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1.
Pancreatology ; 12(3): 215-8, 2012.
Article in English | MEDLINE | ID: mdl-22687376

ABSTRACT

BACKGROUND: Pancreatic pseudolymphoma is extremely rare. METHOD: We present multiple pseudolymphomas in the head and body of the pancreas. The hypoechoic lesions observed by endoscopic ultrasound were enhanced in late-phase angio-computed tomography and homogeneously hypointensive in T1-weighted magnetic resonance imaging (MRI). (18)F-fluorodeoxyglucose positron emission tomography showed strong accumulation in the lesions. The lesions were suspected to be non-functioning islet cell carcinoma. The intraoperative pathological diagnosis for the specimen obtained by a pylorus-preserving pancreaticoduodenectomy was non-neoplastic lymphoid cells. The remnant lesion in the pancreatic body was preserved. RESULTS: Macroscopically, the mass was well-circumscribed gray-white colored lesion. The pathological diagnosis was pancreatic pseudolymphoma. The lesion in the remnant pancreas spontaneously disappeared within one year after the operation. CONCLUSION: The differential diagnosis of pancreatic pseudolymphoma from malignant tumor is very difficult, however, the image findings demonstrated here may be informative. The spontaneous disappearance of pancreatic pseudolymphoma was firstly observed in the present case.


Subject(s)
Pancreatic Diseases/surgery , Pseudolymphoma/surgery , Diagnosis, Differential , Endosonography , Female , Humans , Middle Aged , Pancreas/pathology , Pancreatic Diseases/diagnosis , Pancreatic Neoplasms/diagnosis , Pancreaticoduodenectomy , Remission, Spontaneous
2.
J Exp Clin Cancer Res ; 26(1): 51-60, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17550132

ABSTRACT

Recently, the treatment of advanced gastric cancer by continuous infusion of 5-fluorouracil (5-FU) with low-dose cisplatin (CDDP) has improved efficacy without severe toxicities. The possible effectiveness of 5-FU+low-dose CDDP for colorectal cancer (CRC) is intriguing. One hundred fifty-five patients with far-advanced CRC including at least one measurable lesion were enrolled in a prospective randomized clinical trial funded by the Japanese Foundation for Multidisciplinary Treatment of Cancer. These patients were assigned to the two arms to assess the value of low-dose CDDP when added to a continuous intravenous infusion of 5-FU at a dose of 300 mg/m(2)/24 hrs in a one-week cycle consisting of 5 days of treatment and 2 days of rest for at least 12 weeks. CD-DP was given intravenously at a dose of 3 mg/m(2) on days 1-5 and days 8-12, and then at a dose of 7 mg/m(2) twice a week. Three patients were excluded from the trial. The response rate in the 5-FU+low-dose CDDP arm (n=75) was significantly higher than that in the 5-FU arm (n=77) (25.3% vs. 11.7%; P = 0.037). There was no significant difference in the median overall survival time between the 5-FU+low-dose CDDP arm and the 5-FU arm (479 and 491 days, respectively). Grades 3/4 toxicities occurred infrequently in both arms. The quality of life was almost the same between the arms. Low-dose CDDP improved the response rate while keeping toxicities within clinically acceptable limits. However, this combined treatment did not confer a survival advantage over treatment with continuous infusion of 5-FU alone for patients with far-advanced CRC; that might be attributable to the short CDDP administration setting of 12 weeks.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease Progression , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Japan/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Patient Compliance , Prospective Studies , Quality of Life , Treatment Outcome
3.
J Exp Clin Cancer Res ; 26(4): 459-66, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18365539

ABSTRACT

Few studies exist comparing the clinicopathological features between resectable pancreatic head (Ph) and body/tail ductal cancer (Pbt). Eighty consecutive patients with resectable tumors (Ph-56, Pbt-24) were analyzed. Tumor size was the only significant difference in clinicopathological factors between Ph and Pbt (Ph

Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Aged , Female , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Pancreas , Pancreatectomy , Survival Rate
4.
Clin Oncol (R Coll Radiol) ; 18(9): 678-83, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17100153

