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Naoto Watanabe

Publications and source records attributed to Naoto Watanabe.

35 records · Page 2Linked to original sources
PubMed2004

[The effects of bakumondo-to (mai-men-dong-tang) on asthmatic and non-asthmatic patients with increased cough sensitivity].

UNLABELLED: Some patients with bronchial asthma (BA) have increased throat sensitivity. In some instances, it is envisaged that this may result in increased coughing or wheezing. Bakumondo-to is a traditional herbal medicine that is well known to reduce coughing in patients with BA and chronic bronchitis. AIM: The present study was conducted to investigate the effect of Bakumondo-to on cough sensitivity in patients with BA and non-asthmatic (non-BA) conditions. The effect on respiratory tract inflammation was also examined. METHODS: We examined 21 BA and 22 non-BA subjects whose cough threshold for capsaicin was less than 3.9 microM. We prepared 1000, 500, 250, 125, 62.5, 31.2, 15.6, 7.80, 3.90, 1.95, 0.98, and 0.49 microM solutions. Cough thresholds to a concentration of inhaled capsaicin solution causing 5 or more coughs was measured before treatment and after 2 months or more of treatment with Bakumondo-to (9 g/day, TJ-29). The number of eosinophils in the peripheral blood, the sputum eosinophil ratio, and the ECP level in the serum were also measured before and after treatment. RESULTS: 1. Bakumondo-to significantly improved the cough threshold value in 76% of patients with BA and in 82% with non-BA conditions. 2. Bakumondo-to was more effective in reducing cough sensitivity to capsaicin in BA than in non-BA conditions. 3. While Bakumondo-to did not significantly reduce the sputum eosinophil count, its effectiveness in suppressing cough was greatest in patients whose sputum eosinophil count was > or = 2%. It remains to be established whether Bakumondo-to inhibits eosinophil activation. Our results suggest that Bakumondo-to is an effective therapeutic preparation for cough hypersensitivity accompanying chronic cough disease, especially in cases of severe allergic inflammation.

Adult↗
PubMed2004

The radiotoxicity of 131I therapy of thyroid cancer: assessment by micronucleus assay of B lymphocytes.

UNLABELLED: We investigated cytologic radiation damage in thyroid cancer after (131)I therapy using micronucleus assay (MNA) of B lymphocytes exclusively, as opposed to our previous study in which MNA of all lymphocyte subsets was used. METHODS: We studied 22 thyroid cancer patients treated with 3.7 GBq of (131)I. Peripheral lymphocytes were harvested, and B lymphocytes were isolated by an immunomagnetic method and assayed for the frequency of micronuclei. RESULTS: The frequency of micronuclei among B cells after (131)I therapy was significantly increased relative to that in untreated control subjects, and the (131)I-induced increase in micronuclei frequency among B cells was significantly greater than that among all lymphocytes. CONCLUSION: Compared with the MNA of all lymphocytes, the MNA among specifically B cells may more sensitively detect cytologic radiation damage associated with (131)I therapy of thyroid cancer.

Adult↗
PubMed2004

[Influence of epidural lidocaine injection on vecuronium-induced neuromuscular blockade].

BACKGROUND: We investigated vecuronium-induced neuromuscular blockade in patients with continuous epidural lidocaine injection and those without epidural lidocaine. METHODS: Lower thoracic epidural injection of lidocaine was commenced at a rate of 2-3 mg x kg(-1) x h(-1) following its bolus injection (1.5-2 mg x kg(-1)) only in epidural group. Neuromuscular function was monitored by acceleromyographic train-of-four (TOF) responses of the adductor pollicis muscle to ulnar nerve stimulation after induction of general anesthesia. RESULTS: Neuromuscular block was obtained by vecuronium 0.1 mg x kg(-1) as an intubating dose and was maintained 5-10% of baseline first twitch (T 1) of TOF responses by continuous vecuronium administration. The maximum depression of T 1 response and onset time obtained by vecuronium 0.1 mg x kg(-1) were not different between the groups, but mean clinical duration from administration of the first dose to T 1 recovery to 5% of baseline was significantly prolonged in group with epidural lidocaine (49.5 min), compared to that without lidocaine (32.3 min). Furthermore, maintenance dose of vecuronium obtained in the group with epidural lidocaine (0.034 mg x kg(-1) x h(-1)) was significantly smaller than that in the group without lidocaine (0.060 mg x kg(-1) x h(-1)). CONCLUSIONS: Based on our results, we conclude that lidocaine injected continuously into the epidural space potentiates vecuronium-induced neuromuscular block.

