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Biomedical subjects

Yutaka Tanaka

Publications and source records attributed to Yutaka Tanaka.

At least 19 recordsLinked to original sources
PubMed2007

A possible relationship of nocturnal blood pressure variability with coronary artery disease in diabetic nephropathy.

Evidence suggests a relationship between short-term blood pressure (BP) variability and cardiovascular target-organ damage. Although a blunted nocturnal decrease in BP and reduced heart rate variability have been shown to be associated with cardiovascular morbidity in diabetic patients, little information is available on short-term BP variability. In this study, short-term BP variability was assessed in 36 subjects with type 2 diabetes and overt nephropathy who underwent ambulatory BP monitoring, and the factors that correlated with short-term BP variability were examined. The incidence of coronary artery disease (CAD) was significantly greater in the patients with increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that of cerebrovascular disease was not significantly affected (61% versus 50%). Multiple stepwise regression analysis revealed that serum cholesterol (cholesterol) and plasma norepinephrine (p-NE) were significant and independent contributors to nighttime systolic BP variability (partial R2 = 0.490, p < 0.001; partial R2 = 0.470, p < 0.001) and demonstrated that body mass index and p-NE were primary determinants of nighttime diastolic BP variability (partial R2 = 0.539, p < 0.0005; partial R2 = 0.304, p < 0.05). Diabetic nephropathy patients with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1 mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001), and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability. Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02-9.61]; p < 0.05). The increase in nighttime BP variability is associated with a proportional sympathetic activation in diabetic nephropathy. Elevated short-term BP variability combined with relative sympathetic prevalence during the night might represent an important risk factor for cardiovascular events in the diabetic population.

Aged↗
PubMed2006

Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models.

PURPOSE: To clarify the antitumor activity of trastuzumab and its potential as an effective treatment for gastric cancer patients. METHODS: Levels of HER2 expression in tumor tissues of gastric cancer cell lines were examined using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mRNA quantification. Efficacy of trastuzumab was examined as a single agent or in combination with chemotherapeutic agents widely used clinically for gastric cancers in HER2-overexpressing human gastric cancer xenograft models. RESULTS: Two of nine human gastric cancer xenograft models, NCI-N87 and 4-1ST, showed overexpression of HER2 mRNA and protein by IHC (HercepTest) and HER2 gene amplification by FISH (Pathvysion). HER2 protein showed potent staining in peripheral membranes, similar to the staining pattern of breast cancer. FISH scores were also comparable to those of breast cancer models. Trastuzumab as a single agent inhibited the tumor growth in both of the HER2-overexpressing models but not in the HER2-negative models, GXF97 and MKN-45. In any combination with capecitabine, cisplatin, irinotecan, docetaxel, or paclitaxel, trastuzumab showed more potent antitumor activity than the anticancer agents alone. A three-drug combination of capecitabine, cisplatin, and trastuzumab showed remarkable tumor growth inhibition. In NCI-N87 in vitro, trastuzumab showed direct antiproliferative activity according to cell count or crystal violet dying, and showed indirect antitumor activity such as antibody-dependent cellular cytotoxicity. CONCLUSION: The antitumor activity of trastuzumab observed in human gastric cancer models warrants consideration of its use in clinical treatment regimens for human gastric cancer as a single agent or a combination drug with various chemotherapeutic agents.

Animals↗
PubMed2006

Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models.

PURPOSE: To clarify the potential of parathyroid hormone-related protein (PTHrP) and interleukin-6 (IL-6) as cachectic factors in a colon 26 model and the effects of capecitabine on cancer cachexia as determined by plasma levels of IL-6 and PTHrP and body weight loss. METHODS: From two colon 26 sublines-cancer cachectic clone20 and non-cachectic clone5 plasma levels of PTHrP protein and mRNA expression levels in tumor tissues were compared. An IL-6 neutralizing antibody, a PTHrP neutralizing antibody, and capecitabine were administered into mice bearing clone20 and their anticachectic effects evaluated. RESULTS: The plasma level of PTHrP protein in mice bearing clone20 was higher than that in mice bearing clone5. The expression level of PTHrP mRNA was 49-fold higher in tumor tissues of clone20 than of clone5, according to GeneChip analysis. PTHrP antibody as well as IL-6 antibody suppressed wasting of the body and gastrocnemius and adipose tissue weights. PTHrP antibody suppressed the induction of hypercalcemia but not hypoglycemia or elevation of IL-6, whereas IL-6 antibody suppressed the induction of hypoglycemia but not hypercalcemia or elevation of PTHrP. Capecitabine, a fluorinated pyrimidine anticancer agent, improved body wasting of mice bearing clone20 at a low dose with no reduction of tumor volume. Furthermore, capecitabine lowered the levels of PTHrP and IL-6 in plasma and suppressed hypoglycemia and hypercalcemia in this model. Capecitabine also showed anticachectic effects on cachexia in a cancer model induced by human cervical cancer cell line Y (also known as Yumoto). CONCLUSIONS: PTHrP and IL-6 were found to be factors in the development of cachexia in a colon 26 cancer model, and capecitabine improved cancer cachexia by suppressing the plasma levels of IL-6 and PTHrP in colon 26 and Y cachectic models.

