Biomedical subjects

Tsuneo Imai

Publications and source records attributed to Tsuneo Imai.

18 recordsLinked to original sources

PubMed2005

Intracellular signaling in the induction of apoptosis in a human breast cancer cell line by water extract of Mekabu.

BACKGROUND: We previously reported that water extract of Mekabu, a kind of seaweed, induced apoptosis in a human breast cancer cell line. In the present study we investigated intracellular signaling in apoptosis, with a focus on caspases. METHODS: Mekabu extract, obtained with ultrapure water, was used to induce apoptosis in a human breast cancer cell line, MDA-MB231, and DNA fractionation was investigated by flow cytometry and electrophoresis. In addition, using the caspase detection kit Caspa Tag, activation of caspases 3, 6, 8, and 9 was observed under a fluorescence microscope. Furthermore, using antibodies to caspases 3, 8, 9, and Bid, we conducted a protein analysis by Western blotting to determine the activation of these substances. RESULTS: Obvious ladder formation demonstrating DNA fractionation was seen, confirming that Mekabu extract induced apoptosis. In the fluorescence microscope observations, activation of caspases 3, 6, and 8, but not caspase 9, was seen. Activated caspases 3 and 8 were detected in the Western blotting analysis, but no proteins of activated caspase 9 or Bid were detected. CONCLUSION: Mekabu extract activates caspases 3, 6, and 8 and contributes to intracellular signaling to induce apoptosis in a human breast cancer cell line. This signaling is not via the mitochondria.

Apoptosis↗

PubMed2004

Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1alpha of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a(+/-) mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a(+/-) mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.

Alleles↗

PubMed2004

The alpha4 residues of human DNA topoisomerase IIalpha function in enzymatic activity and anticancer drug sensitivity.

We introduced a series of Pro substitutions within and near the alpha4 helix, a part of the breakage/rejoining region, in human DNA topoisomerase IIalpha, and analyzed if this region is involved in determination of anti-cancer drug sensitivity in a temperature- sensitive yeast strain (top2-4 allele). Among the 19 mutants generated, H759P and N770P showed resistance to etoposide and doxorubicin at the non-permissive temperature, where cell growth depends on activity of the human enzyme. For these residues, mutants with an Ala substitution were further created, in which H759A also showed resistance to etoposide. H759P, H759A and N770P were expressed, purified and subjected to in vitro measurement of drug sensitivity. They generated lower amounts of the etoposide-induced cleavable complexes, and were also found to have lower decatenation activity than the wild-type. In the crystal structure, the yeast equivalent of His759 is found in the vicinity of the Arg713, a putative anchoring residue of the 3'-side of cleaved DNA strands. These results suggest that His759 and the other alpha4 helix residues are involved in the enzymatic activity and drug sensitivity of human DNA topoisomerase IIalpha, via interaction with cleaved DNA.

Amino Acid Sequence↗

PubMed2004

The immunohistochemical analysis of pendrin in the mouse inner ear.

Pendred's syndrome (PS) is an autosomal recessive disorder characterized by deafness and goiter, which are caused by mutations in the Pendred's syndrome gene (PDS). PDS encodes a membrane protein named pendrin that is considered to act as an anion transporter. An expression pattern of the PDS ortholog (Pds) mRNA in the auditory and vestibular systems has been reported in mice, and the localization of pendrin has been reported recently. We generated antipeptide antibodies against human pendrin, and performed immunohistochemical analysis of mouse inner ears. We detected pendrin in the endolymphatic duct and sac, and the utricle, saccule, and external sulcus. In the endolymphatic duct and sac, the expression of pendrin was apparent at the apical membrane. In addition, we detected pendrin in the spiral ligament, Claudius cells, Deiter's cells, and the spiral ganglion of the cochlea. Our results are key to defining the role of pendrin in inner ear development and elucidating the pathogenic mechanisms underlying deafness in PS.

Animals↗

PubMed2004

Is thyroid follicular cancer in Japanese caused by a specific t(2; 3)(q13; p25) translocation generating Pax8-PPAR gamma fusion mRNA?

