Biomedical subjects

Yasuhiro Fujiwara

Publications and source records attributed to Yasuhiro Fujiwara.

At least 19 recordsLinked to original sources

PubMed2026

Quality of life with palbociclib plus tamoxifen in hormone receptor-positive, HER2-negative advanced breast cancer: results from PATHWAY, an Asian international, double-blind, randomized phase 3 trial.

BACKGROUND: In the Asian international PATHWAY trial, palbociclib-tamoxifen demonstrated improved progression-free survival compared with placebo-tamoxifen in patients with HR+/HER2- locally advanced or metastatic breast cancer (ABC). This analysis compared quality of life (QoL) between treatment arms. METHODS: Pre/peri or postmenopausal women with HR+/HER2- ABC were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Patient-reported outcomes were assessed on day 1 of cycles 1 (baseline), 4, and 7, and at the end of treatment (EOT) using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Least-square mean (LSM) changes in scores from baseline were calculated. Kaplan-Meier method was used to calculate time to deterioration (TTD) in the minimally important difference (MID) in the pain subscale. RESULTS: In the comparison between treatment arms, no significant differences were observed in LSM changes in scores from baseline in global QoL (cycle 4: 0.70 [95% confidence interval (CI): -5.00, 6.41]; cycle 7: 2.17 [95% CI: -4.14, 8.48]; EOT: -5.19 [95% CI: -11.64, 1.26]). For both the EORTC QLQ-C30 and QLQ-BR23 functional and symptom subscales, no clinically meaningful differences between treatment arms were found in the LSM changes in scores from baseline. Median TTD in the MID in the pain subscale was 32.5 months (95% CI: 11.7, not estimable) for the palbociclib-tamoxifen arm and 21.2 months (95% CI: 5.5, 43.5) for the placebo-tamoxifen arm (hazard ratio = 0.729 [95% CI: 0.467, 1.138]). CONCLUSIONS: The combination of palbociclib and tamoxifen delayed deterioration in patients' QoL while they experienced reduced risk for disease progression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03423199; study registration date: February 6, 2018.

Humans↗

PubMed2007

Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer.

The multi-disciplinary approach, including surgery, chemotherapy, endocrine therapy and radiation therapy, has become the standard treatment for primary breast cancer patients. The indication of pre-operative chemotherapy has been extended to women with potentially operable breast cancer based on the results of large randomized studies and has become an attractive option that extends the chance of breast conservation. The clinical and pathological responses to pre-operative chemotherapy correlates with long-term outcome. The anthracycline-containing regimen is now considered the standard. Sequential administration of non-cross-resistant drugs, namely taxanes, improves local tumor response but its long-term benefit has been controversial. Prediction of response to pre-operative chemotherapy still remains a challenge. Identification of useful predictive markers and development of molecular-targeted drugs is the key to individualized therapy in the future.

Antineoplastic Agents↗

PubMed2006

Cancer of unknown primary site: review of consecutive cases at the National Cancer Center Hospital of Japan.

BACKGROUND: Cancer of unknown primary (CUP) is not a rare clinical entity, accounting for 3%-5% of all solid malignancies. METHODS: We retrospectively reviewed 86 (38 male/48 female) patients with a diagnosis of CUP (exclusive of female patients with adenocarcinoma involving the axillary lymph nodes alone and patients with squamous cell carcinoma of the cervical lymph nodes) who were referred to the National Cancer Center Hospital between April 1996 and October 2002. RESULTS: The median interval between the first visit to a local community hospital and referral to our hospital was 1 month (range, 1 to 45 months). The histological diagnosis was adenocarcinoma in 61 patients (71%), poorly differentiated carcinoma in 18 patients (21%), and squamous cell carcinoma in 4 patients (5%). Twenty-three female patients had peritoneal carcinomatosis of adenocarcinoma. Seventy-eight patients (91%) received platinum-containing chemotherapy. Sixty-one of the 86 patients (71%) were categorized as a subgroup of CUP without a specific therapy, and 55 of these 61 patients (90%) received platinum-containing regimens. The median survivals of all 86 patients and the 61 patients in the subgroup without a specific therapy in this series were 13 months and 11 months, respectively. CONCLUSION: In this series, the survival of the patients in the CUP subgroup without a specific therapy did not seem worse than that in previous reports. Empirical chemotherapy with platinum-containing regimens may benefit some CUP patients in a subgroup without a specific chemotherapy.

Adenocarcinoma↗

PubMed2006

[Optimization of three-dimensional triple IR fast spoiled gradient recalled acquisition in the steady state (FSPGR) to decrease vascular artifact at 3.0 Tesla].

