bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Primary Tumors Induced in Adult MICE by MSV-H and MSV-H Producer Tumor Cells
Authors: Branca Margherita , Nicoletti Loredana
Published: April 2018

The oncogenic activity of both MSV-H and MSV-H-producer tumor cells (3T3 + MSV-H) in adult mice was investigated and compared. A higher incidence of tumors was observed with MSV-H tumor cells, especially with very small tumor cell doses. No regression was observed in any of the induced tumors.
Clinical Classification and Survival in Chronic Lymphocytic Leukemia
Authors: Santoro Armando , Musumeci Renato , Rilke Franco , Franchi Franca , Valagussa Pinuccia , Bajetta Emilio , Monfardini Silvio
Published: April 2018

Sixty-one consecutive patients with chronic lymphocytic leukemia (CLL) treated at the Istituto Nazionale Tumori of Milan from September 1962 to August 1976 were classified according to the staging system of Rai et al. (16). Analysis of this series showed the following median survival (in months) from diagnosis: stage 0-1, 73; stage II, 44; stage III-IV, 32. In 11 patients without peripheral palpable adenopathies, the lymphangiogram showed abnormal retroperitoneal lymph nodes. Therefore, the initial stage was changed from 0 to I in 5 cases. The median survival for the entire series was 50 months. Patients with « indolent » disease had a median survival of 52 months, while in patients with « active » CLL, the median survival was 32 months. Both sex and age were shown to be poor predictors of survival. Increased duration of survival was observed in patients with less compared to those with more than 30,000 lymphocytes/mm3 (66 versus 41 months). The method of staging proposed by Rai et al. and utilized to classify this series at the time of diagnosis was confirmed to be a reliable predictor for survival.
Antibody Binding to Membrane of Cultured Melanoma Cells by Sera of Melanoma Patients
Authors: Canevari Silvana , Fossati Giuseppe , Vezzoni Paolo , Biguzzi Sergio , Garcia-Puche Jose , Porta Giuseppe Della
Published: April 2018

One hundred and nine sera from 75 patients with malignant melanoma and 69 sera from as many healthy donors were assayed by isotopic antiglobulin technique (IAT) on 2 melanoma cell lines. The same picture of reactivity was observed with patients’ and healthy donors’ sera, and in both groups 35% of the cases were high responders on 1 line and 21% on the other one. The specificity of the reactions was analyzed by absorption experiments using 12 melanoma sera selected for their high binding activity. Pools of human erythrocytes or leukocytes did not remove, except in 1 case respectively, the activity of the sera, suggesting that it was not directed against alloantigens. Quantitative absorption experiments were done with the 2 melanoma lines and with 1 colon carcinoma line. The results, evaluated on the basis of absorption capacity per cell, indicate that the 2 melanoma lines had a similar amount of shared antigens, whereas the colon line was also effective in absorbing out the serum activity, but less frequently and less efficiently. Further experiments performed to analyze the influence of culturing the target cells in presence of fetal bovine serum (FBS), showed that the activity of sera was removed, at various degrees for different sera, by absorption with free FBS, with FBS coupled to Sepharose 4B, and with normal leukocytes cultured overnight with 10% FBS. The same positive melanoma sera became negative when assayed on the same melanoma line cultured in γ-globulin-depleted human AB serum. In conclusion, in our experimental conditions, the activity of melanoma sera seems mostly directed against components of FBS absorbed on cell membrane during culturing.
Restatement of Lymphography in Childhood: Experience with 413 Consecutive Patients in Ten Years
Authors: Musumeci Renato , Certo Antonio , Fontana Franco , Bellani Franca Fossati , Gasparini Marco , Gianni Cristina , Lombardi Fabrizio , Terno Giovanni
Published: April 2018

From January 1969 to June 1978, 413 children under 15 years of age underwent lymphography at the Istituto Nazionale Tumori of Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, the lymphographic-histologic correlation was 94.5% (104/110). This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting a recurrent tumor.
Hormonal Study in Patients Developing Amenorrhea during Adjuvant Chemotherapy for Breast Cancer
Authors: Recchione Camilla , Rossi Anna
Published: April 2018

The sera of 15 premenopausal women with operable breast cancer and who had developed amenorrhea during adjuvant chemotherapy with cyclophosphamide+methotrexate+ fluorouracil were analyzed for the following hormones: 17-beta-estradiol, luteinizing hormone, thyroid stimulating hormone and prolactin. The blood levels did not differ significantly from those found in patients operated on for breast cancer and in spontaneous menopause (controls). These results suggest that the amenorrhea induced by CMF chemotherapy is of ovarian origin.
A Preliminary Report of a Pilot Trial in Adjuvant Chemotherapy of Primary Melanoma
Authors: Kolarić Krsto , Malenica Branko , Roth Anton
Published: April 2018

