Biomedical subjects

S Matsukawa

Publications and source records attributed to S Matsukawa.

At least 19 recordsLinked to original sources

PubMed2000

[Anesthetic management of a patient with hemophilia A for left modified Blalock-Taussig shunt].

We gave anesthesia to a patient with hemophilia A for left modified Blalock-Taussig shunt. The patient was a twenty five-day-old boy with pulmonary atresia. We performed the bolus injection test of factor VIII concentrate in preoperative period. His factor VIII activity increased from 9.3 to 113.3% after a bolus injection of 165 units. To keep his factor VIII activity above 80% in perioperative period, a bolus of 125 units of recombinant factor VIII concentrate was injected at anesthesia induction, 125 units 2 hours after the start of the operation, and 125 units 6 hours after the end of the operation. Factor VIII activity 2 hours after anesthesia induction increased only 37.8%, and we had to infuse recombinant factor VIII concentrate additionally. We measured factor VIII activity during operation, and he finally received total of 415 units of factor VIII concentrate. Hydroxyethyl starch infusion, blood transfusion and bleeding in the perioperative period might have caused the factor VIII activity to decrease beyond our expectation. We should infuse factor VIII concentrate properly measuring the factor VIII activity during this operation.

Anastomosis, Surgical↗

PubMed1999

Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo.

Modulation of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the clinical outcome of cancer treatment. Bax, an apoptosis-promoting member of the bcl-2 family, may be a key factor influencing the chemosensitivity of tumor cells, however, its involvement in cellular sensitivity to anti-cancer drugs remains uncertain in squamous cell carcinoma (SCC). To investigate the role of bax gene expression in modulating cisplatin (CDDP)-induced apoptosis in vitro, an established CDDP-resistant human head and neck SCC (IMC-3 cell line) was transfected with bax gene-bearing mammalian expression vector. Overexpression of the bax gene in CDDP-resistant IMC-3 cells elevated the CDDP susceptibility of tumor cells to a level similar to that of the parental IMC-3 cells. In an in vivo study, percutaneous transfer of apoptosis-promoting bax gene by particle-mediated (gene gun) delivery caused overexpression of Bax in SCC, which was confirmed by immunohistochemical staining, and inhibited the growth of mouse CDDP-resistant SCC. Furthermore, combination therapy with bax gene transfer and subcutaneous administration of CDDP at 3-day intervals markedly inhibited the growth of mouse SCC. Thus, overexpression of bax in SCC by a gene gun system appears to be a rational approach to improving the efficacy of chemotherapy and treatment outcome. We suggest that exogenous bax expression may have therapeutic applications for enhancing chemotherapy in SCC.

Animals↗

PubMed1999

Glutathione depletion induces giant DNA and high-molecular-weight DNA fragmentation associated with apoptosis through lipid peroxidation and protein kinase C activation in C6 glioma cells.

Glutathione (GSH) depletion caused by l-buthionine-(S,R)-sulfoximine (BSO) induced apoptosis that was recognized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endo-labeling (TUNEL), nuclear DNA staining with fluorescence dye, and internucleosomal DNA fragmentation in C6 rat glioma cells. The BSO-induced cell death was associated with caspase-3 activation. Lipid peroxidation and protein kinase C (PK-C) activation were observed during the apoptosis of C6 cells, and these events were inhibited by antioxidants and iron chelators without affecting BSO-induced GSH depletion. Furthermore, approximately 2 Mbp giant DNA fragments were observed in the BSO-treated cells. The giant DNA fragmentation were followed by approximately 30-700 kbp and then less than 100 kbp, including internucleosomal DNA fragmentations. Such serial DNA degradation was prevented by the antioxidants, the iron chelators, and the PK-C inhibitors. These results suggest that during apoptosis induced by GSH-depletion caused by BSO, reactive oxygen species endogenously produced cause lipid peroxidation and that the lipid peroxidation induced PK-C activation, processes which are thought to be involved in the giant DNA, high-molecular-weight DNA, and the internucleosomal DNA fragmentations.

Animals↗

PubMed1999

[Evaluation of left ventricular diastolic function during coronary artery bypass grafting by color M-mode Doppler echocardiography].

