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M G Daidone

Publications and source records attributed to M G Daidone.

At least 91 records · Page 5Linked to original sources
PubMed1990

Proliferative activity of primary breast cancer and of synchronous lymph node metastases evaluated by [3H]-thymidine labelling index.

The [3H]-thymidine labelling index ([3H]TdR LI) has been used to evaluate and comparatively analyse the proliferative activity of different tumour lesions from the same patient. The analysis was performed on the primary tumour and its synchronous lymph node metastasis from 210 patients operated on for breast cancer. A direct relation was observed between the proliferative activity of the two different lesions (Spearman correlation coefficient = 0.46, P less than 0.0001), but there was considerable scatter amongst the data. The [3H]TdR LI of primary and of metastatic lesions belonged to the same proliferation classes in only 47% of the cases. Higher or lower [3H]TdR LI values, categorized on the basis of the tertiles of the frequency distribution, occurred in the node metastasis than in the primary tumour in an almost similar percentage of the remaining cases. Menopause, receptor status and pathological features did not affect interlesion kinetic patterns. The prognostic role of the proliferative activity of the two different lesions was investigated on 107 patients with stage II tumours homogeneously treated with surgery and systemic adjuvant therapy. Relapse-free survival at 3 years was significantly affected by the proliferative activity of the primary tumour but not by that of the lymph node metastasis.

Breast Neoplasms↗
PubMed1990

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer.

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.

Analysis of Variance↗
PubMed1990

Purine salvage enzyme activities in normal and neoplastic human tissues.

The enzymatic pattern of five enzymes involved in the purine salvage pathway, namely purine nucleoside phosphorylase (EC 2.4.2.1), adenosine deaminase (EC 3.5.4.4), 5'-nucleotidase (EC 3.1.3.5), alkaline phosphatase (EC 3.1.3.1), and hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) has been evaluated both in human intestinal and breast carcinomas and compared to that of normal tissues. A higher level of hypoxanthine-guanine phosphoribosyltransferase was associated with tumor tissues. This metabolic alteration should lead to an elevated synthesis of nucleotides in cancer cells, might confer selective growth advantages to neoplastic tissues, and account, at least in part, for the difficulties encountered in the chemotherapy of human tumors, by using compounds affecting only the purine de novo biosynthesis.

5'-Nucleotidase↗
PubMed1989

Cell kinetics of solid tumors with time and its clinical implication.

The proliferative rate has been evaluated for several human tumor types as the fraction of cells in S-phase. The methodologies most often used are autoradiographic determination of 3H-thymidine incorporation and flow cytometric evaluation of DNA content. Cell kinetics determined on various solid primary tumors at the time of diagnosis is not related to pathologic stage but it is an indicator of clinical evolution of the disease similar or superior to other biologic and pathologic prognostic factors. In early disease, submitted to loco-regional treatment as a first-line therapy, the rate of cell proliferation provides prognostic information on relapse-free and overall survival. In this clinical situation, a different metastatic potential can be attributed to tumors with different proliferative rates. In more extensive disease, submitted to systemic treatment, proliferation indices generally influence overall survival, eventhough in responsive tumors a fast proliferative activity could be indicative of higher aggressiveness and remarkable chemosensitiveness. Proliferation indices of the metachronous metastatic lesions is increased over those of the primary tumors as a further evidence of the association between proliferative activity and disease progression.

Cell Division↗
PubMed1989

Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma.

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.

Antineoplastic Agents↗
PubMed1989

Cell kinetics: a prognostic marker in epithelial ovarian cancer.

The proliferative activities (3H-thymidine labeling index, LI) of 72 primary ovarian cancers and 76 metastatic lesions from untreated patients were evaluated. Overall, median LI values for primary and metastatic lesions were similar (7.8 vs 7.0%), but cell kinetics significantly differed in metastases from different sites. The LI of the primary tumor was unrelated to pathologic stage and histology, but was significantly correlated with histologic grading (P = .014). The prognostic relevance of LI was assessed for 43 untreated patients at stage III-IV (90% with bulky residual disease), treated after staging laparatomy with five cycles of cisplatin or of carboplatin. For 19 patients the LI was determined for both primary tumor and metastases, for 15 for the primary, and for 12 for the metastatic lesions. Complete remission (CR) was unrelated to pretreatment LI, although a trend toward a higher rate of CR was observed with rapidly proliferating tumors. Patients with slowly proliferating primary tumors had a higher probability of 1.5-year survival than patients with rapidly proliferating tumors (83 vs 50%). The difference was even greater between patients with both primary and metastatic lesions proliferating slowly (100%) and patients with at least one (61%) or both lesions proliferating rapidly (60%). Pretreatment LI was not predictive for survival in subgroups of patients who attained CR, but it was quite predictive for survival in patients responding only partially or not at all (90 vs 32%, P = .025).

