Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22

Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but not in any non-cancerous tissues examined, except skin. Another S100 gene, S100C, which we co-localized with the psoriasin gene to human chromosome Iq21-q22, was found to be expressed in most tissues and cell lines evaluated. These findings add support to the concept that the S100 genes clustered in human chromosome Iq21-q22 are individually controlled and that some of them may be involved in the regulation of cell transformation and/or differentiation.     

The prognostic significance of beta(2)-microglobulin in patients with Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: Serum beta(2)-microglobulin (s beta(2)m) is an established prognostic factor for multiple myeloma and non-Hodgkin's lymphoma, but only limited data suggest an adverse prognostic significance for Hodgkin's lymphoma (HL). This study was undertaken to examine the impact of s beta(2)m on the prognosis of patients with HL. DESIGN AND METHODS: s beta(2)m was measured by a radioimmunoassay (upper normal limit 2.4 mg/L), in pretreatment serum samples of 232 patients with HL, who were then treated with ABVD or equivalent regimens with or without radiotherapy. Multivariate survival analysis was based on Cox's proportional hazards model. RESULTS: Main patients' characteristics: median age 30.5 years (14-78); 58% males; 68% nodular sclerosis, 20% mixed cellularity and 12% lymphocyte predominance; 34% B-symptoms; 24% Ann Arbor stage I, 49% II, 18% III and 9% IV. Elevated s beta(2)m levels were detected in 65/232 patients (28%) and correlated with older age (p<0.001), mixed cellularity (p=0.03), B-symptoms (p=0.002), advanced stage (p=0.02), > or = 5 involved sites (p=0.02), inguinal/iliac involvement (p=0.009), lymphocytopenia (p=0.002) and elevated lactate dehydrogenase (p=0.01). The 7-year failure free survival (FFS) was 75% vs. 72% for patients with normal vs. elevated s beta(2)m (p=0.15). The corresponding 7-year overall survival (OS) rates were 86% vs. 52% (p=0.003). In multivariate analysis, elevated s beta(2)m was not predictive of FFS, but was independently associated with inferior OS (p=0.01), along with the number of involved sites (p<0.001). INTERPRETATION AND CONCLUSIONS: s beta(2)m is not a potent prognostic factor for FFS in optimally treated patients with HL. However s beta(2)m may be predictive of OS, probably due to its effect on the timing of treatment failure.     

Endometrial stromal sarcoma metastatic to the lung: a detailed analysis of 16 patients

Pulmonary metastases of endometrial stromal sarcoma (ESS) are uncommon and can pose diagnostic problems. We reviewed lung specimens from 16 patients with metastatic ESS. Patients were 31-77 years of age at the time of lung biopsy. Uterine ESSs were diagnosed an average of 9.8 years before lung biopsy in 11 patients. Uterine ESSs were originally called smooth muscle tumors in three additional patients. Thirteen patients were evaluated for new pulmonary nodules, seven of whom were asymptomatic. Nodules were multiple in 14 and solitary in four, ranging from 1.0 to 8.0 cm in greatest dimension. One patient died of metastatic disease; 14 were alive and seven of these were without disease (mean follow-up 4.1 years). Diagnostic considerations in 12 consultation cases included ESS, sclerosing hemangioma, carcinoid tumor, lymphangioleiomyomatosis, endometriosis, hemangiopericytoma, and lymphoma. Tumors were well circumscribed and usually solid, composed of plump spindle cells arranged in short fascicles. Two tumors were predominantly cystic. Sex cord-like stromal differentiation was identified in three. Neoplastic cells stained for vimentin (93%), estrogen and progesterone receptor (100%), smooth muscle actin (57%), desmin (50%), and keratin (46%). Metastatic ESS should be included in the differential diagnosis of nonepithelial neoplasms in women.     

Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group

The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.     

Recent increase in meningitis Caused by Neisseria meningitidis serogroups A and W135, Yaoundé, Cameroon

From 1991 to 1998, Neisseria meningitidis serogroups A, B, and C represented 2%-10% of strains isolated from cases of bacterial meningitis in Yaoundé. During 1999 to 2000, the percentage of meningococci reached 17%, a proportion never reported since recordkeeping began in 1984. The increase of serogroup A meningococci and the emergence of W135 strains highlight the need for increased surveillance for better diagnosis and prevention.     

