenchymal brain metastases of lung cancer at the Osaka Center for Adult Diseases between 1978 and 1990 were reviewed with follow up until March 1992. The aim of this retrospective analysis was to identify prognostic features that were associated with a favourable outcome. The benefits of brain tumour surgery were evaluated in terms of the cause of death (brain metastasis, tumour in another organ, or treatment related) as well as the postoperative changes in functional state indicated by the Karnofsky scale. The overall mean survival time was 11.6 months, and the one and two year survival rates were 24% and 8%. The brain lesion itself was the cause of death in only 19% of the patients; the other 81% died of systemic disease. Functional state improved after surgical excision of the brain tumour in 36%, remained unchanged in 53%, and worsened in 11%. These data suggest that surgical intervention is beneficial for patients with parenchymal brain metastases. Variables significantly associated with a favourable prognosis included surgical excision of the primary lesion, adenocarcinoma as the histological diagnosis, the use of adjuvant treatment, especially chemotherapy, a preoperative score of over 80% on the Karnofsky scale, and metastasis confined to the brain with no extracranial metastatic foci or residual primary tumour. Additional but non-significant contributors to a good prognosis included age under 65 or 70 years, early tumour stage (stage 1), curative lung cancer surgery, a single metastatic brain tumour (v multiple lesions), a solid tumour (v cystic), and a supratentorial location of the brain metastasis. The disease free interval and the cerebrospinal fluid cytology were not significant prognostic factors. On the basis of these findings, it is concluded that the surgical removal of brain metastases of lung cancer should be undertaken if the primary tumour has already been removed whether or not there are extracranial metastases, and that postoperative chemotherapy should generally be given.

Activities of Daily Living↗

Lung cancer found in a patient with absence of the inferior vena cava associated with a left superior vena cava.

A patients with anomalies of the main systemic veins developed lung cancer. In this patient, the large hemiazygos vein emptied into the left superior vena cava which communicated with the right atrium through the coronary sinus. The cancer was located in the right upper lobe and directly invaded the mediastinum. Fortunately, because of the absence of a right superior vena cava in the normal position, the tumor was completely resected by sleeve upper lobectomy without necessitating angioplastic procedures.

Aged↗

Long-term results of postoperative intrathoracic chemo-thermotherapy for lung cancer with pleural dissemination.

BACKGROUND: To overcome the poor prognosis of lung cancer with pleural dissemination, the authors developed postoperative intrathoracic chemo-thermotherapy (PICT). In this report, they present the long-term results for 31 consecutive patients who underwent resection, followed by PICT for lung cancer with pleural dissemination between April 1985 and December 1991. METHODS: Among the patients, there were 26 cases of adenocarcinoma, 3 cases of squamous cell carcinoma, and 1 case each of large and adenosquamous cell carcinoma. Twenty-four of these patients had an initial diagnosis of pleural involvement at thoracotomy. The other seven patients had massive malignant effusion at the time of the initial diagnosis. PICT was started between days 10 to 14 postoperatively. When possible, three courses of this procedure were administered at intervals of 5-7 days. RESULTS: The 5-year cumulative and 5-year local relapse-free survival rates were 24.6% and 76.3%, respectively. The 3-year and 5-year cumulative survival rates for 14 patients without mediastinal lymph node involvement were 68.4% and 42.7%, respectively. Those rates for 17 patients with mediastinal lymph node involvement were 22.7% and 0%, respectively. The 3-year survival rate in the former group was significantly better than that in the latter group. CONCLUSIONS: These results strongly suggest that in patients with pleural dissemination, PICT may be beneficial for regional disease control and improvement of survival, particularly for patients without mediastinal lymph node involvement.

Adenocarcinoma↗

Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion.

The expression of nucleoside diphosphate (NDP) kinase/nm23 has been reported to be inversely related to metastasizing potential of experimental cells and human breast cancer. In the present study, levels of NDP kinase/nm23 gene product in curatively resected human pancreatic adenocarcinomas were examined immunohistochemically using anti-NDP kinase antibody. Immunoreactivity for NDP kinase varied between tumors. Of 31 pancreatic tumors examined, 17 (55%; positive staining group) showed strong immunoreactivity for the NDP kinase, while 14 (45%; negative staining group) showed low or no immunoreactivity. Positive staining was associated with higher incidence of lymph node metastasis (13/17; 77%) and perineural invasion (13/17; 77%) than negative staining (5/14, 36%, P < 0.03; 4/14, 29%, P < 0.01, respectively). Positive staining was also associated with shorter overall survival and relapse-free survival than negative staining (P < 0.01, P < 0.01, respectively). No significant difference in age, sex, size, location of tumor, serum carcinoembryonic antigen (CEA) level, or histological type was found between the two groups. These results showed that, in contrast to the reports on breast cancer, NDP kinase/nm23 expression in human pancreatic cancer is positively associated with lymph node metastasis or perineural invasion and with poor prognosis. These, together with other previous reports, suggest that NDP kinase may play an important role in cancer progression or aggressiveness by altering its expression in a tissue-specific manner.