Antineoplastic Agents↗
PubMed1989

Cell kinetics as a prognostic indicator in node-negative breast cancer.

The consistency of the prognostic role of cell kinetics (evaluated as the [3H]thymidine labeling index, LI) over a period of years has been assessed in 354 patients with resectable node-negative breast cancer subjected only to Halsted or modified radical mastectomy. The risk of disease recurrence and death was proportional to LI values and the pattern was superimposable, regardless of menopausal status, in the two consecutive case series entered in this retrospective study. In particular, tumors with high LI (greater than 2.8%) had a higher 6-year probability (41% vs. 25%, P less than 0.0001) of manifesting local-regional and distant metastases and of dying (19% vs. 5%, P = 0.0005) as compared to tumors with low LI. In tumors with high LI the risk of relapse within the first 2 years from mastectomy was twofold compared to that of tumors with low LI. Multiple regression analysis showed that LI also retained its prognostic significance in both relapse-free and overall survival when tumor size and estrogen receptor status were considered. The present findings confirm that LI can substantially contribute to the selection of high risk node-negative patients who could be candidates for adjuvant chemotherapy.

Adult↗
PubMed1988

Drug sensitivity of different tumor lesions from the same patient evaluated by a short-term assay.

A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p less than 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p less than 0.01), but not to that of the primary tumor.

Antineoplastic Agents↗
PubMed1987

Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay.

An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.

Antineoplastic Agents↗
PubMed1987

Cell kinetics as a prognostic marker in locally advanced breast cancer.

The study analyzes the prognostic implication of cell kinetics on 52 locally advanced breast cancers. All patients were subjected to a multimodal treatment, including primary chemotherapy with doxorubicin and vincristine, surgery, or radiotherapy followed by additional chemotherapy with the same drug regimen. Pretreatment labeling index (LI) is not related to response to primary chemotherapy, whereas it provides information on the course of the disease. In fact, high LI significantly predicts a higher progression rate at the end of the entire combined treatment, a shorter time to disease progression, and a poorer probability of 4-year survival in comparison to low LI. From the present findings, LI appears to be a useful tool to select women with locally advanced breast cancer that would require very aggressive treatment.

Breast Neoplasms↗
PubMed1986

Prognostic implication of labeling index versus estrogen receptors and tumor size in node-negative breast cancer.

The paper analyzes the relation among tumor size (T), estrogen receptor (ER) status, and labeling index (LI) and their relative merits in predicting the relapse-free (RFS) and overall survival (OS) in 215 node-negative women with primary breast cancer. All patients were subjected to Halsted or modified radical mastectomy; none received postoperative irradiation or systemic adjuvant therapy. The 5-year RFS was 75.3% and OS 89.0%. When singly tested, LI and ER were able to significantly predict RFS and OS. In contrast, T influenced only RFS but not OS. The multivariate analysis showed that, in the presence of the two other variables, only LI retained its prognostic significance both for time to relapse (p = 0.0044) and survival (p = 0.035). From the present findings, LI appears to be a new important prognostic variable in the selection of high risk patients for whom adjuvant systemic therapy should perhaps be part of their primary treatment.

Axilla↗
PubMed1986

Cell kinetics of human epithelial ovarian cancers.

Tumor cellular proliferative activity was evaluated by 3H-thymidine labeling index (LI) determination in 73 lesions from 62 patients with ovarian cancers. The median LI value for the overall series was 5.8% and places this tumor type in a position of intermediate proliferative activity. In this case series, the relationship between proliferative activity and different morphologic and pathologic characteristics of the disease was analyzed. Similar median LI values were found for ascitic effusions and solid tumors and, among these, between primary tumors and metastases. No significant relation was observed between proliferative activity and histologic type, whereas a definite direct correlation was found between the kinetic variable and prognostic features such as pathologic stage and histologic grading. In fact median LI was higher for stage IV for stage I and for grade 3 than for grade 1 tumors. The strong association between tumor proliferative rate and conventional prognostic factors suggests that also on this tumor type the kinetic variable could play a role as a prognostic indicator and modulator of aggressiveness.

Adenocarcinoma↗
PubMed1986

Breast cancer: implications of tumor cell kinetics on clinical outcome.

