Biomedical subjects

Y Kawano

Publications and source records attributed to Y Kawano.

At least 145 records · Page 8Linked to original sources

PubMed1999

Expression and characterization of the extracellular domain of guanylyl cyclase C from a baculovirus and Sf21 insect cells.

Guanylyl cyclase (GC)-C, a single-transmembrane receptor protein for heat-stable enterotoxin, guanylin, and uroguanylin, and its N-terminal extracellular domain were prepared at a high level of expression from a system constructed of Sf21 insect cells and recombinant baculovirus. The recombinant GC-C, containing the complete sequence, retained its binding affinity to heat-stable enterotoxin with a KD value (6.2 x 10(-10) M) and cyclase catalytic activity at a level similar to those of GC-C expressed in mammalian cell lines, such as COS-7. The N-terminal extracellular domain was prepared in a form which contained the hexahistidine tail at its C-terminus and was purified as a homogenous protein by Con A and Ni-chelating affinity chromatography from the culture medium of the insect cells. The purified N-terminal extracellular domain of GC-C exhibited the high (KD = 4 x 10(-10) M) and low (KD = 7 x 10(-8) M) affinity sites in binding to heat-stable enterotoxin. These results clearly indicate that the N-terminal extracellular domain of GC-C possesses the same biochemical characteristics as the complete GC-C protein even in the membrane-free form. Moreover, the extracellular domain is able to form an oligomer in a ligand-dependent manner, suggesting that the N-terminal extracellular domains interact with one another in binding to ligands.

Animals↗

PubMed1999

Obstructive jaundice caused by a huge liver cyst riding on the hilum: report of a case.

A 71-year-old man presented to our hospital with obstructive jaundice, found to be caused by a huge liver cyst which was centrally located and riding on the hilum. Percutaneous transhepatic cyst drainage was performed, following which obstruction of the bile duct was relieved and the jaundice subsided. As jaundice recurred after removal of the drainage tube, the patient underwent deroofing, since when he has remained well. Only 13 cases of liver cysts producing obstructive jaundice have been reported in the English literature, most of which were characteristically enormous, located centrally, and riding on the hilum. Liver cysts possessing such features are likely to cause obstructive jaundice by compressing the hepatic hilum. Cyst drainage is helpful for ameliorating the jaundice and making an accurate diagnosis; however, subsequent deroofing or injection therapy is necessary to prevent recurrence.

Aged↗

PubMed1999

Changes in glucose transport and protein kinase Cbeta(2) in rat skeletal muscle induced by hyperglycaemia.

AIMS/HYPOTHESIS: We have previously reported that hyperglycaemia activates glucose transport in skeletal muscle by a Ca(2+)-dependent pathway, which is distinct from the insulin-signalling pathway. The aim of this study was to explain the signalling mechanism by which hyperglycaemia autoregulates glucose transport in skeletal muscle. METHODS: Isolated rat soleus muscle was incubated in the presence of various concentrations of glucose or 3-O-methylglucose and protein kinase C and phospholipase C inhibitors. Glucose transport activity, cell surface glucose transporter 1 and glucose transporter 4 content and protein kinase C translocation was determined. RESULTS: High concentrations of 3-O-methylglucose led to a concentration-dependent increase in [(3)H]-3-O-methylglucose transport in soleus muscle. Dantrolene, an inhibitor of Ca(2+) released from the sarcoplasmic reticulum, decreased the V(max) and the K(m) of the concentration-response curve. Protein kinase C inhibitors (H-7 and GF109203X) inhibited the stimulatory effect of high glucose concentrations on hexose transport, whereas glucose transport stimulated by insulin was unchanged. Incubation of muscle with glucose (25 mmol/l) and 3-O-methylglucose (25 mmol/l) led to a three fold gain in protein kinase Cbeta(2) in the total membrane fraction, whereas membrane content of protein kinase Calpha, beta(1), delta, epsilon and theta were unchanged. A short-term increase in the extracellular glucose concentration did not change cell surface recruitment of glucose transporter 1 or glucose transporter 4, as assessed by exofacial photolabelling with [(3)H]-ATB-BMPA bis-mannose. CONCLUSION/INTERPRETATION: Protein kinase Cbeta(2) is involved in a glucose-sensitive, Ca(2+)-dependent signalling pathway, which is possibly involved in the regulation of glucose transport in skeletal muscle. This glucose-dependent increase in 3-0-methylglucose transport is independent of glucose transporter 4 and glucose transporter 1 translocation to the plasma membrane and may involve modifications of cell surface glucose transporter activity.

