Biomedical subjects

Koichi Yamazaki

Publications and source records attributed to Koichi Yamazaki.

At least 19 recordsLinked to original sources

PubMed2007

Virtual bronchoscopic navigation system shortens the examination time--feasibility study of virtual bronchoscopic navigation system.

Computed tomography (CT)-guided transbronchial biopsy (TBB) using an ultrathin bronchoscope with simulation by virtual bronchoscopy (VB) is effective for diagnosing small peripheral pulmonary lesions. However, we occasionally lose the proper bronchi to the lesion when a bronchoscope is inserted into peripheral bronchi with severe rotation. To overcome this problem, the virtual bronchoscopic navigation system that can display real-time VB images during TBB procedures in comparison with actual bronchi has been developed. We evaluated the usefulness of the virtual bronchoscopic navigation system for CT-guided TBB using an ultrathin bronchoscope (navigation method) to diagnose small peripheral pulmonary lesions, and compared the results to those with previous method that uses VB images in a simulation (simulation method). We performed CT-guided TBB using an ultrathin bronchoscope for 69 patients with 71 small peripheral pulmonary lesions (mean diameter, 13.7 mm) between November 2002 and November 2005 with the navigation method. CT-guided TBB with the navigation method was performed safely without any serious complications for all patients. Mean time to the initial scan, time to the first biopsy and total examination time were 5.3, 8.5 and 24.5 min, respectively. Fifty lesions (70%) were diagnosed by this procedure. Compared to simulation method, diagnostic sensitivity was higher in the navigation method, but the difference was not significant. However, the time to the first biopsy and total examination time were significantly shorter in the navigation method than in the simulation method (p<0.05). In summary, the virtual bronchoscopic navigation system was safely used, effective for diagnosing small peripheral pulmonary lesions, and useful for shortening the examination time of CT-guided TBB using an ultrathin bronchoscope.

Aged↗

PubMed2006

Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L.

Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancers (NSCLCs). However, certain rare EGFR mutations including S768I are reported to confer less in vitro sensitivity to gefitinib, an EGFR-TKI, than major mutations such as exon 19 deletions and L858R and even the wild-type counterpart. Here, we report the first case of adenocarcinoma of the lung in which the patient had rare mutations S768I and V769L and was treated with gefitinib. Disease progressed during 6 weeks of treatment. This case suggests that in vitro sensitivity to gefitinib correlates with distinct clinical responsiveness to gefitinib in various types of EGFR mutations.

Adenocarcinoma↗

PubMed2006

Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses.

OBJECTIVES: Bronchoscopic microsampling (BMS) is a new technique for repeated sampling of bronchial epithelial lining fluid (ELF) to obtain the pharmacokinetic profile of drugs. We analyzed the time versus concentration profiles of telithromycin in bronchial ELF obtained by BMS and compared these finding to those in plasma and alveolar ELF obtained by bronchoalveolar lavage (BAL). METHODS: Bronchial ELF samples were obtained from five healthy subjects using BMS probe at 0, 2, 3, 4, 6, 10 and 24h after single or multiple oral doses of 600 mg of telithromycin. Alveolar ELF was also obtained by BAL 3h after single or multiple oral doses of 600 mg of telithromycin. RESULTS: The areas under the concentration-time curve from 0 to 24h (AUC0-24) of telithromycin in plasma and bronchial ELF were 2.86+/-0.60 and 19.5+/-10.4 mg h/l after single treatment and 3.60+/-0.49 and 42.2+/-22.7 mg h/l after multiple treatments, respectively. Single and multiple oral doses of telithromycin produced significantly (p<0.05) higher AUC0-24 in bronchial ELF compared to those in plasma. While concentrations in bronchial ELF obtained by BMS were significantly lower than those in alveolar ELF obtained by BAL, they tended to be higher than those in plasma after multiple administration. The telithromycin concentrations obtained by BMS method were very consistent in bronchial ELF at different bronchi at one time point and at the same bronchus at different time points. CONCLUSIONS: Using the BMS technique, we could describe the pharmacokinetics of telithromycin in bronchial ELF. Furthermore, BMS was reasonably validated and reconfirmed to be a feasible and reliable method for measuring antimicrobial concentrations in bronchial ELF.

Administration, Oral↗

PubMed2006

Tetramer-blocking assay for defining antigen-specific cytotoxic T lymphocytes using peptide-MHC tetramer.