Animals↗
PubMed2005

Antitumor activity of erlotinib in combination with capecitabine in human tumor xenograft models.

PURPOSE: To examine the antitumor activity and tolerability of a combination comprising erlotinib and capecitabine in human colorectal, breast and epidermal cancer xenograft models. Further aims of the study were to examine the effects of single-agent erlotinib therapy on tumor growth, and on thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels, (enzymes which activate and deactivate capecitabine, respectively) in tumor tissue. METHODS: BALB/c nu/nu mice bearing LoVo and HT-29 (colon cancer), A-431 (vulval cancer), and KPL-4 and MAXF401 (breast cancer) human tumors were treated with erlotinib 100 mg/kg/day and/or capecitabine 359 or 90 mg/kg/day, by oral administration once daily for 14 days. RESULTS: The maximum tolerated dose (MTD) of erlotinib, formulated in carboxymethylcelluose/Tween 80, was identified as 125 mg/kg/day. Erlotinib at a dose of 100 mg/kg/day achieved significant tumor-growth inhibition in the, LoVo, KPL-4, and A-431 models. Some inhibition of MAXF401 tumor growth was observed, but was not significant. In the HT-29 model, erlotinib showed less marked but statistically significant antitumor activity. On day 15, mean tumor-growth inhibition in HT-29, LoVo, KPL-4, MAXF401, and A-431 models was 46, 74, 71, 20, and 85%, respectively. Evaluation of erlotinib/capecitabine combination therapy, at sub-optimal doses, in the three erlotinib-sensitive tumor models LoVo, KPL-4 and A-431, demonstrated at least additive activity with the combination compared with the single agents. In the A-431 and LoVo models, the combination of agents had greater antitumor activity than the single agent capecitabine alone at the MTD. Erlotinib in combination with capecitabine was not associated with significantly increased toxicity compared with single-agent therapy. Erlotinib 100 mg/kg/day induced significant upregulation of TP and DPD in the LoVo model, a significant upregulation of TP in the HT-29, MAXF401 and A-431 models, but had no obvious effect on TP and DPD levels in the KPL-4 model. In the A-431 model, selective upregulation of TP by erlotinib 100 mg/kg resulted in an increased TP:DPD ratio. In the LoVo model, immunohistochemistry revealed marked upregulation of TP (but not DPD by erlotinib). CONCLUSIONS: Erlotinib inhibits tumor growth in a range of human tumor xenograft models, including breast and colorectal cancer (CRC). Erlotinib and capecitabine demonstrated at least additive activity in LoVo, KPL-4 and A-431 tumor models. The antitumor activity of the combination was greater than that of capecitabine alone at the MTD. Erlotinib treatment did affect the TP in the CRC tumor models as confirmed immunohistochemically. The findings of this study support clinical evaluation of erlotinib, both as a single agent and in combination with capecitabine, for the treatment of CRC and breast cancer.

Animals↗
PubMed2005

The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.