3-O-Methylglucose↗

PubMed1999

Effect of the nicotine metabolite 5'-hydroxycotinine on glucose transport and glycogen synthase activity in rat skeletal muscle.

Cigarette smoke contains many potentially harmful substances, including nicotine and nicotine metabolites, which are likely to contribute to altered glucose homeostasis. We determined the effects of nicotine and nicotine derivatives on glucose transport in skeletal muscle. Split rat soleus muscles were pre-incubated in the presence of nicotine (range 0.01-100 microg/ml) or nicotine metabolites including nicotine 1'-N-oxide, cotinine, trans-3'-hydroxycotinine, 5'-hydroxycotinine, gamma-3-pyridyly-oxo-butyric acid and nicotine iminium ion before measurement of 3-O-methylglucose transport rate and glycogen synthase activity. Nicotine (100 microg/ml) did not alter basal 3-O-methylglucose transport. Insulin-stimulated (0.6 nmol/l) glucose transport was unaltered following acute (50 min) exposure to nicotine (0.01-100 microg/ml). The nicotine metabolite 5'-hydroxycotinine increased basal glucose transport and glycogen synthase activity (up to 50%; P<0.05), with no effect on insulin-stimulated glucose transport and glycogen synthase activity. None of the other nicotine metabolites had any effect on basal or insulin-stimulated glucose transport. Acute exposure of skeletal muscle to the nicotine derivative 5'-hydroxycotinine appears to directly increase basal glucose transport and metabolism. Whether this leads to changes in whole-body glucose homeostasis in cigarette smokers requires further investigation.

Animals↗

PubMed1999

Mobilization/harvest and transplantation with blood stem cells, manipulated or unmanipulated.

Collection of peripheral blood stem cells (PBSC) is very feasible without the risk of anesthesia or invasive multiple bone marrow aspirations, because it can be accomplished by modification to the standard apheresis techniques that are routinely used at blood centers for the collection of single donor platelets. Use of PBSC results in rapid and durable trilineage hematopoietic recovery after myeloablative chemotherapy. There has been increasing development in technology for cell processing ('graft engineering'), moving from the experimental to the clinical settings. Although peripheral blood stem cell transplantation (PBSCT) makes 'cell component therapy' far more effective than bone marrow transplantation, its advantages/disadvantages still need to be clarified in children. The following paper presents our pediatric experience of PBSCT.

Child↗

PubMed1999

Facilitated engraftment by intramedullary administered enriched allogeneic CD34+ cells?

An 11-year-old girl with Ph+ CML received a marrow-ablative cytoreductive regimen, but both blood and marrow grafts obtained from her two-loci-mismatched father were rejected. At the third attempt, she was directly injected with purified CD34+ blood cells from the same donor into the bone marrow cavity with regular disposable bone marrow biopsy needles. The peripheral hemogram recovered rapidly thereafter, and she maintained stable complete donor type hematopoiesis until 8 months later, when she developed renal failure due to thrombotic microangiopathy, which was the primary cause of her death. This experience suggests that we revisit an old maneuver in the light of new developments.

Antigens, CD34↗

PubMed1999

Functional interleukin-5 activity in peripheral blood mononuclear cells from adolescents with mite antigen asthma in remission.

BACKGROUND: Asthma improves in most children during adolescence such that a small minority of patients exhibit clinically significant symptoms by the age of 20 years. OBJECTIVE AND METHODS: To investigate late allergic reactions, including eosinophil inflammation, associated with outgrowing mite antigen-induced bronchial asthma during adolescence, the relationship between clinical status and functional activity of interleukin (IL)-5 produced by Dermatophagoides farinae (Df)-stimulated peripheral mononuclear cells (PBMCs) in culture was assessed in mouse IL-3-dependent cells transfected with the human IL-5 receptor gene. RESULTS: Activity of IL-5 spontaneously produced by PBMCs from either patients with mite-sensitive bronchial asthma or nonatopic control subjects was low. The activity of IL-5 produced by PBMCs stimulated with concanavalin A was significantly higher. Upon challenge with specific allergens, such as Df antigen, but not with irrelevant antigens, including ovalbumin, the in vitro activity was increased in patients with active disease and decreased in patients in remission. CONCLUSION: Results suggest that the antigen-specific up-regulation of functional IL-5 activity in late allergic reactions is reduced in patients in remission and likely to result in an improvement in clinical status. The Df antigen may suppress Df-induced responses in patients with asthma in remission.

