Biomedical subjects

T Fujii

Publications and source records attributed to T Fujii.

At least 397 records · Page 22Linked to original sources

PubMed1998

Participation of the prefrontal cortices in prospective memory: evidence from a PET study in humans.

Prospective memory is a memory feature in humans which involves activities for remembering to do something in the future. The present study provides functional neuroanatomy of prospective memory for the first time. We used positron emission tomography (PET) and found several localized brain activations in relation to a prospective memory task required to retain and remember a planned action while performing an ongoing routine activity. Activations were identified in the right dorsolateral and ventrolateral prefrontal cortices, the left frontal pole and anterior cingulate gyrus, the left parahippocampal gyrus, and midline medial frontal lobe. We attributed these activations to several cognitive processes involved in prospective memory, such as holding an intention toward future behavior, checking target items within presented stimuli, and dividing attention between the planned action and the routine activity.

Adult↗

PubMed1998

Importance of left anterior descending coronary artery curvature in determining cross-sectional plaque distribution assessed by intravascular ultrasound.

We assessed the relation between the circumferential distribution of coronary atherosclerotic plaques and the structure of the epicardial coronary arteries in patients with coronary artery disease using intravascular ultrasound in vivo. Coronary atherosclerosis preferentially formed at the inner arc of the curved coronary vessels, and greater vessel curvatures were associated with greater distributions of atherosclerotic lesions along the inner coronary artery wall.

Adult↗

PubMed1998

Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union.

BACKGROUND: Recent studies have shown that anomalous pancreaticobiliary ductal union (APBD) is an important risk factor for the development of gallbladder carcinoma. Epithelial hyperplasia of the gallbladder is one of the characteristic changes, but it is not clear whether epithelial hyperplasia is a premalignant lesion that could lead to cancer in APBD patients. METHODS: Twenty-four APBD patients were classified into two types: patients with bile duct dilation (dilated type) (n 13) and patients without dilation (undilated type) (n = 11). Resected gallbladders obtained from APBD patients and control patients without APBD were examined histologically and with immunohistochemical techniques for the detection of p53 and Ki-67 (as a cell proliferation marker). K-ras mutations were examined using polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis. The patients were also classified, according to extent of epithelial hyperplasia, as having high grade or low grade hyperplasia. RESULTS: Fifteen (63%) of 24 APBD patients had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. The incidence of epithelial hyperplasia was significantly higher in the gallbladders of undilated-type APBD patients (91%) than in those of dilated-type patients (38%) (P < 0.01). Three of 24 APBD patients (13%) had gallbladder carcinoma, and 2 of the 3 gallbladder carcinomas (67%) were accompanied by diffuse epithelial hyperplasia of the gallbladder. Among 21 nonneoplastic gallbladders, diffuse epithelial hyperplasia was observed in all (100%) of the undilated-type APBD and in 4 (33%) of 12 dilated-type APBD (P < 0.001). High grade hyperplasia was observed in 7 of 11 patients (64%) with undilated-type APBD and 2 of 13 patients (15%) with dilated-type APBD (P < 0.05). The incidence of high grade hyperplasia increased with age among patients older than 35 years. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. High grade hyperplasia had a significantly higher Ki-67 LI than low grade hyperplasia (P < 0.001). Two (22%) of 9 high grade hyperplasia cases had K-ras mutations, whereas none of 6 low grade hyperplasia cases had. The types of K-ras mutations in codon 12 were GTT (Val) and GAT (Asp) in each case of hyperplasia; these were identical to those of concomitant carcinomas. Neither hyperplastic nor normal mucosa exhibited p53 overexpression. CONCLUSIONS: The results of this study suggest that hyperplasia of the gallbladder mucosa in APBD patients is an early change that, because of the increased proliferative activity and presence of K-ras mutations, could be considered a premalignant lesion of the gallbladder. An increased cell population of epithelial hyperplasia may predispose the mucosa to mutational events, resulting in an increased risk for the development of gallbladder carcinoma in APBD patients.