ABSTRACT

AIMS: The effects of haematological adverse events on the prognosis of patients with gastric cancer were investigated. MATERIALS AND METHODS: We retrospectively analysed the association between haematological adverse events and prognosis in 23 patients with far advanced or recurrent gastric cancer treated with a JFMC27-9902 regimen consisting of an oral fluorouracil derivative S-1 plus low-dose cisplatin. RESULTS: The patients who suffered grade 2-3 neutropenia (n = 10; median survival time [MST] 679 days) were found to have significantly more favourable prognoses than patients who developed grade 0-1 (n = 10; MST 271 days) or grade 4 neutropenia (n = 3; MST 408 days) (P = 0.0039 and 0.0112, respectively), although no significant differences were found among the clinicopathological factors of any grade groups. With respect to anaemia or thrombocytopenia, there were no significant differences among the MSTs of the groups stratified by toxicity grade. Multivariate survival analysis revealed that grade 2-3 neutropenia is an independent predictor of a more favourable prognosis (hazard ratio = 38.693, P = 0.0004). CONCLUSIONS: These results suggest that S-1 plus low-dose cisplatin against gastric cancer may contribute to long survival when it induces moderate neutropenia.


Subject(s)
Cisplatin/adverse effects , Neutropenia/chemically induced , Oxonic Acid/adverse effects , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Tegafur/adverse effects , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Drug Combinations , Female , Humans , Male , Middle Aged , Multivariate Analysis , Oxonic Acid/administration & dosage , Prognosis , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis , Tegafur/administration & dosage , Time Factors
5.
J Exp Clin Cancer Res ; 25(2): 195-200, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16918130

ABSTRACT

Transplatin (TDDP), a trans-isomer of cisplatin (CDDP), is well known to have faint cytotoxicity because its geometric structure allows less adduct formation with DNA than does CDDP. However, TDDP might have the potential to enhance the anticancer effect of 5-fluorouracil (5-FU) as well as CDDP. In this study, five gastric cancer cell lines were used. Cells were treated with 5-FU, TDDP, TDDP+5-FU, CDDP, and CDDP+5-FU, for 72 hrs. Synergistic effects between TDDP and 5-FU were observed in OCUM-2MD3, OCUM-2M, and OCUM-11, though they were not observed in MKN-45 or MKN-28. The cell lines in which synergistic effects were observed between TDDP and 5-FU were the same ones in which synergistic effects are shown between CDDP and 5-FU. The cell lines without synergism between 5-FU +TDDP/CDDP had lower thymidylate synthase (TS) activities than those with synergism, suggesting TS might be attributable to the synergistic mechanism. TDDP alone, compared to CDDP alone, gave rather low cytotoxicity for these cell lines. In conclusion, TDDP might be a clinically useful modulator of 5-FU.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Cisplatin/pharmacology , Fluorouracil/therapeutic use , Stomach Neoplasms/drug therapy , Drug Synergism , Humans , Stereoisomerism , Tumor Cells, Cultured/drug effects
6.
J Exp Clin Cancer Res ; 25(2): 283-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16918142

ABSTRACT

Recent studies have suggested that Helicobacter pylori (H. pylori)-associated gastritis may play an important role in the pathogenesis of primary gastric lymphoma. Recently, triple therapy using proton pump inhibitor, amoxicillin, and clarithromycin, has been established for the eradication therapy of H. pylori infection, and is also recommended for the treatment of the superficial type of low-grade gastric MALT (mucosa-associated lymphoid tissue ) lymphoma. MALT lymphoma of the gastric stump is rare, and total resection or chemotherapy for MALT lymphoma of the gastric stump has been previously reported. Therefore, there is no evidence that eradication therapy is effective for low-grade MALT lymphoma of the gastric stump. Our case illustrates the remarkable efficacy of eradication of H. pylori for low-grade MALT lymphoma of the gastric stump without other modalities such as surgery and systemic chemotherapy.