Adolescent↗

PubMed1999

Amlodipine, a long-acting calcium channel blocker, attenuates morning blood pressure rise in hypertensive patients.

1. The effects of once-daily calcium channel blockers with different plasma half-lives on diurnal blood pressure changes were examined in hypertensive patients. 2. Patients with essential hypertension, nine men and 13 women aged 61 +/- 2 years, were treated with amlodipine or nitrendipine in a random cross-over design for 12-16 weeks each. The study drugs were given once daily as monotherapy (n = 8) or in combination with other classes of antihypertensive drugs (n = 14). The plasma half-life of amlodipine is as long as 36 h, while that of nitrendipine is 10 h. At the end of each treatment period, 24 h ambulatory blood pressure and pulse rate were monitored. 3. Average office blood pressure was comparably controlled below 140/90 mmHg by either amlodipine or nitrendipine, both in the monotherapy and the combination therapy groups; however, pulse rate was greater in nitrendipine than in amlodipine either in the monotherapy (by 6 b.p.m., P < 0.05) or in the combination therapy (by 5 b.p.m., P < 0.01). 4. In 24 h blood pressure monitoring, morning (05.30-09.00 h) blood pressure was higher in nitrendipine than in amlodipine by 6/4 mmHg in the monotherapy (P < 0.05) and by 7/5 mmHg in the combination therapy (P < 0.03), although the blood pressure in the remainder of the 24 h did not differ between the two treatment periods. In addition, pulse rate in the daytime (09.30-18.00 h) was greater in nitrendipine than in amlodipine by 6 b.p.m. in the monotherapy (P < 0.01) and by 7 b.p.m. in the combination therapy (P < 0.02). 5. These results suggest slow pharmacokinetics of amlodipine provides an advantage in controlling morning blood pressure and mitigating reflex activation of the sympathetic nervous system.

Amlodipine↗

PubMed1999

Effects of propranolol on cardiovascular and neurohumoral actions of alcohol in hypertensive patients.

Alcohol ingestion acutely lowers blood pressure (BP) with vasodilation and sympathetic activation in Oriental subjects. We examined the effects of beta blockade on cardiovascular and neurohumoral actions of alcohol in Japanese men with mild-to-moderate essential hypertension. Ten hypertensive patients (54+/-5 years, mean+/-SE) were given 1 ml/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5-7 days after treatment with propranolol (20 mg three times daily). BP and heart rate (HR) were measured every 30 min for 24 h in each period. Blood sampling and echocardiographic examination were carried out before (17.00 h) and after (19.00 h) intake of alcohol or control drink, Before treatment, alcohol ingestion caused significant decreases in BP, total peripheral resistance and serum potassium concentration, while it increased heart rate (HR), cardiac output (CO), plasma norepinephrine and plasma renin activity (PRA). Treatment with propranolol significantly decreased BP and HR for 24 h. Propranolol and alcohol showed an additive depressor effect on night-time BP, and the alcohol-induced hypotension was similar before and after propranolol treatment. The alcohol-induced changes in HR, CO, PRA and serum potassium were significantly attenuated by propranolol. These results suggest that activation of the sympathetic nervous system plays a role in alcohol-induced cardiac stimulation, renin release and hypokalemia through beta receptors. Moderate doses of beta-blockers may not modify alcohol-induced BP reduction in Oriental subjects with hypertension.

Adrenergic beta-Antagonists↗

PubMed1999

Serum granulocyte colony-stimulating factor kinetics in children receiving intense chemotherapy with or without stem cell support.

