bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboplatin (JM 8), Adriamycin and Cyclophosphamide (JAC) in Advanced Ovarian Carcinoma: A Pilot Study
Authors: Conte Pier Franco , Bruzzone Milena , Chiara Silvana , Rosso Riccardo , Giaccone Giuseppe , Carnino Flavio , Guercio Elso , Ragni Nicola , Foglia Gianni , Bentivoglio Giorgio , Pescetto Giuseppe , Materman Eric , Franks Chris
Published: April 2018

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.
Incidence and Survival of Brain Tumors: A Population-Based Study
Authors: Sant Milena , Crosignani Paolo , Bordo Bianca Maria , Nicola Giancarlo , Bianchi Mario , Berrino Franco
Published: April 2018

Since 1976 the Lombardy Cancer Registry (RTL) has recorded all malignant tumors and the benign tumors of the nervous system, bladder and liver occurring in the Varese province. The aims of this report are: to describe age-specific incidence rates of the different oncotypes of primary nervous system tumors (PNSTs) and to analyze the duration of survival of the patients according to the histotype of the neoplasm. From 1976 to 1981, the RTL recorded 498 PNST: 213 tumors of glial origin, 132 tumors of mesodermal tissues, 15 tumors of multipotential cell origin, 37 tumors of nerve roots, 8 of vascular origin, and 54 PNST in which the histotype was not specified. For tumors of glial origin, the 60–69 year age class showed the highest incidence rate: 16 per 100,000/year. The incidence rate of tumors of mesodermal tissues reached the maximum value of 7.9 per 100,000/year in the age group of 75 years and over. Tumors of multipotential cell origin had a maximum incidence of 2.2 in the 60–69 year age class. The probability of survival at 5 years after diagnosis was computed by the method of Kaplan and Meier (15), and the log rank procedure was used to test statistical differences among survivors. Tumors of glial origin, excluding ependymomas and papillomas of choroid plexus, had a 5-year survival probability of 14%. Age (categorized in ≤50 and > 50 years) and histologic grade (grades I+II and grades III+IV) were analyzed as prognostic factors for tumors of glial origin: a younger age was the most predictive prognostic factor in grade I+II tumors (probability of survival = 53% in the group ≤50 years vs 0 in the group > 50 years; p < 0.005). In the less differentiated tumors there were no differences between the two age groups. Patients with tumors of mesodermal tissues had a 5-year probability of survival of 83%. Subjects younger than 50 years had a probability of survival of 95%, whereas older patients had a probability of 79%. For the other oncotypes, the 5-year survival probability was: 50% for tumors of multipotential cell origin, 63% for ependymomas and papillomas of the choroid plexus, 64% for tumors of vascular derivation, and 21% for PNST with not specified histotype.
Cervical Cancer Screening in Tuscany: A Survey of the Actual State of Cervical Cancer Prevention in the Local Sanitary Units of the Tuscan Region
Authors: Cecchini Silvia , Grazzini Grazia , Ciatto Stefano
Published: April 2018

Every Local Sanitary Unit (USL) of the Tuscan Region was contacted to define screening variables, such as adequacy of the staff involved in prevention, smear technique, data collection and evaluation, laboratory quality control, and modalities of invitations to screening. The reported data show that 21 of 40 USL, but only 9 of 28 USL outside the Florence province (where a common screening program is performed), are performing active invitations to screening. The most serious staff inadequacies concern data evaluation and personnel performing the test. Sixteen of 28 USL outside Florence suggest an annual rescreening, which causes overcrowding of services and a poor availability for the unscreened population. Moreover, the poor quality of data collection makes it impossible to evaluate the benefit offered by the screening programs in the 28 USL outside Florence. Cytologic quality control is often lacking, and the smear technique is inadequate in 10 of 28 USL outside Florence. The lack in the USL of epidemiologic competence and of cost/benefit considerations and the need for political decisions about cancer prevention programs are stressed.
Influence of Tumor Growth Kinetics on Response to Doxorubicin Treatment of C3H Mammary Carcinoma
Authors: Demicheli Romano , Foroni Roberto , Giuliani Fernando C. , Savi Giuseppina
Published: April 2018

The influence of tumor growth kinetics on response to doxorubicin treatment of C3H mammary carcinoma was investigated. Gompertzian growth curves were obtained for the tumor mass of each mouse by a computerized best fit program. The response was assessed by evaluating: a) the total clonogenic cell reduction as a fraction of the initial tumor volume or the tumor volume that should result at the end of treatment in a free growth condition, and b) the partial clonogenic cell reduction at each drug administration, assuming a first order cell kill hypothesis. Slowly growing tumors at each dose level showed a significantly poorer response than rapidly growing tumors. Each response index exhibited a linear correlation with the specific instantaneous growth rate at the time of treatment. Data also suggested a dose-response dependence.
Abnormal Pattern of Mucin Secretion at the Resection Margin of Colorectal Carcinomas
Authors: Andreola Salvatore , Bertario Lucio , Bombelli Luigia , Rossetti Carlo , Gennari Leandro
Published: April 2018

