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  • 1
    Electronic Resource
    Electronic Resource
    Cytosol cathepsin-D content and proliferative activity of human breast cancer (1992)
    Springer
    Breast cancer research and treatment 23 (1992), S. 63-70 
    Details
    ISSN: 1573-7217
    Keywords: cathepsin-D ; proliferative activity ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitogenic properties have been demonstratedin vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p〈0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = −0.6828; p=0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01831477
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  • 2
    Electronic Resource
    Electronic Resource
    Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients (1997)
    Springer
    Supportive care in cancer 5 (1997), S. 130-135 
    Details
    ISSN: 1433-7339
    Keywords: Cancer ; Anorexia ; Cachexia ; Tumour necrosis factor ; Interleukin ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (\gg-IFN)] as possible cofactors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was indentified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P=0.03 andP〈0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P〈0.001 for both), wrist circumference (P〈0.001 for both), KPS (P〈0.001 andP=0.003, respectively) and creatinine (P=0.005 andP=0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of the two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01262570
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  • 3
    Electronic Resource
    Electronic Resource
    Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients (1997)
    Springer
    Supportive care in cancer 5 (1997), S. 130-135 
    Details
    ISSN: 1433-7339
    Keywords: Key words Cancer ; Anorexia ; Cachexia ; Tumour necrosis factor ; Interleukin ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (γ-IFN)] as possible cofactors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was indentified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P=0.03 and P〈0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P〈0.001 for both), wrist circumference (P〈0.001 for both), KPS (P〈0.001 and P=0.003, respectively) and creatinine (P=0.005 and P=0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of the two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01262570
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  • 4
    Electronic Resource
    Electronic Resource
    Adjuvant adoptive immunotherapy with tumour-infiltrating lymphocytes and modulated doses of interleukin-2 in 22 patients with melanoma, colorectal and renal cancer, after radical metastasectomy, and in 12 advanced patients (1998)
    Springer
    Cancer immunology immunotherapy 46 (1998), S. 185-193 
    Details
    ISSN: 1432-0851
    Keywords: Key words Adoptive immunotherapy ; Interleukin-2 ; Tumour-infiltrating lymphocytes ; ζ chain-p56lck
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Adoptive tumour infiltrating lymphocytes (TIL) in combination with a modulated dosage of interleukin-2 (IL-2) can be used with acceptable toxicity in the treatment of immunogenic tumours. Following an experience of reinfusion in advanced melanoma, colorectal and renal cancer patients, treatment was given to disease-free patients after metastasectomy. The high risk of relapse and favourable ratio between reinfused TIL and possible microscopic residual disease determined this choice of adjuvant treatment. A group of 12 patients with advanced disease (7 melanoma, 4 colorectal carcinoma, 1 kidney carcinoma) were treated with TIL (median 5.8×1010 cells) and IL-2 (West’s schedule) modulated towards a lower dosage (from 12 to 6 MIU/day) in order to maintain an acceptable level of toxicity. As treatment was well tolerated, it was offered to another 22 patients in an adjuvant setting after metastasectomy (11 melanoma, 10 colorectal carcinoma, 1 renal cancer), the median dose of TIL reinfused being 4.95×1010 cells. No objective response was observed in advanced patients: all patients progressed after a median of 1.5 months (0–8 months) and median survival was 8 months (3–22+ months). Thirteen patients from the second group are still disease-free after a median of 23+ months (9+–47+ months). The remaining 9 patients relapsed after a median of 5 months (3–18 months). Toxicity was moderate as clinical and hepatic/renal function parameters were used to assess the need for dose reductions. Consequently, there was great diversity in IL-2 dosages administered. In particular, there seemed to be a difference in IL-2 doses administered between disease-free cases and those who progressed (17.5 MIU/day versus 7 MIU/day in melanoma patients; 11.2 MIU/day versus 7.1 MIU/day in colorectal cancer patients). By contrast, no differences were observed between number of TIL reinfused and clinical response. Phenotypical characteristics of reinfused TIL were similar to those reported in the literature: 97% were CD3 and 92% were CD8. Aspecific cytolytic activity was evaluated on 12 cases whereas, in 2 melanoma cases, autologous tumour tissue was available for the specific cytotoxicity test. Perforin levels in TIL measured at the end of culture were generally high or very high. Cytokine levels were measured on the supernatant at the end of culture, with an estreme variability in results. Finally, ζ chain and p56lck were histologically assessed on the resected tissue from which TIL were cultivated. There were virtually none of the former and a complete absence of the latter, which concurs with data reported in the literature. The same immunocytochemical analysis was carried out on TIL at the end of culture. This time an almost complete restoration of both functions was seen, especially in melanoma patients, who are still free from disease. The study is on-going and it has been decided to focus on disease-free patients after metastasectomy in order to increase the number and possibility of clinical and histological correlations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050477
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  • 5
    Electronic Resource
    Electronic Resource
    An efficient method for culturing human breast carcinoma to evaluate antiblastic drug activityin vitro: Experience on 136 primary cancers and on 116 recurrences (1991)