The purpose of this study was to decrease vascular artifacts caused by the in-flow effect in three-dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady state (3D IR FSPGR) at 3.0 Tesla. We developed 3D triple IR (3IR) FSPGR and examined the signal characteristics of the new sequence. We have optimized scan parameters based on simulation, phantom, and in-vivo studies. As a result, optimized parameters (1st TI=600 ms, 3rd TI=500 ms) successfully have produced the vessel signal at more than 40% reduction, while gray-white matter contrast was preserved. Moreover, the reduced artifact was also confirmed by visual inspection of the in-vivo images for which this condition was used. Thus, 3D 3IR FSPGR was a useful sequence for the acquisition of T1-weighted images at 3.0 Tesla.

Adult↗

PubMed2006

Effects of pre- and neonatal exposure to bisphenol A on murine brain development.

Bisphenol A (BPA), known as an environmental endocrine disrupter, is widely used in industry and dentistry. We investigated the effects of fetal and neonatal exposure to bisphenol A (BPA) on the brain development of mice. The density of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in substantia nigra was significantly decreased in BPA-exposed female mice (3 microg/g powder food), but not in the male mice, as compared with that of the control mice. The densities of calbindin D-28 K-, calretinin- and parvalbumin-IR neurons in the cerebral cortex were not different between BPA-exposed and the control mice. The present study indicates that chronic exposure of BPA during prenatal and neonatal periods causes a decrease of TH-positive neurons in substantia nigra only in female mice brain.

Air Pollutants, Occupational↗

PubMed2006

Murine neocortical histogenesis is perturbed by prenatal exposure to low doses of Bisphenol A.

Bisphenol A (BPA) has been shown to disrupt thyroid hormone function. We therefore studied whether prenatal exposure to low-doses of BPA affects the morphology and the expression of some genes related to brain development in the murine fetal neocortex. Pregnant mice were injected subcutaneously with 20 microg/kg of BPA daily from embryonic day 0 (E0). Control animals received vehicle alone. For evaluating cell proliferation, neuronal differentiation and migration, bromodeoxyuridine (BrdU) was injected intraperitoneally into pregnant mice with various regimens and the brains were processed for immunohistochemistry. The total RNA was extracted from the embryonic telencephalon at various embryonic stages. The BrdU-labeled cells examined 1 hour after BrdU injection showed no differences between the BPA-treated and control groups (n = 10, each), which indicated that the proliferation of precursor cells was not affected. The BrdU-labeled cells, analysed 2 days after BrdU injection, were decreased in the ventricular zone of BPA-treated mice at E14.5 and E16.5, whereas they were increased in the cortical plate at E14.5 as compared with those in control mice (n = 10, each). Furthermore, the expression of Math3, Ngn2, Hes1, LICAM, and THRalpha was significantly upregulated at E14.5 in the BPA-treated group. These results suggested that BPA might disrupt normal neocortical development by accelerating neuronal differentiation/migration.

Animals↗

PubMed2006

Prediction of response to repeat utilization of anthracycline in recurrent breast cancer patients previously administered anthracycline-containing chemotherapeutic regimens as neoadjuvant or adjuvant chemotherapy.

PURPOSE: The aim of this study was to identify the predictors of the response to doxorubicin plus cyclophosphamide in patients with recurrent breast cancer (RBC) previously treated with anthracycline-containing regimens in a neoadjuvant or adjuvant setting. METHOD: Between December 1993 and October 2005, 664 patients had received combined doxorubicin plus cyclophosphamide chemotherapy (doxorubicin, 40 mg/m(2), iv on day 1; cyclophosphamide, 500 mg/m(2), iv on day 1, every 21 days) for RBC at our institution. In this study, we retrospectively analyzed the efficacy of doxorubicin plus cyclophosphamide in 99 of these 664 RBC patients who had also previously been administered an anthracycline-based chemotherapy in a neoadjuvant or adjuvant setting. RESULTS: The median cumulative dose of the previously administered anthracycline was 156 mg/m(2). The median disease-free interval (DFI) and median anthracycline-free interval were 33.8 and 43.7 months, respectively. The overall response rate to doxorubicin plus cyclophosphamide therapy was 38.4% (95% CI; range, 28.8-48.0%). The median time to progression and overall survival were 6.2 and 17.5 months, respectively. The results of a multivariate logistic regression analysis revealed a significant association of the response to doxorubicin plus cyclophosphamide therapy with the DFI (P = 0.02); human epidermal receptor type 2 (HER2) status also tended to affect the response rate, however the association was not statistically significant (P = 0.06). CONCLUSION: DFI and HER2 status may be associated with the response to repeat utilization of anthracycline-containing regimens in RBC patients also treated previously with anthracycline-containing chemotherapeutic regimens in a neoadjuvant or adjuvant setting.

