Internalization of a novel, huge lectin from Ibacus novemdentatus (slipper lobster) induces apoptosis of mammalian cancer cells.

An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N-acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N-acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl-D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and -3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects.

Randomized study of orally administered fluorinated pyrimidines (capecitabine versus S-1) in women with metastatic or recurrent breast cancer: Japan Breast Cancer Research Network 05 Trial.

PURPOSE: Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer (MBC). This randomized, multicenter, phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. METHODS: Patients with MBC were randomly assigned to receive capecitabine 825 g/m(2) twice daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body surface area, on days 1-28 every 6 weeks. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 142 patients were enrolled and randomized to either capecitabine (N = 73) or S-1 (N = 69). Median PFS (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1, with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI] 0.52-1.38) (P = 0.48 by log-rank). The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 (P = 0.938). The most common treatment-related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %, capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P = 0.029). CONCLUSIONS: The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC, while their adverse events were different. They are both convenient, orally administered drugs, making them attractive agents for use in outpatient treatment.

Induction of antisporozoite antibodies by biting of transgenic Anopheles stephensi delivering malarial antigen via blood feeding.

We produced a transgenic mosquito expressing a rodent malaria vaccine candidate antigen in the salivary gland. Three tandemly repeated amino acid units from the repeat region of circumsporozoite protein of Plasmodium berghei (PbCS3R) fused to red fluorescent protein (monomeric DsRed) was chosen as a vaccine candidate antigen. Immunoblot and fluorescence microscopic analyses showed the transgene expression in the female salivary gland. The transgene product was released from the proboscis as a component of saliva. The monomeric DsRed-fusion expression system could be suitable for transgene secretion in the saliva of female mosquitoes. Mice repeatedly bitten by transgenic mosquitoes raised antibodies against P. berghei sporozoites, and the sera had protective ability against sporozoite invasion of human hepatoma HepG2 cells. These results suggest that transgene products are immunogenically active in saliva, and induce the antibodies to malaria parasite. These findings indicate that this technology has the potential for production of a 'flying vaccinator' for rodent malaria parasites.

Immune responses to porphyromonas gingivalis infection suppress systemic inflammatory response in experimental murine model.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), and the severity correlates to significance of immune responses. Recently, it has been reported that periodontitis is associated with the development of systemic disease such as diabetes and atherosclerosis because of increasing invasion of oral pathogens to the circulation. However, the association between local and systemic infectious responses is still unclear. In the present study, we examined the differences of biological responses in animals with or without bacterial infection. After Balb/c mice were infected subcutaneously with live P. gingivalis W83, serum, skin and liver were collected according to experimental protocol. The skin and liver tissues were observed pathologically by haematoxylin-eosin staining, and serum IL-6 levels were measured using ELISA method. Throughout the experimental period, conditions of the mice were observed continuously. As expected, severe infiltration of leukocytes were observed at inflamed skin corresponding to the number of bacterial challenges. Although no inflammatory appearance of skin was observed, serum IL-6 levels were increased dramatically (P <0.01, Student's t-test) and liver tissues were injured in the mice without bacterial challenge. Interestingly, although severe inflammatory appearance of the skin was observed, serum IL-6 levels were not increased and no inflammatory responses were observed in the liver of the 3-times bacterially challenged group. Importantly, immunoglobulin G against P. gingivalis W83 was detected in the blood of mice with 3-times bacterial challenge corresponding to improvement of weight loss and survival. In conclusion, although multiple infections develop severe localized inflammation, the immune system should be sufficient to protect the systemic inflammatory responses.

Phase II trial of preoperative chemotherapy for breast cancer: Japan Breast Cancer Research Network (JBCRN)-02 trial.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. PATIENTS AND METHODS: Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 500 mg/m(2)) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). RESULTS: The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER(-), HER2(+)/ER(+), HER2(-)/ER(-), and HER2(-)/ER(+) patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (<15%) was higher than that of patients with higher Ki-67 values (≥15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. CONCLUSION: DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.

Gastric tumor from metastasis of breast cancer.