A recent western study reports that t(2; 3)(q13; p25) translocation resulting in the expression of the Pax8-PPAR gamma fusion gene in patients with thyroid follicular carcinoma (FTC) occurs with high incidence (63%). Furthermore, the products of the fusion gene were shown to suppress the function of PPAR gamma in a predominantly negative manner, conferring them with an oncogenic potential. We examined the expression of this fusion gene in FTC in Japanese patients. From 1989 to 2000, six cases with FTC were surgically treated at our institute. In these carcinoma samples, the expression of mRNAs for the Pax8-PPAR gamma fusion product was analyzed by nested RT-PCR. Their expression was also studied in other thyroid nodules (12 adenomatous goiters, 12 follicular adenomas, 12 papillary carcinomas and 12 normal thyroid tissues) obtained at surgery during the same period. Pax8-PPAR gamma fusion mRNA was not detected in any FTC samples nor in the other samples. Furthermore, none of the 6 FTCs, one follicular adenoma or one normal thyroid analyzed by fluorescence in situ hybridization (FISH) exhibited Pax8-PPAR gamma gene fusion. These findings are in contrast to previous reports and indicate that ethnic background may affect the translocation.

Adenocarcinoma, Follicular↗

PubMed2004

Genomic organization of mouse ZAKI-4 gene that encodes ZAKI-4 alpha and beta isoforms, endogenous calcineurin inhibitors, and changes in the expression of these isoforms by thyroid hormone in adult mouse brain and heart.

OBJECTIVE: ZAKI-4 was identified as a thyroid hormone-responsive gene in cultured human fibroblasts. A single ZAKI-4 gene encodes two isoforms, ZAKI-4 alpha and beta, both inhibiting calcineurin activity. ZAKI-4 alpha and beta differ at their N termini, and show distinct distribution profiles in human tissues. The aim of this study was to elucidate the organization of the mouse ZAKI-4 gene and to determine the effect of thyroid hormone on the expression of ZAKI-4 isoforms in vivo. DESIGN: We cloned mouse homologues of human ZAKI-4 alpha and beta cDNA. Fluorescence in situ hybridization and bioinformatics analysis were employed to determine the gene organization. The effect of thyroid hormone on the expression of ZAKI-4 isoforms in mouse brain and heart was also studied. METHODS: Total RNA extracted from mouse cerebellum was used to clone ZAKI-4 alpha and beta cDNAs by RT-PCR followed by rapid amplification of cDNA ends. Mice were rendered hypothyroid by feeding a low iodine diet supplemented with propylthiouracil for 2 weeks. In one group (hyperthyroid) L-T(3) was injected i.p. for the last 4 days whereas another group (hypothyroid) received vehicle only. Non-treated mice were controls. RESULTS AND CONCLUSION: Mouse ZAKI-4 alpha and beta cDNAs were highly homologous to the human isoforms. The gene was mapped on chromosome 17qC, syntenic to human chromosome 6 where the human ZAKI-4 gene is located. As observed in human, ZAKI-4 alpha mRNA was expressed only in brain whereas beta mRNA was distributed in other tissues as well, such as heart and skeletal muscle. ZAKI-4 alpha mRNA was lower in the cerebral cortex of hypothyroid mice. Injection of L-T(3) caused an increase in ZAKI-4 beta mRNA in heart; however, expression of neither ZAKI-4 alpha nor beta mRNA was influenced by thyroid status in other tissues. These results indicate that expression of ZAKI-4 alpha and beta isoforms is regulated by thyroid hormone in vivo, and the regulation is isoform- and tissue-specific.

Amino Acid Sequence↗

PubMed2003

Intracaval endovascular ultrasonography for large adrenal and retroperitoneal tumors.

