Search PubMed⌕ Search

Biomedical subjects

S Hitomi

Publications and source records attributed to S Hitomi.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Therapy for non-small cell lung cancer: new concepts based on molecular biology].

Recent advances in molecular biology have broadened our knowledge of the biological characteristics of cancer. In the present paper, we review and discuss new modalities of therapy for non-small cell lung cancer (NSCLC) based on biological findings. These modalities include: 1) diagnosis of cancer based on gene abnormalities: 2) decision making on chemo-/radiotherapy based on new biological findings: 3) gene therapy: and 4) new chemotherapeutic agents. Mutation of the p53 gene, which occurs most frequently in NSCLC, is a well-documented molecular target in these modalities. The development of polymerase chain reaction technology has enabled early diagnosis of NSCLC by detection of p53 gene abnormalities in sputum. Transfer of the wild-type p53 gene using a retrovirus vector to cancer tissues with mutant p53 gene has already been tested clinically. Inhibition of tumor neovascularization has been studied extensively in attempts to develop noveal chemotherapeutic agents. Angiostatin or endostatin, an inhibitor of tumor neovascularization is in clinical use. Matrix metalloprotease inhibitions (MMPs) also inhibit neovascularization of tumors. Marimastat, an oral MMP, is expected to prevent cancer metastasis.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Human cytomegalovirus open reading frame UL11 encodes a highly polymorphic protein expressed on the infected cell surface.

Human cytomegalovirus (HCMV) open reading frame (ORF) UL11 locates within a polymorphic region of the viral genome identified previously by a restriction-fragment-length-polymorphism. We report here that ORF UL11 encodes a polymorphic protein expressed on the surface of HCMV-infected cells. First, we determined the nucleotide sequence of ORF UL11 from ten strains and compared it among the strains. Out of 205 amino acids consisting of the predicted N-terminal region beside the putative transmembrane stretch in strain AD169, 88 residues were divergent on more than one strain. In contrast, the predicted C-terminal side including the putative transmembrane domain was identical at the amino acid sequence level. In addition, the number and location of predicted cysteine residues were also conserved. Next, we screened a cDNA library from HCMV-infected cells and obtained a cDNA clone containing the full-length ORF UL11. Finally, we identified the gene product of UL11 on the surface of HCMV-infected cells by FACS analysis with polyclonal antibodies generated against a glutathione S-transferase/UL11 fusion protein. The fusion protein contained a region within the N-terminal side next to the predicted transmembrane stretch. These results indicate that the N-terminal side of UL11 protein containing variable amino acid residues protrudes from the infected cell surface.

Amino Acid Sequence↗
PubMed1997

Tracheal stenosis treated with self-expanding nitinol stent.

A self-expanding nitinol stent was used in 2 patients with inoperable tracheal stenosis due to invasive malignant tumor of the trachea. One was a 70-year-old man with recurrent tumor from adenocarcinoma of the left lung, and the other was a 63-year-old man with recurrent tumor in mediastinal lymph nodes from esophageal cancer. The self-expanding nitinol stent is very useful and effective in inoperable tracheal stenosis due to intraluminal tumor invasion.

Adenocarcinoma↗
PubMed1997

Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion.

OBJECTIVE: Dibutyryl adenosine 3',5'cyclic monophosphate (db-cAMP) is a membrane-permeable analog of adenosine 3',5'cyclic monophosphate (cAMP). We examined the effect of db-cAMP against lung injury caused by cold preservation and ischemia-reperfusion. METHODS: Rats were divided into three groups (each n = 6) according to the presence or absence of db-cAMP in the preservative solution and cold ischemia (4 degrees C for 15 hours). In the fresh group, the lung was flushed with the preservative solution and reperfusion was performed immediately. In the control group and the db-cAMP group, the lung was flushed either with the solution or with a combination of the solution plus db-cAMP, respectively, and preserved at 4 degrees C for 15 hours. The lung was reperfused for 60 minutes in an ex vivo rat lung perfusion model. RESULTS: The shunt ratios of the reperfused lung in the db-cAMP group were 4.0% +/- 1.6% and 3.4% +/- 1.2% 10 and 60 minutes, respectively, after the initiation of reperfusion, being as low as those in the fresh group and significantly lower than those in the control group (p < 0.01). The wet/dry weight ratio of the lung tissue after reperfusion was 5.99 +/- 1.50 in the db-cAMP group, which was similar to that in the fresh group (5.45 +/- 0.23) and significantly lower than that in the control group (14.20 +/- 3.43) (p < 0.01). Electron microscopic examination showed less damage in the pulmonary arterial endothelium in the db-cAMP group. CONCLUSIONS: We conclude that db-cAMP attenuates the lung injury by cold preservation and ischemia-reperfusion, at least partly by protection of the vascular endothelium.