In a previous study, we speculated that the early phase of hematopoietic recovery after PBSC transplantation (PBSCT) is rapid because of the increased production of endogenous cytokines by co-transfused monocytes and lymphocytes (Kawano Y, et al. Blood 81:856, 1993). To clarify this point, the serum level of G-CSF was measured using an ELISA, and various other cytokines, including GM-CSF, macrophage-CSF (M-CSF), SCF, IL-6, IFN-gamma, and soluble IL-2 receptor (IL-2R), were tested for comparison in children receiving conventional or high-dose chemotherapy and autologous transplantation with unmanipulated or purified PBSC. Serum G-CSF levels in patients receiving conventional chemotherapy (n = 21) or PBSCT without exogenous G-CSF treatment (n = 19) increased to 1245 +/- 2337 pg/ml and 2741 +/- 2331 pg/ml, respectively. Likewise, the peak level of G-CSF in patients who did not receive G-CSF was statistically equivalent to the trough level in those who did. There was no significant difference in the speed of hematopoietic recovery with or without G-CSF treatment in both the conventional chemotherapy and PBSCT cohorts. In addition, no meaningful change was observed in the kinetics of other tested factors in either conventional therapy or PBSCT settings, regardless of whether the patient did or did not receive G-CSF. Endogenously produced serum peak G-CSF levels after PBSCT with purified CD34+ cells were identical to those after the same procedure with unmanipulated cells. These results confirm that children receiving intense chemotherapy followed by autologous PBSCT produce a high level of G-CSF during the cytopenic period that is not due to the infusion of a large amount of facilitating cells capable of producing G-CSF.

Adolescent↗

PubMed1999

Comparative evaluation of procedures with a Baxter CS-3000 cell separator for collecting peripheral blood cells from children.

The safety and efficacy of apheresis using a newly developed procedure with a small volume separation container holder (SVSCH, Baxter) for the collection of PBSC from children with cancer were retrospectively compared with our historical experience with other procedures using different equipment and the CS-3000 plus cell separator. The procedures tested included the application of (a) specialized collection protocol 4 using the combination of an SVSCH and a small volume collection chamber (SVCC) (group A: 6 collections in 4 patients), (b) standard lymphocyte collection protocol 3 with GRANULO separation (G) and A-35 collection chambers (group B: 9 collections in 5 patients), and (c) modified collection procedure 1-120 with G and SVCC (group C: 7 collections in 3 patients). Although the retrospective nature of this study and the differences in the cohorts tested prevent a reliable analysis, the percent decrease in the peripheral platelet count after collection tended to be minimum in group A (11% +/- 5% versus 23% +/- 4% [B] or 17% +/- 4% [C]). Moreover, the largest number of CD34+ cells was collected in group A (8.7 +/- 9.4 x 10(5)/100 ml processed blood) compared with groups B (5.5 +/- 7.5 x 10(5)/100 ml processed blood) and C (4.0 +/- 2.8 x 10(5)/100 ml processed blood). These data suggest that a procedure incorporating SVSCH can be safely and effectively applied to small children and enables the selective collection of PBSC with less contamination by platelets, which is useful for subsequent cell processing.

Adolescent↗

PubMed1999

HLA-DPB1*0501-associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies.

In order to clarify the relationship between the clinical phenotype and the human leucocyte antigen (HLA) in multiple sclerosis in Asians, 93 Japanese patients with clinically definite multiple sclerosis underwent clinical MRI and HLA-DPB1 gene typing studies. According to a neurological examination, 29 patients were classified as opticospinal multiple sclerosis, 17 as spinal multiple sclerosis and 47 as Western type multiple sclerosis showing the involvement of multiple sites in the CNS including either the cerebrum, cerebellum or brainstem. The opticospinal multiple sclerosis showed a significantly higher age of onset, higher expanded disability status scale scores and higher CSF cell counts and protein content than the Western type multiple sclerosis. On brain and spinal cord MRI, the opticospinal multiple sclerosis showed a significantly lower number of brain lesions, but a higher frequency of gadolinium-enhancement of the optic nerve and a higher frequency of spinal cord atrophy than in Western type multiple sclerosis. The frequency of the HLA-DPB1*0501 allele was found to be significantly greater in opticospinal multiple sclerosis (93%) than in healthy controls (63%, corrected P value = 0.0091 and relative risk = 7.9), but not in Western type multiple sclerosis (66%) or spinal multiple sclerosis (82%). The marked differences in the clinical and MRI findings as well as in the immunogenetic backgrounds between the opticospinal multiple sclerosis and Western-type multiple sclerosis together suggest that HLA-DPB1*0501-associated opticospinal multiple sclerosis is a distinct subtype of multiple sclerosis.

Adult↗

PubMed1999

Platelet-activating factor stimulates cytokine production by human endometrial stromal cells.