Activation of angiotensin II (Ang II) type 1 receptor (AT1R) signaling is reported to play an important role in cardiac hypertrophy. We previously cloned a novel molecule interacting with the AT1R, which we named ATRAP (for Ang II type 1 receptor-associated protein). Here, we report that overexpression of ATRAP significantly decreases the number of AT1R on the surface of cardiomyocytes, and also decreases the degree of p38 mitogen-activated protein kinase phosphorylation, the activity of the c-fos promoter and protein synthesis upon Ang II treatment. These results indicate that ATRAP significantly promotes downregulation of the AT1R and further attenuates certain Ang II-mediated hypertrophic responses in cardiomyocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and doxifluridine (5'-DFUR) are active agents against colorectal cancer. Each drug, however, has the possibility of causing diarrhea. METHODS AND RESULTS: First, we determined the optimal dosing regimen in murine models. CPT-11 (i.v., q2d x 3) and 5'-DFUR (p.o., qd x 14) were administered to mice bearing a human colorectal cancer xenograft model. Diarrhea was stronger in the simultaneously administered schedule but not much stronger in the sequentially administered schedule compared with monotherapies. Both schedules yielded similar antitumor efficacies. Next, we conducted a phase I study combining CPT-11 on days 1 and 15, and 5'-DFUR on days 3-14 and 17-28 every 5 weeks in 19 patients with metastatic colorectal cancer. The doses of CPT-11 ranged from 80 to 150 mg/m2 and those of 5'-DFUR from 800 to 1,200 mg. Diarrhea of grade 3/4 developed in only 1 patient at 100 mg/m2/800-mg doses. Dose-limiting toxicities were hyperbilirubinemia and skipping doses due to fatigue at 150 mg/m2/1,200-mg doses. CONCLUSION: For the phase II study, the recommended dose was set at CPT-11 150 mg/m2 and 5'-DFUR 800 mg.

Adult↗
PubMed2005

Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells.

Although vascular smooth muscle cells (VSMCs) are widely used in cardiovascular research, their phenotypic change under various culture conditions is problematic to evaluate the experimental results obtained. The levels of angiotensin (Ang) type 1/2 (AT1/AT2) receptors as well as contractile and structural proteins are degraded through culture passages. The present study demonstrated that heparin recovered Ang receptors and differentiation markers, such as desmin, SM-22 and smooth muscle alpha-actin in VSMCs at the ninth passage. Heparin also potenciated Ang II-induced activation for ERK1/2 and p38. These results suggest a potential value of heparin-treated VSMCs as the model for analysis of Ang-mediated signal transduction under physiological condition.

Actins↗
PubMed2005

Characterization of different paresthesias following orthognathic surgery of the mandible.

PURPOSE: Paresthesia is a well known consequence of peripheral nerve injury. However, the neural mechanisms of the 2 recognized types, spontaneous and elicited, are currently unknown. This study aimed to investigate these 2 paresthesias and the possible mechanisms accompanying orthognathic surgery. PATIENTS AND METHODS: Mechanical-touch thresholds and current perception threshold were measured before and 7 days after surgery in 60 chin sites (mental nerve area) of 30 patients who underwent orthognathic surgery. Similar testing was conducted on healthy volunteers (controls). All sites were classified by the presence or absence of each paresthesia: spontaneous paresthesia or no spontaneous paresthesia, and elicited paresthesia or no elicited paresthesia. Presence or absence analyses were followed-up for 6 weeks after surgery. RESULTS: Gender differences and maxillary surgery did not change the incidence of paresthesia during postoperative week 1 (chi-square test, P > .05). A significantly higher mechanical-touch threshold was observed with spontaneous paresthesia compared with no spontaneous paresthesia (Mann-Whitney U-test; P < .05), but not between no elicited paresthesia and elicited paresthesia (Mann-Whitney U-test; P > .05). A significant increase in postsurgery current perception thresholds values compared with presurgery values was observed at 2,000 Hz in spontaneous paresthesia, and at 2,000 and 5 Hz in elicited paresthesia (paired t test, P < .05). The incidence of spontaneous paresthesia decreased more rapidly than elicited, while the latter tended to increase again during the 6-week postsurgical test period. CONCLUSION: The results suggested that both spontaneous and elicited paresthesias are associated with damage and dysfunction in myelinated primary afferent fibers, but additional neural mechanisms are implicated during elicited paresthesia.

Adolescent↗
PubMed2005

Preferential inhibition of bone metastases by 5'-deoxy-5-fluorouridine and capecitabine in the 4T1/luc mouse breast cancer model.