Adult↗
PubMed2003

Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function.

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

Biomarkers, Tumor↗
PubMed2003

Feasibility of 186Re-radioimmunotherapy for treatment in an adjuvant setting of colon cancer.

PURPOSE: (186)Re displays abundant intermediate energy beta emission, and possesses an appropriate physical half-life of 3.7 days. We compared the efficacy of radioimmunotherapy (RIT) with an anti-colorectal cancer monoclonal IgG1, (186)Re-A7, with that of RIT employing (131)I in a mouse liver metastasis model. METHODS: Liver metastases were established by intrasplenic injection of LS180 human colon cancer cells. Based on the results of toxicity assessment with escalated administration doses, 21 MBq (186)Re-A7 and 7 MBq (131)I-A7 were chosen as maximum tolerated doses. In the first experiment, mice underwent RIT at 2 weeks when metastases attain a diameter of several millimeters, and were killed 2 weeks later to assess metastatic burden in the liver. In the second experiment, RIT was conducted at 1 week when metastases of several hundred micrometers in diameter were observed, and survival of mice was examined. RESULTS: (186)Re-A7 RIT inhibited the growth of liver metastases better than (131)I-A7 RIT ( P<0.02). Furthermore, (186)Re-A7 RIT induced better improvement in survival of mice than (131)I-A7 RIT ( P<0.002). (186)Re-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of (186)Re-A7 RIT over (131)I-A7 RIT. CONCLUSION: These results support the use of RIT with (186)Re-MAb in an adjuvant setting in cases involving minimal disease.

Animals↗
PubMed2003

Local delivery of (131)I-MIBG to treat peritoneal neuroblastoma.

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of (131)I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of (131)I-MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of (131)I-MIBG in the treatment of peritoneal neuroblastoma.

3-Iodobenzylguanidine↗
PubMed2003

Comparative fading responses induced by mivacurium, cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat.

PURPOSE: It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). METHODS: In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. RESULTS: At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. CONCLUSION: Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.

Action Potentials↗
PubMed2003

Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.

Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n = 11), mice undergoing i.p. RIT with 131I-A7 (n = 11), mice undergoing i.v. RIT with 131I-A7 (n = 11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n = 5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2 +/- 16.5% of the injected dose per g (% ID/g) and 11.1 +/- 3.6% ID/g at 2 h, respectively (P < 0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0 +/- 2.5 days) did not affect the survival as compared to no treatment (26.7 +/- 1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8 +/- 1.8 days (P < 0.01). Intraperitoneal RIT with 131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P < 0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.

Animals↗
PubMed2003

Functional mapping of regional liver asialoglycoprotein receptor amount from single blood sample and SPECT.

UNLABELLED: The objective of this study was to validate a method for estimating regional liver asialoglycoprotein (ASGP) receptor amount from single blood samples using static SPECT with (99m)Tc-diethylenetriaminepentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA). METHODS: Based on a 2-compartment nonlinear model, regional ASGP receptor amount could be calculated from total liver ASGP receptor amount (Ro) and regional GSA uptake at a specific time. Because Ro could be estimated from single blood samples using an empiric formula, regional GSA uptake obtained as a SPECT voxel count could be converted to regional ASGP receptor amount by solving a nonlinear model equation. To validate this method, data from 62 patients with chronic liver disease underwent dynamic SPECT (30 rotations per 30 min) and simultaneous multiblood sampling and were analyzed by this method. Ro was calculated as the sum of voxel values of parametric receptor images generated from plasma concentration of GSA at 20 min and of static SPECT images generated by merging dynamic SPECT data (12-20 min). Ro was also estimated by fitting time-activity curves (4-30 min) of plasma and whole liver to the nonlinear model using the nonlinear regression method. Ro obtained from the receptor image was compared with that from curve fitting in relation to the results of hepatic function tests (indocyanine green test, hepaplastin test, and branched-chain amino acids/tyrosine plasma concentration ratio) and Child's classification. RESULTS: Ros from the 2 methods showed a significant linear correlation (r(2) = 0.938; P < 0.0001; slope = 0.90; y-intercept = 1.5). Both Ros had significant correlations with the results of hepatic function tests (P < 0.001) and differed significantly among the 3 groups of Child's classification (P < 0.0001). CONCLUSION: The present method could provide a quantitative ASGP receptor image without dynamic data acquisition. This approach could be useful for quantitative evaluation of regional liver function and estimation of residual liver function in hepatectomy.