Animals↗
PubMed1997

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung.

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Acetylcysteine↗
PubMed1997

Extended operation for non-small cell lung cancer invading great vessels and left atrium.

OBJECTIVE: We analyzed the results of surgical treatment in patients with non-small cell lung cancer invading the great vessels (GV) and left atrium (LA) by direct extension and without distant metastases. METHODS: From 1976 to 1993, 42 patients (37/male, 5/female) with lung cancer invading the GV and LA were treated surgically, 13 had invasion of the superior vena cava and innominate vein, 15 of the aorta and subclavian artery, and 14 of the left atrium. In all 42 the diagnosis was confirmed by pathological examination. Surgical resection included pneumonectomy (16 patients) and lobectomy (26 patients). The histologic type was squamous cell carcinoma in 27 patients, adenocarcinoma in 12, and large cell carcinoma in 3. Preoperatively, 13 patients were treated with radiation and chemotherapy. Postoperatively, further treatment was given to 22 patients. All were staged according to the international TNM staging system. Survival was calculated by the Kaplan-Meler method. RESULTS: A total of 15 patients underwent complete resection. Reliability of clinical N factor was 80%. The overall survival was 17% at 3 years (median survival time (MST), 14 months). The operative mortality was 2.4%. Patients with lung cancer invading GV (MST, 19 months) had significantly longer survival than did those with cancer invading LA (MST, 10 months, P = 0.036). There were significant prognostic differences between N0-1 and N2-3 (MST, 22 months; MST, 9 months, respectively, P = 0.0013). Cox regression analysis identified pathological N factor, completeness of resection, and pre- and postoperative radiotherapy as important in affecting survival. CONCLUSIONS: We conclude that patients with pathological N0-1 non-small cell lung cancer invading great vessels can achieve long-term survival with adequate surgical treatment.

Aged↗
PubMed1997

Prognosis of ipsilateral intrapulmonary metastases in resected nonsmall cell lung cancer.

OBJECTIVE: According to the new classification of intrapulmonary metastasis (pm) of lung cancer by the American Joint Committee on Cancer (AJCC), ipsilateral pm is classified as a T factor. We evaluated the prognostic factors of ipsilateral pm after surgical treatment, and validity of the new classification. METHODS: From January 1977 to December 1994, 41 patients (24 males and 17 females) with lung cancer had a postoperative diagnosis of intrapulmonary pm. The histologic type consisted of 27 adenocarcinoma. 12 squamous cell carcinoma, and 1 large cell carcinoma. Twenty patients had pm in the same lobe in which the primary lesion was located, and 21 patients had pm in ipsilateral different lobe(s). Thirty patients underwent lobectomy, 5 bilobectomy and 6 pneumonectomy. Survival was calculated by the Kaplan Meier method, and Cox proportional hazards model was used for multivariate analysis. RESULTS: The overall survival was 25.8% at 5 years (median survival time (MST), 26 months). The 3-year survival of patients with pm in the same lobe was 49% (MST, 33 months), and that of patients with different lobe was 21% (MST, 16 months) (P = 0.237). There were no significant differences in survival in relation to age, sex, histology, pathological N factor, or number of pm. Multivariate analysis identified a significant correlation between survival and T factor proposed by AJCC (P = 0.022). CONCLUSIONS: The new classification seems useful for estimating postoperative prognosis of the resected patients with lung cancer accompanied by ipsilateral pm.

Aged↗
PubMed1997

Time trends and survival after surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC).

OBJECTIVE: To evaluate the role of surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC), time trends and survival after surgery and the prognostic factors were investigated retrospectively. METHODS: Consecutive patients, 155, with p-stage IIIa, pN2 NSCLC who underwent thoracotomy at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between January 1976 and December 1990 were divided into three groups by the period of operation (the earlier period: 1976-1980, n = 49; the middle period: 1981-1985, n = 55; and the later period: 1986-1990, n = 51), and were reviewed. Of the 155 patients, 84 (54.2%) were preoperatively evaluated to have mediastinal lymph nodes metastases (cN2 disease). RESULTS: The 5 year survival rates in the earlier, middle and later periods were 12.1, 18.6, and 43.8%, respectively, showing significant improvement in the later period (P < 0.001, for the later period versus the earlier period or the middle period). The improvement was caused by decrease in the rate of operation-related death (4.1, 1.8, and 0.0%, in the earlier, the middle, and the later period, respectively), increase in the rate of complete tumor resection (59.1, 76.4, and 96.1%, respectively), and decrease in the ratio of pT3N2M0 patients (44.9, 34.5, and 17.6%, respectively) having poor prognosis compared with pT1-2N2M0 patients. Decrease in the ratio of cT3N2M0 patients and for increase in the rate of complete resection could be realized by accurate preoperative diagnosis with introduction of chest computed tomography (CT). Based on the preoperative evaluation, the 5 year survival rates of cT1N2M0, cT2N2M0, and cT3N2M0 patients were 39.4, 30.5, and 10.2%, respectively, showing significant poor prognosis in cT3N2M0 patients. CONCLUSION: In cT1-2N2M0 or pT1-2N2M0 patients, a good prognosis can be realized by complete tumor resection with mediastinal lymph nodes dissection. In contrast, surgical treatment should not be justified in cT3N2M0 or pT3N2M0 patients.