Peptide-MHC tetramers have been engineered to allow accurate detection of antigen-specific cytotoxic C lymphocytes (CTL) by flow cytometry. Here, we propose a novel use for peptide-MHC tetramers in the specific and sensitive analysis of the cytotoxic function of antigen-specific CTL by blocking MHC-restricted antigen-specific cytotoxicity. We found that pretreatment of ovalbumin (OVA)-specific CD8(+) CTL (OT-1 CTL), derived from OT-1 T-cell receptor (TCR)-transgenic mice, with OVA(257-264) peptide-H-2K(b) tetramer caused a marked inhibition of the cytotoxicity against OVA-expressing EG-7 tumor cells. OVA(257-264) peptide-H-2K(b) tetramer did not block the cytotoxicity mediated by 2C mouse (H-2(b))-derived CD8(+) CTL, which recognize allo (H-2L(d)) antigens. Moreover, OT-I CTL activity was not inhibited by an irrelevant HBV(208-216) peptide-H-2K(b) tetramer. These results indicate that the blocking of CTL activity with peptide-MHC tetramer was caused by interference with the interaction between the TCR and H-2K(b)-OVA(257-264) peptide complex, but not with the CD8-MHC class I interaction. The blocking activity of OVA(257-264) peptide-H-2K(b) tetramer was reversible because OT-I CTL pretreated with the tetramer recovered their cytotoxicity after culturing with interleukin-2 for 24 h. The same results were also demonstrated in freshly isolated, in vivo-primed OT-1 CTL sorted by the tetramer. These results demonstrate that peptide-MHC tetramer is a useful tool for defining MHC-restricted antigen-specific CTL function. Moreover, our finding implies that the measurement of CTL activity immediately after tetramer-guided sorting is not a suitable method for evaluating the function of in vivo-induced tetramer-positive CTL. We believe that the tetramer-blocking assay presented here will be useful for functionally monitor the induction of MHC-restricted antigen-specific CTL during vaccination therapy against tumor and infectious diseases.

Animals↗

PubMed2006

Epithelioid sarcoma presenting as pulmonary cysts with cancer antigen 125 expression.

A 39-year-old Japanese woman presented with a swollen right hand and a right-sided pneumothorax. Chest CT revealed bilateral multiple pulmonary thin-walled cysts measuring<or=1 cm in diameter and small nodules. An initial skin biopsy led to a misdiagnosis of metastatic adenocarcinoma, as tumour cells were positive for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and cancer antigen 125. However, chemotherapy proved ineffective, and the skin biopsy was repeated. A final diagnosis of epithelioid sarcoma (ES) was made. Open lung biopsy showed that the pulmonary nodules represented metastases of ES. Although the pulmonary cyst walls did not contain tumour cells, bronchiolar wall adjacent to the cysts had been infiltrated by tumour cells. These findings suggested that pulmonary cysts, a rare form of pulmonary metastases from soft tissue sarcomas, had developed through a ball-valve effect of metastatic tumour in small airways. However, presence of cancer antigen 125 hindered obtaining a correct diagnosis of ES.

Adenocarcinoma↗

PubMed2006

A virtual bronchoscopic navigation system for pulmonary peripheral lesions.

STUDY OBJECTIVES: We performed ultrathin bronchoscopy for pulmonary peripheral lesions using a system that displays virtual bronchoscopy (VB) images to the lesion simultaneously with actual images and navigates the bronchoscope to the target bronchus. We then evaluated the system with regard to its usefulness and problems. DESIGN: A pilot study. SETTING: A tertiary teaching hospital. PATIENTS: The subjects were consecutive patients with small pulmonary peripheral lesions (< or = 30 mm). INTERVENTIONS: Using this system, the rotation, advancement, and retreat of VB images were possible, and the bronchus into which the bronchoscope was to be advanced was displayed. VB images were displayed along with actual images, and the ultrathin bronchoscope was advanced to the target bronchus under direct vision. Under CT and radiographic fluoroscopy, a pair of forceps was inserted into the lesion via the bronchoscope. Thin-section CT images were obtained; after confirming the advancement of the bronchoscope into the target bronchus and the arrival of the forceps at the lesion, a biopsy was performed. RESULTS: Study subjects included 37 patients with 38 lesions. VB images to a median of the sixth- (third- to ninth-) order bronchi could be produced. Using this system, the ultrathin bronchoscope could be advanced into the planned route for 36 of the 38 lesions (94.7%). The system was used for a median of 2.6 min, and the median examination time was 24.9 min. The biopsy forceps could be advanced to the lesion in 33 of the 38 lesions (86.8%), and diagnosis was possible for 31 lesions (81.6%). CONCLUSIONS: This navigation system is useful for ultrathin bronchoscopy for pulmonary peripheral lesions.