Adult↗

PubMed2006

[Vessel contrast and saturation effect at three Tesla in three-dimensional time of flight magnetic resonance angiography].

The purpose of this study was to clarify the effects of the increased field strength of 1.5T vs. 3.0T on blood vessel contrast and saturation in 3D time of flight MR angiography. Vessel contrast and saturation effect were evaluated for various flow velocities and flip angles using a steady-state flow phantom. The results showed increased vessel contrast and decreased saturation of blood on 3.0T compared to 1.5T, due to the following factors: 1) sufficient saturation of stationary tissue by extended T1 relaxation time, 2) increased signal-to-noise ratio (SNR), and 3) high in-flow effect. However, the blood signal on 3.0T revealed a strong tendency to phase dispersion compared to that of 1.5T. Therefore, in order to exploit the characteristic of high field strength in 3.0T, it is suggested that adequate consideration of these factors is important in setting the image acquisition parameters.

Imaging, Three-Dimensional↗

PubMed2006

[Experimental study of coil selection considered from subject size].

We examined the index of coil selection in consideration of subject size to measure signal-to-noise ratio (SNR) and uniformity in a phantom experiment. The QD-Head, 8-channel-Head, and 8-channel-Head-Neck coil were used for head examination, QD-Body, 4-channel-TORSO, and 8-channel-Body coil were used for body examination. In the examination of the head, measurements were performed at various positions in a coil. The SNR measured by the QD-Head coil showed the highest values for 9 cm or 12 cm diameters of the phantom, and 10 cm to 15 cm distance from the coil entrance. The QD-Head coil also showed adequate uniformity at most sizes of phantoms. In the body examination, both multi-channel coils showed an SNR higher than the QD-Body coil for all sizes, but they were inferior to the QD-Body coil in uniformity. The 4-channel-TORSO coil showed an SNR higher than the 8-channel-Body coil when a phantom with a diameter of 21 cm or less was used. Since sensitivity distributions differ according to various cases, the 8-channel coil does not necessarily always show a high SNR. It is necessary to perform coil selection according to the subject's size and purpose.

Magnetic Resonance Imaging↗

PubMed2006

Successful treatment of giant rectal varices by modified percutaneous transhepatic obliteration with sclerosant: Report of a case.

We present a female patient with continuous melena, diagnosed with rectal variceal bleeding. She had a history of esophageal varices, which were treated with endoscopic therapy. Five years after the treatment of esophageal varices, continuous melena occurred. Since colonoscopy showed that the melena was caused by giant rectal varices, we thought that they were not suitable to receive endoscopic treatment. We chose the modified percutaneous transhepatic obliteration with sclerosant, which is one of the interventional radiology techniques but a new clinical procedure for rectal varices. After the patient received this therapy, her condition of rectal varices was markedly improved.

Aged↗

PubMed2006

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

Adult↗

PubMed2006

5-Hydroxy-seco-carotenoids from Pittosporum tobira.

Three 5-hydroxy-seco-carotenoids were isolated from seeds of Pittosporum tobira. These structures were determined to be (3S,3'S,5'?)-3,3'-di(tetradecanoyloxy)-5'-hydroxy-5,6,5',6'-diseco-beta,beta-carotene-5,6,6'-trione (1), (3S,5?,3'S,5'R,6'S,9'Z)-3-tetradecanoyloxy-5',6'-epoxy-5,3'-dihydroxy-5',6'-dihydro-5,6-seco-beta,beta-caroten-6-one (2), and (3S,5?,3'S,5'R,6'R)-3-tetradecanoyloxy-5,3',5'-trihydroxy-6',7'-didehydro-5',6'-dihydro-5,6-seco-beta,beta-caroten-6-one (3) based on analysis of UV-vis, IR, FAB MS, and NMR spectroscopic data.

Carotenoids↗

PubMed2006

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Adult↗

PubMed2006

Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients.