Metastatic tumours of the stomach have been reported to result from various types of cancer. Among them, gastric metastasis from breast cancer has been recognised in 0.3-18% patients (1-4). Here, a rare case of metastatic gastric tumour derived from breast carcinoma is reported. Gastric endoscopy confirmed a large, friable mass (approximately 5 cm in diameter) in the upper part of the gastric body. The mass within the stomach was difficult to distinguish from primary gastric cancer, although biopsies of this lesion revealed the characteristics of adenocarcinoma. In addition, immunohistochemistry showed the positive expression of mammaglobin. Taken together, the evidence pointed to metastasis of breast cancer to the stomach. The patient was treated with hormonal therapy (letrozole), and the size of the metastasis in the stomach was markedly reduced. Therefore, a gastric metastasis from breast cancer was diagnosed successfully using immunohistochemistry and unnecessary surgery was avoided. In conclusion, although gastric metastatic tumours derived from breast carcinoma are rare, their accurate pre-operative diagnosis and appropriate systemic treatment is essential.

Efficacy of S-1 in patients with capecitabine-resistant breast cancer-Japan Breast Cancer Research Network (JBCRN) 04-1 trial.

BACKGROUND: S-1 is an orally administered fluorinated pyrimidine with high activity in metastatic breast carcinoma (MBC) and in chemotherapy-pretreated metastatic breast carcinoma. PATIENTS AND METHODS: Forty patients with MBC who did not respond to capecitabine-based chemo-therapy and then received S-1 were identified from our data base of records between 2006 and 2008. The clinico-pathological data and outcomes of these patients were then reviewed. RESULTS: The overall response rate was 27.8%. The median survival was 19.2 months, and the median time to disease progression was 6.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (15%), nausea (15%), vomiting (7.5%), disorder of taste (7.5%), and diarrhea (5%). However, the majority were mild to moderate in intensity, and only one patient experienced grade 3 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. CONCLUSION: The results of the current study demonstrate that S-1 is an effective and well-tolerated treatment in patients with capecitabine-resistant MBC. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment.

[Pancoast tumors ; modified surgical approaches and techniques].

The surgical treatment of Pancoast tumors is associated with difficulties related to its anatomical locations. Different surgical approaches have been reported but every approaches have some advantages and disadvantages. We report 2 Pancoast tumors cases with unique surgical approaches and our techniques. Case 1 : A 38-year-old man complained of face edema. The chest computed tomography (CT) revealed an right anterior apical tumor with direct invasion of the 1st and 2nd rib. Preoperative chemotherapy with 2 courses of carboplatin [area under the blood concentration-time curve (AUC) 6, day 1] and paclitaxel (80 mg/m2, day1, 8, 15) and concurrent extracorporeal radiation (70 Gy) was used to treat the adenocarcinoma. The skin incision was performed according to Masaoka's anterior approach, and a proximal median sternotomy communicated with an incision in the 4th intercostal space. The clavicula was freed by the L-shaped incision on the manubrium and the 1st cartilage section according to Grunenwald method to retract the section. Case 2 : A 65-year-old man complained back pain. The chest CT revealed an right superior sulcus tumor, displaced bronchus (B1+B3 tracheal bronchus, B2) and pulmonary arteries anomalies. Combined Shaw-Paulson incision and 4 intercostal lateral thoracotomy was performed to right upper lobectomy and systematic lymph nodes dissection.

Prostaglandin F 2 alpha stimulates endothelial nitric oxide synthase depending on the existence of bovine granulosa cells: analysis by co-culture system of endothelial cells, smooth muscle cells and granulosa cells.

