Tumori Journal

Sirice 1974 an anti-smoking campaign consisting of a one-day educational intervention has been carried out in primary schools in Milan by the Italian League against Cancer (Milan Division). All but two of the 165 schools were randomized to evaluate the intervention effect. A total of 8549 children aged 9-10 were allocated to the intervention group and 8897 to the control group. Four years later a self-administered questionnaire was distributed in order to investigate the children's smoking habits. The proportion of smokers was 8.05 % and 8.72 % (p = 0.23) respectively for the intervention and control groups. It was concluded that sporadic educational Intervention carried out during primary school years has little or no impact in preventing cigarette smoking in teenagers.

Soybean and/or sodium ascorbate have been demonstrated to have protective effects against carcinogenicity of the nitrosamine precursors dibutylamine and sodium nitrite in rats. Some immunological aspects of the cellular and humoral compartments of the immune system were investigated in this experimental model. The parameters chosen for the study were the lymphocyte transformation test, migration inhibition test, the demonstration of Fc and Fc plus complement receptors on the lymphocyte surface (EA and EAC rosette-forming test), and the determination of total serum proteins and their fractions. The results indicated that dibutylnitrosamine can be formed in vivo from its precursors dibutylamine and sodium nitrite, and that it affects the immune system of rats which showed an immunosuppressed state present as depressed cellular and humoral immunity. The protective role of soybean and/or ascorbate against carcinogenicity of dibutylamine and sodium nitrite was demonstrated by the absence of tumor formation. These agents were found to be capable of increasing the defense mechanism of rats by enhancing both cellular and humoral immunity in the presence of the carcinogenic nitrosamine precursors dibutylamine and sodium nitrite.

The present study was undertaken to explore the effect of the presence of hepatic tumors induced by diethylnitrosamine (DENA) on the metabolic heme pathway, and to assess whether these tumors can modify the response of rats to the porphyrinogenic drug hexachlorobenzene (HCB) and whether the above mentioned effects occur to a greater extent in females than males. The results obtained showed that: a) Females were more susceptible to the hepatocarcinogenicity of DENA than males. b) Female normal and DENA treated rats were more susceptible than male rats to the porphyrinogenicity of HCB. c) The presence of hepatic DENA induced tumors could diminish basal hepatic ferrochelatase activity. d) Hepatic tumors could modify the response of animals to a porphyrinogenic drug such as HCB. Thus, both female and male DENA/HBC rats accumulated more porphyrins and showed a lower δ-aminolevulinate synthase and uroporphyrinogen I synthase induction than HCB rats. e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB.

The effects of aminoglutethlmide, econazole and ketoconazole on human breast cancer cells In culture were compared with those of tamoxifen using four methods (growth experiments, thymidine incorporation, monoparameter and bivariate DNA content flow cytometry analysis). Aminoglutethlmide (1 nM-10 μM) had no effect on cell proliferation after 8 days of treatment and did not decrease thymidine tritiated incorporation during logarithmic phase. Even at 20 μM, similar results were obtained with flow cytometry. Econazole and ketoconazole (1 nM-1 μM) decreased MCF-7 cell proliferation in a time- and dose- dependent fashion. They also decreased tritiated thymidine incorporation. By using flow cytometry and a monoclonal antibody against bromodeoxyuridine, we showed an accumulation of MCF-7 cells treated by imidazoles derivatives In G0-G1 phase of the cell cycle.

The response of tumorigenic human synovial sarcoma (HSS) cell line to 10^–5M optimum concentration of retinoic acid (RA) included changes in morphology, growth rate, suppression of anchorage-independent growth, induction of high alkaline phosphatase activity and excessive secretion of a 68 kDA glycoprotein of unknown function. HSS cells pretreated with 10^–5M RA exhibited differential response to 3 potent anticancer drugs, namely cisplatin, vincristine and adriamycin. Sensitivity of the cells to cisplatin was found to be considerably enhanced after exposure to retinoic acid.