In a retrospective study, we investigated 56 consecutive patients who had undergone radical intestinal resection for colorectal adenocarcinoma and who had developed local or distant recurrences of the disease. We found that the presence of a predominant sialomucin pattern at the margins of resection of the surgical specimen was correlated with a high percentage of local, endoluminal recurrence in the anastomotic mucosa. In contrast, no correlation could be found when the recurrences occurred in the outer tissues around the anastomosis or at some distance from it.
Studies on Hemotoxicity of Cyclophosphamide, Doxorubicin and Cis-Diamminodichloroplatinum Combined with Sodium-2-Mercaptoethane Sulfonate
Authors: Lerza Roberto , Bogliolo Giuseppe , Mencoboni Manlio , Saviane Alberto , Pannacciulli Ivo
Published: April 2018

The possible protective action of sodium-2-mercaptoethanesulfonate (mesna) on hemotoxicity induced by anticancer drugs was tested in normal mice. Mesna (100 mg/kg b.w.) was injected i.v. 1 h before the i.v. administration of cyclophosphamide (10, 120, and 200 mg/kg b.w.), doxorubicin (4.32, 7.2, and 12 mg/kg b.w.) and cis-diamminedichloroplatinum (5.4, 9, and 15 mg/kg b.w.). Results show that in this experimental model mesna does not seem to protect against toxicity of the tested anticancer drug on hemopoietic progenitor cells.
Psychologic Aspects of Patients Participating in a Phase I Study with the Synthetic Retinoid 4-Hydroxyphenyl Retinamide
Authors: Filiberti Antonio , Tamburini Marcello , Andreoli Claudio , Buranelli Fiamma , Campa Tiziana , Costa Alberto , Dossena Giovanni , Magni Andrea , Pizzichetta Maria , Ventafridda Vittorio
Published: April 2018

One hundred and one patients participating in a phase I study with the synthetic retinoid 4-HPR (4-hydroxyphenyl retinamide) were evaluated. The study was set up by Veronesi et al. during 1986 at the National Cancer Institute of Milan. The patients were randomized into 4 groups. of therapy: 25 in the placebo group, 25 in the group receiving a daily dose of 100 mg of HPR, 26 in the group receiving 200 nig/day of HPR, and 25 in the group receiving 300 mg/day of HPR. All patients were previously treated at our Institute for breast cancer. None had received adjuvant therapy, chemotherapy or hormone therapy. After 4–5 months from the beginning of treatment, all patients received a series of tests to evaluate anxiety, depression and sexual life. Moreover, during one the follow-up checkups after 4–5 months, the patients filled-out a self-scoring mood questionnaire. The results did not show any particular differences between the groups, although we found that the administered drug and experimental setting do not interfere with the psychologic state of the participating patients.
Radio-induced Sarcomas in Survivors of Ewing's Sarcoma
Authors: Boriani Stefano , Picei Piero , Sudanese Alessandra , Toni Aldo , Mancini Antonia , Frezza Giovanni , Barbieri Enza , Baldini Nicola , Monesi Mauro , Ciaroni Daniela , Bacci Gaetano
Published: April 2018

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than 3 years) were considered « at risk » for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS.
A Phase II Study of Mitoxantrone
Authors: Cartei Giuseppe , Mian Sandro , Cendron Roberto , Lamon Stefano , Clocchiatti Luigi , Fasola Gianpiero , Galletti Diego , Sibau Angela
Published: April 2018

Thirty pretreated patients with progressive and measurable solid tumors (24/30 patients) or myeloproliferative diseases (6/30 patients) were given mitoxantrone at the dose of 5 mg/m2/day in 250 ml normal saline over 30 minutes infusion for 3 consecutive days every 3 weeks. A total of 104 cycles were administered, median 3 for each patient. 39/104 cycles were delayed for a median of 9 days (from 2 to 59 days) because of myelodepression grade I to III (median I); no infection or bleeding was observed. Grade I to II alopecia was recorded in 16 patients. Chronic cardiac toxicity was observed in one patient previously treated with adriamycin. Mitoxantrone at the studied dose schedule in heavily pretreated subjects was well tolerated every 3 to 4 weeks. In 25/30 patients evaluable for response, one patient had a PR, another had 25% reduction (both patients previously treated) and eleven patients obtained disease stability. This effectiveness, 1 PR, 1 MR, 11 disease stability, is not negligible when it is considered that mitoxantrone was the seventh median line of therapy and the fifth median antiblastic drug.
Increased Level of Soluble Interleukin-2 Receptor in Advanced Solid Tumors: A Preliminary Study
Authors: Rovelli Franco , Lissoni Paolo , Crispino Sergio , Barni Sandro , Fumagalli Gabriele , Paolorossi Franco , Tancini Gabriele
Published: April 2018