5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine are oral anti-cancer agents, which are enzymatically converted to 5-fluorouracil (5-FU) by thymidine phosphorylase in humans and uridine phosphorylase in mice. Since the activity of these phosphorylases is higher in cancerous tissue than in normal tissue, systemic administration of 5'-DFUR and capecitabine achieves high intratumoral 5-FU levels and low adverse effects on non-tumoral tissue. Accordingly, 5'-DFUR and capecitabine are widely used for the treatment of cancer patients. In the present study, we examined the effects of 5'-DFUR and capecitabine on bone metastases, one of the most common complications of breast cancer, using an animal model in which inoculation of 4T1/luc mouse breast cancer cells into the mammary fat pads of female BALB/c mice developed spontaneous metastases in distant organs including bone, lung and liver. Mice received 4T1/luc cell inoculation in the mammary fat pad at day 0 and oral 5'-DFUR (31, 62, 123 or 246 mg/kg) or capecitabine (90, 180 or 359 mg/kg) daily from day 7 to day 21. Both 5'-DFUR and capecitabine significantly inhibited orthotopic tumor formation and distant metastases to bone, lung and liver in a dose-dependent manner. Of note, the lowest dose of 5'-DFUR (31 mg/kg) and capecitabine (90 mg/kg), which failed to inhibit orthotopic tumor development and the lung and liver metastases, significantly reduced the bone metastases. In conclusion, our results suggest that oral 5'-DFUR and capecitabine are effective for the treatment of primary and secondary breast tumors. Most notably, they also suggest that these agents are preferentially beneficial for bone metastases.

Administration, Oral↗
PubMed2004

Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression.

The cAMP-signaling pathway plays a crucial role in the regulation of the renin gene, but the mechanism involved remains poorly understood. We have focused our studies of renin gene regulation on the unique cAMP responsive element (huREN/CNRE, -135 to -107) in the human renin promoter. We have cloned a protein that binds to this unique CNRE and demonstrated that this protein is liver X receptor-alpha (LXRalpha), a transcriptional factor of the nuclear receptor family. Transient expression of LXRalpha in human renin-producing Calu-6 cells increased cAMP inducibility of human renin promoter. Similarly, LXRalpha-stably transfected Calu-6 cells exhibited increased cAMP inducibility of renin promoter as well as the endogenous renin gene. Site-directed mutation of huREN/CNRE, which disrupted LXRalpha binding, decreased cAMP-induced transcriptional activity of human renin promoter. Furthermore, we demonstrated that the binding of LXRalpha derived from human juxtaglomerular cells, the main production site of renin in the kidney, to the huREN/CNRE in vivo. These results suggest that LXRalpha plays an important role in the cAMP-mediated regulation of human renin gene transcription by binding to CNRE.

Cell Line↗
PubMed2004

Efficacy of steroid treatment for sensory impairment after orthognathic surgery.

PURPOSE: Steroid hormones are therapeutic for motor and/or sensory dysfunctions caused by nerve injury. However, the timing for giving such medicine is unclear. This study aimed to estimate the efficacy of steroid treatment and determine an appropriate start time after sensory impairment. PATIENTS AND METHODS: Twenty-seven patients with sensory impairment who received orthognathic surgery were classified into groups called 1W (n = 6), 3W (n = 6), or 6W (n = 8) group on the basis of start time for steroid treatment, being 1 week, 3 weeks, or 6 weeks after surgery, respectively, and a no steroid treatment (NST) group (a control group) (n = 6) that did not receive treatment for 10 to 12 weeks after surgery. Sensory impairment was diagnosed if postoperative first week mechanical-touch threshold was over 4.0 as measured by Semmes aesthesiometer. Prednisolone treatment was administered orally to patients at 30 mg for 7 days, 15 mg for 4 days, and 5 mg for 3 days. Mechanical-touch threshold and thermal perceptions were compared before and after treatment. RESULTS: At 1 week postoperatively, there were no significant differences in mechanical-touch threshold among the 4 groups (analysis of variance, P >.05). Changes in mechanical-touch threshold in the 1W group showed no significant improvement (analysis of variance, P >.05), but in the 3W and 6W groups, there were significant differences compared with the NST group (Dunns methods, P <.05). CONCLUSIONS: Steroid treatment for sensory impairment after orthognathic surgery has the potential to accelerate recovery and it appears desirable to start treatment later than 1 week postoperatively.

Administration, Oral↗
PubMed2004

Major psychological factors affecting acceptance of gene-recombination technology.