Subject(s)
Helicobacter Infections/drug therapy , Helicobacter pylori , Lymphoma, B-Cell, Marginal Zone/drug therapy , Stomach Neoplasms/drug therapy , Aged , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/pathology , Humans , Lymphoma, B-Cell, Marginal Zone/virology , Male , Omeprazole/therapeutic use , Remission Induction , Stomach Neoplasms/virology
7.
Br J Cancer ; 91(5): 873-8, 2004 Aug 31.
Article in English | MEDLINE | ID: mdl-15280913

ABSTRACT

The usefulness of serum CYFRA 21-1 (cytokeratin-19 fragments) in monitoring the recurrence of breast cancer and in evaluating therapeutic effects was studied retrospectively. The sera from 173 patients with primary breast cancer or recurrent disease were measured for CYFRA 21-1, carcinoembryonic antigen (CEA), and carbohydrate antigen 15-3 (CA 15-3) levels. The positive rates of serum CYFRA 21-1 for stage IV (n=12) or recurrent disease (n=26) were 83.3 and 84.6%, respectively, while those of serum CEA were 41.7 and 26.9%, and those of serum CA 15-3 were 83.3 and 34.6%. The elevated preoperative levels of serum CYFRA 21-1 decreased to normal levels after curative operation, whereas the levels remained abnormally high after noncurative operation. There was a significantly high frequency of recurrence in patients with elevated levels of serum CYFRA 21-1 preoperatively compared to those with normal levels of the marker preoperatively. The serum CYFRA 21-1 levels were well correlated with response to chemotherapy. The positive rate of serum CYFRA 21-1 alone was higher than that of an assay combining CEA with CA 15-3, in both primary and recurrent cases (28.8 vs 18.8 and 84.6 vs 46.2%, respectively). These observations suggest that serum CYFRA 21-1 may be a reliable marker of recurrence or therapeutic efficacy.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carcinoembryonic Antigen/blood , Female , Humans , Immunoradiometric Assay , Keratin-19 , Keratins , Mucin-1/blood , Neoplasm Recurrence, Local/blood , Prognosis , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Treatment Outcome
8.
Ann Nucl Med ; 15(3): 217-24, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11545191

ABSTRACT

UNLABELLED: The purpose of this study was to investigate the feasibility of [18F]2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in patients with a pancreatic mass by comparing the results with those of X-ray computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: Eighty-six patients with pancreatic lesions, included 65 malignant tumors and 21 benign masses (55 masses were proven histologically and the others were diagnosed clinically), were studied. The diagnostic factors of CT and MR imaging were evaluated, and those of FDG PET were also evaluated for malignant and benign masses by visual interpretation and quantitative interpretation with the standardized uptake value (SUV) and SUVgluc which was designed to reduce the effects of a high blood sugar level. Visual interpretations were evaluated only in FDG PET images, and quantitative interpretations were evaluated by referring to CT and/or MR imaging. The correlation between SUV and the degree of histological differentiation in pancreatic ductal adenocarcinoma was investigated. RESULTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for CT imaging were 91, 62, 88, 68 and 84%, and for MR imaging 78, 70, 88, 54 and 76%, respectively. In visual interpretation of FDG PET images, the sensitivity, specificity, PPV, NPV and accuracy were 82, 81, 93, 59 and 81%, respectively. Significant differences between malignant and benign lesions existed in SUV and SUVgluc (p < 0.0001, each). With the cutoff value of SUV as 2.1 and SUVgluc as 2.2, the accuracy of diagnosis was maximal. With that cutoff value, the sensitivity, specificity, PPV, NPV and accuracy for SUV were 89, 76, 92, 70 and 86%, and for SUVgluc 91, 76, 92, 73 and 87%, respectively. The sensitivity and NPV of SUVgluc were higher than those of SUV, which suggests that SUVgluc may be more useful in reducing the number of overlooked malignant tumors. The specificity and PPV of FDG PET were superior to those of CT and MR imaging. There were no significant differences between the SUVs of moderately differentiated adenocarcinomas and those of well differentiated adenocarcinomas. CONCLUSION: To improve the diagnostic procedure for classifying masses, FDG PET with not only SUV but also SUV corrected by the blood sugar level is required in addition to morphological diagnosis by CT and/or MR imaging.