Both activated normal and transformed lymphocytes produce not only cell-associated but also cell-free IL-2R. Evidence of high serum concentrations of IL-2R appears to serve as a tumor marker in patients with lymphomas On the contrary, the role of soluble IL-2R in solid neoplasms has still to be defined. This investigation was carried out to analyze soluble IL-2R production in human solid tumors. The study included 35 patients with solid tumors (12 without and 23 with metastases), 58 healthy subjects and 6 lymphoma patients. Among cancer patients, lung and breast carcinoma were the two most frequent neoplasms. In each subject or patient, serum levels of IL-2R were measured by using an enzyme immunoassay. Moreover, in 14/23 patients with metastatic solid tumors, lymphocyte subpopulations were also evaluated. Serum levels of IL-2R were significantly higher in the cancer patients than in the normal subjects. The patients with metastatic solid tumors showed significantly higher mean levels than those without metastases, and similar to those observed in the lymphoma patients. Finally, there was no correlation between serum levels of IL-2R and the T4/T8 ratio, which was reduced in 5/14 cancer patients. Further studies will be needed to establish if elevated concentrations of IL-2R in the serum can contribute to the immunoincompetence of patients with disseminated solid neoplasms.
G6PD Deficiency and Breast Cancer
Authors: Forteleoni Gavino , Argiolas Lino , Farris Antonio , Ferraris Anna Maria , Gaetani Gian Franco , Meloni Tullio
Published: April 2018

A study of the relative 2dG6P utilization in mononuclear cells from a group of 150 women with breast cancer was undertaken to evaluate a possible negative correlation between G6PD deficiency and cancer, as suggested by some authors. Twenty-one women (14.00 %) were heterozygotes and 2 were homozygotes (1.33 %). The prevalence found was not different from that expected. It would therefore seem that the G6PD Mediterranean allele does not play a protective role against the development of breast cancer.
Assay of Gcdfp-15 by Elisa: An Available Method for in Vitro Studies of Functional Differentiation in Human Breast Cancer
Authors: Revillion-Carette Françoise , Hornez Louis , Vandewalle Brigitte , Lefebvre Jean
Published: April 2018

An enzyme-linked immunosorbent assay (ELISA) was applied to a light protein, isolated from human breast cyst fluid (BCF) termed « gross cystic disease fluid protein - 15 Kda » (GCDFP-15), a potential differentiation marker in in vitro human breast cancer studies. The detection limits of this procedure, performed in microtiter plates, were 0.5 to 250 ng/well corresponding to 10 ng/ml to 5 ng/ml of sample or antigen solution. Possible cross-reaction with various antigens, especially those found in culture media, were investigated. The correlation coefficient between enzymoassay and radioimmunoassay was 0.978. The results showed that quantification of GCDFP-15 by ELISA is a specific and highly sensitive method. This procedure may be of interest in in vitro studies on the functional differentiation of breast cancer cells.
Plasma and Tissue Cea and Tpa Markers in Operable Breast Cancer. Preliminary Results
Authors: Jotti Gloria Saccani , Bombardieri Emilio , Fontanesi Marta , Becchi Gabriella , Bocchi Paolo , Palli Dante , Rusca Michele , Rusconi Alberto , Pizzorno Beatrice , Tardini Armando
Published: April 2018

CEA and TPA were studied in sera and in histologic specimens of 200 patients with benign (77) or malignant (123) breast pathology. The frequency and expression of the two markers was different in benign and in cancer tissues. Histologic positivity and high levels of circulating markers were observed more frequently in cancer patients than in patients with benign disease. Tissue positivity for the two tumor markers did not always correlate with elevated levels of circulating markers. Positive CEA and TPA incidence was higher in tissue samples than in serum samples. In the breast cancer group, among 33 patients with histologic positivity for CEA, only 5 cases had circulating CEA levels higher than 5 ng/ml; among 91 patients with histologic positivity for TPA, only 45 cases showed circulating levels for TPA higher than 95 U/l. These findings confirm that tumor size, secretory characteristics and vascular supply are factors affecting the achievement of high circulating marker levels. Combined marker measurement in serum and tissues can provide more information about the presence of a given tumor marker. A limited evaluation of the prognostic meaning of the study of combined CEA and TPA in sera and in tissues was carried out during the follow-up of 60 evaluable patients. Only 5 patients had cancer relapses in the first 12 months from surgery; in 2 of 5 patients TPA was positive initially and at the time of recurrence, in serum as well as in tissues. Circulating CEA gave negative findings in all relapsed patients; 2 of them showed weak positivity only in the histologic staining at the time of presentation.
Neurothekeoma of the Thumb. A Case Report
Authors: Donofrio Vittoria , Passeretti Umberto , Russo Sergio , Boscaino Amedeo , De Rosa Gaetano
Published: April 2018

A benign tumor of nerve sheath origin occurring in the dermis of a thumb is described. Histologically, these lesions contained nests and cords of large cells surrounded by thin bands of collagen fibers scattered in a myxoid background. The immunocytochemical reaction for S-100 protein was positive.
Prognosis after Nonradical Resections for Small Cell Lung Carcinoma (SCLC)
Authors: Bedini Amedeo Vittorio , Cataldo Ignazio , Bidoli Paolo , Valente Maurizio , Tavecchio Luca , Muscolino Giuseppe , Ravasi Gianni
Published: April 2018