Adolescent↗
PubMed2003

[Effects of Bakumondo-to (Mai-Men-Dong-Tang) on cough sensitivity to capsaicin in asthmatic patients with cough hypersensitivity].

UNLABELLED: Some patients with bronchial asthma have increased cough sensitivity. In such patients coughing may be an inducer of wheeze. The aim of the present study was to investigate the effect of Bakumondo-to on the cough sensitivity and respiratory tract inflammation in asthmatic patients with increased cough sensitivity. In addition influences of intensity of respiratory tract inflammation, gender, type of asthma, and disease period on the effect of Bakumondo-to on the cough sensitivity were examined. Twenty-one bronchial asthmatics whose cough thresholds to capsaicin were less than 3.9 microM were examined. METHODS: Cough thresholds to capsaicin (concentration of inhaled capsaicin solution causing 5 or more coughs) was measured before and after 2 months or more treatment with Bakumondo-to (9 g/day, TJ-29). Number of eosinophils in peripheral blood, sputum eosinophil ratio, and ECP level in the serum were also measured before and after treatment. RESULTS: Bakumondo-to significantly increased the cough threshold. Although respiratory tract inflammation was not significantly improved, number of eosinophils in peripheral blood, sputum eosinophil ratio and ECP level in the serum were remarkably decreased more than the half. And Bakumondo-to was more effective in asthmatic subjects with severe airway inflammation. Furthermore, a greater effect of it was observed in women. A greater effect was also observed in patients having a disease duration of less than 1 year. CONCLUSION: Our results suggest that Bakumondo-to may be an effective therapeutic preparation for coughing in asthmatic patients with cough hypersensitivity.

Adolescent↗
PubMed2002

Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells.

The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of <1 mm in diameter can be observed at 1 week and these lesions can attain a size of several millimetres at 2 weeks. Daily AT with 2-methoxyoestradiol (2-ME), 75 mg/kg, was initiated at 1 week. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, (131)I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on (131)I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or (131)I-A7 RIT significantly suppressed metastasis growth ( P<0.0001): metastasis weight was 5.96+/-0.87 g in non-treated controls, 2.67+/-1.89 g in cases receiving AT and 0.85+/-0.68 g in those receiving (131)I-A7 RIT. Combination of AT and (131)I-A7 RIT more effectively suppressed the growth to 0.28+/-0.32 g ( P<0.05 vs RIT alone). The effect of (131)I-HPMS-1 RIT, which suppressed metastasis growth to 2.25+/-0.88 g, was significant in comparison with the control ( P<0.0001); however, the combination of AT and (131)I-HPMS-1 RIT (which suppressed growth to 1.41+/-0.68 g) was far less effective than the combination of AT and (131)I-A7 RIT. AT did not decrease (131)I-A7 accumulation in metastases. AT did not affect RIT myelotoxicity. The results of this study demonstrating the combined effects of AT and (131)I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease.

Angiogenesis Inhibitors↗
PubMed2002

Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with (99m)Tc-sestamibi, (201)Tl chloride and (99m)Tc-HL91.