Subject(s)
Fluorodeoxyglucose F18/therapeutic use , Pancreatic Diseases/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Radiopharmaceuticals , Tomography, Emission-Computed , Aged , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pancreatic Diseases/diagnosis , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Reproducibility of Results , Retrospective Studies , Statistics, Nonparametric , Tomography, X-Ray Computed
9.
Int J Oncol ; 19(4): 709-15, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11562745

ABSTRACT

We investigated the effect of TGF-beta1 on liver metastasis of pancreatic cancer using surgical specimens of pancreatic cancer and human pancreatic cancer cell lines Capan-2 and SW1990. Immunostaining of TGF-beta1 showed that TGF-beta1 positivity was significantly related to venous invasion and tumor staging, and also relatively associated with liver metastasis. Cellular invasion and protease production of MMP-2 and u-PA, and in vivo liver metastasis were significantly enhanced after treatment of cells with TGF-beta1. These findings suggest that TGF-beta1 might play an important role in enhancing liver metastasis of pancreatic cancer.


Subject(s)
Adenocarcinoma/secondary , Liver Neoplasms/secondary , Pancreatic Neoplasms/pathology , Transforming Growth Factor beta/pharmacology , Tumor Cells, Cultured/drug effects , Adenocarcinoma/metabolism , Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Immunoenzyme Techniques , Liver Neoplasms/metabolism , Male , Matrix Metalloproteinases/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Staging , Neoplasm Transplantation , Pancreatic Neoplasms/metabolism , Pancreaticoduodenectomy , Transforming Growth Factor beta/metabolism , Tumor Cells, Cultured/metabolism , Urokinase-Type Plasminogen Activator/metabolism
10.
Int J Oncol ; 19(2): 373-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11445854

ABSTRACT

We studied apoptosis and thymidylate synthase (TS) inductions by 5-fluorouracil (5-FU) in gastric cancer cells with wild-type p53 (MKN-45 and MKN-74) and with mutated p53 (MKN-28 and KATO-III). Apoptotic inductions in MKN-45 and MKN-74 were stronger than those in MKN-28 and KATO-III, suggesting that wild-type p53 may contribute to the induction of apoptosis. After continuous exposure to 0.1 microg/ml of 5-FU for 96 h, no TS induction was obtained in KATO-III, while approximately twice the amount of TS was observed compared to non-treatment cells in MKN-45, MKN-74, and MKN-28. The results of immunohistochemical staining for TS and p53 showed no relation between these two protein expressions in endoscopic biopsy specimens of 25 patients with advanced gastric cancer. These results indicated that p53 status may not play a pivotal role in regulating TS expression. We found no significantly different effects of 5-FU between intermittent (repeat of 24-h continuous infusion and 24-h drug-free) and continuous treatments in either MKN-28 or stem cells (CD34+ hematopoietic progenitor cells) when the same area under the time-concentration curve of 5-FU was administered. The TS induction in MKN-28 cells by intermittent treatment was significantly higher than that by continuous treatment; however, most TSs in both types of 5-FU treatment cells were of the inactive form, i.e., TS bound to FdUMP, a 5-FU metabolite. Therefore, neither intermittent nor continuous treatment appears to induce 5-FU resistance related to the level of increment free TS. In conclusion, our observations suggested that p53 mutation may be associated with apoptotic induction by 5-FU; however, p53 status may not strongly affect TS induction by 5-FU. Intermittent treatment can be replaced with continuous treatment without causing 5-FU resistance.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Fluorouracil/pharmacology , Stomach Neoplasms/pathology , Thymidylate Synthase/drug effects , Tumor Suppressor Protein p53/genetics , Cell Survival/drug effects , DNA Mutational Analysis , DNA, Neoplasm/chemistry , DNA, Neoplasm/genetics , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Mutation , Polymorphism, Single-Stranded Conformational , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Thymidylate Synthase/metabolism , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism , Tumor Suppressor Protein p53/metabolism
11.
Int J Oncol ; 19(1): 53-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408922

ABSTRACT

18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a unique imaging diagnostic tool to evaluate glucose metabolism and hexokinase activity which may reflect the aggressiveness of a tumor. Thirty-seven patients with primary pancreatic cancer were evaluated with 18F-FDG-PET. Thirteen patients underwent resection for the pancreatic cancer and 24 patients had unresectable tumors. The standardized uptake values (SUV) of 18F-FDG in the primary tumors were calculated. No correlations were found between the SUV in the tumors and the metastatic status to the peritoneal/liver, TNM factors/stage, or resectability. The patients were divided into 2 groups with high and low SUV, with the cut-off value being 3.0 (median SUV value of 37 cases). No differences in the probability of survival were observed between the 2 groups in the patients with resectable tumors. However, in the patients with unresectable tumors, those in the high SUV group had a significantly shorter prognosis than those in the low SUV group. Moreover, a multivariate analysis of survival indicated that SUV is an independent prognostic factor for patients with unresectable pancreatic cancer.