Prostaglandin F(2 alpha) (PGF(2 alpha)) induces luteolysis in the mid but not in the early luteal phase; despite this, both the early and the mid corpus luteum (CL) have PGF(2 alpha) receptor (FPr). We previously indicated that the luteal blood flow surrounding the CL drastically increases prior to a decrease of progesterone (P) in the cows, suggesting that an acute increase of luteal blood flow may be an early sign of luteolysis in response to PGF(2 alpha) and that this may be induced by a vasorelaxant nitric oxide (NO). The aim of this study was to investigate the luteal stage-dependent and the site-restricted effect of PGF(2 alpha) and NO on the mRNA expressions and P secretion. To mimic the local luteal region both of peripheral and central areas of the CL, we utilized co-cultures using bovine aorta endothelial cells (EC), smooth muscle cells (SMC) and luteinizing granulosa cells (GC) or fully-luteinized GC. PGF(2 alpha) stimulated the expression of endothelial NO synthase (eNOS) mRNA at 0.5 h in mix-cultures of EC and SMC with fully-luteinized GC but not with luteinizing GC. The expression of eNOS mRNA in EC was increased by PGF(2 alpha) at 1 h only when EC was cultured together with fully-luteinized GC but not with luteinizing GC. In all co-cultures, PGF(2 alpha) did not affect the mRNA expression of FPr. Treatment of NO donor inhibited P secretion at 0.5 h. In conclusion, the present study suggests that the coexistence of the mature luteal cells (fully-luteinized GC) with EC/SMC may be crucial for acquiring functional NO synthesis induced by PGF(2 alpha).

Beta(2)-Adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP.

AIMS/HYPOTHESIS: In skeletal muscle, the storage of glycogen by insulin is regulated by glycogen synthase, which is regulated by glycogen synthase kinase 3 (GSK3). Here we examined whether adrenergic receptor activation, which can increase glucose uptake, regulates glycogen synthesis in L6 skeletal muscle cells. METHODS: We used L6 cells and measured glycogen synthesis (as incorporation of D: -[U-(14)C]glucose into glycogen) and GSK3 phosphorylation following adrenergic activation. RESULTS: Insulin (negative logarithm of median effective concentration [pEC(50)] 8.2 +/- 0.3) and the beta-adrenergic agonist isoprenaline (pEC(50) 7.5 +/- 0.3) induced a twofold increase in glycogen synthesis in a concentration-dependent manner. The alpha(1)-adrenergic agonist cirazoline and alpha(2)-adrenergic agonist clonidine had no effect. Both insulin and isoprenaline phosphorylated GSK3. The beta-adrenergic effect on glycogen synthesis is mediated by beta(2)-adrenoceptors and not beta(1)-/beta(3)-adrenoceptors, and was not mimicked by 8-bromo-cyclic AMP or cholera toxin, and also was insensitive to pertussis toxin, indicating no involvement of cyclic AMP or inhibitory G-protein (G(i)) signalling in the beta(2)-adrenergic effect on glycogen synthesis. 12-O-tetra-decanoylphorbol-13-acetate (TPA) increased glycogen synthesis 2.5-fold and phosphorylated GSK3 fourfold. Inhibition of protein kinase C (PKC) isoforms with 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrollo(3,4-c)-carbazole (Gö6976; inhibits conventional and novel PKCs) or 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Gö6983; inhibits conventional, novel and atypical PKCs) inhibited the stimulatory TPA effect, but did not significantly inhibit glycogen synthesis mediated by insulin or isoprenaline. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin inhibited the effects of insulin and isoprenaline on glycogen synthesis. CONCLUSIONS/INTERPRETATION: These results demonstrate that in L6 skeletal muscle cells adrenergic stimulation through beta(2)-adrenoceptors, but not involving cyclic AMP or G(i), activates a PI3K pathway that stimulates glycogen synthesis through GSK3.

Enucleated L929 mouse fibroblasts support invasion and multiplication of Shigella flexneri 5a

Invasive bacteria can induce their own uptake and specify their intracellular localization; hence it is commonly assumed that proximate modulation of host cell transcription is not required for infection. However, bacteria can also modulate, directly or indirectly, the transcription of many host cell genes, whose role in the infection may be difficult to determine by global gene expression. Is the host cell nucleus proximately required for intracellular infection and, if so, for which pathogens and at what stages of infection? Enucleated cells were previously infected with Toxoplasma gondii, Chlamydia psittaci, C. trachomatis, or Rickettsia prowazekii. We enucleated L929 mouse fibroblasts by centrifugation in the presence of cytochalasin B, and compared the infection with Shigella flexneri M90T 5a of nucleated and enucleated cells. Percent infection and bacterial loads were estimated with a gentamicin suppression assay in cultures fixed and stained at different times after infection. Enucleation reduced by about half the percent of infected cells, a finding that may reflect the reduced endocytic ability of L929 cytoplasts. However, average numbers of bacteria and frequency distributions of bacterial numbers per cell at different times were similar in enucleated and nucleated cells. Bacteria with actin-rich tails were detected in both cytoplasts and nucleated cells. Lastly, cytoplasts were similarly infected 2 and 24 h after enucleation, suggesting that short-lived mRNAs were not involved in the infection. Productive S. flexneri infection could thus take place in cells unable to modulate gene transcription, RNA processing, or nucleus-dependent signaling cascades.