A prospective study was carried out on a recent marker for breast cancer, CA549, a mucine-like acid glycoprotein present in the fat membranes of human milk. Fifty healthy control subjects and 91 with benign conditions, 103 mammary cancer patients and 256 patients with other types of malignancy were studied. For comparison, CEA and CA15-3 were also investigated. The CA549 cutoff was 11 U/ml. In breast cancer the marker was below the cutoff in 9 cases (92.8 %); in malignancies other than breast cancer it was above the cutoff in 5 to 50 % of patients. In breast cancer it was raised in 83.3 % of cases (CA15-3 showed 82.9% and CEA 50 %). In breast cancer after radical surgery, CA549 was normal in patients who were in TNM stage I but above the cutoff in 57.1 % of those at more advanced stages. The follow-up study is ongoing among these patients. In all the study conditions, CA549 favorably compared to CA15-3 values, with sensitivity and specificity greater than CEA.

Various clinical studies have demonstrated that high-dose medroxyprogesterone acetate (HD-MPA) can reduce hematologic toxicity in patients receiving chemotherapy for advanced solid tumors. The underlying mechanism(s) of this action is still unknown. A direct effect of MPA on hemopoietic cells has been postulated, but in vitro studies have given contradictory results. To clarify the biologic activity of MPA on hemopoiesis we have evaluated in vitro growth of pluripotent and committed progenitor cells from bone marrow cells which were preincubated in vitro with various doses of MPA and subsequently treated with or without the S-phase-specific drug arabinoside-cytosine (Ara-C). Four healthy subjects and 8 patients with advanced stage solid tumors with no bone marrow involvement were studied. In our experimental model we did not observe any effect of MPA on Ara-C killing of progenitor cells from either bone marrow mononuclear cells or bone marrow mononuclear cells depleted of T-lymphocytes and adherent cells. These results suggest that MPA does not act directly (or indirectly through the production of cytokines by T-lymphocytes and/or monocytes and macrophages) on bone marrow progenitors. In addition, the supposed mechanism of rendering stem cells less susceptible to the insult of cytotoxic drugs by lowering the number of progenitors in the S-phase has been ruled out by ceil kinetic studies.

Flow cytometric methods for the assessment of nuclear and chromosomal DNA content and of cell proliferation (including methods based on pulse-chase of bromodeuxyuridine and on monoclonal antibodies against nuclear oncoproteins and proliferation-associated antigens) are illustrated by examples and analyzed critically. The impact of most of these techniques for the study of human solid tumors, with exception of nuclear DNA content evaluation, appears still limited. In particular, new studies of cell lines and clinical material from human tumors using new proliferation markers and multiparameter flow cytometry are necessary to solve a considerable number of methodologic and scientific problems.

The numbers of peripheral blood (PB) granulocyte-macrophage colony forming units (CFU-GM) were evaluated in five patients treated with multiple weekly cycles of recombinant interleukin-2 (IL2). A 4.5-12 fold increase in the number of CFU-GM was evident within 8 days after the beginning of the treatment. The maximal increase in the absolute numbers of CFU-GM/ml blood caused by the IL2 treatment, ranged from 14 to 57 times the baseline values and was reached after two or three cycles of IL2. IL2-activated PBMC, added in vitro to the PBMC of a normal donor did not modify the number of CFU-GM present in the donor PBMC. CFU-GM were also recovered from frozen samples of in vivo IL2-activated PBMC.

A total of 14 patients with locally advanced and unresectable head and neck (SCCHN) or non small cell lung cancer were treated with a definitive course of radiation therapy with conventional fractionation and 30 mg/m² carboplatin (CBDCA) given daily as an i.v. infusion during the 1st, 3rd, 5th and 7th weeks of the combined treatment. The planned tumor dose of at least 7000 cGy was reached in all SCCHN patients except 1 (6600 cGy). The 2 NSCLC patients received 6320 and 5980 cGy, respectively. The planned total CBDCA-dose of 600 mg/m² was administered in all patients. No treatment delays were required in 10 patients. Interruptions for severe mucositis or myelosuppression occurred in 4 patients (28.6 %), but in no case did the delay exceed 1 week. Complete response was obtained in 8 patients (57.1 %); 7 of the 12 with SCCHN and 1 of the 2 with NSCLC. The other 6 patients achieved a partial response. Granulocytopenia of WHO grade 3 occurred in 1 patient; apart from vomiting and mucositis, toxicities above grade 2 were not observed.

Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m² on day 1, fluorouracil 1000 mg/m² daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m² with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54 %) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53 % CR and 18 % PR following locoregional treatment. Survival at 12 months was 61 % and its actuarial probability at 24 months 31 %. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35 %, vomiting in 26 %, stomatitis in 57 %, anemia in 22 %, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.

Long-term results and statistical analysis of prognostic factors in a series of 214 patients with distant metastases from differentiated thyroid cancer (DTC) are reported here. These 214 were part of a total series of 1457 patients with DTC referred to our center from 1967 to 1987. All patients underwent surgery and 131-I therapy and were treated with TSH suppressive doses of thyroid hormones. After a mean follow-up of 7.3 years including clinical, scintigraphic, radiological and laboratory investigations, 24.4 % of patients were alive without disease, 36.5 % alive with disease, 1.8 % dead without disease and 37.3 % dead with disease. One of the main factors influencing the survival in our series was 131-I uptake (RIU) by metastatic tissue. No case of complete remission of disease was observed among patients with nonfunctioning metastases. Another important factor was the site of metastases, patients with bone metastases having the worst prognosis. The patient's age at diagnosis represented another important factor for survival; patients over 40 years, particularly those over 60 years had a bad prognosis. A clear interrelation was found among the factors advanced age, nonfunctioning metastases and bone metastases. Patients with these last clinical features were considered to be at high risk and generally had a fatal outcome. Another significant prognostic factor revealed by univariate analysis was the histologic type. Patients with follicular tumor showed a poorer prognosis in comparison to papillary tumor. When multivariate analysis was applied, the factors age at diagnosis, site of metastases and RIU proved to have a significant influence on survival, but not the histologic type. Lastly, the relative rate of males was higher in the group of patients with metastases in comparison to the whole series of DTC patients. Despite this, the factor sex did not influence survival.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4 % and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25 % PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.

Liposarcoma is a soft tissue tumor usually observed in adults. Although occasional cases have been reported in childhood, it is virtually unknown in infants and small children. Our experience documents a case of liposarcoma in a 6-year-old girl, an extremely rare occurrence in this age-group. The patient underwent wide local excision followed by chemotherapy. Histologically, the tumor was a myxoid type. Differential diagnosis and problems concerning prognosis and therapy of this tumor in children are discussed.

A new combination chemotherapy including mitoxantrone 10 mg/m² i.v. on day 1 and 5-fluorouracil 400 mg/m² i.v. plus folinic acid 200 mg/m² i.v. on days 1-5 was administered every 28 days to 13 patients with locally advanced or metastatic colon (1 case), rectosigmoid colon (4 cases), or rectum (8 cases) carcinoma. The median number of cycles performed was 3 (range, 1-9). No patient achieved complete or partial remission with this regimen, whereas 5 showed a stable disease lasting 3-8 months. Acute toxicity was mild/moderate in intensity and comparable to that reported with the standard 5-fluorouracil + folinic acid combination. Since we observed no major responses in our 13 consecutive patients, we consider that the overall activity of our regimen, at the doses and schedule utilized, was only moderately effective in advanced colorectal carcinoma.

The authors describe the case of a 75-year-old female who was hospitalized for anemia of unknown origin. Physical examination revealed a swelling in the right mammary region, where a mastectomy scar was present from surgery for a breast carcinoma. On admission, laboratory tests disclosed anemia (Hb, 8.5 g/dl), with a reticulocyte count of 65,000/mm³ and slightly increased bilirubin. Immunohematologic study revealed the presence of a red cell autoantibody with anti-D specificity in the serum and in the eluate from the patient's erythrocytes. A biopsy of the swelling was performed and histologic examination showed the presence of metastatic cells of breast carcinoma. The patient was given chemotherapy and radiotherapy. At this writing the anemia was absent, the Immunohematologic study was negative, the swelling was greatly reduced, and no other metastatic lesions of breast carcinoma were present.

We describe a case of histologically confirmed malignant melanoma of the nipple. The rare occurrence of these lesions accounts for the relative lack of criteria for standard surgical treatment. After a conventional workup including mammography, chest X ray, bone scan, liver ultrasonography and cytologic smear of the lesion, we used specific radiolabeled monoclonal antibody and external photoscanning to differentiate melanoma from Paget's disease. The patient underwent wide local excision of the lesion and axillary node dissection, and tumor control is optimal since she has no evidence of disease after 5 years of follow-up.