Out of 52 consecutive patients resected for small cell lung carcinoma (SCLC) from 1976 to 1986, 19 were selected because they underwent nonradical surgery, 10 of them for locoregional spread and 9 for distant metastases. Of the former subset all received postoperative radiotherapy and 8 chemotherapy also. Three patients are alive and disease-free 37, 56 and 91 months after resection. Four patients had a distant recurrence, and 3 a locoregional failure. Patients of the latter subgroup received chemotherapy in 7 instances. None survived more than 16 months, distant metastases being the cause of death. In these patients NO status was associated with 13.3 months of mean survival, N1 with 8.5 months, and N2 with 6.7 months. Surgery and adjuvant treatments seem effective in achieving local control of SCLC despite nonradical resections. Tumor burden at locoregional sites does not preclude the possibility of long term survival.
Effects of 5-FU and cis-DDP Combination on Human Colorectal Tumor Xenografts
Authors: Pratesi Graziella , Manzotti Carla , Tortorete Monica , Prosperi Ennio , Zunino Franco
Published: April 2018

The antitumor efficacy of the cis-diamminedichloroplatinum (cisDDP) and 5 fluorouracil (5FU) combination was evaluated in a panel of eight human colorectal carcinoma xenografts. Tumors differed in origin (primary or metastatic), differentiation degree and chemotherapy treatment. Xenografts were treated with repeated i.v. injections of cisDDP, 5FU, or both drugs at 24-h interval. Compared with controls, cisDDP achieved a significant tumor growth inhibition in five out of eight tumor lines, and 5FU in four out of seven. One of two unresponsive tumor lines was significantly inhibited by the combination, that was also more effective than either drug alone (p < 0.05) in one responsive xenograft. Comparing the effects of the combination according to which drug was administered first, lower drug doses were tolerated using the cisDDP-5FU sequence, but the antitumor effects were similar at equitoxic doses. These results indicate a potential therapeutic benefit of the cisDDP-5FU combination for colorectal carcinoma patients and show that toxicity of the combination Is influenced by the drug sequence.
Follow-up of a Sessile Juvenile Polyp of the Colon: A Case Report
Authors: Pestalozza Alessandra , Frigerio Laura Francesca , Andreola Salvatore , Bartoli Cesare
Published: April 2018

The aim of this case report is to underline some unusual features of a colonic juvenile polyp found in a young adult: lack of symptoms, site, sessile morphology and increase in size (> 50% in 2 years). The usefulness of the radiological survey to indicate endoscopic polypectomy is emphasized.
Primary Melanoma of the Ovary in a 25 Year Old Primigravida - A Case Report
Authors: Shroff Chandralekha P. , Borges Anita M. , Deodhar K.P.
Published: April 2018

A 25 year old primigravida with edema of the left foot and fetal distress during 36 weeks gestational period underwent an emergency lower segment cesarian section (LSCS). During surgery ascites and a left ovarian tumor with omental seedlings were observed. Cytopathology of the ascitic fluid, histopathology of the ovarian tumor and the omental seedlings showed features of a malignant melanoma, further confirmed at electron microscopy. Considering the age of the patient and the intra-abdominal restriction of metastasis of the neoplasms this tumor appeared to be a primary melanoma of the ovary. This case is reported since there is no reference to a pure melanoma of the ovary occurring in a young primigravida in the literature.
Detection of Bone Marrow Involvement in Patients with Cancer
Authors: Federico Massimo , Magin Richard L. , Swartz Harold M. , Wright Robert M. , Silingardi Vittorio
Published: April 2018

Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is already the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow.
Immunoglobulin Allotypes in Familial Malignant Melanoma
Authors: Martinetti Miryam , Tarenzi Carolina , Salvaneschi Laura , Illeni Maria Teresa , Lombardo Claudia , Rovini Dario , Placucci Marco , Pellegris Giuseppe
Published: April 2018

There is some evidence that genes at loci on the lower end of chromosome 14, encoding for the immunoglobulin heavy chains allotypes (Gm), may influence susceptibility to human tumors. We examined the Gm and Km (IgK light chain) allotype distribution in a sample of 41 patients with familial malignant melanoma and in 79 healthy relatives. An increased frequency of the haplotype carrying the Gm (2) allotype, namely Gm (1, 2, 17;..; 21), seemed to be peculiar to patients, since it was almost twice as frequent in them than in the healthy population and four times as frequent with respect to the healthy relatives. Our findings are in keeping with previous suggestions that in Caucasian melanoma patients genes of the immunoglobulin heavy chain constant region, or Gm-linked genes, may enhance susceptibility to malignant melanoma.
Relation between Primary Tumor Shape and Biological Behavior in Breast Cancer
Authors: Giardina Carmela , Ricco Rosalia , Lettini Teresa , Gentile Antonia , Serio Gabriella , De Benedictis Giuseppe , Delfino V. Pesce
Published: April 2018