Although preimplantation embryo and decidual cells secrete significant amounts of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF); its precise function in early pregnancy has yet to be established. To investigate the effect of PAF on cytokine synthesis, we measured the cytokine concentration in the culture media of two human cell lines: normal endometrial stromal cells (ESC) and endometrial stromal sarcoma cells (MaMi), following stimulation with a non-metabolized PAF analogue, carbamyl-PAF (C-PAF). Enzyme-linked immunosorbent assays were used to measure five cytokines: interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein-1alpha (MIP-1alpha) and tumour necrosis factor-alpha (TNF-alpha). We also evaluated the mRNA expression for IL-6 and IL-8 in ESC after C-PAF stimulation using Northern blot analysis. Non-stimulated ESC and MaMi cells both secreted IL-6, IL-8, and M-CSF, but not MIP-1alpha or TNF-alpha. The concentrations of IL-6, IL-8, M-CSF, MIP-1alpha, and TNF-alpha in the culture media of both cell lines increased in parallel with increasing amounts of C-PAF. C-PAF stimulated IL-6 and IL-8 transcription in ESC. These results suggest that PAF secretion by decidual tissues and developing embryos may induce cytokine synthesis by the ESC, as part of the cytokine network in the feto-maternal unit. An increase in the local cytokine concentration may be an important factor in the maintenance of early stages of gestation.

Adult↗

PubMed1999

Expression of hepatocyte growth factor in cultured human endometrial stromal cells is induced through a protein kinase C-dependent pathway.

To examine the production of hepatocyte growth factor (HGF) by human endometrial stromal cells (ESC) in vitro, concentrations of HGF in the culture media of ESC were measured after the addition of various amounts of 12-O-tetradecanoylphorbol 13-acetate (TPA), forskolin, lipopolysaccharide (LPS), interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFNgamma), or ethynylestradiol-17alpha using an ELISA. The expression of HGF mRNA was also assayed by a reverse transcription-polymerase chain reaction. The concentration of HGF in the culture media of unstimulated ESC was below the detection level of the assay. TPA stimulated the secretion of HGF by ESC in a dose-dependent manner. TPA also induced the transcription of HGF mRNA by ESC. Forskolin, LPS, IL-1beta, IL-6, IL-8, TNFalpha, IFNgamma, or ethynylestradiol-17alpha did not alter HGF mRNA or protein levels. TPA-stimulated production of HGF was partially inhibited by the addition of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or sphingosine. These results suggest that a protein kinase C-dependent pathway may play an important role in the regulation of HGF production by ESC. HGF secreted by ESC may be involved in the regeneration of the endometrium during the normal menstrual cycle.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Postexercise glucose uptake and glycogen synthesis in skeletal muscle from GLUT4-deficient mice.

To determine the role of GLUT4 on postexercise glucose transport and glycogen resynthesis in skeletal muscle, GLUT4-deficient and wild-type mice were studied after a 3 h swim exercise. In wild-type mice, insulin and swimming each increased 2-deoxyglucose uptake by twofold in extensor digitorum longus muscle. In contrast, insulin did not increase 2-deoxyglucose glucose uptake in muscle from GLUT4-null mice. Swimming increased glucose transport twofold in muscle from fed GLUT4-null mice, with no effect noted in fasted GLUT4-null mice. This exercise-associated 2-deoxyglucose glucose uptake was not accompanied by increased cell surface GLUT1 content. Glucose transport in GLUT4-null muscle was increased 1.6-fold over basal levels after electrical stimulation. Contraction-induced glucose transport activity was fourfold greater in wild-type vs. GLUT4-null muscle. Glycogen content in gastrocnemius muscle was similar between wild-type and GLUT4-null mice and was reduced approximately 50% after exercise. After 5 h carbohydrate refeeding, muscle glycogen content was fully restored in wild-type, with no change in GLUT4-null mice. After 24 h carbohydrate refeeding, muscle glycogen in GLUT4-null mice was restored to fed levels. In conclusion, GLUT4 is the major transporter responsible for exercise-induced glucose transport. Also, postexercise glycogen resynthesis in muscle was greatly delayed; unlike wild-type mice, glycogen supercompensation was not found. GLUT4 it is not essential for glycogen repletion since muscle glycogen levels in previously exercised GLUT4-null mice were totally restored after 24 h carbohydrate refeeding.-Ryder, J. W., Kawano, Y., Galuska, D., Fahlman, R., Wallberg-Henriksson, H., Charron, M. J., Zierath, J. R. Postexercise glucose uptake and glycogen synthesis in skeletal muscle from GLUT4-deficient mice.