Recombinant interleukin-2 treatment decreases P-glycoprotein activity and paclitaxel metabolism in mice

Recombinant rIL-2 was reported to be able to decrease P-glycoprotein (P-gp) expression in cultured cells from human colon carcinoma. P-gp is considered an important factor in the control of Taxol efflux from tumor cells. Based on the premise that Taxol pharmacokinetic parameters could be modified as a result of diminished P-gp expression induced by recombinant interleukin (rIL)-2 and that this might elicit an interaction between the two drugs, we evaluated the pharmacokinetics of a novel strategy combining i.p. immunotherapy with rIL-2 and a cytotoxic agent, Taxol. Mice were allocated to two groups treated with rIL-2 (15 microg x 2/day from day 1 to 4) then Taxol (10 mg/kg i.p. day 5) or Taxol (10 mg/kg i.p.) alone (control group). The Taxol + rIL-2 combination provoked the development of ascites, presumably due to the presence of Cremophor EL in the Taxol preparation. Paclitaxel was measured in plasma and ascites by HPLC with UV detection. Paclitaxel pharmacokinetics were strongly modified by rIL-2 pretreatment. Compared to that observed in control mice, the apparent volume of distribution increased dramatically (Vd/F = 18.2 versus 4.1 l/kg) and the apparent plasma clearance decreased (Cl/F = 1.12 versus 1.66 l/h/kg). P-gp expression was determined in the liver, lung, intestine, brain and kidney in the two groups by immunodetection with the C219 anti-P-gp monoclonal antibody. A significant decrease in P-gp expression was observed in the intestine and in the brain in the rIL-2-pretreated mice as compared to controls. To study the functionality of P-gp, we compared digoxin (a model P-gp substrate) pharmacokinetics before and after pretreatment with rIL-2 (10 microg x 2/day from day 1 to 4), after a single 1 microg oral dose of digoxin used to quantify P-gp activity. Results showed a decrease in oral digoxin clearance after rIL-2 pretreatment indicating modified P-gp activity. We conclude that rIL-2 pretreatment is able to decrease P-gp activity and paclitaxel metabolism in vivo. This is the first study to demonstrate a decrease in P-gp activity and expression in organs such as the brain in vivo. A novel strategy combining immunotherapy with rIL-2 and a cytotoxic agent could potentially improve clinical results, particularly in brain cancer.     

Characterization of an O-glycosylated plaque-associated protein from Alzheimer disease brain

In this work we characterized a 90-kDa glycoprotein from Alzheimer disease (9OAzgp) brain extracts that is recognized by the GalNAc-specific lectin from Amaranthus leucocarpus (ALL), as determined through Western blot. The 90Azgp was purified by electro-elution, and its amino acid sequence determined from peptides obtained after trypsin digestion through MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight), and compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/2001) database. The 90Azgp showed 32% and 42% homology with the KIAA0310 protein from human brain and the human gastric mucin, respectively. Presence of O-glycosidically linked glycans in the proteins recognized by ALL was confirmed by inhibition of the lectin-glycoprotein interaction through hapten-inhibition assays and also by elimination of the O-glycosidically linked glycans after treatment with O-glycanase from Diplococcus pneumoniae. Electron transmission microscopy confirmed that the receptor recognized by the lectin is processed in the Golgi apparatus of AD neurons. Although the specific role of this glycoprotein has not been identified, considering that the presence of this lectin receptor co-localized with neuritic plaques and in AD sprouting neurons, it could suggest that the O-glycosyl-protein identified by the A. leucocarpus lectin participates in the pathogenesis of neurodegenerative diseases.     

Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia

Theory of mind (ToM), the specific ability to attribute thoughts and feelings to oneself and others is generally impaired in schizophrenia. Previous studies demonstrated a deficit of the attribution of intentions to others among patients having formal thought disorder. During nonverbal tasks, such a function requires both the visual perception of human figures and the understanding of their intentions. These processes are considered to involve the superior temporal sulcus and the medial prefrontal cortex, respectively. Are the functional patterns of activation associated with those processes abnormal in schizophrenia? Seven schizophrenic patients on medication performed a nonverbal attribution of intentions task as well as two matched physical logic tasks, with and without human figures, while H2O15 PET-scanning was performed. Data from the patients were compared to those of eight healthy controls matched for verbal IQ and sex. The experimental design allowed dissociating the effect of the perception of human figures from that of the attribution of intentions. During attribution of intentions, significant activations in the right prefrontal cortex were detected in the control subjects. Those activations were not found in the schizophrenic group. However, in both groups, the perception of human figure elicited bilateral activation of the occipitotemporal regions and of the posterior part of the superior temporal sulcus. Schizophrenic patients performing a nonverbal attribution of intentions task have an abnormal cerebral activity.