BACKGROUND: An accurate diagnosis of inferior vena cava (IVC) invasion is important in deciding the surgical strategy for a large adrenal tumor. We investigated the diagnostic value of intracaval endovascular ultrasonography (ICEUS) for invasion of the IVC by a large adrenal tumor. METHODS: Nine of 163 patients with adrenal and retroperitoneal tumors underwent ICEUS between 1993 and 2002. Intravascular ultrasonography was performed through the right femoral vein with the use of an 8Fr, 20-MHz transducer. The diagnostic criterion for detecting IVC invasion with ICEUS was identification of destruction of a single echogenic layer of the IVC wall or identification of an intracaval tumor mass. The ICEUS finding was confirmed by pathologic examination. RESULTS: The mean diameter of the tumors in 9 patients undergoing ICEUS and resection was 12.6 cm (range, 8.6-16 cm). Pathologic diagnosis varied: adrenocortical carcinoma, 4; malignant pheochromocytoma, 1; leiomyosarcoma, 1; metastatic lung cancer, 1; paraganglioma, 1; and neurilemmoma, 1. Vascular invasion was identified in 2 patients by ICEUS and confirmed by examination of resected specimens. The sensitivity, specificity, and positive predictive values of ICEUS for the diagnosis of the IVC invasion were 100%, 100%, and 100%, respectively. However, these values for computed tomography were 100%, 14%, and 25%, respectively; and for cavography, 100%, 57%, and 40%, respectively. CONCLUSIONS: ICEUS provides confirmatory information regarding tumor invasion of the IVC. This modality also can assist in formulating an operative strategy for large adrenal or retroperitoneal tumors.

Adrenal Gland Neoplasms↗

PubMed2003

Laparoscopic adrenalectomy for incidentaloma and bilateral adrenal disease.

Adrenalectomy is ideally suited to minimally invasive surgery based on the characteristics of adrenal tumours, which are usually small and benign. The aim of this study was to verify that laparoscopic adrenalectomy is minimally invasive and to assess the indication of laparoscopic adrenalectomy for incidentaloma. From October 1995 through August 2002, 133 patients underwent adrenal surgery at the Department of Surgery II, Nagoya University School of Medicine. Of these, 111 underwent laparoscopic adrenalectomy. All laparoscopic adrenalectomies were performed using the transabdominal lateral approach. In 50 of 133 patients, the adrenal tumours were incidentally discovered. There were 27 non-functioning adrenal tumours and six of seven preclinical Cushing's test syndrome cases incidentally discovered. Six of 27 non-functioning adrenal tumour patients underwent open adrenalectomy because of large tumour size or malignancy. Based on the present criteria for laparoscopic adrenalectomy, 15 of 133 patients were retrospectively considered to have required open adrenalectomy. The average size of a non-functioning adrenal tumour was 5.8 cm in diameter, which was equal to the average size of a phaeochromocytoma. A simultaneous bilateral laparoscopic adrenalectomy was performed in a patient in poor condition with advanced Cushing's syndrome due to adrenocorticotrophic hormone-independent macronodular adrenocortical hyperplasia (AIMAH). The adrenal glands were successfully removed without fragmentation in this patient, and the postoperative course was uneventful, thanks to the minimally invasive surgery. The laparoscopic technique assures less morbidity and faster recovery, and appears to be equally effective in eradicating functioning and non-functioning adrenal masses. The benefits of the laparoscopic approach to adrenalectomy should not result in a more aggressive attitude toward the excision of clinically silent, benign-appearing adrenal incidentalomas.

Adenoma↗

PubMed2003

Cys611Ser mutation in RET proto-oncogene in a kindred with medullary thyroid carcinoma and Hirschsprung's disease.

Germline mutations in the RET proto-oncogene are responsible for the development of human hereditary diseases, including multiple endocrine neoplasia (MEN) type 2A and 2B, familial medullary thyroid carcinoma (FMTC), and Hirschsprung's disease (HSCR). It has been reported that some families developed both MEN 2A/FMTC and HSCR, in which a mutation in a cysteine residue at codon 609, 618, or 620 in the RET gene was present. Here we report a novel RET mutation detected in a Japanese family with medullary thyroid carcinoma and HSCR. A germline mutation in cysteine 611 of the RET gene was identified in this family, which introduced an amino-acid change from cysteine to serine. By biological and biochemical analyses of mutant RET proteins, we previously predicted the potentiality that amino-acid substitution for cysteine 611 as well as cysteines 609, 618, and 620 would promote the development of MEN 2A/FMTC and HSCR. This clinical case substantiates our suggestion for the mechanism of the development of both the diseases.

Amino Acid Substitution↗

PubMed2003

HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm.