Weak visualization of tumours in pre-therapeutic scintigrams with technetium-99m sestamibi (MIBI) is likely a predictive sign of unfavourable tumour response to radiotherapy and chemotherapy. However, factors relating to this scintigraphic finding are not well understood. The presence of hypoxic tumour cells is one of the major reasons for therapeutic failure; consequently, we attempted to determine whether oxygenation status affects (99m)Tc-MIBI accumulation in tumour cells. LS180 human colon cancer and T24 human bladder cancer cells were incubated in air or N(2) gas at 37 degrees C. Cellular uptake of (99m)Tc-MIBI was subsequently determined at 15, 60 and 120 min. Uptake of thallium-201 chloride was also assessed. Uptake of (99m)Tc-HL91 was assessed as a hypoxic marker. Accumulation of the tracers in LS180 xenografts was observed in mice treated with 5 mg/kg hydralazine and compared with that in untreated mice. pO(2) in the medium and tumours was measured with O(2) microelectrodes. N(2) gas flow gradually reduced pO(2) in the cell suspension to 1-2 mmHg in 60 min. Cellular uptake of (99m)Tc-MIBI in LS180 cells decreased by approximately 30% in N(2) gas in comparison to that in air throughout the study. Hypoxia had a more prominent influence on (201)Tl uptake, which displayed a reduction of approximately 60% in N(2) gas at 120 min, than on (99m)Tc-MIBI uptake. On the other hand, N(2) gas induced an increase of 170% in (99m)Tc-HL91 uptake at 120 min, indicating the hypoxic condition of cells. The results of in vitro assays employing the T24 cell line were similar to those obtained with the LS180 cell line. Hydralazine treatment markedly reduced (99m)Tc-MIBI and (201)Tl accumulation in LS180 xenografts; moreover, intratumoural pO(2) decreased from 14.5 +/- 6.6 mmHg to 7.6 +/- 6.2 mmHg. (99m)Tc-HL91 accumulation in xenografts was markedly increased by hydralazine. In conclusion, hypoxia reduced accumulation of (99m)Tc-MIBI and (201)Tl in tumour cells. Accordingly, hypoxia may be an important factor in terms of the interpretation of scintigraphic findings obtained with these tracers for pre-therapeutic prediction of tumour response to treatment. Furthermore, the enhanced (99m)Tc-HL91 accumulation in hypoxic tumour cells indicates the usefulness of this tracer in this regard.

Animals↗
PubMed2002

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI.

This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.

Adolescent↗
PubMed2002

Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: a preliminary report.

Previous research has found frontal lobe involvement in memory impairment in schizophrenia. In the present study, proton magnetic resonance spectroscopy was performed in 13 young patients with schizophrenia and 13 normal control subjects. Spectra were obtained from a voxel of 2 x 2 x 1.5 cm(3) in the bilateral inferior frontal gyrus and thalamus. Subjects were given a verbal learning task and stimulus category repetition (SCR) was calculated from the performance of the task. Significantly reduced N-acetylaspartate (NAA)/choline-containing compounds ratios were found in the left inferior frontal cortex of patients compared with controls. The total number of words recalled by patients was significantly lower than that recalled by controls. In all subjects, SCR scores were positively correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex, which showed a trend towards a decrease in patients. These results support the notion of metabolic abnormalities in the left inferior frontal region related to verbal memory deficits in patients with schizophrenia.

Adolescent↗
PubMed2002

Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice.

The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of beta-emitters suggested by a mathematical model. In the present study, the efficacy of RIT with an anti-colorectal cancer IgG1 A7 conjugated with 186Re was examined in a liver metastasis model established by intrasplenic inoculation of human colon cancer cells. In this model, small metastases of less than 1 mm in diameter can be observed 1 week after cell inoculation. Metastases attain a diameter of several millimeters at 2 weeks. 186Re-A7 accumulated exclusively in metastases, displaying a value of 24.1 +/- 8.7% ID/g 2 days after the injection. 186Re-A7 accumulation in liver metastases increased with decreasing size. RIT with 7 MBq 186Re-A7 at 2 weeks significantly suppressed the growth of metastases; weight of metastases 4 weeks after cell inoculation was 5.96 +/- 0.87 g in nontreated control mice and 1.25 +/- 0.75 g in mice receiving 186Re-A7 RIT (p < 0.0001). RIT at 1 week more effectively inhibited metastatic growth to 0.08 +/- 0.05 g (p < 0.002 vs. RIT at 2 weeks). RIT with a class-matched irrelevant MAb 186Re-HPMS-1 at 1 week after cell inoculation somewhat suppressed metastatic growth, 3.39 +/- 0.25 g at 4 weeks, as compared with the control; however, 186Re-HPMS-1 RIT was far less effective than 186Re-A7 RIT (p < 0.0001). These results support the use of RIT with 186Re-MAb in an adjuvant setting in cases involving minimal disease. Factors such as higher and homogeneous MAb accumulation in small nodules, better perfusion, and subsequent better oxygenation likely compensate for the loss of beta radiation outside small metastases.

Animals↗
PubMed2002

Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.

UNLABELLED: Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. METHODS: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq (131)I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. RESULTS: Antiangiogenic therapy and RIT with (131)I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using (131)I-HPMS-1 was far less effective than (131)I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). CONCLUSION: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

Angiogenesis Inhibitors↗