The relevance of tumor proliferative activity as an indicator of biologic aggressiveness was analyzed on a series of 506 patients with primary breast cancer. In 258 patients with operable tumors without nodal and distant metastases, none of whom was subjected to postoperative irradiation or systemic adjuvant therapy, proliferative activity was significantly correlated with prognosis; 6-year relapse-free survival (RFS) and overall survival (OS) were higher for patients with slowly proliferating tumors for patient with fast-proliferating tumors (RFS: 80.5% vs 59.6%, p = 0.00004; OS: 90.8% vs 74.4%, p = 0.002). On a series of 196 patients with node-positive operable tumors, subjected to 6 or 12 cycles of cyclophosphamide, methotrexate and 5-fluorouracil, a trend in favor of longer 6-year RFS was observed for patients with slowly proliferating tumors than for patients with fast-proliferating tumors (62.5% vs 48.3%, p = 0.08), whereas proliferative activity did not influence OS. In 52 patients with locally advanced disease treated with a multimodality approach, including chemotherapy (adriamycin and vincristine), surgery or radiotherapy, tumor proliferative activity was a strong indicator of biologic aggressivity, since women with slowly proliferating cancers had a higher 4-year probability of OS than women with fast-proliferating tumors (68.1% vs 36.7%, p = 0.02).

Actuarial Analysis↗
PubMed1985

In vitro activity of alkylating agents on human tumors as measured by a short-term antimetabolic assay.

The activity of some alkylating agents widely used in clinical practice was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. The effect of CCNU, chlorambucil, cisplatin, melphalan, prednimustine, procarbazine and the pro-active derivatives of cyclophosphamide and ifosfamide, 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide, was tested on non-Hodgkin lymphomas, germ cell testicular tumors, breast and ovarian cancers. Similar effects were generally produced by the drugs on both DNA and RNA precursor incorporation, and the in vitro response rates were similar to those clinically obtained for the same tumor types by using the same drugs in monochemotherapy. The effects of different alkylating agents on the individual tumors were not significantly associated, except for the analogues 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide, for which a significant agreement rate was observed. No evidence of acquired resistance to 4-hydroperoxycyclophosphamide and cisplatin after clinical treatment with the same drug was found in samples from ovarian cancer and non-Hodgkin lymphoma, but there was a definite trend in germ cell testicular tumors to lower sensitivity to cisplatin in previously treated patients.

Alkylating Agents↗
PubMed1985

Cell kinetics as a prognostic marker in node-negative breast cancer.

The relevance of cell kinetics of the primary tumor as a marker of biologic aggressivity was verified on a series of 258 patients with operable breast cancer without nodal and distant metastases, who underwent radical mastectomy without any other treatment until relapse. The cell proliferative rate, evaluated in vitro on fresh tumor material and expressed as 3H-thymidine labeling index, was found to be an important discriminant of metastatic potential. Patients with slowly proliferating tumors showed a higher probability of 6-year relapse-free survival in comparison to those with fast-proliferating tumors (80.5% versus 59.6%, P = 0.00004). This finding was true for premenopausal and paramenopausal (P = 0.00005) as well as for postmenopausal patients (P = 0.01). The kinetic variable was also a discriminant of 6-year survival for the overall series (P = 0.003) and for premenopausal and paramenopausal patients (P = 0.003) regardless of the type of treatment after relapse. These findings show the relevance of the kinetic variable as an important prognostic marker in breast cancer.

Actuarial Analysis↗
PubMed1985

Reliability of an in vitro short-term assay to predict the drug sensitivity of human breast cancer.

The feasibility and reliability of an in vitro assay that evaluates drug interference on nucleic acid precursor incorporation were investigated on 135 previously untreated locally advanced breast cancers. The assay, which was carried out on tumor fragments incubated for 3 hours with drugs, proved to be feasible on a sufficiently high percentage of biopsy specimens (70%) for routine clinical use. In vitro drug activity evaluated with this assay appeared to reproduce the clinical patterns of sensitivity of the tumor type as well as of the individual tumors. In fact, in vitro response rates to conventional agents resembled the clinical response rates reported for the same agents used in monochemotherapy. From a retrospective--correlative study carried out on 41 patients treated in vitro and in vivo with the same drugs (Adriamycin [doxorubicin] and vincristine), in vitro effect of Adriamycin on 3H-uridine incorporation appeared significantly correlated with clinical response (overall agreement, 78%; P = 0.0032) with specific agreements of sensitivity and resistance of 75% and 81%, respectively.

Antineoplastic Combined Chemotherapy Protocols↗