It is generally known that even with permanent sections, the differential diagnosis between follicular adenoma and follicular carcinoma is often difficult to determine. It is not unusual to encounter patients diagnosed with benign follicular adenoma whose diagnoses have to be changed to malignancies because of recurrence or metastasis. As the monoclonal antibody HBME-1 produced by mesothelioma cells has been shown to have reactivity in thyroid carcinomas, we investigated the diagnostic usefulness of HBME-1 in follicular neoplasms. Immunohistochemical staining for HBME-1 was performed on 205 various thyroid tumors using the labeled streptavadin biotin peroxidase method. When hematoxylin-eosin (HE) staining was performed again for this study and all cases were examined in accordance with the WHO Histological Classifications 2nd Edition, 87.2% (54/62) of adenomatous goiter and 72.6% (45/62) of follicular adenoma were negative. On the other hand, 84.6% (33/39) of follicular carcinoma and 97.2% (35/36) of papillary carcinoma were positive. All anaplastic (2/2) and medullary (4/4) carcinoma were negative. Examination in follicular neoplasms had a sensitivity of 84.6%, specificity of 72.6%, positive predictive value of 66.0% and overall accuracy of 77.2%. Among the cases treated as follicular adenoma clinically, the diagnosis of 13 cases was changed to follicular carcinoma, and 6 cases to papillary carcinoma for this study. These cases showed strong HBME-1 positivity. Two of the follicular carcinoma cases experienced recurrence. We conclude that immunohistochemical staining with HBME-1 may be useful clinically to pick out cases with a high risk of recurrence in follicular carcinoma, and that benign adenoma cases need close follow-up.

Adenocarcinoma, Follicular↗

PubMed2003

Mild persistent hypercalcitoninemia after total thyroidectomy in patients with papillary thyroid carcinoma.

Total thyroidectomy was performed in 455 patients with differentiated thyroid carcinoma between 1978 and 1999. Serum calcitonin (CT) was determined preoperatively in all patients using polyclonal antibodies. Among the subjects, 25 patients showed elevated serum calcitonin levels preoperatively. Pathological diagnoses of 18 patients were confirmed as medullary thyroid carcinoma (MTC) postoperatively. Eight patients were diagnosed as papillary thyroid carcinoma (PTC) in the final pathological diagnosis without evidence of minimal foci of MTC or C cell hyperplasia, and they showed elevated CT levels preoperatively. Hypercalcitoninemia in 8 patients with PTC continued through out the 24 follow-up months with normal CEA levels. Extrathyroidal CT-producing diseases were all neglected, and precise pathological examination showed negative evidence of minute MTC or C cell hyperplasia in these 8 patients. Serum CT levels were simultaneously determined by a different CT assay kit using the same blood samples in 7 of 8 patients. Serum CT levels were all within normal values in another CT kit applying a different polyclonal antibody, although elevated CT values continued in the routine CT kit. The recognition of polymeric or fragmented CT by polyclonal antibody was thought to be the causative factor for the hypercalcitoninemia after total thyroidectomy in the patients with PTC. Knowledge of the false positive CT determination makes it important to employ different CT assay kits, especially the new generation of two-site immunoassays using two monoclonal antibodies against distinct epitopes of human CT, although the new generation kits are not clinically available in Japan.

Adolescent↗

PubMed2003

Sodium bicarbonate infusion test: a new method for evaluating parathyroid function.

We have developed a new test for estimating the secretory capacity of parathyroid hormone (PTH) from the parathyroid gland. Sodium bicarbonate solution [8.4% (w/v); 35 ml/m(2) body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium, plasma PTH (intact, midregion, carboxy-terminus) and related parameters were serially obtained. In 8 healthy volunteers, the mean (+/-SE) plasma ionized calcium fell promptly and significantly (from 1.21 +/- 0.01 to 1.11 +/- 0.01 mmol/L) after the sodium bicarbonate infusion. The mean (+/-SE) plasma intact PTH increased promptly and significantly, by more than four fold (42.3 +/- 4.2 to 182.4 +/- 34.7 pg/ml), and then gradually returned to basal levels. In patients with partial hypoparathyroidism who have detectable basal plasma levels of PTH, the absolute increment in PTH levels was much less, and in the plasma obtained from patients with complete hypoparathyroidism, absolutely no response was observed. Plasma obtained from patients diagnosed with primary hyperparathyroidism (parathyroid adenoma or hyperplasia) has high basal PTH levels. The response to the sodium bicarbonate infusion in these patients was markedly blunted (less than a two-fold increase in all cases examined). No significant adverse effects were observed during the procedure. Therefore, the sodium bicarbonate infusion test is a simple and sensitive method to stimulate PTH release, and is clinically useful for evaluating parathyroid gland function.

