Carcinoembryonic antigen estimation in nipple discharge as an adjunctive tool in the diagnosis of early breast cancer

To assess the usefulness of carcinoembryonic antigen (CEA) estimation in nipple discharge for the detection of nonpalpable breast cancer, CEA activity in nipple discharge was measured by enzyme immunoassay using monoclonal antibody. The specificity of the antibody for breast cancer was assessed by an immunohistochemical method. Mean CEA levels in the nipple discharge from 18 patients with benign breast diseases (ten intraductal papilloma; eight fibrocystic disease) was 43 ng/ml (SD, 34 ng/ml), suggesting an upper reference limit of 100 ng/ml. Six of seven nonpalpable breast cancer patients had higher CEA levels than this tentative cutoff value, as did three of five patients with borderline lesions. The incidence of elevated CEA levels in nipple discharge correlated significantly with the incidence of intratumoral antigen expression. These results lead us to conclude that CEA measurement in nipple discharge may be a useful adjunct in the diagnosis of nonpalpable breast cancer.     

Identification of regions of alpha-catenin required for desmosome organization in epithelial cells

Alpha-catenin, a cadherin-associated protein, links cadherin/beta-catenin and cadherin/plakoglobin complexes to the actin cytoskeleton. This protein is required for the function of cadherins, cell adhesion molecules. We transfected an alpha-catenin-deficient colon carcinoma line, which cannot organize desmosomes, with a series of alpha-catenin mutant constructs. We examined the formation of desmosomes in these cells by immunofluorescence staining using anti-desmoglein and anti-desmoplakin antibodies. The results demonstrated that either the middle or the carboxy-terminal region of alpha-catenin was required for desmosome formation. Immunoblot analysis revealed that the amounts of desmoglein and desmoplakin did not differ significantly between cells that were capable of forming desmosomes and those that failed to form desmosomes. Cell surface biotinylation revealed that desmoglein was retained intracellularly in cells that could not organize desmosomes. The internal domain binds vinculin and alpha-actinin, actin-binding proteins, while the carboxy-terminal domain has the ability to bind and bundle actin filaments. These results indicate that the interaction of alpha-catenin and actin functions in the assembly of desmosomes in epithelial cells.     

Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma

OBJECTIVE: Although treatment for advanced or recurrent endometrial carcinoma has improved over recent years with the introduction of paclitaxel- and platinum-based chemotherapy, in most, the disease remains incurable because of resistance to chemotherapy. In the previous study, we have shown that placental leucine aminopeptidase (P-LAP) is associated with poor prognosis. The objective of this study was to determine whether P-LAP expression affects the chemosensitivity in endometrial carcinoma patients. METHODS: Here, we investigated the effect of P-LAP to response for paclitaxel and carboplatin in advanced and recurrence endometrial carcinoma. Furthermore, we transfected P-LAP cDNA into endometrial carcinoma cells (AMEC) and investigated cell growth and apoptosis by paclitaxel or carboplatin. RESULTS: In 15 of 17 patients, P-LAP was positive. Twelve of seventeen patients were evaluable for response. Among the eight patients strongly positive for P-LAP, only two patients (25%) showed PR. However, all four patients who were weakly positive for P-LAP showed either complete response (CR) or partial response (PR). P-LAP overexpressor (P-LAP2 and P-LAP8) and a vector control were used to assay chemosensitivity. P-LAP2 clone displayed a 1.7-fold increase in IC(50) against paclitaxel and carboplatin when compared with the vector control, and P-LAP8 clone displayed a 1.6-fold increased in IC(50) against paclitaxel and carboplatin when compared with V1. Compared to vector control cells, apoptotic effect by carboplatin treatment was clearly inhibited in P-LAP2 and P-LAP8 cells. Carboplatin, 10(-6) M, induced the 12.5-fold rate of apoptosis compared to that without treatment at 48 h in vector control cells. However, in P-LAP2 and P-LAP8 clones, 10(-6) M carboplatin induced only 3.2- and 5.1-fold rates of apoptosis, respectively, compared to that of without treatment. CONCLUSIONS: P-LAP was suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma.     

Polyamine levels in brain and plasma after acute restraint or water-immersion restraint stress in mice

To investigate the relationship between polyamines and stress, we measured polyamine levels in the frontal cortex, hippocampus, hypothalamus, and plasma of mice after acute restraint or water-immersion restraint stress. In all parts of the brain, putrescine levels were elevated (139-157% of the control) 24 h after water-immersion restraint stress. In the case of restraint, however, elevation of the putrescine level (130% of the control) was detected only in the frontal cortex. Spermidine and spermine levels were unchanged or slightly reduced (80-85% of the control) in the brain 6 and 24 h after water-immersion restraint stress. There was no change in plasma polyamine levels at any time subsequent to the stress. Pretreatment with diazepam (5 mg/kg, i.p.) completely blocked the stress-induced putrescine increases. These results indicate that the magnitude of the putrescine increase is dependent upon the intensity of the stressor, and suggest that polyamine metabolism is linked to psychological stress.     