Subject(s)
Adenocarcinoma/diagnostic imaging , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Pancreatic Neoplasms/diagnostic imaging , Radiopharmaceuticals , Tomography, Emission-Computed/methods , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , False Positive Reactions , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Predictive Value of Tests , Prognosis , Survival Rate
12.
Int J Mol Med ; 7(5): 479-83, 2001 May.
Article in English | MEDLINE | ID: mdl-11295107

ABSTRACT

We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to investigate the clinical significance of p53-p21 pathway in this disease. One hundred sixty-four primary gastric carcinoma specimens were immunohistochemically stained for p53 and p21 protein, and clinicopathological features of the cases were examined. P53 was stained negatively, while p21 was stained positively in each normal stomach epithelium. P53, and p21 positive staining was observed in 82 (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21 pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less aggressive characteristics, and no recurrent disease after curative resection. While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in 32.9% of the tumors, displayed significantly more aggressive characteristics, poorer survival and higher recurrence rate than the tumors demonstrating other staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The combined evaluation of p53 and p21 expression in gastric carcinoma tissues is suggested to have clinical importance by indicating not only the malignant potential of each tumor, but also the prognosis of this disease.


Subject(s)
Adenocarcinoma/pathology , Cyclins/analysis , Stomach Neoplasms/pathology , Tumor Suppressor Protein p53/analysis , Adenocarcinoma/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Cyclin-Dependent Kinase Inhibitor p21 , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Stomach Neoplasms/metabolism , Survival Analysis
13.
Gan To Kagaku Ryoho ; 27(13): 2123-7, 2000 Nov.
Article in Japanese | MEDLINE | ID: mdl-11103246

ABSTRACT

The cases of 3 female patients with metastatic breast cancer treated with oral UFT and cyclophosphamide (CPA) are reported. Patient 1 had lymph node and bone metastases. Patient 2 had bone metastasis. Patient 3 had skin, lymph node, and peritoneal metastases. All had a history of mastectomy and chemo- and/or endocrine therapy for metastatic lesions. Patients 2 and 3 had also undergone CAF combination chemotherapy. However, the lesions did not change. UFT 400 mg and CPA 100 mg, everyday, were administered to patient 1. UFT 400 mg and CPA 100 mg, 2 weeks, and UFT 400 mg, 2 weeks, were given every 4 weeks to patient 2. UFT 300 mg and CPA 150 mg, 6 weeks per 8 weeks were given to patient 3. Improvements in the metastatic lesions were seen 4 weeks after the beginning of UFT and CPA therapy. Therapy is now continuing, and no patients had a progression of the disease. All had leukopenia 2 or 4 weeks after the beginning of this therapy, and two temporarily stopped the therapy. No other side-effect was observed. Oral UFT and CPA combination therapy was considered useful for metastatic breast cancer. To prevent leukopenia and prolong the term of treatment efficacy, a treatment regimen will need to be established.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Tegafur/administration & dosage , Uracil/administration & dosage , Administration, Oral , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Lymphatic Metastasis , Middle Aged , Peritoneal Neoplasms/secondary , Skin Neoplasms/secondary
14.
Clin Cancer Res ; 6(10): 4069-72, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11051258