Adenocarcinoma↗

cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. I. Distribution within the central nervous system after intravenous and intracarotid infusion.

The distribution of cis-diamminedichloroplatinum (CDDP) was studied in 23 patients undergoing surgical resection of brain tumors metastatic from lung cancer. CDDP (100 mg/m2) was administered intravenously (i.v.) or intra-arterially (IA) at the time of surgery, and various fluids and tissues were sampled for measurement of drug concentration. Comparison of the two routes of administration disclosed that the plasma level was slightly lower after IA than after i.v. infusion, whereas there was no difference between the two routes in terms of drug diffusion into the brain tissue adjacent to the tumor. However, IA administration resulted in an intratumoral drug concentration twice as high as that achieved with i.v. infusion. The tumor:plasma and tumor:adjacent brain ratios of drug concentration after IA injection were also twice those measured after i.v. administration. The distribution pattern of CDDP is characteristic of water-soluble agents. All patients experienced tolerable nausea and vomiting. Creatinine clearance was moderately reduced in ten cases, but no serious renal toxicity was observed. Seizures occurred postoperatively in nine patients. Infrequent side effects were myelosuppression, ototoxicity, and postoperative intracranial bleeding. All adverse effects disappeared with conservative treatment or no intervention.

Aged↗

cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. II: Clinical effects.

Parenchymal brain tumors, which were metastases of primary lung cancer, were surgically removed from 25 patients. During the operation, patients were administered (intravenous or intracarotid) 100 mg/sq m of cis-diamminedichloroplatinum (CDDP) and postoperatively, they received intravenous CDDP at 3-month intervals for 1 year. The results of this mode of treatment were compared with those obtained in 25 patients who underwent the same surgery but received other anticancer agents and in 39 patients who received no postoperative chemotherapy. Patients in the CDDP-treated group survived much longer than both of the other treatment groups. In the CDDP, but not in the other two groups, survival was significantly longer in patients who had undergone resection of their lung tumors than in those who had not. The stage of lung cancer was not found to significantly influence survival time among CDDP-treated patients. Brain metastasis was the cause of death in 12% of the patients who received CDDP, in 16% those treated with other drugs, and in 26% of those who received no chemotherapy. The incidence of local and remote intracranial tumor recurrence, including meningeal carcinomatosis, was similar in the three groups. However, the mean interval from resection of the metastatic brain tumor to local or remote recurrence was longer in the CDDP-treated group than in the other two groups, and the 2-year-survival rate was significantly higher after CDDP administration. These results suggest that CDDP may be useful in the therapy of metastatic brain tumors derived from lung cancer.

Brain Neoplasms↗

Successful surgery of malignant fibrous histiocytoma in the lung with gross extension into the right main pulmonary artery.

We report on successful surgical treatment of a 49-year-old female suffering from malignant fibrous histiocytoma which arose from the lower lobe of the right lung with gross extension into the right main pulmonary artery, mimicking pulmonary thromboembolism. With the aid of a percutaneous cardiopulmonary support system, right pneumonectomy with resection of the right main pulmonary artery and reconstruction of the pulmonary artery was performed. Surgical management and the unique clinicopathological features of this case are discussed.

Diagnosis, Differential↗

Cathepsin B expression in tumour cells and laminin distribution in pulmonary adenocarcinoma.

AIMS: To determine the correlation between cathepsin B expression and laminin distribution in pulmonary adenocarcinoma tissue. METHODS: The distribution of cathepsin B and laminin was examined in 28 formalin fixed, paraffin wax embedded specimens of pulmonary adenocarcinoma tissue, using a double immunostaining technique with commercially available antibodies to cathepsin B and laminin, respectively. RESULTS: Tumour cells in 23 (82%) cases reacted to cathepsin B: 13 cases were weakly positive and 10 were strongly positive. Laminin in tumour associated basement membrane produced various staining patterns: two cases had an almost continuous distribution of laminin in tumour associated basement membrane in the tumour tissues, while a moderately discontinuous laminin distribution pattern was found in 12 cases, and a highly fragmented pattern was found in 14 cases. The degree of cathepsin B expression in tumour cells was significantly correlated with the break up of laminin staining. In some cases a discontinuous pattern of tumour associated laminin was frequently observed adjacent to cathepsin B positive tumour cell nests. CONCLUSIONS: Considering that cathepsin B has the capacity to degrade basement membrane components, including laminin, the inverse correlation shown in this study between the increase in cathepsin B expression by tumour cells and the diminution of laminin in tumour associated basement membrane could reflect local progression and spread by pulmonary adenocarcinoma.

Adenocarcinoma↗