It is well known that level of skin invasion and tumor thickness are significant prognostic factors in the evolution of primary melanoma. The prognosis of primary melanoma Clark III to V skin invasion level and more than 1.5 mm thick confirms this statement. Even the prophylactic dissection of regional lymph nodes has not improved results. In an attempt to obtain better results in the treatment of primary melanomas, a pilot trial was carried out combining surgery and adjuvant chemotherapy. A group of 21 patients with Clark III, IV and V level primary melanoma who underwent adjuvant polychemotherapy (velba + dactinomycin + procarbazine) for 1 year after surgery showed a very low incidence of recurrences (5%) after 24 months of observation. The historical control group, with the same level of tumor skin invasion, treated only surgically had in the same follow-up period a recurrence rate of 65%. This difference was statistically significant (p < 0.01). All patients who received adjuvant chemotherapy survived 2 years whereas survival was 77% (p < 0.05) in the surgical historical control group. Favorable results with the same protocol of adjuvant chemotherapy were not obtained in the group of 16 patients with stage II melanoma when compared with primary tumors. However, 4 recurrences were observed after 12 months of observation; toxic side effects of adjuvant chemotherapy were mild and tolerable. Considering the insufficient number of clinical trials with adjuvant chemotherapy, as well as sometimes controversial results, further randomized clinical studies are needed to establish the actual value of this combined method in the treatment of primary melanoma with a high risk of dissemination.
17β-estradiol, 5α-Dihydrotestosterone, Progesterone and Cortisol Receptors in Normal and Neoplastic Human Endometrium
Authors: Prodi Giorgio , De Giovanni Carla , Galli Maria Cristina , Gola Gerardo , Grilli Sandro , Rocchetta Riccardo , Orlandi Camillo
Published: April 2018

Using the value of 0.24 fmoles/μg DNA as breaking point between high and low binding capacities, we quantified receptors for 17β-estradiol (ER), 5α-dihydrotestosterone (DHTR), progesterone (PR) and cortisol (CR) in normal and neoplastic human uterine tissues. Concerning receptors occurrence, significant relationships were observed between ER and PR, ER and DHTR, and DHTR and PR. A direct correlation between the presence of ER and tumor grading was found: PR was less frequent in grade II and absent in grade III endometrial carcinoma, however this was not a significant correlation. In endometrial carcinoma at least 1 of the receptors was detected in 67-91% of the cases, 3 receptors (ER, DHTR, PR) in 56%, and all 4 receptors in 45%. The simultaneous detection of multiple receptors could play an important role in determining hormone response.
Researches about Knowledge of Self-Examination and some Problems about Breast Cancer
Authors: Tamburini Marcello , Pozzi Giuseppe , Re Alberto , Fossati Vittorio , Di Pietro Sergio
Published: April 2018

A research on the degree of knowledge about the problem of breast self-examination was carried out in a group of 500 women in the Out-patients Department of the Cancer Institute in Milan.

The women were given a questionnaire to fill up at home and to return at the moment of the medical examination.

The analysis of data showed that, though the level of education of the subjects was fairly good, the knowledge and the practise of the periodical self-examination as a method for an early diagnosis was very low. 70% of the women declared to have some knowledge about the method, but only 9% declared to practise it regularly.
Alien H-2 Antigens on a Chemically Induced Fibrosarcoma: Further Evidence in Crude Membrane and Soluble Extracts of the Tumor
Authors: Pierotti Marco A. , Miotti Silvia , Invernizzi Giovanni , Parmiani Giorgio
Published: April 2018

Crude membranes (CM) were obtained from in vivo subcutaneous nodules of the methylcholanthrene-incuded BALB/c fibrosarcoma C-1 by forcing tumor fragments through a mechanical press and subsequent differential centrifugation. This immunogenic tumor has been previously shown to express both H-2d and extra H-2k-like antigens. Original H-2d and alien H-2k antigenic activities were present in CM C-1 as judged by the specific inhibition of the C'-dependent cytotoxicity of monospecific H-2 alloantisera on normal 51Cr-labelled lymphoid cells. Both K- and D-end private H-2d antigens (31 and 4), and H-2d public antigens 8, 29, 35 were detected in CM C-1. In addition, the alien H-2Kk.23 private specificity and the public H-2k.1, 5, and 25 were also found in CM C-1. A weak but reproducible activity attributable to the Dk private antigen 32 was also revealed in this material. A hierarchy in the expression of both H-2d and H-2k specificities was evident in CM C-1 which paralleled, although with an overall lower antigenic activity, those of two other BALB/c (H-2d) fibrosarcomas and of a C3Hf (H-2k) lymphoma, respectively. CM from normal BALB/c and C3Hf spleens, while expressing higher amounts of all the tested H-2 antigens, displayed a hierarchy of the different specificities similar to that of neoplastic tissues. Crude soluble (CS) material was obtained from CM C-1 by deoxycholate treatment and was tested in the inhibition assay for the presence of H-2d and alien H-2k antigens. Only specificities with the highest expression in CM were found in CS, i.e. H-2.4 and 29 for H-2d and H-2.25 for H-2*. Both CM and CS from C-1, but not from another control BALB/c sarcoma, were able to significantly inhibit the activity of an oligospecific serum to the Kk-coded antigens.
Macrophages in Skin Cancer: Quantitative and Functional Studies
Authors: Dammacco Franco , Miglietta Antonio , Lospalluti Mario , Meneghini Carlo , Bonomo Lorenzo
Published: April 2018