Adolescent↗

PubMed1998

Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism.

Crystal structures of L-2-haloacid dehalogenase from Pseudomonas sp. YL complexed with monochloroacetate, L-2-chlorobutyrate, L-2-chloro-3-methylbutyrate, or L-2-chloro-4-methylvalerate were determined at 1.83-, 2.0-, 2.2-, and 2.2-A resolutions, respectively, using the complex crystals prepared with the S175A mutant, which are isomorphous with those of the wild-type enzyme. These structures exhibit unique structural features that correspond to those of the reaction intermediates. In each case, the nucleophile Asp-10 is esterified with the dechlorinated moiety of the substrate. The substrate moieties in all but the monochloroacetate intermediate have a D-configuration at the C2 atom. The overall polypeptide fold of each of the intermediates is similar to that of the wild-type enzyme. However, it is clear that the Asp-10-Ser-20 region moves to the active site in all of the intermediates, and the Tyr-91-Asp-102 and Leu-117-Arg-135 regions make conformational changes in all but the monochloroacetate intermediates. Ser-118 is located near the carboxyl group of the substrate moiety; this residue probably serves as a binding residue for the substrate carboxyl group. The hydrophobic pocket, which is primarily composed of the Tyr-12, Gln-42, Leu-45, Phe-60, Lys-151, Asn-177, and Trp-179 side chains, exists around the alkyl group of the substrate moiety. This pocket may play an important role in stabilizing the alkyl group of the substrate moiety through hydrophobic interactions, and may also play a role in determining the stereospecificity of the enzyme. Moreover, a water molecule, which is absent in the substrate-free enzyme, is present in the vicinities of the carboxyl carbon of Asp-10 and the side chains of Asp-180, Asn-177, and Ala-175 in each intermediate. This water molecule may hydrolyze the ester intermediate and its substrate. These findings crystallographically demonstrate that the enzyme reaction proceeds through the formation of an ester intermediate with the enzyme's nucleophile Asp-10.

Binding Sites↗

PubMed1998

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

We used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

Adult↗

PubMed1998

Phenylethanolamine-N-methyltransferase - immunoreactive nerve terminals afferent to the mouse substantia nigra.

In the substantia nigra pars compacta, many phenylethanolamine-N-methyltransferase immunoreactive (PNMT-ir) terminals as well as serotonin-ir terminals were observed for the first time to be very closely situated to the tyrosine hydroxylase (TH)-ir, aromatic L-amino acid decarboxylase-ir, and GTP cyclohydrolase I (GCH)-ir dopaminergic cells [Nagatsu, I., Arai, R., Sakai, M., Yamawaki, Y., Takeuchi, T., Karasawa, N. and Nagatsu, T., Neurosci. Lett., 224 (1997) 185-188]. Immunohistochemical colocalization of TH with GCH or PNMT in the somata and dendrites of TH-positive neurons in the rostral ventrolateral reticular formation of the medulla oblongata (C1 region, [Hokfelt, T., Fuxe, K., Goldstein, M. and Johansson, O., Brain Res., 66 (1974) 235-251]) was proved by a double-labeling immunofluorescence method with a confocal laser-scanning microscope, indicating that the neurons are adrenergic. These results suggest that dopaminergic neurons in the substantia nigra receive PNMT-ir, adrenergic afferents from the C1 region of the medulla oblongata.

Animals↗

PubMed1998

Isolation and expression of a human SRY-related cDNA hSOX20.

SOX is a family of genes related to the testis-determining gene, SRY. We have isolated and sequenced an hSOX20 cDNA from a cell line of human embryonic carcinoma. This cDNA contains an open reading frame (ORF) encoding 233 amino acids. The protein encompasses an SRY-type HMG box exhibiting strong homologies to those of mouse Sox15 and Sox16. Various adult and fetal tissues were tested for hSOX20 mRNA by Northern analysis. Its expression is restricted to the fetal testis and the size of the transcript is 1.5 knt. Electrophoretic mobility shift assay indicated that recombinant hSOX20 polypeptide is capable of binding to AACAAT sequence.

