Prognostic value of quality-of-life scores in patients with breast cancer undergoing preoperative chemotherapy.

Background: Recently, evaluation of quality of life (QOL) has been recognized as a significant outcome measure in the treatment of several cancers. In this study, the Anti-Cancer Drugs-Breast (ACD-B) QOL score was used to assess disease-specific survival in women with breast cancer undergoing preoperative chemotherapy (POC). Methods: QOL-ACD-B scores were evaluated before and after POC. The cut-off value of QOL-ACD-B contributing to events such as relapse or death was calculated by receiver operating characteristic (ROC) curve analysis. Results: In 300 women with breast cancer treated with POC, QOL was significantly reduced (P < 0·001). A high QOL-ACD-B score before POC was an independent factor in the multivariable analysis of overall survival (hazard ratio 0·26, 95 per cent c.i. 0·04 to 0·96). Conclusion: Evaluation by QOL-ACD-B before POC may be useful to predict the prognosis of patients with breast cancer undergoing POC.

Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in fine-needle aspirates from early breast carcinomas: pre-operative determination of malignant potential.

AIMS: Although axillary lymph nodes status, tumour size, hormonal-receptor status and histological grade at diagnosis are frequently used to orient the treatment of breast cancer patients, some tumours recur in patients with early stage disease. Pre-operative assessment of individual tumour characteristics, based on oncogenes and growth factors related to tumour growth, invasion or metastasis, may guide the treatment for patients with breast carcinomas. METHODS: We examine here the prognostic significance of cyclin D1, urokinase type plasminogen activator, vascular endothelial growth factor (VEGF), platelet-derived growth factor, and c-erbB2 expression in pre-operatively obtained fine-needle aspirates from breast carcinomas less than or equal to 3 cm in size. Correlation between mRNA expression of these factors and clinicopathological characteristics was analysed. RESULTS: The level of c-erbB2 mRNA expression was significantly higher in tumours with lymph node metastases than in those without lymph node metastases. VEGF mRNA expression positively correlated with the degree of angiogenesis as quantitated by immunohistological staining with a CD31 monoclonal antibody. CONCLUSIONS: Analysis of c-erbB2 and VEGF mRNA expression in fine-needle aspirates may be useful in assessing the malignant potential of individual breast carcinomas, leading to a pre-operative discrimination of a high-risk group.

Preoperative assessment of tumor angiogenesis by vascular endothelial growth factor mRNA expression in homogenate samples of breast carcinoma: fine-needle aspirates vs. resection samples.

BACKGROUND AND OBJECTIVES: Tumor angiogenesis is receiving increased attention as a prognostic factor and also as a possible target for new anticancer agents. We investigated whether extent of vascular endothelial growth factor (VEGF) mRNA expression correlated with degree of neovascularization, and whether this expression in fine-needle aspirates could be a marker for assessing angiogenic potential of breast tumors. METHODS: VEGF mRNA expression was semiquantitated by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blotting. Tumor neovascularization was assessed by immunohistochemical staining with anti-CD31 (PECAM) antibody. RESULTS: There was a positive correlation between degree of neovascularization and semiquantitated VEGF mRNA expression in invasive ductal carcinomas (r2 = 0.346, n = 48, P < 0.05). Extent of VEGF mRNA expression in fine-needle aspirates was closely correlated with that in resected invasive ductal carcinomas equal to or less than 3 cm in size (r2 = 0.874, n = 14, P < 0.05). CONCLUSION: These data suggest that semiquantitation of VEGF mRNA expression in fine-needle aspirates is useful for assessing angiogenic potential of invasive ductal carcinomas.

Immunologic assessment of host defense impairment in patients with septic multiple organ failure: relationship between complement activation and changes in neutrophil function.

BACKGROUND: The pathogenesis of gram-negative sepsis-induced multiple organ failure (MOF) remains to be elucidated. METHODS: Blood samples were obtained from eleven patients with septic MOF, three patients with sepsis, three patients who underwent operation, and three healthy volunteers. In these patients the relationship between changes in polymorphonuclear neutrophil (PMN) function and complement activation was investigated. RESULTS: PMNs from patients with sepsis exhibited enhanced endothelial cell adhesion, enhanced chemotaxis, increased oxygen radical generation, and increased lysosomal enzyme release. Although PMNs from patients with septic MOF also exhibited enhanced adhesion and chemical mediator production, chemotaxis was markedly depressed. Complement activation in septic MOF was indicated by decreases in total complement activity and complement component 4 (C4) and increases in C3a and C4a des-Arginine. Increases in plasma concentrations of circulating immunoglobulin G immune complexes and decreases in PMN Fc gamma R expression suggest that the classic pathway is the main pathway of complement activation. On the other hand, we could not detect decreases in C4 or increases in C4a des-Arginine in patients with sepsis, suggesting that the alternate pathway is the main pathway of complement activation. Increases in serum concentrations of the membrane attack (SC5b-9) complex also suggested that activated complement itself may participate in organ injury in patients with septic MOF. Moreover, PMN up-regulation of surface inhibitory factors of complement activation likely allows these neutrophils to survive and function. CONCLUSIONS: The combination of changes in PMN function and complement activation appears to be intimately associated with the pathogenesis of septic MOF.

[Immunological assessment of the pathogenesis of septic-MOF: relationship between complement activation and changes in neutrophil functions].

We investigated the pathogenesis of septic-MOF through the relationship between changes in neutrophil functions and degree of complement activation. The patients' neutrophils exhibited enhanced adherence to HUVEC, suppressed chemotaxis toward C5a, enhanced production of oxygen radicals and lysosomal enzymes. These changes in neutrophil functions related to complement activation elicited via classical pathway. Moreover, the activated complement participated in tissue injuries due to the cytolytic action of the terminal complement complexes such as membrane attack complex (MAC). In conclusion, the combination of neutrophil and complement was strongly associated with the pathogenesis of the septic-MOF.