Adult↗
PubMed1997

"Reversed" latissimus dorsi musculocutaneous flap for closure of large bronchopleural fistula.

The patient was a 54-year-old male with diabetes mellitus and liver abscess perforating into the right lung through the diaphragm. After right lower lobectomy of the lung, S3-segmentectomy of the liver, and debridement of the subdiaphragmatic abscess a bronchopleural fistula appeared. After open-drainage thoractomy, secondary operation for closure of a large bronchopleural fistula and obliteration of the empyema cavities was performed with a "reversed" latissimus dorsi musculocutaneous flap.

Bronchial Fistula↗
PubMed1997

Oral sustained-release cisplatin preparation for rats and mice.

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.

Administration, Oral↗
PubMed1997

Dark and light neurons in the human brain, with special reference to their reactions to Golgi's silver nitrate, luxol fast blue MBS and azocarmine G.

Sections from the human somatosensory cortex were observed with a light microscope. The neurons were classified into light and dark ones. The light neurons were slightly stained with thionin, luxol fast blue MBS and azocarmine G (80% of all neurons). The dark neurons were more or less shrunken, and stained intensely with these dyes (20% of all neurons). Double staining with luxol fast blue MBS and azocarmine G was especially useful to demonstrate the dark neurons, since it clearly stained even their fine processes. Neither light nor dark neurons were reactive to nick end labeling for detection of DNA fragmentation. Triple staining with Golgi's silver nitrate (or Gallyas's ammoniacal silver carbonate), luxol fast blue MBS and azocarmine G show that the majority of the dark neurons were argyrophilic (argyrophilic dark neurons, 15% of all neurons), while some of them were not argyrophilic (non-argyrophilic dark neurons, 5% of all neurons). Triple staining also showed that the light neurons were only occasionally argyrophilic (argyrophilic light neurons, 5% of all neurons); usually, the light neurons were not argyrophilic (non-argyrophilic light neurons, 75% of all neurons). The results confirm that dark neurons usually represent certain populations of neurons in the human brain, and that they are basically identical to the argyrophilic neurons. The discussion suggests that the argyrophilic light and dark neurons are excited cells, the non-argyrophilic dark neurons are exhausted cells, and the non-argyrophilic light neurons are resting cells. Triple staining further demonstrated that some glial cells were darkened and stained with Golgi's silver nitrate or Gallyas's silver carbonate. Additional Golgi's silver block staining showed that the argyrophilic neurons stained by the conventional block staining method usually possessed a shrunken cell body, which was characteristic of the dark neurons.

Aged↗
PubMed1997

Perineuronal sulfated proteoglycans and cell surface glycoproteins in the visual cortex of adult and newborn cats.

Sections of the visual cortex of newborn (1-4 weeks after birth) and adult cats were stained with cationic iron colloid, aldehyde fuchsin or lectins (lectin Vicia villosa, soybean and Wisteria floribunda agglutinins). Many neurons in the adult cat visual cortex contained perineuronal sulfated proteoglycans detectable with cationic iron colloid and aldehyde fuchsin, or cell surface glycoproteins reactive to lectins. Double staining indicated that some of the lectin-labeled neurons were not stained with cationic iron colloid, and also that some of the cationic iron colloid-stained neurons were not labeled with lectins. The perineuronal sulfated proteoglycans and cell surface glycoproteins developed 3 weeks after birth. In the newborn cats 1-2 weeks after birth, no neurons were reactive to cationic iron colloid, aldehyde fuchsin or lectins. In the newborn cats 3-4 weeks after birth, it was clearly observed that the cytoplasm of the glial cells closely associated with the neurons containing the perineuronal sulfated proteoglycans showed an intense reaction to cationic iron colloid and aldehyde fuchsin, and that the Golgi complexes of the neurons with cell surface glycoproteins were intensely labeled with lectins. These findings suggest that the perineuronal sulfated proteoglycans are derived from the associated glial cells, and that the cell surface glycoproteins are produced by the associated nerve cells.

Animals↗
PubMed1997

Thymic interdigitating cells express thioredoxin (TRX/ADF): an immunohistochemical study of 82 thymus and thymoma samples.