The number of tumor-infiltrating macrophages was estimated in 43 patients with skin cancer, including 18 cases of squamous cell and 25 cases of basal cell carcinoma. Macrophages were identified in cell cultures by 2 assays, namely phagocytosis and resistance to detachment by trypsin. The average percentage of adherent cells for the 2 groups of skin tumors was 4.5 ± 2.6 and 10.2 ± 5.2, respectively, and the difference was statistically significant. Follow-up studies after surgical excision of the primary neoplasm showed a relatively low macrophage content in 2 of the 4 cases in which local recurrences occurred. Preliminary functional studies suggested that soluble factors may be released by neoplastic cells, accounting for the inhibitory effect of tumor cell supernatants on macrophage Chemotaxis in vitro.
Correlation between Clinical Response to Bilateral Oophorectomy, Estrogen Receptors and Urinary Androgen Excretion in 49 Patients with Advanced Breast Cancer
Authors: Preda Ferdinando , Pizzocaro Giorgio , Oriana Saro , Riboldi Gianluca , Severini Aldo , Di Fronzo Giovanni , Secreto Giorgio , Grattarola Renzo
Published: April 2018

The aim of this study was to find out if it is possible to predict the clinical response to bilateral oophorectomy in premenopausal patients with advanced breast cancer. Two methods of determination were used before oophorectomy: 1) the presence of estrogen receptors in the tumor tissue; 2) the urinary concentration of androgens. The clinical response to oophorectomy was evaluated after a six-month follow-up. Determinations carried out on 49 patients showed that a significant correlation exists between clinical response to oophorectomy and androgenic activity alone or in combination with estrogen receptors when both tests give concordant results.
Combination Chemotherapy with 5-Fluorouracil and Methyl-ccnu for the Treatment of Advanced Gastrointestinal Cancer
Authors: Brutti Alberto , Liberati A. Maria , Biscottini Bruno , Fatati Giuseppe , Sini Sergio , Barzi A. Maria , Grignani Fausto
Published: April 2018

Sixteen patients with advanced gastrointestinal cancer (colorectal 12/16, gastric 4/16) were treated with a combination of 5-fluorouracil (5-FU) plus 1-(2-chlorethyl)-3(4-methyl–cycloexyl)-1-nitrosourea (Me-CCNU). The therapeutic program consisted of orally administered Me-CCNU (140 mg/m2) and intravenous 5-FU (9.5 mg/kg by bolus injection for 5 days). The cycles were repeated at 6-week intervals. At the beginning of the therapy, 11/16 patients were in performance status (PS) 0-1 and 5 patients in PS 2-3. Eight patients developed early progressive disease between the 1st and 2nd course of therapy. Only a minor tumor response was observed in the remaining 50 % of the patients. However, the patients with stabilized disease lived longer (11.8 months) than non-responders (3.5 months).
Hodgkin's Disease in Children. Pathologic Study of 87 Cases
Authors: Carbone Antonino
Published: April 2018

From 1963 to 1977 at the Istituto Nazionale Tumori at Milan, 112 patients below the age of 16 years with Hodgkin's disease (HD) were observed, representing 13.2 % of all the cases of this disease seen during the stated time interval. Eighty-seven of these cases are the subject of the present study. Fifty-nine patients were males and 28 females (2.1:1 ratio). The age range varied from 2 years 10 months to 15 years 10 months (median 10 years). Forty-three (49.4%) children, of whom 35 were males and 8 females, were below the age of 10 years at the onset of their disease. The clinical staging resulted in 34 patients as stage I, 33 as stage II, 13 as stage III and 7 as stage IV. The histologic type was nodular sclerosis (NS) in 49 cases (56.3 %), lymphocytic predominance (LP) in 15 cases (17.2 %), mixed cellularity (MC) type in 9 cases (10.3 %) and lymphocytic depletion (LD) in 8 cases (9.2 %). In the remaining 6 cases the histologic classification was not applicable. LP type in 15/15 (100 %) patients was associated with stages I and II, and NS in 38/49 (77 %) patients was related to stage I and stage II. The latter was also the istologic type most often encountered in patients with stage II disease (23/33 or 70 %). Eleven patients have died, and their survival varied from 6 to 47 months (median 30 months). The histologic type was LD in 4 cases, NS in 3 cases, MC in 1 case, and LP in 1 case. In the other 2 nonsurvivors, the histologic type was not identifiable. Of the 23 patients with more than a 5-year survival, 14 (60.8 %) had NS HD. As in adults, LP and NS were associated with early stages of the disease and with long survival.
Argentaffin Pulmonary Tumorlets
Authors: Zanetta Giovanni , Zanoni Marta , Colombo Fausto
Published: April 2018

