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L Dal Maso,
M Lise,
P Zambon,
F Falcini,
E Crocetti,
D Serraino,
C Cirilli,
R Zanetti,
M Vercelli,
S Ferretti,
F Stracci,
V De Lisi,
S Busco, G Tagliabue,
M Budroni,
R Tumino,
A Giacomin,
S Franceschi
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ABSTRACT: In Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported.
TC cases <85 years of age reported to Italian cancer registries during 1991-2005 were included. Age-standardized IRs were computed for all TC and age-period-cohort effects were estimated for papillary TC.
IRs of TC were twofold higher in 2001-2005 than in 1991-1995 (18 and 8 per 100,000 women, 6 and 3 per 100,000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age-period-cohort models showed a strong period effect in both sexes (rate ratio for 2001-2009 versus 1991-1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45-49 years) than men (65-69 years).
The strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated.
Annals of Oncology 10/2010; 22(4):957-63. · 6.43 Impact Factor
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L Dal Maso,
J Polesel,
D Serraino,
M Lise,
P Piselli,
F Falcini,
A Russo,
T Intrieri,
M Vercelli,
P Zambon, [......],
A Donato,
A Giacomin,
F Bellù,
M Fusco,
A Madeddu,
S Vitarelli,
R Tessandori,
R Tumino,
B Suligoi,
S Franceschi
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ABSTRACT: A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16-69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997-2004 compared with 1986-1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997-2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.
British Journal of Cancer 02/2009; 100(5):840-7. · 5.04 Impact Factor
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G Corrao,
A Zambon,
V Conti,
F Nicotra,
C La Vecchia,
C Fornari,
G Cesana,
P Contiero, G Tagliabue,
R E Nappi,
L Merlino
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ABSTRACT: The effects of persistence with hormone replacement therapy (HRT) on the risk of hospitalization for cancer and of the route of HRT administration on the risk of breast and colorectal cancer were explored in a large cohort study.
The 73 505 women residing in Lombardia (Italy), aged 45-75 years, who received at least one HRT prescription during 1998-2000 were followed until 2005. Among these, 3687 experienced cancer hospitalization. Proportional hazards model was fitted to estimate the association between cumulative HRT persistence and cancer risk.
Compared with women who took HRT for <6 months, those exposed for >2 years showed hazard ratios (HR) of 0.78 (95% confidence interval 0.68-0.92) for colorectal cancer and 1.34 (1.13-1.58) for breast cancer. HR for breast cancer associated with long-term use of transdermal and oral HRT were, respectively, 1.27 (1.07-1.51) and 2.14 (1.43-3.21).
Evidence that long-term use of HRT is associated with increased risk of breast cancer and decreased risk of colorectal cancer is supplied from this study from a southern European population. Our findings indicate that transdermal therapy might have lower effect than oral therapy in increasing breast cancer risk.
Annals of Oncology 01/2008; 19(1):150-5. · 6.43 Impact Factor
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ABSTRACT: Record linkage, the process of bringing together separately compiled but related records from different databases, is essential in many areas of biomedical research. We developed a record linkage program (EpiLink), which employs a simple mathematical approach. We describe the program and present results obtained testing it in a linkage task.
EpiLink was designed to be flexible with user-friendly settings to tailor linkage and operating parameters to specific linkage tasks, and employ deterministic, probabilistic or sequential deterministic-probabilistic linkage strategies as required. The user can also standardize data format, examine linkage results and accept or discard them. We used EpiLink to link a subset of cases of the Lombardy Cancer Registry (20,724 records) with the Social Security file of the population (1,021,846 records) covered by the registry. The linkage strategy was deterministic, followed by several probabilistic linkage steps.
Manual inspection of the results showed that EpiLink achieved 98.8% specificity and 96.5% sensitivity.
EpiLink is a practical and accurate means of linking records from different databases that can be used by non-statisticians and is efficient in terms of human and financial resources.
Methods of Information in Medicine 02/2005; 44(1):66-71. · 1.53 Impact Factor
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L Dal Maso,
J Polesel,
V Ascoli,
P Zambon,
M Budroni,
S Ferretti,
R Tumino, G Tagliabue,
S Patriarca,
M Federico, [......],
F Bellù,
F Falcini,
E Crocetti,
V De Lisi,
S Vitarelli,
S Piffer,
F Stracci,
D Serraino,
G Rezza,
S Franceschi
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ABSTRACT: To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life.