Animals↗

PubMed1999

Autonomic function in hypertensive patients with neurovascular compression of the ventrolateral medulla oblongata.

OBJECTIVE: To study whether abnormalities of autonomic function exist in patients with essential hypertension and neurovascular compression (NVC) of the medulla oblongata. SUBJECTS AND METHODS: We studied 25 untreated patients with essential hypertension (13 men and 12 women, 27-74 years old). High-resolution magnetic resonance imaging and magnetic resonance angiography were used to detect NVC. Twenty-four-hour ambulatory monitoring of blood pressure and electrocardiogram were performed, and the power spectrum of heart rate variability was analyzed. On a separate day, various autonomic activity tests, including mental stress, hand grip, cold pressor, and Valsalva maneuver were performed. Baroreflex sensitivity was calculated from changes of blood pressure and R-R interval during phenylephrine infusion. A clonidine suppression test was also performed, with measurement of plasma catecholamine levels. RESULTS: Fourteen of 25 patients (56%) had NVC (C group), and 11 patients did not have NVC (NC group). There were no significant differences in age, sex, family history, or duration of hypertension between the C and NC groups. Average 24-h systolic blood pressure was similar between the two groups, although 24-h diastolic blood pressure was higher in the C group than the NC group. Daytime, night-time, and 24-h heart rate was significantly higher in the C group than in the NC group. Night-time low frequency/high frequency ratio was slightly higher in the C group. Plasma norepinephrine levels were significantly higher (467 +/- 217 versus 299 +/- 122 pg/ml), and baroflex sensitivity was slightly lower in the C group than in the NC group. Responses of blood pressure and heart rate to mental stress, cold pressor, hand grip, Valsalva maneuver, phenylephrine infusion, and clonidine tests were not significantly different between the two groups. CONCLUSIONS: NVC of the medulla oblongata was frequently found in patients with essential hypertension. Patients with NVC appeared to have enhanced sympathetic nervous activity compared with those without the compression.

Adult↗

PubMed1999

Crystallization and preliminary X-ray diffraction studies of bleomycin-binding protein encoded on the transposon Tn5.

A bleomycin-binding protein, designated BLMT, encoded on the transposon Tn5 was crystallized using the vapour-diffusion method in a form suitable for X-ray diffraction analysis. Crystals were grown at pH 6.5 in 0.1 M sodium cacodylate and 0.2 M calcium acetate, using 25% PEG 6000 as a precipitant. They belong to the orthorhombic system, space group C2221, with unit-cell dimensions a = 81.56, b = 85.25, c = 78.91 A and one dimer in the asymmetric unit. The diffraction intensity data were collected on beamline 18B of the Photon Factory to 2.0 A resolution with a merging R value of 0.052. The diffraction data set is 91% complete.

Acetyltransferases↗

PubMed1999

p53 status predicts the efficacy of postoperative oral administration of tegafur for completely resected non-small cell lung cancer.

Although postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) had not been reported to be effective, it has been reported recently that oral administration of tegafur (1-[2-tetrahydrofuryl]-5-fluorouracil, FT) may improve the postoperative prognosis. In the present paper, to examine whether p53 status affects the efficacy of FT as postoperative adjuvant chemotherapy for NSCLC, a total of 236 consecutive patients with completely resected pathologic stage I-IIIa NSCLC were retrospectively reviewed. p53 status was determined by immunohistochemical staining. For all patients, the 5-year survival rate of patients with FT administration (FT group) was 78.1%, being significantly higher than that (69.1%) of patients without FT administration (control group) (P=0.046). For patients without immunohistochemical evidence of p53 overexpression, the 5-year survival rate in the FT group was 87.1%, being significantly higher than that (74.0%) in the control group (P=0.036). This demonstrates an improvement of postoperative prognosis by FT administration. On the other hand, for patients with p53 overexpression, there was no significant difference in the postoperative prognosis between the FT group and the control group (5-year survival rate 63.2% and 60.1%, respectively; P=0.514), demonstrating that FT administration was not effective for these patients. In conclusion, p53 status may be useful for predicting the efficacy of postoperative adjuvant chemotherapy using FT. A prospective randomized study stratified by p53 status is needed to clarify the effect of postoperative FT administration.

Administration, Oral↗