Transfusion-related acute lung injury following allogeneic bone marrow transplantation in a patient with acute lymphoblastic leukemia

Transfusion-related acute lung injury (TRALI) is a clinical syndrome characterized by bilateral pulmonary edema in association with transfusions. We encountered a 23-year-old woman with acute lymphoblastic leukemia, in whom TRALI without anti-human leukocyte antigen class I and anti-granulocyte antibodies developed following allogeneic bone marrow transplantation. TRALI improved mainly in association with treatment of saline and ventilation support after several days, but graft-versus-host disease and thrombotic microangiopathy developed, resulting in death due to multiple organ failure. This case indicates that TRALI can also occur following allogeneic bone marrow transplantation.     

Association between social support and depression in the elderly Japanese population

To determine the association between social support and depression in elderly Japanese, we conducted a Comprehensive Geriatric Assessment among residents aged 70 years or over. Out of 2,730 eligible subjects, 1,179 participated in the survey and 1,146 (480 men and 666 women) were analyzed. The Geriatric Depression Scale (GDS) was used to estimate depression status. The subjects were divided into two groups: depressive (GDS>11 or taking antidepressant drugs) and non-depressive (GDS<11). Various levels of social support were assessed by the following questions: Do you have someone (1) whom you can consult when you are in trouble ? (2) whom you can consult when your physical condition is not good ? (3) who can help you in daily housework ? (4) who can take you to a hospital when you don't feel well ? (5) who can take care of you when you are ill in bed? In multivariate logistic regression analysis, the calculated odds ratios (95% CIs) for the lack of each type of social support for depression status were: (1) 2.5 (1.5-4.1),(2) 1.9 (1.1-3.2),(3) 2.7 (1.7-4.4),(4) 1.9 (1.1-3.2),(5) 2.8 (1.6-4.9) in men, and (1) 1.2 (0.8-1.8),(2) 1.2 (0.8-1.8),(3) 1.4 (1.0-2.0),(4) 1.6 (1.1-2.3),(5) 2.0 (1.4-2.9) in women. A significant association was found between social support and depression in this elderly population. We also found that this association was stronger in men.     

Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia

OBJECTIVE: Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia. METHODS: Histologic sections of formalin-fixed, paraffin-embedded specimens from 11 patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting. RESULTS: P-LAP immunoreactivity was detected in 2 of 11 benign cystadenomas. None of the 11 benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 immunoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adenocarcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP immunoreactivity and GLUT4 immunoreactivity (correlation coefficient [r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression. CONCLUSIONS: P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelial malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed.     

Effect of intra-arterial infusion of adriamycin on locally advanced primary breast cancer--third report. Clinical Study Group of Adriamycin for Breast Cancer in Japan

The purpose of this study was to define the optimal dose and schedules for intra-arterial administration of adriamycin (ADR) in the treatment of locally advanced breast cancer. ADR was given intra-arterially to 110 patients with locally advanced breast cancer at a dose of 30 mg/time or 50 mg/time twice or once a week, respectively, with a total dose of 150 mg. The local effects and side effects of ADR as well as the prognosis were analysed in 91 evaluable cases. Overall response rates for ADR were as high as 62.2% (63/91) in the primary lesions and 80.0% (40/50) in metastatic lymph nodes. There was no difference in the response rate between cases receiving 30 mg and those receiving 50 mg at each infusion. However, a significantly higher response rate was noted, in patients infused ADR through both the subclavian and internal thoracic arteries (dual route group) in comparison with those infused through the subclavian artery alone (single route group). Histological effects of ADR on the primary lesion were assessed in accordance with the criteria proposed by Shimosato et al. Overall histological response rate (greater than Grade II b) was obtained in 29.4% (16/51), which was lower than the clinical effects. Histological effects were more potent in the 30 mg group than in the 50 mg group, but in relation to the route of administration, there was no significant difference between the groups. As for side effects, signs of systemic toxicity such as alopecia, leukopenia and gastrointestinal disorders were frequently observed, but there was no difference between the dose groups, and these side effects were considered to be tolerable. Prognostically, 50% survival time was 32.6 months, and the patients who received dual-route administration showed better survival.