Effect of fructose-rich high-fat diet on glucose sensitivity and atherosclerosis in nonhuman primate.

The present study examined a new model of impaired glucose tolerance (IGT) in a nonhuman primate fed with a high-fructose and high-fat (HFF) diet that contained 15% lard, 31% fructose, and 1% cholesterol. Female cynomolgus monkeys (age, 3-4 years) were divided into two groups: 1) those fed with normal control diet (N = 5) and 2) those fed with HFF diet (N = 5). In the HFF diet group, total cholesterol and low-density lipoprotein cholesterol in blood were significantly increased four- to fivefold when compared with the normal control diet group. No difference in the blood glucose, insulin, hemoglobin A1c, and triglyceride levels was detected between the two groups. Plasma levels of adiponectin, but not of resistin, were significantly higher in HFF diet at 20 weeks after HFF diet feeding. Oral glucose tolerance test was performed before HFF diet feeding and at 12 and 24 weeks after HFF diet feeding, but no significant changes in glucose sensitivity were observed even 24 weeks after HFF diet feeding. Twenty-four weeks after HFF diet feeding, accumulated foam cells and infiltrated macrophages were histologically detected in the thoracic aorta, in addition to a fatty liver. Interestingly, the pancreatic beta cells appeared normal in the HFF diet group. These results show that a chronic HFF diet does not induce IGT but can cause atherosclerotic lesions in conjunction with the generation of a fatty liver phenotype in cynomolgus monkey; however, the present results are very preliminary and they need to be validated in larger-scale studies in the future.

Structure and property of self-assemble valinyl bolaform amides having different chirality.

Bolaform amides were designed from N,N'-bis(carboethoxy-L-valinyl)-diaminoethane (1) by linking t-butyloxycarbonyl-valine through ethylenediamine (EDA) to enable spectroscopic and X-ray diffraction analyses. N,N'-Bis(Boc-L-valinyl)-diaminoethane (2) and N,N'-bis(Boc-D-valinyl)-diaminoethane (3) were composed of L-Val and D-Val, respectively. N-(Boc-L-valinyl)-N'-(Boc-D-valinyl)-diaminoethane (4) was composed of both L-Val and D-Val, and was achiral (meso-peptide). Peptide 5 was a 1:1 mixture of 2 and 3, and was also achiral (racemate). These peptides mediated gelation of corn oil at a concentration of approximately 1%. Within crystals, the peptides formed beta-sheet ribbons, but differences were observed in hydrogen-bonding patterns and side-chain arrangements. These differences were also deduced from temperature dependence of amide protons. Force-field calculations based on the crystal structures indicated that association of beta-sheet ribbons had energy benefits, and it was assumed that molecular aggregation progressed spontaneously. These structural studies indicated the chirality of amino acids affected for the properties of bolaform amides.

HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death.

The Drosophila spinster (spin) gene product is required for programmed cell death in the nervous and reproductive systems. We have identified a human homologue of the Drosophila spin gene product (HSpin1). HSpin1 bound to Bcl-2 and apoptosis regulator Bcl-X (Bcl-xL), but not to proapoptotic members such as Bcl-2-associated X protein and Bcl-2 homologous antagonist killer, in cells treated with TNF-alpha. Exogenous expression of HSpin1 resulted in the cell death without inducing a release of cytochrome c from mitochondria. Overexpression of Bcl-xL inhibited the HSpin1-induced cell death. Interestingly, a necrosis inhibitor, pyrrolidine dithiocarbomate, but not the pancaspase inhibitors, carbobenzoxy-VAD-fluoromethyl ketone and p35, blocked the HSpin1-induced cell death. HSpin1-induced cell death increases autophagic vacuole and mature form of cathepsin D, suggesting a novel caspase-independent cell death, which is link to autophagy.

Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human colon cancer cell lines in vitro.

Recently, we reported that cycloprodigiosin hydrochloride (cPrG.HCl), a novel H+/Cl- symporter, induces acidification of the cytosol and leads to apoptosis on rat and human liver cancer cells. In the present study, the effects of cPrG.HCl, a H+/Cl- symporter, were examined in colon cancer cell lines in vitro. In the MTT assay, cPrG.HCl inhibited the growth of two colon cancer cell lines (WiDr and SW480) in a dose- and time-dependent manner. The cPrG.HCl treatment of both types of cells induced apoptosis as confirmed by the appearance of a sub-G1 population and intranucleosomal DNA fragmentation. In addition, cPrG.HCl lowered pHi (below pH 6.8) respectively. Therefore, these results suggest that cPrG.HCl may be useful for the treatment of colon cancer cells.

Statistical analysis of diagnostic failure of fine needle aspiration cytology (FNAC) in breast cancer.

Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among those, 57 cases failed in accurate diagnosis of malignancy and 243 were successful. Fourteen clinicopathological factors altogether were analyzed to elucidate any correlation with FNAC failure using uni- and multivariate analysis. The univariate analysis in each clinicopathlogical factor showed that these error cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers, small-sized of tumors, scattered type of cancer cell distribution in tumor tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with benign-like ultrasound findings and with low TNM stage. The multivariate analysis revealed tumor grade was the strongest factor for all, followed by cellular distribution type of cancer cells and benign-like ultrasound findings. From these results, we speculated that diagnostic failure of FNAC at first clinic visit seemed to be caused by mainly two histocytological factors: extrinsic factor (structural factors of tissue-like tumor cells' distribution pattern, etc.); and intrinsic one (cellular factors of low atypism such as benign-like ultrasound finding, low tumor grade, and so on).

FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells.

FTY720, a metabolite from Isaria sinclairii, has been developed to be a potent immunosuppressive drug with induction of apoptosis in T cells and several cell lines. We investigated whether FTY720 induces apoptosis in human glioma cell lines, since they are relatively resistant to multiple apoptotic stimuli. In human glioma cells including T98G, FTY720 induced apoptosiswith ED50 between 1 to 10 microg/ml, while etoposidedid not induce apoptosis at the same doses. Among the caspase family proteases, mainly caspase-6 was activated during the apoptosis by FTY720 but not etoposide. In addition, FTY720 caused tyrosine dephosphorylation of FAK and did not activate a FAK-PI3-kinase survival pathway. This was confirmed also by the observation that orthovanadate prevented FTY720-induced dephosphorylation of FAK and inhibited FTY720-induced cell death. We assumed that FTY720 induced FAK dephosphorylation and cut off the FAK-PI3-kinase pathway resulting in the induction of apoptosis via caspase-6 activation in these glioma cells.

New diagnostic approach to intracystic lesions of the breast by fiberoptic ductoscopy.

Intracystic tumors of the breast are uncommon and, at the time of ultrasonography and aspiration cytology, it is difficult to distinguish cancer from a benign tumor. The Fiberoptic Ductoscopy System (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast. FDS was inserted through the cannulae into the cavity and we observed the intracystic tumors (3 intracystic papillomas and 2 intracytsic papillary carcinomas). The appearance of the malignant tumors was irregular, rough-shaped and they tended to bleed. On the contrary, benign tumors had smooth surfaces without bleeding. Cytological findings showed malignant cells in one out of two breast cancer patients. In addition, in the immunohistochemical study of resected tumor tissues from 5 patients, we observed positive reactions with anti-ErbB-2 antibody in 2 intracystic papillary carcinomas. In contrast, none of the histologically confirmed benign lesions (3 intracystic papillomas) gave positive results. In conclusion, the use of FDS as a non-invasive technique may provide valuable information.