The objective of the present study was to evaluate the effects of the coronary artery bypass graft surgery (CABG) and cardioplegic arrest on left ventricular diastolic function. Ten patients with coronary artery disease were studied by transesophageal Doppler echocardiography. Doppler measurements included peak velocity during early filling (peak E velocity), peak velocity during atrial contraction (peak A velocity), and the ratio of peak E velocity to peak A velocity (E/A). The rate of propagation of peak early filling flow velocity (FPV) was also measured using color M-mode Doppler echocardiography. Hemodynamic and Doppler-derived variables were measured before and after sternotomy, after the end of cardiopulmonary bypass (CPB) and after closure of the sternum. E/A showed a significant decrease after sternotomy and did not return to the pre CPB level. FPV increased after CPB. FPV was correlated with E/A (r = 0.54, P = 0.013 pre-CPB; r = 0.54, P = 0.014 post-CPB). E/A showed a significant correlation with heart rate. After the influence of heart rate had been eliminated by the analysis of covariance, corrected E/A value showed a significant increase post-CPB compared to that in pre-CPB (0.68 +/- 0.29 to 1.10 +/- 0.29, P < 0.05). In conclusion, FPV and heart-rate-corrected E/A increased after CPB. This suggests improvement of diastolic function during CABG.

Aged↗

PubMed1998

Effects of brief glucocorticoid exposure on growth of vascular smooth muscle cells in culture.

While prolonged exposure of vascular smooth muscle cells (VSMC) to glucocorticoid has been shown to inhibit cell proliferation, the effect of a brief pulse exposure is not known. We studied the short-term effects of pulse exposure to dexamethasone (DEX) on DNA synthesis in cultured VSMC. VSMC were pulsed with DEx for varying time intervals and [3H]thymidine incorporation into cells after 24 h was measured. Exposure to DEX for 24 h decreased [3H]thymidine incorporation, while pulse treatments with DEX from 2 min to 6 h significantly increased [3H]thymidine incorporation. Maximal proliferative effect was observed with a 20-min exposure. The effect of a 20-min pulse was dose-dependent, with the half-maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid receptor antagonist, RU486, inhibited the proliferative effect of DEx. Concentrated conditioned medium from cells exposed to 10(-6) M DEX increased [3H]thymidine incorporation by other VSMC in a dose-dependent manner. These results suggest that short-term pulse DEX exposure is capable of producing one or more autocrine growth factors in VSMC via a glucocorticoid receptor action. This effect of glucocorticoid pulses may contribute to the pathogenesis of arteriosclerosis and hypertension.

Animals↗

PubMed1998

Relationship between flushing pressure and nitric oxide production in preserved lungs.

BACKGROUND: Nitric oxide (NO) is considered to be one of the endogenous inhibitory factors of ischemic reperfusion injury. In this study, the NO-producing ability of the preserved lung, flushed at various pulmonary artery pressures (flushing pressure), was studied during reperfusion using an ex vivo rabbit lung perfusion model. METHODS: The lungs were flushed with 200 ml of preservation solution with flushing pressures adjusted to 15, 15, 20, and 25 mmHg for groups 1, 2, 3, and 4, respectively (n=5 in each group). In the control group (group 1), the heart-lung block was harvested after flushing and the lungs were assessed without preservation. In the other groups, the harvested blocks were preserved at 8 degrees C for 24 hr and reperfused with homologous blood for pulmonary functional assessment. Pulmonary function was assessed by measuring mean airway pressure, mean pulmonary arterial pressure, partial oxygen tension of pulmonary venous effluent blood, and pulmonary wet-dry weight ratio. The sequential changes in the concentration of NO-related substances (NO-RS) in the serum of reperfused blood were also measured by chemiluminescence. RESULTS: During reperfusion, biphasic increases in NO-RS were observed in all groups. In groups 3 and 4, the increases in NO-RS were significantly lower than those of groups 1 and 2, and pulmonary function deteriorated. CONCLUSION: These data suggest that in order to maintain the endogenous NO-producing ability of preserved lung, the flushing pressure must be less than 20 mmHg.

Animals↗

PubMed1998

Active oxygen-mediated chromosomal 1-2 Mbp giant DNA fragmentation into internucleosomal DNA fragmentation in apoptosis of glioma cells induced by glutamate.