Adult↗

PubMed2006

Elevated pleural fluid RCAS1 is a diagnostic marker and outcome predictor in lung cancer patients.

RCAS1, a type II membrane protein also secreted in soluble form, may be important in tumor cell evasion of immune surveillance and contribute to the aggressiveness of human tumors. We examined the implications of elevated pleural fluid RCAS1 at the onset of effusion in lung cancer patients. Of 102 patients presenting with pleural effusion, 59 proved to have a malignant effusion and 43, nonmalignant. Malignant effusions exhibited higher RCAS1 concentrations than nonmalignant effusions (mean +/- SD; 36.3 +/- 114 vs. 2.7 +/- 1.8 U/ml; p=0.014). Lung cancer patients with pleural fluid RCAS1 concentrations below 15 U/ml had a longer mean survival than those with higher concentrations (4.7 vs. 1.7 months; p<0.05). By multivariate analysis, pleural fluid RCAS1 was an independent prognostic factor in lung cancer patients with effusion. In conclusion, RCAS1 determination at onset of pleural effusion is informative for both diagnosis and outcome prediction in lung cancer patients.

Adult↗

PubMed2005

E1AF/PEA3 activates the Rho/Rho-associated kinase pathway to increase the malignancy potential of non-small-cell lung cancer cells.

E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rho-associated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells.

Adenovirus E1A Proteins↗

PubMed2005

Susceptibility to oxygen desaturation during bronchoscopy in elderly patients with pulmonary fibrosis.

BACKGROUND: Fiber-optic flexible bronchoscopy (FFB) is a frequently performed procedure for the diagnosis and treatment of pulmonary disorders. However, hypoxemia occasionally occurs during FFB. OBJECTIVES: We attempted to examine the causes of arterial oxygen desaturation during FFB. METHODS: We studied 336 patients who underwent FFB without intervention between June 1, 2001 and September 30, 2002. Arterial oxygen saturation (SpO2) was continuously monitored using oximetry with a recording system. We analyzed the relationship between a reduction in SpO2 during FFB and various clinical parameters or background lung diseases. RESULTS: Of the 336 patients, 73 (22%) had an episode of oxygen desaturation (SpO2 <90% over 10 s). Of patients over 80 years old, 55% had an episode of oxygen desaturation, which was significantly higher than 27% observed in the patients of 80 and less than 80 years old (p < 0.05). Patients with pulmonary fibrosis had a higher risk of desaturation (55%) compared to patients with other complications or patients without any complication (p < 0.05). Multivariable analysis revealed that both age and pulmonary fibrosis were independent predictors of oxygen desaturation. However, the majority of the patients (94%) did not require routine oxygen supplementation. CONCLUSION: Although FFB is safe and does not require oxygen supplementation in most cases, age over 80 years and pulmonary fibrosis are high risk factors for significant oxygen desaturation during FFB.

Adult↗

PubMed2005

Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy.

PURPOSE: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. METHODS AND MATERIALS: Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 set-ups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). RESULTS: In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within +/-2 mm in 95% and +/-1 mm in 80% during treatment. The variation in the distances between the implanted markers was >2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. CONCLUSION: The fixation of markers into the bronchial tree was useful for the setup for peripheral lung cancer and had an accuracy of +/-2 mm during the 1-2-week treatment period. The relationship between the markers and tumor can change significantly after 2 weeks, suggesting that adaptive four-dimensional RT is required.

Adult↗

PubMed2005

Real-time monitoring of a digestive tract marker to reduce adverse effects of moving organs at risk (OAR) in radiotherapy for thoracic and abdominal tumors.

PURPOSE: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin. METHODS AND MATERIALS: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker. RESULTS: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm. CONCLUSION: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system.

Abdominal Neoplasms↗

PubMed2005

Small cell carcinoma of the lung exclusively localized within the left descending pulmonary artery.

We encountered a 69-year-old woman displaying a filling defect within the left descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A subsequent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination of transbronchial needle aspiration specimens revealed small cell carcinoma. The patient underwent concurrent radiation therapy and chemotherapy with cisplatin and etoposide, resulting in tumor shrinkage and recanalization of the involved PA. This is the first case of small cell carcinoma localized exclusively within the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.

Aged↗

PubMed2005

Transbronchial biopsy using endobronchial ultrasonography with a guide sheath and virtual bronchoscopic navigation.