The left lung, surgically removed from a patient, was found to be bronchiectasic and polycystic. Using light microscopy it was possible to locate multiple tumorlets originating from the Kulchitsky cells of the bronchial and bronchiolar mucosae. With the traditional histochemical staining, argyrophilia and argentaffinity were demonstrated. The latter, not previously reported in the literature, suggests the presence of different monoamines in the neurosecretory cytoplasmic granules of the tumorlet cells.
Hepatocellular Carcinoma with Intracytoplasmic Hyaline Globules
Authors: Muretto Pietro , Piantelli Mauro , Tison Vittorio
Published: April 2018

A case of hepatocellular carcinoma with intracytoplasmic hyaline globules is reported. By serological, histochemical, immunofluorescent and electron microscopic studies the authors maintain that in this case intracytoplasmic hyaline globules represent lysosomal structures. According to Von Ardenne's theory, these lysosomal globules appear related to neoplastic cells necrosis.
Hexachlorocyclohexane-Induced Tumorigenicity in Mice under Different Experimental Conditions
Authors: Md. Munir Khan , Soman Chitralekha Sudhakar , Bhide Sumati Vasudeo
Published: April 2018

Continuous administration of 500 ppm hexachlorocyclohexane (HCH) in the diet induced 100 % liver tumors in mice, but none were observed in rats and hamsters treated with the same dose of HCH. In Swiss male mice, tumor incidence at earlier ages was greater than that observed in corresponding age groups of Swiss female mice. It was further observed that in Swiss females, sex hormones retarded the tumorigenic effect of HCH; in BALB/c mice a similar phenomenon was not observed.
Electron Microscopy Applied to Fine-Needle Aspiration. A Report of Six Cases from Various Sites
Authors: Cinti Saverio , Ferretti Maurizio , Amati Silvana , Balercia Giancarlo , Vecchi Adalberto , Osculati Francesco
Published: April 2018

The authors report the results obtained from the application of electron microscopy techniques to the cytology of fine-needle-aspirated samples of neoplastic lesions from various body sites. These results show that the tissue structure, which is usually lost during the squashing necessary for light microscopy cytology, is preserved when the samples are processed for ultrastructural analysis. Electron microscopy also allows a highly detailed study of the cell's inner structures. Thus, when this technique is applied, fine needle-aspirated samples can be regarded as actual microbiopsies. However, because of the high cost of ultrastructural techniques, we suggest that actual analysis be performed only in selected cases, whereas fixation and inclusion for electron microscopy could be done routinely.
Treatment and Follow-Up of Metastatic Cancer with no Clinical Evidence of a Primary Lesion
Authors: Canónico Abel N.
Published: April 2018

From 1965 to 1981, 43 cases of metastatic tumors were examined without localizing the initial primary site. All the cases were subjected to intensive studies to detect the primary, and most cases received multidisciplinary treatment. In 19 cases it was not possible to discover the primary tumor, and 6 of them are alive 2 to 9 years after the diagnosis. In 24 cases the primary tumor was subsequently located, but 23 of them died 1 to 5 years after diagnosis of the primary. One case is alive after 9 years. The actual point of view vis-a-vis this pathology and the rationale and active plan to obtain worthwhile results are discussed.
Metastatic Spread of Stage I Melanoma of the Skin
Authors:   W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma (Chairman U. Veronesi), Cascinelli Natale , Preda Ferdinando , Vaglini Maurizio , Orefice Sergio , Bufalino Rosaria , Morabito Alberto , Nava Maurizio , Santinami Mario
Published: April 2018

1164 patients with stage I melanoma of the skin who were submitted to wide excision only of the primary tumor were studied to evaluate the rates of regional lymph node and distant metastases. Of these, 516 (44.3%) had a recurrence of the disease which was at regional lymph nodes in 264 (22.7%), at distant sites in 91 (7.8%), and simultaneously at regional lymph nodes and distant sites in 161 (13.8%). Most of the patients had a relapse within 5 years: regional node metastases were most frequently observed during the first 3 years, and distant metastases appeared later. The ratio regional:distant metastases was not different (P > 0.05) when subgroups of patients were considered according to prognostic criteria (sex, site of origin, levels, thickness, ulceration). Sex, levels, thickness and ulceration were found to be significantly related with the frequency of recurrences (regional and distant). It is concluded that the prognostic criteria considered do not predict whether the tumor will metastasize to regional nodes or to distant sites.
Treatment of 49 Unrandomized Patients with Advanced Hodgkin's Disease
Authors: Chisesi Teodoro , Ricciardi Orlando , Dal Fior Sandra , Cappellari Francesco , Pozza Franco , Battista Raffaele , Cortelazzo Sergio , Capnist Giovanni , D'Emilio Anna , Rodeghiero Francesco , Dini Enrico
Published: April 2018