C6 glioma cells treated with 10 mM glutamate reduced intracellular GSH to one-seventh of the initial level, and induced cytolysis accompanied by apoptosis. The treated cells produced extracellular H2O2. The cytolysis of the C6 cells induced by glutamate was prevented by antioxidants such as N-acetylcysteine (NAC), ascorbic acid (ASC), catalase, and NaN3, iron chelators such as deferoxamine and 1,10-phenanthroline, and oxygen radical scavengers such as 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN). The effect of these antioxidants, iron chelators, and oxygen radical scavengers on the cytolysis of C6 cells was dependent on the dose and the intracellular GSH level. Furthermore, 1-2 Mbp chromosomal DNA (giant DNA) fragments were observed during cytolysis. The giant DNA fragments were further cleaved into smaller DNA fragments of 200-800 kbp, and then to fragments of less than 300 kbp in size including chromosomal ladder DNA fragments. Such serial chromosomal DNA degradations induced by glutamate were also inhibited by addition of these antioxidants, iron chelators, and oxygen radical scavengers. These findings suggest that glutamate induces GSH depletion, and consequently, apoptosis through endogenously produced active oxygen species in C6 glioma cells and that the apoptosis is accompanied by 1-2 Mbp giant DNA fragmentation prior to the internucleosomal DNA fragmentation.

Acetylcysteine↗

PubMed1998

The activation of eNOS by copper ion (Cu2+) in human pulmonary arterial endothelial cells (HPAEC).

We have previously reported that Cu2+ endothelium-dependently dilated rat pulmonary arterial rings in a few minutes by increasing NO production via constitutive endothelial nitric oxide synthase (eNOS) activation in rat pulmonary arterial endothelial cells (Eur. J. Pharmacol., 1997). In the present study, using cultured human pulmonary arterial endothelial cells (HPAEC), we assessed the effects of divalent cations (Cu2+, Mn2+, Zn2+, and Fe2+) on NOS activity in crude cell extracts and intact cells. NO synthase activity was measured by monitoring the conversion of L-[14C] arginine to L-[14C] citrulline. The NOS enzyme in crude HPAEC extract showed similar characteristics to previously reported eNOS from other sources. All the divalent cations tested suppressed the NOS activity in crude cell extract by about 50% at 1 x 10(-4) M, but only Cu2+ from 10(-6) M increased eNOS activation dose dependently with a significant elevation in whole-cell assay. Extracellular Ca2+ was prerequisite to the eNOS activation by Cu2+ in intact cells. Furthermore, we measured NO production determined as NOx (NO, .NO2-, and .NO3-) from HPAEC using NO chemiluminescence analyzer. HPAEC monolayers were treated with either buffer alone, Cu2+ (10(-4) M) or thapsigargin (10(-6) M). The amount of .NOx increased from 10.93 (pmoml/ml/10(6) cells) to 41.27 (pmol/ml/10(6) cells) by thapsigargin (10(-6) M) and to 45.24 (pmol/ml/10(6) cells) by Cu2+ (10(-4) M). The increase in NOx by Cu2+ was inhibited by L-NMMA. These results indicated that Cu2+, but not Mn2+, Zn2+, and Fe2+, causes the activation of eNOS, while Cu2+, Mn2+, Zn2+, and Fe2+ directly suppressed eNOS activity extracted from HPAEC. Further, our study showed that extracellular Ca2+ was essential for eNOS activation by Cu2+.

Arginine↗

PubMed1998

Leukotoxin (9, 10-epoxy-12-octadecenoate) impairs energy and redox state of isolated perfused rat lung.

We investigated the perturbation of energy balance and redox state in leukotoxin (9, 10-epoxy-12octadecenoate) (Lx)- and endothelin-1 (ET-1)-induced lung injury, using isolated perfused rat lungs. To examine any relationship between these parameters, intracellular levels of adenine nucleotides, pyridine coenzymes and glutathione were determined by reversed-phase high-performance liquid chromatography (HPLC) in the freeze-dried tissues of isolated rat lungs. The tissue samples were perfused with a physiological salt solution containing either Lx only, Lx plus NG-monomethyl-L-arginine (L-NMMA), Lx plus NG-monomethyl-D-arginine (D-NMMA), Lx plus superoxide dismutase (SOD) or ET-1 only. In isolated perfused lung tissue, 10 mol of Lx caused permeability-increased lung injury, and 10 nM of ET-1, which caused a comparable increase in wet lung weight, evoked pulmonary capillary hypertensive lung injury. Lx-injured lungs showed decreases in the contents of ATP, NADPH, NADH, reduced glutathione (GSH), (2ATP + ADP)/2(ATP + ADP + AMP) ratio (energy charge) and NADH/NAD+ ratio, and increased the contents of ADP and AMP compared with the vehicle control and ET-1-injured lungs. Such effects of Lx were significantly attenuated by pretreatment with 0.4 mM L-NMMA or 500 units/ml of SOD, but not with 0.4 mM D-NMMA. On the other hand, the ET-1-injured lung evidenced decreased tissue GSH. These findings indicate that Lx shifted the lung redox state toward oxidation and that Lx-induced lung injury was involved in the imbalance of the energy and redox state via production of nitric oxide and/or superoxide anion.