Adult↗

PubMed1998

Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer.

PURPOSE: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. MATERIALS & METHODS: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. RESULTS: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). CONCLUSION: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less distant metastasis better DFS and overall survival than those with AC. Multivariate analysis revealed that DNA index and Ki-67 status were significant predictors for DDC and DFS in patients with AC, but only mitotic index was a significant predictor of overall survival for patients with SCC.

Adenocarcinoma↗

PubMed1998

Application of the resident plasmid integration technique to construct a strain of Streptococcus godronii able to express the Bacillus circulans cycloisomaltooligosaccharide glucanotransferase gene, and secrete its active gene product.

A novel transformation technique, resident plasmid integration, for the cloning of foreign DNA in oral streptococci was described recently (T. Shiroza and H.K. Kuramitsu, Plasmid 34 (1995) 85-95. This technique is based on the integration of linearized foreign genes by recombination-proficient bacteria onto a resident plasmid, if an appropriate selection marker is flanked by the same anchor sites present in the resident plasmid. Since the transforming vehicles for this system included a pUC-derived replication origin, the high level expression in Escherichia coli cells hindered the cloning of certain genes. In the present study, new plasmids were constructed, two resident plasmids, four integration plasmids, and four cloning plasmids, all of which possess the medium-copy number replication origin, p15A ori, isolated from pACYC177. The resident plasmids consisted of the following three components: the p15A ori (0.65-kb Bg/II fragment), the pVA380-1 basic replicon functional in mutans streptococci (2.5-kb BamHI fragment), and either an erythromycin resistance or a spectinomycin resistance gene (0.9- or 1.1-kb BamHI fragment, respectively). Most of the basic replicon of pVA380-1, except for the 3'-portion of the 0.2-kb region, in the resident plasmid was replaced with a kanamycin resistance gene to construct the four integration plasmids. Therefore, the upstream and downstream anchor sites for the double cross-over event in this new system were 0.65-kb p15A ori and the 0.2-kb portion of the 3'-end of pVA380-1 replicon, respectively. This system was used to clone the gene coding for cycloisomaltooligosaccharide glucanotransferase which produces cycloisomaltooligosaccharide, a potent inhibitor of oral streptococcal glucosyltransferase, isolated from Bacillus circulans chromosome, into Streptococcus gordonii, and its gene product was successfully secreted into the culture media. Plasmids described here should be useful tools for introducing heterologous DNA into resident plasmids following integration in oral streptococci.

Bacillus↗

PubMed1998

Selective cytotoxicity of farnesylamine to pancreatic carcinoma cells and Ki-ras-transformed fibroblasts.

Farnesyl protein transferase (FPTase) catalyses the post-translational modification of proteins by a farnesyl pyrophosphate. One of the substrates of this enzyme is p21ras, the product of the ras oncogene. We examined whether farnesylamine, one of the FPTase inhibitors (FTI), is selectively cytotoxic in pancreatic carcinoma cells and Ki-ras-transformed fibroblasts. Furthermore, we investigated whether the cytotoxicity of farnesylamine is caused by the induction of apoptosis in these cells. Using the FPTase assay, we found that farnesylamine inhibited FPTase in vitro. Immunoprecipitation showed that farnesylamine inhibited farnesylation of p21ras in vivo. In addition, 24 and 5 microM farnesylamine were required to achieve 50% cytotoxicity in pancreatic carcinoma cells containing activated Ki-ras and Ki-ras-transformed NIH/3T3 cells, respectively. The parental NIH/3T3 cells were resistant to the cytotoxic effect of farnesylamine at concentrations less than 100 microM. After incubation with farnesylamine, DNA fragmentation was observed in both pancreatic carcinoma cells and Ki-ras-transformed fibroblasts at cytotoxic doses of this compound but not in NIH/3T3 cells. These results indicate that the mechanism of cell death induced by farnesylamine is apoptosis, and this apoptosis occurred specifically in pancreatic carcinoma cells containing mutated Ki-ras and the Ki-ras-transformed cells. Because raf is downstream of ras (p21ras) in the ras-raf-mitogen-activated protein kinase signaling pathway, we used c-raf-1-transformed fibroblasts, which proved to be resistant to apoptosis induced by farnesylamine. This supports the theory that inhibition of ras signaling may be related to the induction of apoptosis. These data further suggest that farnesylamine could be useful as a chemotherapeutic agent in cancers that very frequently contain a Ki-ras oncogene mutation, e.g., pancreatic cancer.