ABSTRACT

The utility of serum KL-6 as a tumor marker for breast cancer was evaluated in this study. The sera from 146 patients with breast cancer, 13 with benign breast disease, and 108 healthy individuals were measured for KL-6 titer using a sandwich enzyme immunoassay method. Carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) titers were also tested in the same sera from the patients. The mean KL-6 titer of patients with primary breast cancer was 673 units/ml, which was significantly higher than that of benign and healthy individuals (P = 0.037 and P < 0.0001, respectively). The titer of patients with relapsed breast cancer was 1964 units/ml, which was also higher than that of primary cancer (P = 0.013). KL-6 titer was related to tumor stage, distant metastasis, and relapse site (P = 0.0053, P < 0.0001, and P = 0.0251, respectively). Using the cutoff value of 467 units/ml, the sensitivity of KL-6 was 31% for primary breast cancer (16% for stage I and 29% for stage II) and 73% for relapsed breast cancer (50% for local relapse and 89% for distant relapse). The specificity was 92%. The sensitivity of KL-6 was higher than that of CA15-3 and CEA. Combination of the three markers, followed by KL-6 and CEA, raised the sensitivity for primary breast cancer. Single use of KL-6 demonstrated a higher sensitivity than in each combination for relapsed breast cancer. In conclusion, serum KL-6 may be helpful for clinical use as a tumor marker for breast cancer, and it may play an important role, especially in the surveillance of disease relapse.


Subject(s)
Biomarkers, Tumor/biosynthesis , Breast Neoplasms/blood , Breast Neoplasms/metabolism , Peptide Fragments/blood , Procollagen/blood , Adolescent , Adult , Antigens , Antigens, Neoplasm , Breast Diseases/blood , Breast Neoplasms/diagnosis , Carcinoembryonic Antigen/blood , Female , Glycoproteins , Humans , Immunoenzyme Techniques , Middle Aged , Mucin-1/blood , Mucins , Recurrence , Sensitivity and Specificity
15.
Int J Mol Med ; 6(5): 553-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11029523

ABSTRACT

Recent studies have shown that caspases, which are cystein proteases, elevate endonuclease activity and induce apoptosis. Caspase-1, an interleukin-1beta converting enzyme, has been reported to be related with anti-cancer drug induced apoptosis as well as with caspase-3. To elucidate the caspase-1 activity, which might be a predictor for the effect of chemotherapy, we examined the changes of caspase-1 activity induced after exposure to cisplatin (CDDP) in six gastric cancer cell lines. A high correlation between the 50% inhibitory concentration (IC50) and caspase-1 activity ratio was shown (r=0.83, p=0.041) (caspase-1 activity ratio: the caspase-1 activity of cells at 4 h after CDDP treatment/the caspase-1 activity of untreated cells). Further, we examined the correlation between caspase-1 activity and apoptosis induced by CDDP in two cell lines that have very different CDDP sensitivities; OCUM-2M and OCUM-2M/DDP (IC50; 0. 85+/-0.4 microg/ml and 9.0+/-1.2 microg/ml, respectively). The apoptotic index of OCUM-2M was significantly higher than that of OCUM-2M/DDP (19.8+/-3.8% vs. 4.5+/-1.2%, respectively; p=0.0005). In both cell lines, caspase-1 activity began to increase immediately after exposure to CDDP and peaked at approximately 4 h after cessation of exposure to CDDP, and gradually decreased thereafter. The caspase-1 activity of OCUM-2M was approximately 1.8-times higher than that of OCUM-2M/DDP at 4 h after exposure to CDDP. Taken together, our results indicate that evaluating the changes of caspase-1 activity after exposure to CDDP may be useful to predict apoptosis following CDDP treatment in gastric cancer cells.


Subject(s)
Apoptosis/drug effects , Caspase 1/metabolism , Cisplatin/pharmacology , Stomach Neoplasms/enzymology , Antineoplastic Agents/pharmacology , DNA/analysis , In Situ Nick-End Labeling , Inhibitory Concentration 50 , Polymorphism, Single-Stranded Conformational , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein
16.
Cancer ; 89(6): 1285-90, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-11002224