British Journal of Cancer 02/2005; 92(1):188-93. · 5.04 Impact Factor
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ABSTRACT: The aim of the study was to investigate the variations in prostate cancer prognosis during a period of major diagnostic change, such as the introduction of the prostate-specific antigen (PSA) test. Data were provided by 14 Italian cancer registries (CRs). Incidence and follow-up information was collected for patients diagnosed from 1978 to 1994. Relative survival was computed taking into account incidence period, age, tumour stage and grade at diagnosis. A multivariate analysis was carried out to evaluate the independent simultaneous effect on survival of some prognostic determinants. A large geographical variability was observed: in 1993-1994 Italian survival rates ranged from 76% to 52%, with a north-south gradient. A striking prognostic improvement (up to +27 percentage points) between the late 1980s and the early 1990s occurred in almost all CRs, particularly with regard to younger patients. Multivariate analysis showed a strong influence of incidence period on survival, also after correction by tumour stage. The slowdown of metastatic cancers suggests that the survival improvement could be due both to the introduction of an effective opportunistic screening and to a quantitative change in the application of clinical treatment, even if the effect of the lead-time bias phenomenon has to be taken into account.
European Journal of Cancer Prevention 05/2003; 12(2):145-52. · 2.13 Impact Factor
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IARC scientific publications 02/2002; 156:537-9.
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IARC scientific publications 02/2002; 156:535-6.
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IARC scientific publications 02/2002; 156:67-8.
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L Dal Maso,
G Rezza,
P Zambon, G Tagliabue,
E Crocetti,
M Vercelli,
R Zanetti,
F Falcini,
G Tonini,
L Mangone,
V De Lisi,
S Ferretti,
R Tumino,
G Stanta,
S Vitarelli,
D Serraino,
S Franceschi
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ABSTRACT: To compare the presentation and prognosis of non-Hodgkin lymphoma (NHL) in people with AIDS (PWA) and in the general Italian population, a record linkage study was carried out. The fraction of NHLs attributable to HIV/AIDS was also estimated. Information from the National AIDS Registry (RAIDS) was linked with records from 13 cancer registries (CR), covering about 15% of the Italian population. During the period 1985--94, among PWA ages 15--49, 136 NHLs were identified (8% of all NHLs) and were compared with 1,481 concurrent incident NHL cases of the same age group among non-PWA. Percentages above 13% of all NHLs were registered in the northern areas of Genoa and Varese, i.e., the most heavily affected by the AIDS epidemic. Between 1 year prior to and 3.5 years after AIDS diagnosis, PWA showed an overall standardised incidence ratio (SIR) for NHL of 302. SIR was particularly high (394) within 3 months after AIDS diagnosis and subsequently declined to 170. SIR was somewhat higher in females (428) than in males (280) but similar among intravenous-drug users (299) and other HIV-transmission groups (309). High-grade NHL, particularly immunoblastic and Burkitt's lymphoma, were twice as frequent among PWA than non-PWA. Conversely, low-grade NHL were less frequent. Except for the high proportion of brain localisation, no clear difference emerged in the pattern of NHL presentation site in PWA compared with non-PWA. At variance with NHL in the general population, among PWA histological grade had little impact on survival, which overall appeared to be very poor (2-year survival: 10%; 95% confidence interval: 3%--17%). Our present linkage of RAIDS and CRs represents an efficient tool for the surveillance of trends in incidence and survival of NHL among PWA in Italy.
International Journal of Cancer 09/2001; 93(3):430-5. · 5.44 Impact Factor
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ABSTRACT: The aim of this study is to evaluate the consistency between routine methods for coding urinary bladder tumours in eight Italian cancer registries and the European Network of cancer registries (ENCR) criteria. Furthermore, it aims to evaluating the impact of the discordance on survival data. Eight cancer registries took part in the study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and Varese. The first 100 cases of neoplasm of the urinary bladder incident in the years 1993-1994 were identified from the files of each registry. The original pathology reports were made available. A working group considered eligible to the study 699 cases of microscopically confirmed transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR criteria, each of these was classified according to morphology code (8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/ invasive). Information of tumour behaviour was classified as follows: (i) present, when expressly stated in the original report, (ii) deducible, when not expressly stated but suggested by the pathologist's description, and (iii) absent, when impossible to determine on the basis of the original pathology report. The working group classification of tumour behaviour and the classification of the registry of origin were compared. There was a full concordance in the case of complete agreement on the morphology code, and partial concordance when only the invasive or non-invasive behaviour code was agreed upon. As much as 92.5% cases were microscopically confirmed. Tumour behaviour was expressly stated in the original report of 69.2% cases, not stated but suggested by the pathologist's description in 21.2% cases, and impossible to determine in 9.6%. Agreement between the panel and the registry of origin was complete in 71.2% cases and partial in 12.3% while there was a complete discordance in 16.5% cases. The panel interpreted as non-invasive 111 cases coded as invasive by the registry of origin. Conversely, it was estimated that 24% cases included in incidence data were non-invasive. This article discusses the impact of misclassification on survival data.