Adenine Nucleotides↗

PubMed1998

Interleukin-10 production during and after upper abdominal surgery.

STUDY OBJECTIVE: To evaluate the influence of major abdominal surgery on the plasma levels of interleukin-10 (IL-10). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 10 ASA physical status I and II patients undergoing upper abdominal surgery. INTERVENTIONS: All patients received combined general-epidural anesthesia with isoflurane and nitrous oxide, after insertion of an epidural catheter at T8-T9 dosed with 1.5% lidocaine. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin-6 (IL-6), interleukin-8 (IL-8), and IL-10 levels were determined with an enzyme-linked immunosorbent assay at preanesthesia, 0, 2, and 4 hours during surgery, and at the end of surgery, followed by sampling on the morning of postoperative days 1 (POD1) and 3 (POD3). Before anesthesia and at 0 hours of surgery, IL-10 was not detected. In all ten patients, the plasma levels of IL-10 showed significant elevations and achieved their maximal value 4 hours after the skin incision (p < 0.05 vs. baseline). The plasma IL-10 levels returned to preanesthesia levels on POD3. The plasma levels of IL-6 and IL-8 also increased in the perioperative period. The peak cytokine levels correlated (r = 0. 915, p = 0.0001 for IL-6 vs. IL-8; r = 0.82, p = 0.025 for IL-6 vs. IL-10; and r = 0.641, p = 0.06 for IL-8 vs. IL-10). The peak plasma IL-10 levels significantly correlated with the amount of intraoperative blood loss (r = 0.69, p < 0.05). CONCLUSIONS: In patients undergoing major abdominal surgery, plasma IL-10 levels were elevated during and after operation. IL-10 may modulate the inflammatory responses in the perioperative period.

Abdomen↗

PubMed1998

The activation of nitric oxide synthase by copper ion is mediated by intracellular Ca2+ mobilization in human pulmonary arterial endothelial cells.

The aim of the study was to elucidate the vasodilatory mechanism due to Cu2+ by assessing nitric oxide (NO) production as determined by NOx (NO, NO2-, and NO3-) that is released from human pulmonary arterial endothelial cell (HPAEC) monolayers using a NO chemiluminescence analyzer, and also to assess Ca2+ movement using 45Ca and fura 2 in HPAEC. Cu2+ (10(-6)-10(-4) M) significantly increased NO production in a dose-dependent manner when extracellular Ca2+ was present. 45Ca influx into the adherent cells was dose-dependently enhanced by Cu(2+) (10(-6)-10(-4) M), but not by Mn(2+), Zn(2+) or Fe(2+). [Ca2+]i, measured by monitoring the fluorescence changes of fura 2, was significantly elevated in the presence of Cu2+. The increase in [Ca2+]i induced by Cu2+ was inhibited by either diethyldithiocarbamate (DDC) or the depletion of extracellular Ca2+. The dihydropyridine receptor agonist, BayK8644, significantly attenuated the Cu2+-induced increase in [Ca2+]i in a dose dependent manner and nitrendipine or nifedipine, the dihydropyridine receptor antagonists, dose-dependently inhibited a Cu2+-induced increase in [Ca2+]i. These results suggest that Cu2+ activates eNOS through the mechanism of [Ca2+]i elevation due to Ca2+ influx into HPAEC and that the Cu2+-induced [Ca2+]i elevation in HPAEC is likely due to activation of the dihydropyridine-like receptors.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Effect of surfactant on respiratory failure associated with thoracic aneurysm surgery.