3T3 Cells↗

PubMed1998

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.

Alanine Transaminase↗

PubMed1998

Pulmonary histoplasmosis in a Japanese male: report of a case.

A case of pulmonary histoplasmosis, which is rare in Japan, is reported herein. A 43-year-old man who had worked in Mexico for 2 years and had come back to Japan 3 months earlier, presented at our hospital because of an abnormal shadow on his chest roentogenogram with no symptoms. His chest roentogenogram as well as chest computed tomograms revealed a 2-cm-diameter nodule in the anterior basal segment of his right lung and an enlargement of the subcarinal lymph node. Although these pictures seemed to indicate an advanced lung cancer, no malignant cells were found based on the brushing cytology findings after bronchoscopy. An exploratory thoracoscopic tumor resection and biopsy of the enlarged lymph node led to a histological diagnosis of an abscess due to histoplasma. The hospital course was uneventful. Postoperatively, amphotericin B was administered for 1 year. This is the eighth case of pulmonary histoplasmosis reported in Japan. A pulmonary nodule together with mediastinal lymphoadenopathy seems to be characteristic in these patients. Histoplasmosis should therefore be considered in the differential diagnosis, since overseas travel has now become common-place for the Japanese.

Adult↗

PubMed1998

Age-related changes of element contents in the human meniscus.

The relative contents (RCs) of elements in the human menisci from 23 subjects in the age range between 65 and 93 yr were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of sulfur, calcium, and phosphorus in menisci increased progressively until the 80s, being the highest in the 80s, and thereafter decreased. The RCs of magnesium in menisci increased progressively until the 90s. Regarding the medial and lateral menisci, higher RCs of magnesium and iron, and a lower RC of phosphorus were found in lateral menisci in comparison with those in medial menisci. There were sexual differences in the RCs of calcium and phosphorus of medial and lateral menisci. The RCs of calcium and phosphorus were about 50% higher in women's menisci than in men's. Histological examinations showed that structureless mucoid masses were observed in the menisci, with very high RCs of calcium and phosphorus being detected.

Aged↗

PubMed1998

Multifocal serous cystadenoma of the pancreas. A case report and review of the literature.

Serous cystadenoma of the pancreas is usually unifocal; multifocal tumors are rare. We report a case of multifocal serous cystadenoma of the pancreas in a 48-yr-old female complaining of general malaise. Serum tumor markers, such as CA 19-9, DUPAN-2, and Span-1, were elevated. Abdominal ultrasound (US) and computed tomography (CT) scans revealed two distinct cystic masses in the head and body of the pancreas, respectively. The patient underwent total pancreatectomy. The resected pancreas contained two discrete cystic masses in the head and body; no solid components were observed. Microscopically, the inner surfaces of the cysts were evenly lined by a single layer of low cuboidal or significantly attenuated epithelial cells containing clear cytoplasm and abundant glycogen without other morphological alterations. The histogenesis of serous cystadenoma is not clear; multicentric tumors may be helpful in understanding histogenesis.

Abdomen↗

PubMed1998

[A case report of incomplete endocardial cushion defect with mitral stenosis in an elderly patient].