Epidemiologia e prevenzione 02/2001; 25(3 Suppl):42-7. · 0.65 Impact Factor
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ABSTRACT: Twenty-three human xenografts, including five colon, five gastric, nine lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC), cyclophosphamide (CTX) and cisplatin (DDP). In 12 cases, at least one of the drugs produced complete or partial remission, in 2, a minor regression was observed and in the other 9, treatment was ineffective. The level of sensitivity to each drug, using a score from 1 to 5, was correlated to three biochemical parameters reported to be involved in resistance to alkylating agents: glutathione (GSH), glutathione transferase (GST) and O6-alkylguanine-DNA-alkyltransferase (AGT). A wide variability was found in these parameters in the xenografts investigated. No correlation was found between any of the three parameters and sensitivity to the drugs used or between sensitivity to one drug and to any of the other drugs tested. These results illustrate the complexity of the question of resistance to alkylating agents and indicate that, at least in xenografts, the biochemical parameters examined are not predictive of response to alkylating agents.
European Journal of Cancer 11/1998; 34(11):1749-55. · 5.54 Impact Factor
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ABSTRACT: Glutathione (GSH), glutathione S-transferase (GST) activity and GSTpi expression were measured in 10 human bladder tumors and adjacent uninvolved specimens from Egyptian patients with a history of schistosomal infection. GSH was higher in the tumor than in surrounding uninvolved tissue (not significant). Total GST activity per mg tissue protein and GSTpi expression were higher in tumor tissues (P < 0.05) than in uninvolved tissues. There was a positive correlation between GST activity and GSH content and between total GST activity and GSTpi expression in both tumor and uninvolved tissues.
Cancer Letters 01/1998; 121(1):19-23. · 4.24 Impact Factor
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ABSTRACT: Some new alkylating agents which bind to the minor groove of DNA and have sequence-specific patterns of alkylation have shown anti-neoplastic activity in pre-clinical systems. Two of them, carzelesin and tallimustine, are now in phase II. Considering the severe dose-limiting bone marrow toxicity of both these drugs in clinical use, it was of interest to investigate the mechanism of their myelotoxicity in a detailed pre-clinical study and compare it with a conventional alkylating agent, such as melphalan. The origin and progression of the myelotoxicity of carzelesin, tallimustine and melphalan were investigated comparatively in mice, combining data on bone marrow and peripheral blood cellularity with data on the proliferative activity of bone marrow cells, obtained by in vivo administration of bromodeoxyuridine. Significant differences were found between the hematopoietic response to the 3 drugs, though all caused severe leukopenia. Carzelesin induced a short-term increase in myeloid proliferative activity, which prevented the high leukocytopenia on day 3 observed with the other drugs. However, when this effect was exhausted, a second nadir was seen in peripheral blood, with a new wave of cell proliferation of all lineages in the bone marrow. Reconstruction of the lymphoid lineage was slow for all 3 drugs but particularly difficult with high-dose tallimustine. In general, the hematopoietic system response to tallimustine was dampened, with no overshoots, suggesting either lasting effects or extensive cytotoxicity from the early to late precursors of all lineages.
International Journal of Cancer 10/1997; 72(5):801-9. · 5.44 Impact Factor
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ABSTRACT: Conflicting data have been reported about the association between glutathione S-transferase (GST), a family of proteins implicated in detoxification of cytotoxic drugs in human ovarian in vitro models, and response to chemotherapy and prognosis in ovarian cancer patients. The aim of this study was to analyze the possible clinical role of GST activity in a large series of primary ovarian cancer patients.