Forty-nine patients with previously untreated advanced Hodgkin's disease were treated in our Institution between 1973 and 1981. Treatment modalities of these patients were reviewed, and they were divided into 3 groups according to the treatment employed: 13 patients received MOPP only, 22 patients received MOPP plus involved field radiotherapy, and 14 received alternating MOPP/ABVD chemotherapy. The response rates for the 3 groups were respectively 38.5%, 63.6% and 78.6%. A longer follow-up is needed to assess a significant difference in survival curves. The advantages of adjuvant radiotherapy and alternating non-cross-resistant drugs in advanced Hodgkin's disease are discussed.
Multiple Myeloma Plasma Cell Kinetics: Rapid and Reliable Evaluation using 5-Bromo-2-Deoxyuridine (BrdUrd) DNA Incorporation Detected by an Anti-BrdUrd Monoclonal Antibody
Authors: Boccadoro Mario , Redoglio Valter , Gavarotti Paolo , Pileri Alessandro
Published: April 2018

In 19 patients with monoclonal gammopathy, plasma cell proliferative activity was evaluated using 5-bromo-2-deoxyuridine (BrdUrd) incorporation, as revealed by an anti-BrdUrd monoclonal antibody. A simultaneous standard labelled thymidine incorporation was carried out in all patients as reference test. The BrdUrd method was confirmed as a reliable test and is recommended for routine clinical application in monoclonal gammopathies.
The Incidence of Cancer in Contralateral Reduction Mammaplasty after Mastectomy and Reconstruction of the Removed Breast
Authors: de Mascarel I. , Trojani M. , Coindre J.M. , Faucher A.
Published: April 2018

Fourty-one patients underwent breast reconstruction after mastectomy for cancer and reduction plasty of the second breast, over a 36-month period. These plasties were performed only for reasons of asymmetry, in the absence of any positive preoperative finding. Histologic examination using semiserial sectioning of the whole excised sample detected a high frequency of unsuspected cancer 14/41 (34%). There was a strong predominance of in situ carcinomas 11/41 (27%) over invasive carcinomas 3/41 (7%). These results were compared with those of other bilateral cancer series. When such cancers were detected by random biopsies or mastectomies, the rate of in situ carcinomas was much greater than in cancers detected only by physical and mammographic examination.
Chemotherapy and Surgery in the Treatment of Ovarian Cancer Bulky Disease
Authors: De Lena Mario , Lorusso Vito , Brandi Mario , De Leonardis Antonio , Traversa Armando , Marzullo Franco
Published: April 2018

Thirty-six patients with stage III-IV ovarian cancer, bulky disease, were treated with adriamycin and cyclophosphamide administered in two different dosages. Three or four cycles of chemotherapy were administered before the first surgery to facilitate the surgical debulking. After surgery, 6 additional cycles of chemotherapy were administered, and a second look was performed. Clinical CR+PR was observed in 19/30 (63%) evaluable patients after the first part of chemotherapy, but pathologic CR+PR was confirmed in only 13 (43%) patients. After the second part of chemotherapy and the second surgery, 5/30 (17%) patients had pathologic CR and 3/30 (10%) showed residual disease. The two regimens demonstrated similar activity (67% vs 56% clinical CR+PR) but a very different toxicity. In fact, 50% of patients treated with higher doses showed severe leukopenia and 25% severe thrombocytopenia, and 2/13 died of sepsis. The significant activity of adriamycin plus cyclophosphamide in ovarian cancer was confirmed, and increasing the dosage of the two drugs did not increase their activity but only their toxicity.
Time Dependency in Human Cancer
Authors: Hayes Richard B. , Vineis Paolo
Published: April 2018

The concept of latency period has developed in chronic disease epidemiology by analogy with the incubation period associated with infectious diseases. We discuss the use of the concept of mean latency period to describe the temporal development of cancer and the underlying conceptual and methodologic problems. The respective roles of age at diagnosis, age at start of exposure, duration of exposure, and years since exposure in modifying cancer risks are considered. Multistep models for the development of cancer are illustrated, and their use and limitations for interpreting temporal associations in cancer development are discussed. Rather than trying to define exposure-disease relationships as being characterized by a long or a short latency period, It seems more promising to study the temporal sequence of disease development as a multistep process.
Effectiveness and Toxicity of «Beld» Polychemotherapy in Advanced Malignant Melanoma
Authors: Cartei Giuseppe , Ceschia Tino , Marsilio Pietro , Clocchiatti Luigi , Fasola Gianpiero , Morandini Giorgio , Galletti Diego , Sibau Angela
Published: April 2018

From January 1985 to December 1987, 17 patients with advanced malignant melanoma were treated with the poly-chemotherapy regimen BELD (bleomycin, 15 mg subcutaneously on day 1 and 4, vindesine 3 mg/m2 intravenously on day 1 and 5, CCNU 80 mg/m2 orally on day 1 and DTIC 200 mg/m2 intravenously on day 1 through 5) proposed as effective (CR + PR 45%) and tolerable. All patients were evaluable for toxicity and 14/17 also for response after 2 BELD cycles (total n. of cycles was 54). Criteria for response were just the same as those used by Young et al. A complete remission and a partial remission (2/14) have been observed at lymph nodal level, the unique sites of the disease in these two patients. Remission lasted 6 and 4 months, respectively. Two other patients showed a minimal response of 2 and 3 months duration (lymphonodal and cutis, respectively); 9 patients had stabilized disease of 5 months median duration. One case of progression of disease was observed. However, toxicity was relevant because of 2 early deaths after the first cycle, most probably therapy related; nausea and vomiting (82%), leukopenia (17%) and muscle rigors (11%).
A Phase II Study of the Administration of Recombinant Interleukin 2 (rIL-2) Plus Lymphokine Activated Killer (LAK) Cells in Stage IV Melanoma Patients
Authors: Cascinelli Natale , Belli Filiberto , Marchini Silvana , Marolda Raffaele , Prada Augusto , Sciorelli Gianalfredo , Villani Fabrizio , Gambacorti-Passerini Carlo , Galazka Andrew , Parmiani Giorgio
Published: April 2018