OBJECTIVE: To study the effects of surfactant administration on the left lung after surgical repair of descending aortic aneurysms on postoperative respiratory failure. DESIGN: Randomized, prospective, controlled study. SETTING: Clinical investigation. PATIENTS: Eleven patients with respiratory failure associated with thoracic aneurysm surgery. INTERVENTION: Eleven adult patients with acute respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to the operated side of the lung by intrabronchial instillation in six patients (surfactant group), whereas nothing was instilled in the other five patients (control group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, blood gas, and peak inspiratory pressure were measured at the end of surgery, before surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2 ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/- 26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs, improvements in the PaO2/FIO2 ratios were observed in the surfactant group, whereas the control group showed no improvement. Two hours after surfactant instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). CONCLUSION: Surfactant administration immediately after surgery restored gas exchange in postoperative respiratory failure associated with thoracic aneurysm surgery.

Acute Disease↗

PubMed1998

Dexamethasone modulates the expression of endothelin-1 and -A receptors in A7r5 vascular smooth muscle cells.

Endothelin-1 (ET-1) is synthesized and released by vascular smooth-muscle cells (VSMCs). Glucocorticoids induce the release of ET-1 from VSMCs into the medium. We investigated whether glucocorticoids modulate ET-1 action by an autocrine production of ET-1 in A7r5 VSMCs. Dexamethasone (100 nM) stimulated the release of ET-1 into the medium. Treatment with 100 nM dexamethasone for 24 h reduced the peak increase of intracellular free Ca2+ induced by ET-1 (100 nM) by 50%, an effect that was dose-dependently inhibited by the specific ET(A)-receptor antagonist FR139317. Scatchard plots of [125I]-ET-1 binding revealed that dexamethasone reduced the number of maximal ET-1 binding sites without altering their binding affinity. FR139317 reversed the decrease in ET-1 binding capacity induced by dexamethasone. Northern blot analysis revealed that dexamethasone increased the level of prepro-ET-1 messenger RNA (mRNA) and decreased the level of ET(A)-receptor mRNA. FR139317 prevented the decrease in the level of ET(A)-receptor mRNA induced by dexamethasone. Results indicate that dexamethasone downregulates ET(A) receptors in A7r5 VSMCs at the mRNA level, in part by the autocrine production of ET-1.

Animals↗

PubMed1998

Changes in messenger ribonucleic acid species in gerbil brain perturbation.

The differential display technique was applied to observe the molecular dynamism of messenger ribonucleic acid (mRNA) in this study. Using this technique, the changes in mRNAs in brain perturbation such as ischemia was observed to understand the molecular base of the reaction. The transient cerebral ischemia was induced by clipping both common carotid arteries for 5 minutes in Mongolian gerbils. The total RNA was extracted from the hippocampal tissue samples before ischemia, 6 hours and 2 days after ischemia. The mRNAs were reverse transcribed and subsequently amplified by polymerase chain reaction (PCR). PCR products were displayed by autoradiography as ladders on a denaturing polyacrylamide gel. According to the autoradiography, mRNAs were divided into three patterns: 1) mRNAs obtained from the control decreased at 6 hours after 5-minute ischemia and disappeared at 2 days completely; 2) decreased mRNAs at 6 hours after ischemia recovered at 2 days; and 3) new mRNAs appeared after cerebral ischemia. Located bands of interest on a gel were cut out and reamplification of complementary deoxyribonucleic acid was performed. The pGEM-T Vector System was used for subcloning of the amplified PCR products. The differential display technique is the powerful method for detecting genes that are unique to ischemic processes and reactions.

Animals↗

PubMed1998

Efficacious diagnosis of primary and metastatic human carcinomas with a combination of p53 mutation analysis and clonality analysis of androgen receptor gene.

It is occasionally difficult to differentiate between multiple primary and metastatic tumors in case of multiple carcinomas. p53 gene mutation pattern by PCR-SSCP and a clonality analysis on the human androgen receptor gene (HUMARA) in multiple tumors were used to distinguish whether carcinomas were multiple primary tumors or a metastasis. Three female patients with multiple carcinomas, who had undergone surgical resection, were selected for these analyses as typical candidates from 11 cases tested. In the first case with bilateral breast cancer the combined analyses were performed on DNA extracted from tumor portions in paraffin sections of each tumor sample and the results indicated that the carcinomas consisted of a primary carcinoma and metastatic tumors. The carcinomas in the second patient consisted of multiple primary carcinomas and the tumors in the third patient consisted of two independent primary carcinomas with different clonal origins. Thus a combination of p53 gene mutation analysis and clonality analysis on HUMARA provided useful, reliable evidence which can help in discriminating multiple primary tumors from metastatic tumors.