    Springer
    Breast cancer research and treatment 17 (1991), S. 231-238 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer cell culture ; chemosensitivity assay ; in vitro ; drug response ; doxorubicin ; epidoxorubicin ; vinblastine ; cis platinum ; idarubicinol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The feasibility of techniques developed for isolating and culturing human mammary epithelial cells of malignant origin was confirmed in 136 primary breast cancers, 116 hypodermal metastases, and 8 metastatic lymph nodes. In 115 (84%) primary breast cancers and in 81 (70%) hypodermal recurrences we observed a goodin vitro cellular proliferation. These proliferating cells, at the second passage, were used for a clonal assay suitable for quantitating drug sensitivity. With this clonal assay median cloning efficiencies of 14% and 6% were obtained respectively in primaries and in skin recurrences. We examined thein vitro response to different drugs and confirmed the test's ability to detect heterogeneity in response to same drugs (doxorubicin, 4′-epidoxorubicin, vinblastine, cis platinum, and idarubicinol) among the different breast carcinoma cultures as well as heterogeneity among subpopulations within a single carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01806372
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  • 6
    Electronic Resource
    Electronic Resource
    Cell kinetics and hormonal features in relation to pathological stage in breast cancer (1991)
    Springer
    Breast cancer research and treatment 18 (1991), S. 19-25 
    Details
    ISSN: 1573-7217
    Keywords: thymidine labeling index ; proliferative rate ; estrogen receptors ; progesterone receptors ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferative activity (expressed as3H-thymidine labeling index,3H-TdR LI) was evaluated on a series of 281 primary tumors recruited in two years in 6 different institutions from central Italy.3H-TdR LI proved to be low in intraductal, or well and moderately differentiated, or hormone receptor positive tumors. Conversely, no relation was observed between3H-TdR LI and menopause, tumor size, or lymph node involvement. An inverse relation was observed between3H-TdR LI and hormone receptor content. Specific patterns of3H-TdR LI value and ER content association were observed as a function of menopause, lymph nodal status, and degree of lymph nodal involvement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01975439
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  • 7
    Electronic Resource
    Electronic Resource
    Prognostic significance of biologic markers in node-negative breast cancer patients: a prospective study (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 181-192 
    Details
    ISSN: 1573-7217
    Keywords: biologic markers ; node-negative breast cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally thought that future advances in the treatment and cure of breast cancer patients will be made possible through a deeper understanding of tumor biology and an improved capability to define the prognosis of each single patient. This will lead to the formulation of new, more selective, and patient-tailored therapies. It is therefore important, when studying potential prognostic factors, to follow methodologic requirements and guidelines which involve the carrying out of prospective studies as confirmatory steps. Repeatedly or recently investigated prognostic markers (tumor size, menopausal status, ER, PgR, 3H thymidine labeling index, c-erbB-2 and p27 expression) were evaluated on a series of 286 prospectively recruited node negative breast cancer patients who underwent loco-regional treatment alone and were closely followed. The individual and relative prognostic contribution of each variable with respect to other factors, as well as their ability to identify node negative patients at risk, were assessed by univariate and multivariate analysis. At a five-year follow-up, only tumor size (p = 0.021) and TLI (p = 0.016) individually proved to be significant prognostic indicators of relapse-free survival. Conversely, p27 expression was not related to RFS and c-erbB-2 expression appeared to have only a short-term effect on patient prognosis. TLI and tumor size, tested in multivariate analysis along with ER and menopausal status, maintained their independent prognostic relevance. The study, performed on a large series of node-negative patients given loco-regional treatment alone, for the first time prospectively recruited, showed the prognostic relevance of TLI and its independence from other clinico-pathologic and biologic factors over a five-year period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006464426977
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  • 8
    Electronic Resource
    Electronic Resource
    Quantitative immunohistochemical determination of cathepsin-D and its relation with other variables (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 7-13 
    Details
    ISSN: 1573-7217
    Keywords: Cathepsin D ; hormone receptors ; immunohistochemistry ; proliferative activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of cathepsin D was evaluated by immunohistochemistry on histologic sections from formalinfixed samples in a series of 436 primary breast cancers. The fraction of cathepsin D-positive tumor cells was not related to tumor size or hormone receptor status, and only weakly related to proliferative activity, evaluated as the3H-thymidine labeling index. Conversely, a higher fraction of positive cells was observed in nodepositive than in node-negative tumors (p = 0.05). A matched comparison between immunohistochemical and immunoradiometric results on individual tumors was carried out on 100 cases and showed a significant association but with a correlation coefficient of 0.46. The agreement of results from the two assays was higher in ER− than in ER+ tumors, which sometimes showed an immunostaining limited to macrophages and normal epithelial cells. In situ evaluation has the main advantage of being specifically applicable to detection in tumor cells and allows the simultaneous determination of different biologic aspects for a more complete understanding of breast cancer biology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682695
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