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 μg/m5 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 μg/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III–IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 μg/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5x109 to 60x109/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.
4'Epidoxorubicin Plus Verapamil in Anthracycline - Refractory Cancer Patients
Authors: Demicheli Romano , Jirillo Antonio , Bonciarelli Giorgio , Lonardi Federico , Balli Mario , Bandello Attilio
Published: April 2018

Four patients refractory to doxorubicin (DX) and 9 patients refractory to 4'epidoxorubicin (4'EpiDX) were treated with verapamil (VRP) (120 mg every 6 h for 3 days) plus 4'EpiDX (80 mg/m2 i.v. bolus, together with the 6th VRP administration). Three patients had partial remissions lasting 3, 3.5 and 7 months, respectively. Toxicity grading did not exceed usual levels. The study demonstrates that VRP, when added at conventional doses to 4'EpiDX, can induce objective responses in some patients refractory to anthracyclines.
A Preliminary Clinical Study of Cyclophosphamide with Reduced Glutathione Asc Uroprotector
Authors: Nobile Maria Teresa , Vidili Maria Giuseppina , Benasso Marco , Venturini Marco , Tedeschi Michele , Zunino Franco , Rosso Riccardo
Published: April 2018

Reduced glutathione (GSH) has been reported to be an effective protector against cyclophosphamide-induced urotoxicity in experimental models, providing protection comparable to that of mesna. This paper describes our preliminary results of the clinical use of GSH in combination with cyclophosphamide. GSH was administered i.v. in two divided doses of 2.5 g, 15 min before and 30 min after escalating doses of cyclophosphamide ranging from 1.2 up to 1.6 g/m2 (1-h infusion). GSH was well tolerated and did not produce unexpected toxicity. The lack of bladder damage, including microscopic hematuria, supports the protective role of this thiol compound.
The Rat Model in the Comparative Evaluation of Anthracyclines Cardiotoxicity
Authors: Lanza Enrica , Rozza Annalinda , Favalli Luigia , Monti Elena , Poggi Paola , Villani Fabrizio
Published: April 2018

In the present investigation, the cardiotoxic effects of three anthracycline analogs (doxorubicin, 4′-epi-doxorubicin and 4′-deoxy-doxorubicin) were compared. For this purpose, 9.0 mg/kg of doxorubicin, divided into three closely spaced sub-doses, were injected intravenously in rats. The two derivatives were administered according to the same time schedule and their doses were chosen on the basis of the clinically adopted ratio, doxorubicin : 4′-epidoxorubicin : 4′-deoxy-doxorubicin = 1:1: 0.5. The degree of cardiomyopathy induced by the three anthracyclines was evaluated by ECG changes and morphological alterations. Doxorubicin was found to produce a significant degree of cardiotoxicity, thus confirming the validity of the experimental model adopted. Both 4′-substituted derivatives proved to be less cardiotoxic than the parent compound, although not completely devoid of this side effect.
Ki-67 Labeling Index in Breast Cancer
Authors: Crispino Sergio , Brenna Ambrogio , Colombo Daniela , Flores Bajardo , D'Amico Silvestro , Lissoni Paolo , Barni Sandro , Paolorossi Franco , Bratina Giorgio , Tancini Gabriele
Published: April 2018

Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70 %. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.
Bone Marrow Biopsy in the Staging of Small Cell Lung Cancer
Authors: Franciosi Vittorio , Bisagni Giancarlo , Ceci Guido , Boni Corrado , De Lisi Vincenzo , Di Blasio Beatrice , Lottici Renata , Passalacqua Rodolfo , Cocconi Giorgio
Published: April 2018

From April 1982 to December 1987, 71 patients with small cell lung cancer entered a randomized clinical trial, and underwent bone marrow biopsy (BMB) as part of staging procedures. We identified 8 patients (11 %) with bone marrow metastases, 6 with extensive disease independently of BMB, and 2 with extensive disease on the basis of the BMB only. BMB determined a change in the stage in only 3 % (2/71) of the cases. No differences were found in the hematological parameters of the patients with or without bone marrow metastases. The median survival of the patients with bone marrow involvement was the same (41 weeks) as those with extensive disease but without bone marrow involvement. We conclude that unilateral BMB without aspiration detects a substantial proportion of bone marrow metastases in patients with extensive disease. This fact does not worsen the prognosis. A small proportion of patients with apparently limited disease has bone marrow involvement. The technique therefore contributes, to a small extent, to the definition of the clinical stage of the disease. However, bone marrow involvement is an important data of natural history, and therefore new methods to better assess this peculiar site of the disease are needed.
Investigation of the Applicability of Histological Classification of Bronchial Carcinoma According to the World Health Organization
Authors: Čačić Mirjana , Oberman Božidar , Dvornik Gordan
Published: April 2018