Adult↗

PubMed2002

Reoperation for renal hyperparathyroidism.

Reoperation for secondary hyperparathyroidism (HPT) due to uremia (2HPT) may be required among patients with persistent renal failure if not all parathyroid glands are removed at the initial operation. Between March 1981 and July 2001, altogether 1,110 patients underwent total parathyroidectomy with forearm autograft for advanced 2HPT in our department. In this study, we evaluated the clinical features of patients who required reoperation and classified them into persistent HPT [the lowest intact parathyroid (PTH) level after initial operation remained higher than 60 pg/ml] and recurrent HPT (the lowest intact PTH level was normalized after surgery but reelevated became high enough to require reoperation). Removal of residual glands was indicated in 30 (2.7%) cases for persistent or recurrent HPT. All remaining glands were detected by preoperative imaging diagnoses. In 44 (4.0%) patients persistent HPT was recognized and in 15 of them (1.4% of all cases) reoperation was required. In 11 cases, the responsible glands were supernumerary ones removed from the mediastinum. In 4 cases, the glands were resected from the neck. In 15 cases (1.4%), reoperation was performed for recurrent HPT when residual glands were left either in the neck or in the thymic tongue. In all but one case, the missed glands were supernumerary. This study reveals that it is often difficult to avoid persistent HPT induced by mediastinal supernumerary glands and recurrent HPT caused by small glands left in the neck. Our findings indicate that patients with uremia should be closely followed considering the possibility that persistent or recurrent HPT may occur after parathyroidectomy.

Adult↗

PubMed2002

Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells.

VEGF (vascular endothelial growth factor) secreted from tumor cells including breast cancer serves as a potent angiogenic factor which favors tumor growth and metastasis. Indeed, a higher concentration of serum VEGF has been shown to associate with a poorer prognosis in patients with breast cancer. On the other hand, constitutive expression of a transcription factor, NF-kappaB was correlated with progression and metastasis in a number of human breast cancers, suggesting a possible regulation of VEGF expression by NF-kappaB. We thus investigated the relationship between the expression of VEGF and constitutive NF-kappaB activity in three breast cancer cell lines, MCF-7, T47D, and MDA-MB-231. The basal levels of VEGF mRNA expression correlated with those of nuclear NF-kappaB activity in these cell lines. The highest NF-KB activity in MDA-MB-231 cells was associated with the highest expression of VEGF mRNA, while the activity and the mRNA levels were moderate in MCF cells and the lowest in T47D cells. In MDA-MB-231 cells, inhibition of NF-KB by adenovirus-mediated expression of a dominant negative NF-kappaB or by a proteasome inhibitor, MG132, decreased the VEGF mRNA. These results suggest that NF-kappaB is involved in the upregulation of VEGF mRNA and inhibition of the activity could be a new approach for the treatment of breast cancer by preventing angiogenesis.

Breast Neoplasms↗

PubMed2001

Cases with fewer than four parathyroid glands in patients with renal hyperparathyroidism at initial parathyroidectomy.