The study included a large series of primary untreated ovarian cancer patients who underwent cytoreductive surgery and chemotherapy and who were followed up in a single institution. GST activity levels were assessed in tumor extracts by using a biochemical assay. A cut-off of 250 units of enzymatic activity was chosen according to the receiver operating characteristics (ROC) curve.
GST activity levels were distributed in an asymmetrical manner (median: 266 units; range: 4-918 units) and did not seem to be associated with stage, histopathological grading, ascites, or residual tumor after surgery. Higher GST activity levels were found in patients who responded to chemotherapy (median: 298 units, range: 50-691) than in those who responded only partially (median: 227 units, range: 19-747) or not at all to chemotherapy (median: 246 units, range: 4-811) (H = 7.02, P = 0.029). Moreover, the percentage of cases with > 250 units was significantly higher among complete responders (66%) than partial responders (37%) or non-responders (48%) (chi 2 = 7.32; P = 0.025). When multivariate analysis, including clinico-pathological parameters and GST activity status as predictors of response to chemotherapy, was carried out, residual tumor, stage and GST status retained independent predictive value. Patients with high GST activity had more favourable prognosis than those with low GST activity. The median PFS was 42 months for patients with high GST activity compared to 17 months for those with low GST activity (P = 0.037). The median overall survival was 72 months for high-GST-activity and 42 months for low-GST-activity patients (P = 0.043). Substantially similar results were obtained in the subgroup of stage II-III-IV ovarian cancer patients. Multivariate analysis including the clinico-pathological parameters and GST activity status was performed in stage III-IV ovarian cancer patients: Stage IV disease, residual tumor > 2 cm, the presence of ascites and low GST activity status retained independent negative prognostic roles.
A direct association between high GST activity and a better clinical outcome in terms of response to chemotherapy and survival has been observed in a large series of primary untreated ovarian cancer patients. These results, which are contrary to the expectations raised by in vitro studies, emphasize the need for caution when translating in vitro-generated hypotheses to the clinical setting.
Annals of Oncology 05/1997; 8(4):343-50. · 6.43 Impact Factor
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ABSTRACT: The benzoyl nitrogen mustard derivative of distamycin A, tallimustine, belongs to a new class of alkylating agents, known as DNA minor groove alkylating agents. It alkylates adenine N3 with high sequence specificity, causing no alkylation of guanine N7, the main site of alkylation of clinically used nitrogen mustards such as L-PAM. The present study investigated the in vivo antitumour activity of a combination of tallimustine and melphalan (L-PAM). Two murine tumours were used: i.p. (intraperitoneally) transplanted L1210 leukaemia and i.m. (intramuscularly) transplanted M5076 ovarian reticulum cell sarcoma (M5). In L1210, which is only marginally sensitive to tallimustine, the combination of tallimustine 3 mg/kg i.p. with L-PAM 10 mg/kg i.p. was as effective as 20 mg/kg L-PAM, which is the maximum tolerated dose. In M5, which is sensitive to both drugs, the combination was superior to either drug alone. The results suggest that the combination of tallimustine and L-PAM--or possibly in general, minor groove alkylators and major groove alkylators--may be therapeutically advantageous and therefore should be investigated clinically.
European Journal of Cancer 03/1997; 33(2):284-7. · 5.54 Impact Factor
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ABSTRACT: In order to simulate drug resistance observed in the clinic, two cisplatin-resistant cell lines were produced from a murine ovarian reticulosarcoma, M5076 (M5), by pulse (M5/CDDP) and continuous (M5/CDDPc) treatment with cis-diamminedichloroplatinum(II)(CDDP). These cell lines showed a similar stable low level of resistance (approximately 3-fold) to CDDP and cross-resistance to carboplatin, iproplatin and the new alkylating agent tallimustine, but not to L-PAM (L-phenylalanine mustard) and BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea). Collateral sensitivity to two inhibitors of topoisomerase II, VP16 (etoposide) and doxorubicin (Dox), but cross-resistance to the topoisomerase I inhibitor, camptothecin, were observed. The two cell lines were also sensitive to 5-fluorouracil. No increase in the level of glutathione or activity of glutathione S-transferase could be observed in resistant cells compared with the parental M5 cells. Total DNA platination immediately after treatment was similar in the parental and resistant cell lines. Repair of total DNA platination, measured after 24 h of recovery, was undetectable in M5 and M5/CDDP cells, but was 33% in M5/ CDDPc cells. Initial DNA-interstrand cross-links (DNA-ISC) were six times higher in M5 than in M5/CDDP cells, but 24 h after treatment, both lines had completely repaired this damage. M5/ CDDPc cells did not show formation of DNA-ISC at any time after treatment. The two resistant cell lines were tumorigenic when implanted in mice and resistant to CDDP treatment in vivo. The CDDP resistant tumours were not cross-resistant in vivo to L-PAM, BCNU and Dox, which had been active in vitro, nor to tallimustine, which had been cross-resistant in vitro. Mechanisms of resistance in M5/CDDP and M5-CDDPc seem to be based on a lower formation of DNA-ISC combined, for the latter cell line, with a higher repair capacity for total DNA platination.