According to the World Health Organization histological classification of bronchial tumors, clear and giant cell carcinomas are two subtypes of large cell carcinoma. As clear and giant cells can also be observed in other types of bronchial carcinoma, we investigated the frequency of the finding of these cells in different histological types. The tumor size and degree of differentiation, the amount of necrosis and keratinization, and the presence of giant and clear cells were analyzed. Statistical analysis by χ2 test showed (for all classified histological types of bronchial carcinomas, except small cell carcinoma) that: 1) larger tumors had a great quantity of giant cells (P < 0.05; P < 0.01), 2) large tumors had more clear cells (P < 0.05; P < 0.01) and 3) tumors with a greater amount of necrosis had a larger number of giant and clear cells (P<0.05; P < 0.01). Findings of an identical cytological characteristic can cause some difficulty in determination of bronchial cancer.
Clear Cell Carcinoma of the Larynx: Immunocytochemical Study
Authors: Dalla Palma Paolo , Blandamura Stella
Published: April 2018

A case of clear cell carcinoma of the larynx with multiple metastases is reported. The histological and immunohistochemical characteristics of this tumor are discussed as well as the main differential diagnoses. An origin from seromucous glands of the larynx is proposed. A literature review showed that clear cell carcinoma of the larynx is rare and is characterized by extremely high aggressiveness.
Analysis of 16 Patients with Metastatic Squamous Cell Carcinoma of the Head and Neck: Implications for Treatment
Authors: Benasso Marco , Ferro Alejandro , Bacigalupo Almalina , Toma Salvatore , Vitriolo Silvio , Rosso Riccardo , Merlano Marco
Published: April 2018

The present paper reports a retrospective analysis of 16 patients with distant metastases from squamous cell carcinoma of the head and neck observed in our Institute in the last 10 years. Nine patients out of 16 underwent chemotherapy (7 patients), chemotherapy and radiotherapy (1 patient), or an alternating chemo-radiotherapy regimen (1 patient). The remaining 7 patients were not considered for a palliative treatment because of a poor performance status. Two complete responses, 2 partial responses, 2 stable diseases and 3 progressions were observed, with an overall response rate of 44 %. Chemotherapy, when administrable, showed a temporary effectiveness, at least in patients with lung metastases. The combination of cisplatin and 5-fluorouracil seems to maintain the efficacy already shown in patients with locally relapsed disease.
Changing Patterns in Gastric Carcinoma
Authors: Sidoni Angelo , Lancia Daniela , Pietropaoli Nadia , Ferri Ivana
Published: April 2018

In order to document any modifications in age and sex distributions, tumor locations and histological types, a retrospective study was performed comparing 377 consecutive cases of gastric cancers observed from 1942 to 1956 with 359 cases diagnosed from 1986 to 1987. The mean age at diagnosis rose from 57 to 66 years with no significant male/female ratio variations (1.6 vs 1.7). Tumors located in the proximal stomach increased from 13 to 23 % (p < 0.001) whereas those arising in the distal stomach decreased from 66 to 50 % (p < 0.001). Intestinal type gastric carcinoma decreased from 65.5 to 52.6 % (p < 0.001). The diffuse type rose from 24 to 43 % (p < 0.001) and the mucoid type fell from 10.3 to 4.4 % (p < 0.001). In spite of the overall decline in intestinal type carcinomas, this form remained more common in the upper third area and increased from 55 to 70% (p<0.001). Significant modifications in the distribution of diffuse, mucoid and signet ring cell type carcinomas were also noted. The possible significance and implications of these observations are discussed.
The Role of Induction Chemotherapy in Inoperable Ovarian Cancer
Authors: Donadio Michela , Bonardi Gianmaria , Iberti Valter , Bertetto Oscar , Carnino Flavio , Iskra Lilliana , Mossetti Carlo , Calciati Alessandro
Published: April 2018

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR+PR was observed in 24/30 (80 %) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1 %) patients had a complete macroscopic resection; 9/24 (37.5 %) patients had a partial resection (residual tumor <2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28 %. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.
Establishment of a Human Medulloblastoma Cell Line (Bo-101) Demonstrating Skeletal Muscle Differentiation
Authors: Giangaspero Felice , Pession Annalisa , Trerè Davide , Badiali Manuela , Galassi Ercole , Ceccarelli Claudio , Cavazzana Andrea , Betts Christine M. , Paolucci Paolo , Stella Mario , Montaldi Anna
Published: April 2018