The aim of this study was to investigate the biological significance of tumor shape in breast cancer by considering the shape not as a casual event but as an expression of the behavior and natural history of the tumor. The shape was studied by an analytical morphometry procedure and was related to axillary metastases, which up to now are the most meaningful prognostic factors in this disease. Fifty cases of infiltrating breast carcinoma (25 N+ and 25 N-) were investigated. The shape, studied on subgross sections of the tumor, was considered as the result of two components: the subtle contour irregularities and the main distortions of the figure. The procedures used allowed us to distinguish and to parametrize these two components in order to submit them to univariate analysis (Student's t test), a principal components analysis and, finally, a multivariate discriminant analysis (Hotelling test). The utilized analytical procedures by work-station S.A.M. (S.A.M. work station is a product of « Metamorphosis ») consisted of three steps: 1) Extraction of tumor function curve obtained by Kth order polynomials which gives a smoothing effect to the original curve; 2) Evaluation of contour irregularities by Fourier harmonic analysis; 3) Evaluation of shape asymmetry by SAE (shape asymmetry evaluator). We considered also the roundness factors of the original and function curves and finally the maximum tumor diameter. Three parameters relating to contour irregularities (sum and mean value of Fourier harmonic amplitude and percentage of superimposed points) and parameters relating to main distortions of the figure (mean value of SAE) were highly significant (p < 0.001). The roundness factor of the original curve was more significant (p < 0.001) than that of the function curve (p < 0.01) whereas maximum tumor diameter was not significant when tested by Student's t test. Multivariate discriminant analysis allowed 20 % of error to be reached by using 3 parameters relating to the shape analysis and the two roundness factors. By using 8 parameters, including maximum tumor diameter, the percentage error was 16 %. The results obtained, while they stress the usefulness of the employed procedure, reveal that shape of the tumor, together with its dimensions, is an important expression of the biological behavior relating to metastatic spread.
Mitoxantrone as First-Salvage Chemotherapy in Relapsed Breast Cancer
Authors: Brambilla Cristina , Moliterni Angela , Codazzi Donatella , Villani Fabrizio , Crippa Flavio , Bonadonna Gianni
Published: April 2018

Mitoxantrone was administered at the dose of 14 mg/m2 i.v. every 3 weeks to 25 consecutive women with measurable progressive disease who relapsed after adjuvant CMF and endocrine therapy. The treatment plan consisted in the delivery of 6 cycles, unless disease progression or severe toxicity occurred. All patients were evaluable for drug response and toxicity. One patient achieved complete remission and 6 partial remission, for a total response rate of 28%. Objective tumor response was observed in all major sites of disease. The median time to achieve remission was 3 months. The median duration of response was 7 months (range, 5–39+), and the median survival for the entire group was 10 months (range, 3–39). Results were influenced only by the duration of diseasefree status from the end of adjuvant CMF chemotherapy. In fact, all tumor responses were documented in woman with free intervals exceeding 1 year (7 of 17 or 41 %). Treatment was generally well tolerated, with 10 patients developing leukopenia at some time during treatment. Only 2 patients received less than 75 % of the projected dose because of granulocytopenia. Complete alopecia occurred in only 2 cases. Three patients developed a fall > 15 % in left ventricular ejection fraction, but no episode of congestive heart failure was observed. We conclude that mitoxantrone is an effective and safe drug which can be utilized in women relapsing after adjuvant CMF.
Diagnosis and First-Line Treatment of Patients with Lung Cancer in Italian General Hospitals
Authors:   G.I.V.I.O. (Interdisciplinary Group For Cancer Care Evaluation), Italy, Alexanian Alexan , Apolone Giovanni , Roberto Grilli Roldano Fossati , Mosconi Paola , Nicolucci Antonio , Liberati Alessandro , Di Biagio G. , Testore F. , Michetti G. , Beltrami V. , Iarussi T. , Bonati P.L. , Rossetti A. , Buccheri G.F. , Manichetti C. , Indelli M. , Malacarne P. , Ghiringhelli P. , Olivadoti O. , Cella C. , Lepore S. , Isa L. , Scapaticci R. , Sargenti A. , Sevieri G.F. , Lanzetti V. , Nascimben O. , Soresi E. , Mezzetti M. , Confalonieri C. , Pavia G.F. , Rizzi A. , Di Costanzo F. , Tagliaventi M. , Trotti A. Boidi , Fracchia F. , Rovea P. , Verna V. , Bian A. Rosa
Published: April 2018

The quality of diagnostic and therapeutic care was examined in a series of 380 consecutive newly diagnosed cases of primary lung cancer seen in 20 Italian general hospitals between January and June 1987. At diagnosis most patients (78%) had one or more symptoms related to the tumor, and in an additional 9 % symptoms were related to the presence of distant metastases. The median diagnostic time lag between first symptoms and final diagnosis was 50 days with a significantly longer delay in patients first seen by their general practitioner compared with those who sought first care in hospital outpatient departments. The diagnostic process was satisfactorily carried out in fewer than two-thirds of the patients leading to complete ascertainment of disease stage and histology in 58% cases with significantly better performance in more specialized institutions. Analysis of the first-line treatment profile indicated a rather aggressive therapeutic attitude In the case of patients with non-small cell lung cancer – 28% of them had chemotherapy despite the lack of any proof of efficacy in controlled clinical trials – and a failure to identify among the patients with small cell disease those amenable to more aggressive treatment. The lack of progress in the treatment of lung cancer over the last decades seems to have resulted in widely varying practice patterns where a mixture of aggressive and laissez-faire attitudes does not take into account that in the absence of effective therapies a more conservative attitude would at least have some advantage in terms of quality of remaining life for many patients.
VP16, Epirubicin and Procarbazine in the Treatment of Advanced Non-Small-Cell Lung Cancer
Authors: Altavilla Giuseppe , Adamo Vincenzo , Alafaci Elisabetta , Buemi Barbara , Caristi Nicola , Condemi Giovanni , Toscano Giuseppe
Published: April 2018