Thymic ID cells are involved in the differentiation of mature T cells which are resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent, acts as a redox regulator, and it can attenuate the induction of apoptosis of T lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma samples were examined to identify the expression of TRX/ADF in human thymic tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were found distributed in the thymic medulla. These TRXh cells were negative for CD3, a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme, macrophage/monocyte markers, but were positive for S100 protein and HLA-DR complex. Our results revealed that the TRXh cells in the thymic medulla were ID cells. As TRX/ADF has an important and fundamental role in cellular responses acting against oxidative stress, TRX/ADF may provide an explanation of cellular interaction between the medullary ID cells and the mature T cells.

Adolescent↗
PubMed1997

[Adjuvant chemotherapy for non-small cell lung cancer].

Surgery is the first choice for patients in the early stage of non-small cell lung cancer (NSC-LC). But, even for pathologic stage I patients, the post-operative survival remains unsatisfactory; the five-year survival rate is around 70 percent, in spite of potential curative resections. Therefore, post-operative adjuvant chemotherapy is considered to be necessary to improve the survival. Although many prospective randomized studies of post-operative adjuvant chemotherapy have been conducted, the efficacy of post-operative chemotherapy for NSCLC has not been proved (a consensus report of post-operative adjuvant treatment for NSCLC, 3rd IASLC Workshop, Bruges, August 1993). It has been recently reported by the West Japan Study Group for Lung Cancer Surgery (WJSG) that oral administration of UFT (a mixture of tegafur and uracil) as a post-operative adjuvant chemotherapy is effective for patients with complete resected NSCLC (stage I to III) and that UFT administration is tolerable with mild adverse effects in most patients. In order to improve postoperative survival of patients with more advanced stage NSCLC (e.g., bulky N2, III b), we has introduced biochemical modulation therapy using 5-FU, UFT combined with CDDP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Postoperative adjuvant chemotherapy for non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery. The Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy.

Given that no therapeutic methods of postoperative adjuvant chemotherapy for non-small-cell lung cancer have been established, we selected UFT (tegafur and uracil) for investigation because UFT is less injurious to the host than intensive chemotherapies. The second study of the West Japan Study Group for Lung Cancer Surgery showed that the 5-year survival rates were 64.1% in the UFT group (UFT 400 mg/day for 1 year after surgery) and 49.1% in the control group (surgery alone). Thus, the survival rate for all patients was improved significantly in the UFT group as compared with the control group (log rank test, P = .033; generalized Wilcoxon test, P = .019). To establish the usefulness of long-term oral administration of UFT as an adjuvant therapy for completely resected non-small-cell lung cancer, the nationwide Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy is now conducting a comparative study of surgery alone versus surgery and UFT in patients with pathologic stage I adenocarcinoma.

Antineoplastic Agents↗
PubMed1996

Effects of Euro-Collins, University of Wisconsin, and new extracellular-type trehalase-containing Kyoto solutions in an ex vivo rat lung preservation model.

BACKGROUND: We have previously reported the effects of trehalose-based extracellular-type Kyoto (ET-K) solution in lung preservation. Now, we have developed a new ET-K solution by adding three substances--N-acetyl cysteine, dibutyryl cyclic AMP, and nitroglycerin, to ET-K solution. We studied the effects of new ET-K solution in lung preservation, and compare it with Euro-Collins (EC) and University of Wisconsin (UW) solutions using an ex vivo rat reperfusion model. METHODS: The perfusion circuit was initiated by 30 ml of fresh mixed venous blood obtained from three haparinized rats. By means of a double-head roller pump, the blood passed from the venous blood reservoir through the pulmonary artery to be perfused in the examined lung. The lung effluent was returned at the same flow rate to the deoxygenator fresh lung. Four experimental groups were allocated. In group 1 (fresh group, n=6), lung was flushed with saline and reperfused immediately. In the other groups (group 2: new ET-K group, n=6; group 3: UW group, n=6; and group 4: EC group, n=6), lung was flushed with the new ET-K and prostanglandin E1 (PGE1), UW and PGE1, and EC and PGE1, respectively. After 17-hr preservation, the preserved lung was reperfused. RESULTS: In all six animals of the EC group, ventilation of the experimental lung was discontinued at 20 min after reperfusion because of the exudate in the endotracheal tube that resulted from pulmonary edema. The shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure in the new ET-K and UW groups were significantly better than those in the EC group, but were almost equal to those in the fresh group. CONCLUSION: The postpreservation pulmonary functions with the new ET-K solution were better than those with the EC solution, and were equal to those with the UW solution. This new solution is expected to contribute to the increase in donor lungs for clinical lung transplantation. In addition, this ex vivo rat reperfusion model is simple and highly reliable, and can be widely used in the studies of pulmonary preservation.

Adenosine↗