ABSTRACT

BACKGROUND: The search for new tumor markers for breast carcinoma has been an area of vigorous study; nonetheless, to the authors' knowledge little new information has emerged beyond the clinical usefulness of CA 15-3. The authors studied serum CYFRA 21-1 in breast carcinoma based on evidence that breast carcinoma expresses cytokeratin 19 fragments and that CYFRA 21-1 is a specific antigen for cytokeratin 19 fragments. METHODS: The serum samples of 86 patients with primary breast carcinoma, 14 patients with recurrent breast carcinoma, 22 patients with benign mammary disease, and 25 healthy controls were provided for measurements of CYFRA 21-1, carcinoembryonic antigen (CEA), and CA 15-3. The relation between clinicopathologic features, prognosis, and disease free survival with serum CYFRA 21-1 titers was studied. RESULTS: There was no difference between the serum CYFRA 21-1 titers from patients with benign mammary disease and those from healthy controls. The sensitivities of CYFRA 21-1 for patients with International Union Against Cancer Stage IV and recurrent tumors were 60% and 64.2%, respectively, which were as high as those for CA 15-3 and superior to those for CEA. The hematogenous recurrence showed a very high sensitivity of 89%. According to the increments of T, N, and M factor numbers, the serum CYFRA 21-1 titers were elevated. No correlation between CYFRA 21-1 and CEA was observed and the correlation between CYFRA 21-1 and CA 15-3 was weak. The univariate and multivariate analyses for survival revealed that serum CYFRA 21-1 levels were an independent indicator of prognosis. CONCLUSIONS: The measurement of the serum CYFRA 21-1 titer in patients with breast carcinoma may be useful in monitoring for recurrence and evaluating the therapeutic effect in patients with advanced disease.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Breast Neoplasms/immunology , Breast Diseases/blood , Breast Diseases/immunology , Breast Neoplasms/blood , Breast Neoplasms/pathology , Carcinoembryonic Antigen/blood , Female , Humans , Keratin-19 , Keratins , Middle Aged , Mucin-1/blood , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/immunology , Neoplasm Staging , Prognosis , Proportional Hazards Models , Sensitivity and Specificity
17.
Gan To Kagaku Ryoho ; 27(3): 335-40, 2000 Mar.
Article in Japanese | MEDLINE | ID: mdl-10740625

ABSTRACT

We herein summarize the reports on genetic changes in precancerous lesions in the gastrointestinal tract. It has been reported that with esophageal lesions such as dysplasia and Barrett's esophagus there is a high frequency of p53 mutations. Among gastric lesions, some cases of chronic atrophic gastritis have been shown to harbor K-ras mutations. p53 and APC mutations in intestinal metaplasia have also been demonstrated, as have APC mutations in flat adenomas. With colorectal lesions, it has been reported that K-ras, DCC, p53 mutations commonly occur while APC mutations are also seen in cases of adenoma-carcinoma. p53 and K-ras mutations have been demonstrated with serrated adenoma, and K-ras mutations with hyperplastic polyps APC mutations in familial polyposis coli, LKB1 mutations in Peutz-Jeghers syndrome, and SMAD4/DPC4 mutations in juvenile polyposis syndrome have been found. Besides these genes, other genetic changes likely occur in carcinogenesis among those with hereditary diseases. K-ras mutations in aberrant crypt foci and hMSH2 mutations in ulcerative colitis have been found. Research into the genetic changes associated with cancerous lesions should lead to the development of early diagnosis and treatment methods for gastrointestinal cancer as well as the improved comprehension of carcinogenesis.


Subject(s)
Gastrointestinal Neoplasms/genetics , Genome, Human , Precancerous Conditions/genetics , Adenoma/genetics , Adenomatous Polyposis Coli/genetics , Barrett Esophagus/genetics , Colorectal Neoplasms/genetics , Esophageal Neoplasms/genetics , Gastric Mucosa/pathology , Gastritis, Atrophic/genetics , Genes, APC , Genes, p53 , Genes, ras , Humans , Metaplasia/genetics , Mutation , Stomach Neoplasms/genetics
18.
Clin Cancer Res ; 6(3): 1175-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10741749