The purpose of this study was to verify the validity of a causal model that was made to predict the acceptance of gene-recombination technology. A structural equation model was used as a causal model. First of all, based on preceding studies, the factors of perceived risk, perceived benefit, and trust were set up as important psychological factors determining acceptance of gene-recombination technology in the structural equation model. An additional factor, "sense of bioethics," which I consider to be important for acceptance of biotechnology, was added to the model. Based on previous studies, trust was set up to have an indirect influence on the acceptance of gene-recombination technology through perceived risk and perceived benefit in the model. Participants were 231 undergraduate students in Japan who answered a questionnaire with a 5-point bipolar scale. The results indicated that the proposed model fits the data well, and showed that acceptance of gene-recombination technology is explained largely by four factors, that is, perceived risk, perceived benefit, trust, and sense of bioethics, whether the technology is applied to plants, animals, or human beings. However, the relative importance of the four factors was found to vary depending on whether the gene-recombination technology was applied to plants, animals, or human beings. Specifically, the factor of sense of bioethics is the most important factor in acceptance of plant gene-recombination technology and animal gene-recombination technology, and the factors of trust and perceived risk are the most important factors in acceptance of human being gene-recombination technology.

Adolescent↗
PubMed2003

[Optimal dosing schedule in combination therapy with irinotecan and doxifluridine in a human colorectal cancer xenograft model].

A combination therapy with CPT-11 and 5-FU/LV has been recently established as a first-line therapy for metastatic colorectal cancer. However, severe adverse effects have also been reported from this combination therapy, and a modality to reduce the adverse effects is desired. 5'-DFUR, a pro-drug of 5-FU, shows less myelotoxicity than 5-FU, and thus it may be a better partner to combine with CPT-11. However, since each drug has the possibility of inducing diarrhea, there is concern about their use in combination therapy. Therefore, in the present study, our aim was to establish an optimal schedule in murine models, which shows no increase in diarrhea but maintains potent antitumor activity. In non-tumor bearing mice, CPT-11 was given i.v. at 100 mg/kg/day q2d x 3, and 5'-DFUR was given p.o. at 172 mg/kg/day daily for 14 days. Each of these doses caused diarrhea in the single treatment. CPT-11 was administered simultaneously or sequentially with 5'-DFUR. With the simultaneously administered schedule, the diarrhea appeared stronger than that found in the CPT-11 single or in the 5'-DFUR single treatment groups. On the other hand, with the sequentially administered schedule the diarrhea was not much stronger than that found in the single agent treatment groups. When CPT-11 and 5'-DFUR administrations were separated by three-day intervals, the diarrhea was not augmented at all. In mice bearing human colorectal cancer COLO 205, the antitumor activity of CPT-11 in the combination with 5'-DFUR was additive in all of the examined schedules. The efficacy in the sequential schedule was the same as in the simultaneous schedule. These results suggest that a sequential administration schedule of CPT-11 and 5'-DFUR would be more tolerable than and equally efficacious to the simultaneous administration schedule. Clinical study of this sequential administration in combination therapy is warranted.

Animals↗
PubMed2003

Topographic distribution of misery perfusion in relation to internal and superficial borderzones.

BACKGROUND AND PURPOSE: Whether misery perfusion (MP) commonly accompanies brain borderzones (BZs) in patients with major cerebral artery occlusion remains unclear. We elucidated topographic patterns of chronic hemodynamic failure in such patients. METHODS: Twenty-four patients with unilateral occlusion or severe stenosis (>75% in diameter) of the internal carotid artery (ICA) or middle cerebral arterial (MCA) trunk with minimal or no infarct underwent PET with (15)O-labeled gas inhalation. Mean cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, oxygen extraction fraction (OEF), and CBV/CBF ratio were determined in the superficial BZs, internal BZ, and MCA territory excluding BZs. Values in BZs were standardized and compared with those in controls. Topographic distributions of regions with OEF greater than that in controls were determined. RESULTS: Values in patients and controls were not significantly different. Topographic distributions included matched perfusion in 10 patients, MP in only the ipsilateral internal BZ in four, MP in both ipsilateral internal and superficial BZs in two, MP in the ipsilateral MCA territory including BZs in one, MP in the ipsilateral MCA territory including BZs and contralateral BZs in two, and MP in the ipsilateral MCA territories including BZs in five. CONCLUSION: Only 25% of the patients had MP localized in affected BZs Although localized MP more frequently accompanied the internal BZ than other regions, no patient had elevated OEF in the superficial BZ alone. These results are inconsistent with clinical observations that 80% of BZ infarctions develop superficially. Thus, hemodynamic mechanisms may not cause most superficial BZ infarctions.