Aged↗

PubMed1998

Expression of c-MET/HGF receptor mRNA and protein in human non-malignant and malignant prostate tissues.

We previously reported the expression of hepatocyte growth factor (HGF), a ligand for c-MET, at the level of mRNA and protein in human prostate tissues. The present study was carried out to evaluate the relationship between c-MET expression and cancer cell proliferation or effect of cancer therapy. The expression both in mRNA and protein levels of c-MET proto-oncogene was determined semi-quantitatively by reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis for prostate tissues from 32 Japanese male subjects. In addition, tissue localization of c-MET translation product was examined by immunohistochemistry for corresponding specimens. Although there was significantly higher c-MET protein expression in malignant (prostate cancer treated with/without neoadjuvant endocrine therapy) than in non-malignant prostate tissues (normal prostate and benign prostate hyperplasia; BPH), unexpectedly, c-MET mRNA showed high expression in the non-malignant group. Thus, there was no parallelism between mRNA and protein expressions of c-MET. Endocrine therapy did not alter c-MET mRNA and protein expressions in human prostate cancer. Immunohistochemical localization and expression of c-MET protein was found to be intense in cancer cells and weak in epithelia of normal and hyperplastic prostates. Unconcerted expression of mRNA and protein of c-MET, the reason of which is uninterpretable, is supposed to be one of characteristics of human prostate cancer.

Aged↗

PubMed1998

Usefulness of metyrapone treatment to suppress cancer metastasis facilitated by surgical stress.

BACKGROUND: One causative factor of tumor metastasis enhanced by surgical stress is thought to be hypersecretion of endogenous glucocorticoids. This study evaluated the effectiveness of metyrapone treatment and adrenalectomy in preventing the harmful effects of glucocorticoids in the enhancement of tumor metastasis resulting from surgical stress. METHODS: The effect of dexamethasone on pulmonary metastasis of MRMT-1 cells and on the number of peripheral lymphocytes was evaluated in rats. To evaluate the suppressive effect of adrenalectomy and metyrapone treatment on operation-induced enhancement of metastasis, several parameters such as induction of pulmonary metastasis, serum corticosterone levels, and the number of blood lymphocytes and apoptotic thymocytes were determined. RESULTS: With dexamethasone treatment, the number of peripheral lymphocytes rapidly decreased; in contrast, pulmonary metastasis increased. The serum corticosterone level was doubled at 1 hour, apoptotic thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at 6 hours, and blood lymphocyte numbers were decreased at 3 hours after laparotomy, which facilitated about a 10-fold increase in the pulmonary metastasis. These changes were almost completely suppressed by preoperative adrenalectomy and metyrapone treatment. CONCLUSIONS: Preoperative metyrapone treatment, which suppresses hypersecretion of endogenous glucocorticoids as a result of operation, modulates the enhancement of cancer metastases and may be an effective treatment.

Adrenalectomy↗

PubMed1998

Enhanced hepatocyte growth factor level in human prostate cancer treated with endocrine therapy.

Hepatocyte growth factor (HGF) has been revealed to have various functions such as regeneration, cancer invasion and tumor suppression in normal and cancer cells of different organs. To compare HGF expression in non-malignant prostate tissues and prostate cancers pretreated with or without neoadjuvant endocrine therapy (pretreated PC and non-treated PC), the amounts of HGF protein and mRNA were quantitated by Western blot analysis and reverse transcription-competitive polymerase chain reaction. The biologically active HGF (baHGF), which was converted by an HGF activator protein from secretory type proHGF, showed significantly higher expression in pretreated PC than in non-treated PC. The amounts of baHGF in pretreated PC were similar to those in non-malignant prostate tissues. There was no difference in the expression level of full-length HGF mRNA encoding secretory type HGF among the three groups. No variance of tissue content of short variant HGF mRNA encoding a competitive HGF antagonist among the three groups indicated that short variant HGF protein in prostate cancer seemed not to function similarly to a competitive HGF antagonist in benign prostate tissues. These results suggest that the tissue level of baHGF in non-treated and pretreated PC depends on activation of proHGF supplied from distal organs rather than de novo HGF mRNA synthesis in prostate glands. Increased baHGF in pretreated PC is expected to relate to tumor suppression in vivo.

Antineoplastic Agents, Hormonal↗