European Journal of Cancer 11/1996; 32A(11):2011-8. · 5.54 Impact Factor
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ABSTRACT: In a series of 213 incident cases of laryngeal cancer, interviewed 10 years ago in the framework of a population-based case-control study, survival has been evaluated in relation to tobacco, alcohol consumption and dietary habits. The occurrence of other primaries and stage at diagnosis were taken into account as possible confounding factors. Heavy tobacco smoking appeared to worsen the prognosis in a dose-dependent manner. No effect was apparent for alcohol. The consumption of vegetables, citrus fruit, olive oil and orange juice was associated with a better prognosis; an opposite association was found for butter and milk. A tentative differentiation between dietary patterns showed a 36% advantage in survival for those whose dietary habits corresponded to the "Mediterranean diet". Our results support the hypothesis that diet may interfere with the mechanisms of cancer progression, and suggest that dietary intervention could be a means of improving survival in laryngeal cancer patients.
International Journal of Cancer 02/1996; 65(3):308-13. · 5.44 Impact Factor
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ABSTRACT: The glutathione (GSH)-glutathione S-transferase (GST) detoxification system is an important element in cellular defence against injurious agents and anticancer drugs. GST isoenzymes may represent biochemical markers of neoplastic transformation, and, possibly, drug resistance is associated with altered GST-isoenzyme levels. The ability to measure GST-isoenzymes in cell populations would be useful for several biological and clinical applications. We have developed an immunofluorescence flow cytometric method for the simultaneous detection of different GST-isoenzymes and of DNA in fixed cells. Due to the impossibility of working under saturating conditions for the anti-GST antibody, a normalizing procedure was developed to permit quantitative analysis of single cells labelled with the anti-GST antibody at high dilution. A theoretical model and experimental data supported the use of this procedure. The method proposed is general and could be applied to other antibodies in order to obtain quantitative data outside saturating conditions. The method was challenged in different applications in order to compare it with other classical techniques. First, we characterized sublines resistant to different anticancer drugs with respect to variations of GST isotypes. In a second application, we studied the intercellular heterogeneity of GST content in mouse renal cells. In addition, GST was determined in aneuploid cells from solid tumor biopsies by separation from diploid cells on the basis of DNA content. Finally, GST distribution during cell-cycle progression was studied in two different cell lines by the biparametric analysis of GST/DNA.
Cytometry 07/1995; 20(2):134-45.
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ABSTRACT: The therapeutic efficacy of cell cycle phase-specific drugs can be improved by repeated administrations, the dosing interval being related to the cell cycle time of the susceptible normal host tissue. Kinetic measurements of bone marrow cell proliferation, with bromodeoxyuridine labeling and flow cytometry analysis, were used to determine the optimal dosing intervals of 1-beta-D-arabinofuranosylcytosine for minimizing bone marrow cell damage in mice. The results showed that cells surviving a single dose 1-beta-D-arabinofuranosylcytosine treatment remained temporarily blocked at the G1-S boundary, and upon release from the block the cells crossed through S phase in a nearly synchronized way. The optimal spacing of repeated treatments, evaluated by measurements of the drug-induced transit times through the different cell cycle phases, equaled the bone marrow cell cycle time following treatment. Repeated 1-beta-D-arabinofuranosylcytosine injections according to this protocol markedly diminished drug toxicity in C3H mice, as compared to protocols of other time intervals. A therapeutic schedule based on these measurements was highly effective in lymphoma-bearing mice: the designed protocol of dosing intervals significantly delayed tumor growth whereas other intervals were highly toxic.
Cancer Research 01/1995; 54(24):6446-51. · 7.86 Impact Factor