A permanent cell line, BO-101, was derived from a classic vermian medulloblastoma in a 9-year-old child. This line grew in vitro in adherent cultures and grew in athymic mice as serially transplantable intracranial and subcutaneous xenografts. Intracranial neoplasms grew as masses of small cells, which focally showed large cells with intense immunoreactivity for desmin, myoglobin and α-striated actin. The rhabdomyoblastic nature of these cells was confirmed ultrastructurally. The primary neoplasm showed immunoreactivity for synaptophysin, neuron-specific enolase and vimentin. A large panel of monoclonal antibodies and antisera against neuronal and glial antigens failed to show glial and neuronal immunoreactivity in the cell culture and xenografts. Despite the marked genotypic and phenotypic differences, the original neoplasm and the cell line share a common chromosomal marker del (12) (p 13.1). The BO-101 line differs phenotypically and genotypically from previously established medulloblastoma cell lines and further supports the heterogeneous biologic proprieties of the cell populations that constitute these neoplasms.
Morpho-Functional Study of Vascular Fluorochrome Delivery to Lung and Liver Metastases of Lewis Lung Carcinoma (3Ll)
Authors: Aliño Salvador F. , Rodeño Emilia , Simón Josu , Garcia-Sanz Manuel , Alvarez Francisco J. , Hilario Enrique
Published: April 2018

The growth of 3LL liver and lung metastases related to Its vascular organization was studied by morphological and functional methods, using the Hoechst 33342 fluorescent DNA staining technique. Experimental liver and lung metastases were produced in syngeneic C57BL/6 mice by injection of 3LL tumor cells into a lateral tail vein or into the spleen, respectively. The resulting neoplasms were composed of large cells arranged in sheets with a thin irregularly distributed stroma. Scattered blood vessels with an open or closed lumen were observed within the tumor. Functional study of H33342 diffusion showed a single and reticular fluorescent pattern in liver metastases. In contrast, in lung metastases the fluorochrome diffusion revealed two different fluorescent patterns related to the location of the metastasis. Thus, parenchymal and subpleural metastasis presented a fluorescent pattern similar to that observed in the liver whereas metastases located around blood vessels and conducting airways never displayed fluorescence. In summary, our results suggest that the target metastatic organ and/or intra-organ location modulates the characteristics of metabolic exchange of the tumor cells In relation to the vascular organization of the metastatic focus.
High-Dose Epirubicin as a Single Agent in the Treatment of Patients with Advanced Breast Cancer
Authors: Fountzilas George , Skarlos Demosthenis , Pavlidis Nicolas A. , Makrantonakis Paris , Tsavaris Nick , Kalogera-Fountzila Anna , Giannakakis Theodoros , Beer Mario , Kosmidis Paris ,   A Hellenic Co-Operative Oncology Group Study
Published: April 2018

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37 %), thrombocytopenia (8 %), alopecia (81 %), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose Intensity.
Adenoid Cystic Carcinoma of Sweat Glands: Report of two Cases
Authors: Urso Carmelo , Giannini Augusto , Rubino Ida , Bondi Roberto
Published: April 2018

Two cases of primary cutaneous adenoid cystic carcinoma (ACC) of sweat gland origin are reported. The patients were a 83-year-old man and a 40-year-old woman. Histologically, the neoplasms showed the classic appearence of ACC. CEA, actin and S-100 protein were immunocytochemically demonstrated to be contained in some neoplastic cells. The literature on sweat gland ACC is reviewed and the clinlcopathologic profile of this rare tumor considered.
Kaposi's Sarcoma: A Clinico-Pathologic Overview
Authors: Bisceglia Michele , Bosman Cesare , Carlesimo Onorio A. , Innocenzi Daniele , Quirke Philip
Published: April 2018

A careful overview of the classical appearances of Kaposi's sarcoma (KS) as well as of its variants were reviewed from the clinical and pathological point of view. The growth phases (stages) and the cellular patterns were histopathologically compared with emphasis on the developmental progression of disease as well as mitotic activity. Other morphological aspects were also assessed such as the features of the early phases and the incidence of hyaline bodies. One hundred and forty-three lesions from 96 patients mostly of the Italian sporadic type were investigated. A complete list of those entities which should be considered in differential diagnosis is shown and the dilemma of whether KS is a neoplasia or a hyperplasia is discussed.
Preliminary Study on Auxiliary Value of Serum Basic Fetoprotein in Diagnosing Lung Cancer
Authors: Mizushima Yutaka , Tsuji Hiroshi , Izumi Saburo , Hirata Hitoshi , Kin Yoshimasa , Kawasaki Akira , Matsui Shoko , Yokoyama Akihito , Morikage Toshihiko , Yano Saburo
Published: April 2018

To characterize basic fetoprotein (BFP) as a new tumor marker, we measured serum levels of BFP and 5 other tumor markers (CA19-9, CEA, NSE, SCC, and TPA) concomitantly in 65 patients with lung cancer, 57 patients with benign pulmonary disease, and 40 healthy volunteers. The sensitivity of BFP was 43%, the specificity 82% and the accuracy 61%. The positivity increased in relation to stage of the disease. There was no correlation between positivity of BFP and histologic type. On the whole, BFP appeared to be analogous to TPA in terms of broad spectrum and to have an auxiliary value in diagnosing lung cancer.