We report the results obtained in the treatment of 52 advanced non-small-cell lung cancer patients with the combination chemotherapy VP16 (120 mg/m2 i.v., days 1-2-3), epirubicin (50 mg/m2 i.v., day 1) and procarbazine (100 mg/m2 p.o., days 1 through 8). The courses were repeated every 21 days. No patient had been pretreated. A median of 5 courses was administered. Partial response was obtained in 33 % and no change in 21 % of patients. Median remission time was 6.5 months, and median survival of responders was 10 months. The best response rate and median survival were obtained in the lowest grade performance status patients and in locally advanced disease patients. Major chemotherapy related toxicities were grade 1–2 leukopenia and grade 2–3 alopecia.
The Problem of Carcinogenic Hazard Evaluation for New Chemicals: General Considerations about the Carcinogenic Process
Authors: Parodi Silvio , Taningher Maurizio , Romano Paolo , Santi Leonardo
Published: April 2018

We discuss the problem of oncogenic hazard evaluation for new chemicals. In the recent past, assessment of global carcinogenicity in rodents was considered the most significant type of information. It has recently emerged that this type of information is not adequate to distinguish initiation and genotoxicity from promotion-like effects. In this report we suggest that hazards from initiating agents and hazards from promoting agents should be treated separately. In this perspective, long-term experiments for carcinogenicity in rodents should still play an important role but a less central one. Initiation-promotion experiments in different target organs are recommended. We suggest a strategy of hazard evaluation related to the initiating potential as distinct from overall carcinogenicity. The problem of utilizing not only the qualitative component of the available information, but also the quantitative component, is considered. Finally, we discuss a possible hazard evaluation for promoting effects, but conclude that this area is very much in its infancy. Possible contributions of computer science technology to the problem of oncogenic hazard evaluation are briefly introduced.
The Different Genotoxicity of P-Dichlorobenzene in Mouse and Rat: Measurement of the in Vivo and in Vitro Covalent Interaction with Nucleic Acids
Authors: Lattanzi Giovanna , Bartoli Silvana , Bonora Bruna , Colacci Annamaria , Grilli Sandro , Niero Alessandra , Mazzullo Mario
Published: April 2018

Twenty-two hours after i.p. injection to male Wistar rats and BALB/c mice para-dichlorobenzene (p-DCB) is bound covalently to DNA from liver, kidney, lung and stomach of mice but not of rats. DNA adducts in mouse liver are repaired in seventy-two hours. The covalent binding index value, calculated on the labelling of mouse liver DNA, classifies p-DCB as a weak initiator with an oncogenic activity lower than that of chlorobenzene. The labelling of RNA and proteins from the different organs of both species is, however, low. In vitro interaction with calf thymus DNA mediated by mouse and rat microsomes from liver and lung did occur. Binding extent was strongly reduced by addition of 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) to the microsomal standard incubation mixture, whereas it was enhanced by adding GSH. Cytosolic fractions from kidney and lung were able to induce binding of p-DCB to DNA to a lower extent with respect to microsome-mediated binding. These results indicate that microsomal mixed function oxidase system and microsomal GSH-transferases can be involved in overall activating metabolism whereas cytosolic GSH-transferases play a minor role. This study, which is a part of a structure-activity relationship approach on benzene and its haloderivatives, provides the first evidence of genotoxicity of p-DCB in mammalian cell. It allows to partly explain variations of susceptibility of different species to hepatocarcinogenesis and of hepatotoxicity of different isomers.
Genomic Alterations in Human Breast Cancer: A Review
Authors: Mariani-Costantinl Renato , Merlo Giorgio , Frati Luigi
Published: April 2018

We review and discuss data on the genetic alterations documented in human breast carcinomas at the molecular level. These alterations may result in: 1) deletion of genetic material (chromosome 11p, 13q, 3p, 1q, 17p); 2) amplification of genes or entire chromosomal segments (c-myc, c-erb-B2, locus DF3/PUM, loci on 11q13); 3) rearrangements (c-myc); 4) point mutations (c-ras). Presently available informations do not allow the development of cohesive pathogenetic models but indicate that the molecular basis of human breast cancer is heterogeneous.
Methylation State of Cellular Genes and Oncogenes as a Marker of Malignancy in Human Carcinomas
Authors: Barbieri Raffaella , Gambari Roberto , Buzzoni Daniele , Piva Roberta , Orlando Patrizia , Mischiati Carlo , del Senno Laura , Nastruzzi Claudio , Giacomini Patrizio , Natali Pier Giorgio
Published: April 2018