Drug resistance is a major obstacle to the successful chemotherapy. Several ATP-binding cassette (ABC) transporters including ABCB1, ABCC1 and ABCG2 have been known to be important mediators of chemoresistance. Using oligonucleotide microarrays (HG-U133 Plus 2.0; Affymetrix), we analyzed the ABC transporter gene expression profiles in breast cancer patients who underwent sequential weekly paclitaxel/FEC (5-fluorouracil, epirubicin and cyclophosphamide) neoadjuvant chemotherapy. We compared the ABC transporter expression profile between two classes of pretreatment tumor samples divided by the patients' pathological response to neoadjuvant chemotherapy (residual disease [RD] versus pathologic complete response [pCR]) ABCB3, ABCC7 and ABCF2 showed significantly high expression in the pCR. Several ABC transporters including ABCC5, ABCA12, ABCA1 ABCC13, ABCB6 and ABCC11 showed significantly increased expression in the RD (p<0.05). We evaluated the feasibility of developing a multigene predictor model of pathologic response to neoadjuvant chemotherapy using gene expression profiles of ABC transporters. The prediction error was evaluated by leave-one-out cross-validation (LOOCV). A multigene predictor model with the ABC transporters differentially expressed between the two classes (p<or=0.003) showed an average 92.8% of predictive accuracy (95% CI, 88.0-97.4%) with a 93.2% (95% CI, 85.2-100%) positive predictive value for pCR, a 93.6% (95% CI, 87.8-99.4%) negative predictive value, a sensitivity of 88.1%(95% CI, 76.8-99.4%), and a specificity of 95.9% (91.1% CI, 87.8-100%). Our results suggest that several ABC transporters in human breast cancer cells may affect the clinical response to neoadjuvant chemotherapy, and transcriptional profiling of these genes may be useful to predict the pathologic response to sequential weekly paclitaxel/FEC in breast cancer patients.

ATP-Binding Cassette Transporters↗

PubMed2006

Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin.

A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.

Aged↗

PubMed2006

Close association between activated platelets and neutrophils in the active phase of ulcerative colitis in humans.

BACKGROUND: Neutrophils are considered to play a causative role in inflammatory mucosal injury in ulcerative colitis (UC), and an association between platelets and neutrophils may contribute to the progression of the inflammatory processes. To test this hypothesis, we performed immunohistochemical and flow cytometric analyses on tissue and blood samples from patients with UC. MATERIALS AND METHODS: Colonic mucosal tissues of patients with active (n = 27) or inactive (n = 16) UC and normal controls (n = 11) were subjected to immunohistochemical staining for markers of activated platelets (glycoprotein IIb/IIIa and P-selectin) and neutrophils (neutrophil elastase, myeloperoxidase, and CD66b). The amounts of stained cells were evaluated by computer-aided morphometry. Peripheral blood samples from patients (n = 8) and healthy volunteers (n = 8) were subjected to comparative flow cytometric analysis of activated platelets. RESULTS: P-selectin-positive activated platelets were frequently aggregated in the inflamed mucosa, especially in ulcerative lesions, and were close to regions of dense neutrophil infiltration. An increase in the number of activated platelets in the colonic lesions was associated with an increase in infiltrating neutrophils and was related to the severity of the disease. The flow cytometric analysis indicated that circulating platelets of patients with UC were highly activated. CONCLUSIONS: The present study demonstrated that a close association between activated platelets and neutrophils is a prominent pathological change in both the affected colonic mucosa and peripheral blood of patients with active-phase UC. This suggests that platelet-neutrophil association may play an important role in the progression of inflammatory processes in UC.

Adult↗

PubMed2006

Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication.

BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.

Adult↗

PubMed2006

Evaluation of deep small bowel involvement by double-balloon enteroscopy in Crohn's disease.

OBJECTIVES: Double-balloon enteroscopy (DBE) enables inspection of deep small bowel, and total small bowel examination can be performed by either antegrade or retrograde DBE. The aim of this study was to evaluate ileal involvement, which cannot be achieved using conventional colonoscopy, by DBE in patients with Crohn's disease. METHODS: From December 2003 to September 2005, a total of 44 patients with Crohn's disease underwent 53 examinations using DBE. RESULTS: Forty patients with Crohn's disease, seven women and 33 men, underwent DBE, and the ileum was investigated in 38 patients. There were 25 cases of ileitis, 2 of colitis, and 13 of ileocolitis. Jejunal lesions were found in two and ileal lesions proximal to the terminal ileum were found in 24 patients with Crohn's disease. DBE was superior to radiological study to detect aphthae, erosions, and small ulcers in the ileum. Small bowel stricture was demonstrated in six and nine patients with DBE and small bowel barium study (SBBS), respectively. An additional mucosal finding was demonstrated in one of the eight patients who underwent wireless capsule endoscopy, and one patient had a capsule removed by DBE that had become lodged because of an ileal stricture. One ileal perforation because of overtube balloon pressure occurred in 53 examinations of patients with Crohn's disease (1.9%). CONCLUSION: DBE is useful to evaluate small bowel lesions in patients with Crohn's disease; however, special attention should be paid to mesenteric longitudinal ulcers during insertion and the overtube balloon should not be inflated if a clear intestinal view is not possible.

Adult↗