The following paper describes a mitral valve replacement (SJM 27 mm), the patch closure (EPTFE) of an ostium primum atrial septal defect and tricuspid annuloplasty (De Vega's method) in a 64-year-old female patient with an incomplete endocardial cushion defect and mitral stenosis. Surgery revealed thickened, mitral valve leaflets and the presence of a cleft, findings similar to those observed in case of rheumatic degeneration. Investigation of patient hemodynamics confirmed a diagnosis of Lutembacher syndrome and a lower with left ventricle volume. After surgery, the volume of left ventricle increased and the patients clinical course was uneventful.

Endocardial Cushion Defects↗

PubMed1998

[Surgical treatment of total anomalous pulmonary venous connection--clinical aspects of pulmonary venous obstruction].

During November 1986 and May 1997, 19 patients with total anomalous pulmonary venous connection (TAPVC) underwent repair surgery. 20 operations including two reoperations were performed. 8 of 19 patients were classified as Darling type Ia, 5 as type IIa, 4 as type III and 2 patients were type IV. Two patients were operated under emergency circumstances within 24 hours after admission, 7 patients were after a short term stabilization of 4.4 days, and the other 11 patients received surgical treatment after a mean of 8.8 days as scheduled cases. For the anostomosis, the common pulmonary venous chamber or the vertical vein was connected with the left atrium in type Ia and III cases; in type IIa and IV cases the cut-back method was performed. Persistent pulmonary hypertension and post-operative pulmonary venous obstruction (PVO) affected the post-operative clinical course. Persistent pulmonary hypertension caused the death of one patient with type IIa and III each, just after operation. One type IV patient died 50 days after operation. The autopsy revealed post-operative obstructions of the remote parts of the pulmonary veins on the anostomosis site. Two patients (type IIa, III) successfully underwent reoperation due to PVO. Post-operative cardiac catheterization was performed after 12 month in 12 cases. Persistent pulmonary hypertension was found in 4 patients, and a type III patient was reoperated because of stenosis of the anostomosis site. The other three patients had persistent pulmonary hypertension without any demonstrable PVO. Persistent pulmonary hypertension and PVO are combined as TAPVC complex. The difficulty to reoperated patients with persistent pulmonary hypertension caused by PVO is one major problem. So preoperative prevention of PVO by normalization the morphologic changes of the pulmonary veins by using drugs could be a different view point in TAPVC therapy after the initial operation.

Anastomosis, Surgical↗

PubMed1998

Expression of the cyclin-dependent kinase inhibitor, p21Waf-1/Cip-1/Sdi-1, in human vascular smooth muscle cells in the proliferating state.

Excess proliferation of vascular smooth muscle cells (SMC) is an important aspect of atherogenesis. Cell-cycle regulatory proteins such as cyclin and cyclin-dependent kinases are vital for cell-cycle progression. To understand the role of the cyclin-dependent kinase inhibitor, p21Waf-1/Cip-1/Sdi-1 (p21Waf-1), on human atherogenesis, we tested p21Waf-1 expression in human atherosclerotic lesions and cultured SMC. Immunohistochemical staining revealed that SMC in neointimal lesions expressed p21Waf-1. No evidence of the p53 protein could be detected. By Western blotting, cultured SMC obtained from a neonate revealed that a higher level of p21Waf-1 expression correlated with a higher expression of proliferating cell nuclear antigen and a lower expression of the contractile protein than that observed in cells obtained from aged donors. When the phenotypes of SMC were changed by modification of serum concentration and cell densities, p21Waf- expression was maximal in serum-stimulated SMC at low cell densities despite the low expression of p53. Furthermore, serum stimulation transiently increased the p21Waf-1 expression of quiescent SMC, which was synchronized with the transition from the G0/G1 to the S phase as well as with cyclin D1 expression. These results may suggest that the negative regulator of cell-cycle progression also plays a role in regulating the appropriate cell-cycle progression in SMC. Growth stimuli may induce both growth-promoting and growth-inhibitory factors in SMC. The balance between these two opposing factors may play an important role in the determination of cell-cycle progression.

Arteriosclerosis↗

PubMed1998

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