The methylation pattern of the human HLA-DRα gene was analyzed in primary tumors and lymph node metastases isolated from patients with a variety of tumors, including thyroid, pancreas, breast and gastric carcinomas and melanomas. In normal tissues (including breast, muscle, brain, sperm, T-and B-lymphocytes) the HLA-DRα gene is hypermethylated at CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region was located in the 5′ portion of the gene. Our results indicate that the HLA-DRα gene is hypomethylated in metastatic lymph nodes, as well as in the carcinomas and melanomas studied. These findings lend support to the hypothesis that DNA hypomethylation of the human HLA-DRα gene may represent a molecular marker of malignant tumors.
Kinetics and Regulation of Tyrosine Phosphorylation of the Platelet Derived Growth Factor Receptor
Authors: Alberghina Lilia , Zippel Renata , Martegani Enzo , Sturani Emmapaola
Published: April 2018

Platelet derived growth factor (PDGF) interaction with the cells induces rapid tyrosine phosphorylation of the PDGF receptor in a dose dependent manner. At 37 °C phosphorylation of the receptor is followed by its dephosphorylation and internalization. It is observed that the higher the ligand concentration, the more transient is the response, and the observed kinetics are explained by a simple kinetic model. At 4 °C the phosphorylated form of the receptor is more stable; however, if PDGF is dissociated from the cell surface-associated ligand-receptor complexes, the receptors are rapidly dephosphorylated, indicating that phosphatases specific for phosphotyrosine groups are very active within the cells. In fact, addition of orthovanadate stabilizes the phosphorylated form of the receptor and helps in recognizing possible physiological substrates of the PDGF receptor kinase. The expression of PDGF receptors on the cell surface has been investigated under different growth conditions: a positive correlation exists between the amount of PDGF receptors and the duplication times of exponentially growing cultures. Moreover, during exponential growth the PDGF receptors are scarcely expressed, and their number increases reaching a maximal value when the population enters the stationary phase.
Relationship between Cambrl Expression and Tumor Progression in Small cell Lung Carcinomas
Authors: Martignone Stefania , Bedini Amedeo Vittorio , Ciavolella Antonella , Ménard Sylvie , Patriarca Carlo , Pilotti Silvana , Ravasi Gianni , Tagliabue Elda , Colnaghi Maria Ines
Published: April 2018

In order to study the possible relationship between antigenic phenotype and tumor progression, 63 small cell lung carcinomas (SCLC) biopsies derived from primary or metastatic tumors were tested by immunofluorescence and immunoperoxidase techniques with an anti-carcinoma monoclonal antibody designated MBr1. Primary tumors were found to be less reactive with MBr1 than the local and distant metastatic lesions (57 % versus 75 % and 89 % positivity respectively). A life table analysis on the tested cases indicated an inverse association between the expression of the marker recognized by the MBr1 MAb (CaMBr1) and overall survival (p < 0.01): patients with MBr1-positive tumors showed a shorter survival time in comparison to patients whose tumors did not express the marker. The same correlation between survival and CaMBr1 expression was found even when only the 31 cases of early stage disease patients were considered (p < 0.05). Different tumor aggressiveness or resistance to therapy of MBr1-positive tumors could be responsible for the shorter survival time of the patients.
Modulation by Ifn-Gamma of the Metastatic Ability of Murine, Human, and H-2-Transfected Tumor Cells
Authors: Lollini Pier-Luigi , De Giovanni Carla , Nicoletti Giordano , Scotlandi Katia , Landuzzi Lorena , Nanni Patrizia
Published: April 2018

Interferon-gamma (IFN-gamma) can enhance the experimental metastatic ability of B16 melanoma. The in vitro treatment with IFN-gamma of four clones derived from the murine mammary adenocarcinoma TS/A increased the number of lung colonies observed after intravenous injection in syngeneic mice. The spontaneous metastatic ability of these clones was not altered by the IFN-gamma pretreatment nor by daily intratumor injection of low-dose IFN-gamma. The experimental metastatic ability in nude mice of the human rhabdomyosarcoma cell line RD was decreased by in vitro pretreatment with IFN-gamma. To study the role played by major histocompatibility complex gene products in the IFN-gamma-mediated enhancement of B16 experimental metastasis, a mutant B16 clone, B78H1, was transfected with the H-2Kb gene. B78H1 cells are not capable of expressing H-2b even after treatment with IFN-gamma; IFN-gamma readily induced high levels of H-2Kb in a set of transfected clones, but did not enhance their experimental metastatic ability.
Giant Cell Tumor of Bone: A Model for the in Vitro Human Osteoclast Characterization
Authors: Campanacci Mario , Bagnara Gian Paolo , Serra Massimo , Giovannini Marco , Tornasi Paolo , Pileri Stefano , Poggi Simonetta , Lollini Pier Luigi , Picci Piero , Paolucci Guido
Published: April 2018

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.
Methodological Issues in a Multicentric Study of Gastric Cancer and Diet in Italy: Study Design, Data Sources and Quality Controls
Authors: Buiatti Eva , Palli Domenico , Amadori Dino , Marubini Ettore , Puntoni Riccardo , Avellini Claudio , Bianchi Simonetta , Cipriani Francesco , Cocco Pierluigi , Decarli Adriano , Vindigni Carla , Blot William
Published: April 2018