ABSTRACT

We studied the correlation between serum soluble intercellular molecule 1 (sICAM-1) and clinicopathological features in patients with gastric cancer. The impact of sICAM-1 on prognosis was also evaluated. The sera from 224 patients with gastric cancer, 44 healthy individuals, and 35 patients with benign gastrointestinal diseases (4 patients with submucosal stomach tumors, 6 patients with gastric ulcers, 1 patient with Crohn disease, 2 patients with ulcerative colitis, 7 patients with gall stones, 5 patients with chronic pancreatitis, and 10 patients with liver cirrhosis) were measured for sICAM-1 titer using a sandwich enzyme immunoassay method. There was no correlation between the serum titer of sICAM-1 and the age or gender of healthy controls. Among patients with benign gastrointestinal diseases, the patients with liver cirrhosis had a significantly higher mean serum sICAM-1 titer than that of healthy controls (P < 0.0001). The mean serum sICAM-1 titer of all patients with gastric cancer was not significantly different from that of healthy controls. However, among the patients with stage IV and recurrent disease, the serum sICAM-1 titer of those with hematogenous metastasis was significantly higher than that of patients without hematogenous metastasis (P = 0.001). The patients with a high serum sICAM-1 titer of more than 304 ng/ml (mean of healthy controls plus SD) showed a significantly worse prognosis than patients with a low serum sICAM-1 titer (P = 0.010). Nevertheless, serum sICAM-1 titer was not an independent predictor of prognosis by multivariate analysis. In conclusion, serum sICAM-1 cannot be used as a tumor marker for early diagnosis. However, sICAM-1 in sera may still be worthwhile to measure for monitoring hematogenous metastasis.


Subject(s)
Gastric Mucosa/pathology , Intercellular Adhesion Molecule-1/blood , Stomach Neoplasms/blood , Adult , Aged , Aged, 80 and over , Female , Gastrointestinal Diseases/blood , Humans , Male , Middle Aged , Stomach Neoplasms/pathology , Survival Analysis
19.
Surg Endosc ; 14(12): 1149-52, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11148786

ABSTRACT

BACKGROUND: This pilot study was conducted to estimate the use of the thoracoscopic surgery as a new approach for the internal mammary nodes (IMN) in breast cancer. PATIENTS AND METHODS: For this study, 21 women with breast cancer who underwent the approach for nodes IMN were enrolled. All the women had suspicious IMN metastasis and no distant metastasis. RESULTS: Thoracoscopic IMN dissection was performed safely for 20 of the women, with an average operative time of 44 min. One woman was excluded from the procedure because of pleural adhesion. The patients were restricted from walking for 1.3 days because of chest drainage, but no patients had severe complication or chest wall deformity after the operation. Six patients had positive IMN outcomes. After surgery, 10 of the 20 patients had a lower tumor node metastases (TNM) staging. Two patients who tested positive for IMN and three who tested negative experienced a relapse, but none had pleural dissemination in a median follow-up period of 24 months. CONCLUSION: Thoracoscopic surgery may be useful in managing patients with IMN.


Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision/methods , Thoracoscopy/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Lymph Node Excision/instrumentation , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Thoracoscopes
20.
Int J Mol Med ; 2(4): 461-4, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9857235

ABSTRACT

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenesis factor. We investigated the correlation between dThdPase activity in gastric cancer tissue and clinicopathological factors. Thirty-three cancer tissue specimens and 23 adjacent normal gastric mucosal specimens were obtained from surgery. Measurement of dThdPase activity was based on the amount of 5-fluorouracil formed from 5'-deoxy-5-fluorouridine by dThdPase. Mean dThdPase activity in cancer tissue was approximately 3.2 times higher than that in normal tissue. Cancerous tissues with venous invasion had about twice the dThdPase activity as cancerous tissues without venous invasion. Other clinicopathological features were not related to dThdPase activity. A correlation between dThdPase activity and immunosuppressive acidic protein level was observed (r = 0.532, P = 0.005). dThdPase activity in gastric cancer cells was found to be correlated with venous invasion, supporting previous findings that it plays a role in tumor angiogenesis.


Subject(s)
Neovascularization, Pathologic/pathology , Stomach Neoplasms/enzymology , Thymidine Phosphorylase/metabolism , Adult , Aged , Biomarkers, Tumor/analysis , Female , Gastric Mucosa/enzymology , Gastric Mucosa/pathology , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Neovascularization, Pathologic/enzymology , Pilot Projects , Stomach Neoplasms/blood supply , Stomach Neoplasms/pathology , Veins/pathology
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