STUDY OBJECTIVES: We evaluated the feasibility, safety, and efficacy of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) and virtual bronchoscopy (VB) navigation for small peripheral pulmonary lesions < or = 30 mm in diameter. DESIGN: Pilot study. SETTING: A national university hospital. PATIENTS: We performed TBB using EBUS-GS with VB navigation for 29 patients with 30 small peripheral pulmonary lesions (average diameter, 18.6 mm) between January 1, 2004, and August 31, 2004. INTERVENTIONS: VB images were reconstructed from helical CT data. TBB was then performed using EBUS-GS with VB navigation. RESULTS: In all patients, TBB was performed safely with no complications. Bronchi seen on VB imaging were highly consistent with the actual structures confirmed using fiberoptic bronchoscopy. Following VB navigation, the endobronchial ultrasonography (EBUS) probe was inserted into third- to sixth-generation bronchi. Twenty-four lesions (80%) were visualized on EBUS images. Average durations of the initial EBUS examination of lesions, first biopsy, and the total procedure were 9.56 min, 11.99 min, and 25.72 min, respectively. Nineteen lesions (63.3%) were diagnosed from histopathologic or cytologic examination. Diagnostic sensitivities were 44.4% (8 of 18) for lesions < 20 mm in mean diameter and 91.7% (11 of 12) for lesions 20 to 30 mm in mean diameter. CONCLUSIONS: In summary, TBB using EBUS-GS with VB navigation was safely performed and was effective in diagnosing small peripheral pulmonary lesions.

Adult↗

PubMed2005

[A case of Clostridium difficile colitis associated with paclitaxel and carboplatin chemotherapy for lung cancer].

A 41-year-old man admitted complaining of dyspnea was found to have lung adenocarcinoma (T4N3M1, stage IV) originating from S1+2. He underwent chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) and partial remission was obtained. However, on the 11th day of the fourth course of chemotherapy, he developed lower abdominal pain, grade 3 bloody diarrhea and grade 2 vomiting. The stool contained Clostridium difficile (CD) toxin and stool culture revealed C. difficile growth. We diagnosed CD colitis. Fortunately his symptoms recovered by fasting and fluid replacement until the next day. It has been reported that CD colitis occurrs in approximately 2% of patients with gynecological cancers receiving PTX-including chemotherapy. We thus speculate that the CD colitis of the present case was due to PTX. Although the mechanism of CD colitis by chemotherapeutical agents remains undetermined, direct damage to intestinal mucosa or changes in intestinal bacterial flora are possible. As severe CD colitis can be life threatening, we have to be aware of the possibility of it occurring in patients undergoing chemotherapy.

Adenocarcinoma↗

PubMed2004

B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

PURPOSE: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs. EXPERIMENTAL DESIGN: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically. RESULTS: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02). CONCLUSIONS: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.

Adult↗

PubMed2004

The characteristics of human NKT cells in lung cancer--CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients.

The activation of human Valpha24+Vbeta11+natural killer T cells (NKT) cells (Valpha24 NKT cells) induces effective antitumor responses with secondary immune effects through activation of conventional T cells and natural killer cells. In this study, we attempted to analyze the characteristics of human NKT cells in lung cancer patients. Valpha24 NKT cells stimulated with alpha-GalCer from healthy volunteers exhibited direct cytotoxic activity against two (RERF-LC-OK and PC-3) of seven human lung cancer cell lines studied. Cytotoxicity by Valpha24 NKT cells against human lung cancer cells was dependent on the perforin pathway and independent of Fas/FasL pathway. Intracellular adhesion molecule (ICAM)-1 expression on tumor cells was clearly associated with the cytotoxicity of Valpha24 NKT cells. On the other hand, the proportion of Valpha24 NKT cells in the patients with lung cancer was lower than that in the healthy volunteers. Furthermore, the proliferative response of Valpha24 NKT cells to alpha-GalCer was significantly lower in the peripheral blood mononuclear cells in the patients with lung cancer. Addition of granulocyte colony-stimulating factor moderately restored the low proliferative response of Valpha24 NKT cells in the patients with lung cancer, however the percentage by which the response was restored in these patients was still lower than the natural response in healthy volunteers. These results suggest that Valpha24 NKT cells may play a pivotal role or the antitumor response in lung cancer.

Adult↗

PubMed2004

Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non-small-cell lung cancer.

OBJECTIVE: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2). Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was recommended for a phase II study.

Adenocarcinoma↗

PubMed2004

Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P < 0.01), in those with regional lymph node metastasis (P < 0.05) and in those that had invaded beyond the submucosa (P < 0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.

Aged↗