The authors examine the problems of planning and conducting a multicentric case-control study on diet and gastric cancer in Italy. The solutions chosen for the study design, cases and controls identification, dietary interview, production of a common protocol for the field work are discussed. Results on the evaluation of the quality and comparability of collected data are presented. Further, compliance of cases and controls to the interview and to the blood and urine sampling with reasons of non-response are shown. Finally, the phases of the study and the methods for improving and controlling omogeneity among Centers are summarized.
Pattern of Cervical Screening Utilization in Italy
Authors: Ferraroni Monica , La Vecchia Carlo , Pagano Romano , Negri Eva , Parazzini Fabio , Decarli Adriano
Published: April 2018

The pattern of cervical screening utilization in Italy was analyzed using data from the 1986-1987 National Health Survey on the basis of a sample of 27,455 women aged 20 to 79 randomly selected within strata of municipality of residence and age in order to be representative of the whole Italian population. Overall, about 17% of women aged 20 to 79 were screened per year, for a total of 3.5 to 4 million cervical smears per year. The highest frequency was reported in younger middle age, about one in four women being screened per year in the age groups 30 to 49, and there was a substantial decline above age 50. Cervical smear rates were higher in Northern areas (22 %), where mortality from cervical cancer is lower, than in the Centre (16%) and South (11 %) of the country. Further, there was a strong positive social class gradient in the utilization of cervical screening, in relation to both education and occupation. In spite of the absence of any organised mass screening program, cervical screening is a relatively common procedure among Italian women. However, this study provides further quantitative evidence of a markedly irrational utilization of non-organized cervical screening, which tends to end up selectively used by the groups in which cervical cancer is less common.
Sensitivity Pattern of Normal and Ha-Ras Transformed Nih3T3 Fibroblasts to Antineoplastic Drugs
Authors: Toffoli Giuseppe , Viel Alessandra , Tumiotto Loretta , Buttazzi Patrizio , Biscontin Gabriella , Boiocchi Mauro
Published: April 2018

Ha-ras-transformed NIH3T3 fibroblasts were compared with the parental cell line to investigate the influence of the Ha-ras oncogene on cellular chemosensitivity to antineoplastic drugs. Four NIH3T3 cell clones independently transformed by the Ha-ras oncogene, activated by mutation or overexpression, were analyzed: 3 clones were obtained by transfection of NIH3T3 cells with a mutation-activated Ha-ras gene and 1 clone by transfection of a large copy number of the normal Ha-ras protooncogene. Chemosensitivity of the transformed clones and of the parental cell line was analyzed when cells were in the same condition of proliferative activity and cell cycle phase distribution. No significant differences in chemosensitivity were observed between transformed and untrans-formed cell lines to doxorubicin, VP-16, cis-platinum or mitomycin C. Therefore, data suggest that activated Ha-ras oncogenes have no role in sensitivity to these antineoplastic agents.
Relative Role of Host and tumor in the Growth Pattern of Murine and Human Neoplasms following Subcutaneous Transplantation in Mice
Authors: Demichell Romano , Pratesi Graziella , Foroni Roberto , Barbagini Maria Grazia , Tortoreto Monica
Published: April 2018

The growth patterns of two murine and eight human tumors, bilaterally implanted into subcutaneous tissue of groups of recipient mice, were studied. A Gompertz equation was fitted to experimental data for each individual implant and the Gompertz parameters were utilized as quantitative growth characteristics. The relative roles of the tumor-implanted flank (right versus left), of the individual host and of the tumor were analyzed by the paired t-test, simple linear regression model, one-way and two-way analysis of variance. Sixty pairs of Gompertz curves were obtained in seventy animals. Heterogeneity was the main characteristic of the growth pattern in all tumors under study, with a wide variability among the Gompertz parameters. Statistical analysis of experimental data showed that only the tumor systematically influenced the growth characteristics, whereas neither the tumor-implanted flank nor the individual host played a significant role. These results have both theoretical and practical implications.
Multiparametric Evaluation of Retinoic Acid-Induced Terminal Differentiation of Blastoid Cells from Acute Non-Lymphocytic Leukemia Patients in Vitro
Authors: Joshi Kalpana S. , Rao S.G. Ananda , Joshi D.S. , Nene S. , Advani S.H. , Bhisey A.N.
Published: April 2018

Recent findings that retinoic acid (RA) induces terminal granulocytic differentiation of the human promyelocytic leukemia cell line HL-60 in vitro and blast cell maturation in patients suffering from acute non-lymphocytic leukemia (ANLL) prompted an investigation on the ability of this agent to induce terminal maturation in blast cells from ANLL patients in vitro. We tested the ability of RA at 3×10–6 M, 3×10–7 M and 3×108– M concentrations to induce differentiation in blastold cells from 16 patients with ANLL using cytochemical and cytologic parameters, in addition to cytofluorometric methods. Leukemic cells in primary culture from all the patients underwent cytochemical and biochemical changes after treatment with RA. However, the extent of differentiation-positive cell clones (D+ clones) varied from patient to patient. Morphologic maturation was observed in a significant number of bone marrow samples. Leukocyte alkaline phosphatase and NBT reduction ability of cells, which are biochemical markers of granulocytic differentiation, were also significantly increased with a simultaneous decrease in DNA and RNA synthesis (which was estimated using a Phywe ICP-11 impulse flow cytometer).