In the surgical treatment of secondary hyperparathyroidism (2HPT) due to uremia, it is considered necessary to remove all parathyroid glands from the neck to prevent persistent and recurrent parathyroid hyperfunction. However, in some cases fewer than four parathyroid glands can be recognized at initial operation; in the present study, we evaluated the long-term prognosis and estimated surgical strategy in such cases. Between March 1981 and January 1999, 822 patients underwent total parathyroidectomy (PTx) with forearm autograft for advanced 2HPT at the Department of Transplant Surgery of Nagoya Second Red Cross Hospital. In 21 cases (2.6%) fewer than four parathyroid glands were macroscopically found at the initial operation. These cases were followed up and their parathyroid function was evaluated by measurement of intact parathyroid hormone (PTH). In 20 of the 21 cases three glands were found, in 1 patient only two glands. In 5 of these cases the fourth gland was identified first after postoperative histopathologic evaluation. In all these cases the intact PTH level was normalized. In 8 of the remaining 16 cases high PTH levels persisted after the initial operation, including 3 patients who underwent neck reexploration. However, in the other 7 patients PTH levels dropped within normal range immediately after PTx and a fourth gland has never been recognized. One patient was lost to follow-up. Thus, using our operative strategy, 12 of 822 cases (0.85%) did not develop persistent or recurrent HPT even though only three glands were identified at the operation. To avoid postoperative hypoparathyroidism, autotransplantation should be performed when fewer than four parathyroid glands are found at the initial operation.

Adult↗

PubMedDate not supplied

Paclitaxel administered weekly in patients with docetaxel-resistant metastatic breast cancer: a single-center study.

AIMS AND BACKGROUND: We evaluated retrospectively the efficacy and toxicity of paclitaxel in patients with docetaxel-resistant metastatic breast cancer. STUDY DESIGN: Paclitaxel (80 mg/m2) was administered weekly to 44 patients who had previously received chemotherapy regimens for metastatic breast cancer. All patients had progressive disease in spite of having received docetaxel therapy. RESULTS: Treatment was repeated until there was evidence of disease progression. Objective responses were obtained in 14 of 44 assessable patients (31.8%; 95% confidence interval, 17.5-46.1). Fourteen patients had partial responses; none responded completely. Seven of 14 responders had primary resistance to docetaxel therapy. The median duration of response was 6.1 months (range, 2.1-12.7). The median time to progression was 5.0 months. Clinically severe adverse events (grade 3 or 4) included neutropenia (27.2%), leukopenia (25.0%), neuropathy-sensory (13.6%), febrile neutropenia (6.8%), anemia (2.2%), constipation (2.2%), and edema (2.2%). Treatment was generally well tolerated and could be continued on an out-patient basis. CONCLUSIONS: Weekly paclitaxel is effective in patients with docetaxel-resistant metastatic breast cancer. This observation suggests partial cross-resistance between paclitaxel and docetaxel. There was no evidence for additive cumulative toxic effects of the two taxanes.

Adult↗

PubMedDate not supplied

Efficacy and safety of trastuzumab as a single agent in heavily pretreated patients with HER-2/neu-overexpressing metastatic breast cancer.

AIMS AND BACKGROUND: The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer. STUDY DESIGN: Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly. RESULTS: Patients received a median of 16.7 weekly infusions (range, 1-66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7-40.4). The median duration of response was 6.4 months (range, 2.5-14.0). The median time to progression was 3.1 months (range, 0.2-16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2). CONCLUSIONS: Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.

Adult↗

PubMedDate not supplied

Multi-slice CT of thyroid nodules: comparison with ultrasonography.

PURPOSE: To evaluate the usefulness of multi-slice computed tomography (MSCT) in comparison with ultrasonography (US) for the differentiation of benign from malignant thyroid nodules and the evaluation of tumor extension. MATERIALS AND METHODS: Thirty patients with thyroid nodules (14 malignant, 16 benign) who underwent both MSCT and US participated in the present study. MSCT with contrast enhancement was performed, and 3D shaded volume rendering (SVR) and multiplanar reconstruction (MPR) were employed to differentiate benign from malignant nodules and to evaluate tumor extension. US images were obtained using a 7.5 MHz annular array probe. A three-point rating scale was used for image interpretation, and the kappa statistic was employed to evaluate agreement between MSCT and US. RESULTS: Sensitivity in differentiating benign from malignant nodules was found to be 85.7% for US and 78.6% for MSCT. Disagreement between MSCT and US occurred in assessing the homogeneity of the solid component and the presence of fibrous capsule. In two of seven T4 cases, MPR provided a more accurate diagnosis than US examination in detecting extracapsular invasion. CONCLUSION: For differential diagnosis of thyroid nodules, US was found to be better than MSCT. However, MSCT could be useful for the evaluation of advanced cases with suspicion of extracapsular extension.

Diagnosis, Differential↗