Adult↗
PubMed2002

[New trials for improving diagnostic accuracy of stress technetium-99m-tetrofosmin single photon emission computed tomography].

OBJECTIVES: This study evaluated the influence of extra-cardiac accumulation in technetium-99m-tetrofosmin myocardial single photon emission computed tomography (SPECT) imaging. METHODS: Technetium-99m-tetrofosmin myocardial SPECT was performed in 247 patients from 1997 to 1999. To evaluate the sensitivity, 42 patients with inferior infarction were selected. To evaluate the specificity, 32 patients with no significant perfusion defect and low pretest likelihood (< 15%) of coronary artery disease and 13 patients with normal coronary angiography were selected. Firstly, the SPECT raw data were evaluated according to the effects of diaphragm and breast, the position and the degree of accumulation of the liver, gall bladder and intestine. Then, the myocardial tracer uptake was scored semiquantitatively from 0 (normal) to 4 (perfusion defect) in the 13 segments of the left ventricle. RESULTS: The specificity was 86.7% and the sensitivity was 92.8%. Perfusion abnormality of the inferior wall was observed in 6 of 45 patients with a low pretest likelihood of coronary artery disease. These 6 patients were classified into the false positive group, and the other 39 patients were classified into the true negative group. The liver position and the liver accumulation on the stress images were significantly higher in the false positive group than in the true negative group (p < 0.001), but only the liver position on the rest images was significantly higher in the false positive group (p < 0.001). By estimating the defect 1 point lower for the high-positioned liver patients, specificity improved from 86.7% to 100% and sensitivity did not change. CONCLUSIONS: Inferior perfusion defect on technetium-99m-tetrofosmin myocardial SPECT of high-positioned liver patients needs to be evaluated with special caution.

Aged↗
PubMed2002

[Biventricular pacing using two pacemakers and triggered VVT mode in patients with atrial fibrillation and congestive heart failure: a case report].

A 76-year-old female had undergone implantation of a single chamber pacemaker for sick sinus syndrome 20 years previously. She developed chronic atrial fibrillation and required repeated admission due to congestive heart failure. She had significant mitral and tricuspid regurgitation. Paradoxical movement of the intraventricular septum was severe. Due to right ventricular apical pacing, significant interventricular conduction delay was present with a paced QRS duration of 189 msec. The left ventricular pacing lead was positioned via the coronary sinus. The mode of the previously implanted pacemaker was set at VVT. Biventricular pacing could be achieved even in intrinsic beats by VVT mode. The battery life time was improved. This method is useful in patients with conventional pacemakers.

Aged↗
PubMed2001

Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine/5'-dFUrd in human breast cancer models.

The anti-HER-2 antibody, trastuzumab (Herceptin), and the oral fluoropyrimidine, capecitabine (Xeloda), are both effective in breast cancer with different modes of action and toxicity profiles. Therefore, the efficacy in combination therapy of these agents for the treatment of HER-2-overexpressing breast cancer was of interest. An antagonistic interaction in vitro between trastuzumab and 5-fluorouracil (5-FUra) in combination has previously been reported. In the same study, the in vivo antitumor activity of this combination was investigated. However, the results were inconclusive since 5-FUra at the dose used had sufficient antitumor efficacy as a single agent and therefore it was not possible to clarify the potential difference between 5-FUra alone and the combination. In the present study, we investigated the efficacy of trastuzumab in combination with capecitabine or its intermediate metabolite 5'-dFUrd in HER-2-overexpressing human breast cancer cell lines and xenograft models. In vivo antitumor activity of the combination was at least additive, in terms of tumor growth inhibition and tumor growth delay, in human breast cancer models KPL-4 and BT-474. The combination treatment in vivo was superior to the treatment with either single agent alone, even though in vitro treatment with trastuzumab and 5'-dFUrd/5-FUra showed antagonistic antiproliferative activity in these cell lines. The reason for the discrepancy between the in vivo and in vitro results was not clarified. However, observed additive in vivo antitumor activity clearly indicates that the clinical efficacy of the combination of trastuzumab and capecitabine/5'-dFUrd against HER-2-overexpressing breast cancer is worth investigating.

Animals↗