bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthracycline in Colorectal Carcinoma: An in Vitro Short-Term Assay to Predict Drug Sensitivity. Preliminary Results
Authors: Seminara Patrizia , Franchi Fabrizio , Mulieri Massimo , D'Amelio Raffaele , Pisanelli Giovanni Codacci , Aronne Teresa , Manfredi Dante
Published: April 2018

The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0 % and 14.3 % for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.
Carcinogenic Effects of Infantile and Long-Term 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Treatment in the Mouse
Authors: Della Porta Giuseppe , Dragani Tommaso A. , Sozzi Gabriella
Published: April 2018

An infantile carcinogenesis assay was carried out with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) injections administered intraperitoneally at 0, 1, 30 and 60 μg/kg b.w. doses to (C57BL/6J × C3Hf)F1 (B6C3) and to (C57BL/6J × BALB/c)F1 (B6C) mice, starting from the 10th day of life, once weekly repeated 5 times. Animals were then observed until 78 weeks of age. The induction of thymic lymphomas was related to treatment at 60 μg/kg dose level in both sexes of both hybrids, and at 30 μg/kg dose level in both sexes of B6C mice and in male but not female B6C3 mice. The incidence of hepatocellular adenomas was increased by TCDD treatment at 60 μg/kg dose level in B6C3 of both sexes but not in B6C mice. Hepatocellular carcinomas were seen at increased incidence at 30 and 60 μg/kg doses in B6C3 males but not in B6C3 females or in B6C mice of both sexes. The incidence of other tumor types was not related to treatment in both hybrids. A long-term carcinogenesis bioassay with TCDD was carried out in B6C3 mice treated by gavage at 0, 2.5 and 5.0 μg/kg b.w. doses from 6 weeks of age, once weekly for 52 weeks. The animals were observed until 110 weeks of age. An increased incidence of hepatocellular adenomas and carcinomas was related to treatment, at both doses and in both sexes. The incidence of other tumor types was uniformly low in treated and control groups, without any association with treatment, in both sexes.
Primary Lymphomas of the Brain: A Clinico-Pathologic Review of 37 Cases
Authors: Schiffer Davide , Chiò Adriano , Giordana Maria Teresa , Novero Domenico , Palestro Giorgio , Soffietti Riccardo , Vasario Ezio
Published: April 2018

The clinico-pathologic data of 37 primary lymphomas of the brain were retrospectively reviewed. The tumors were classified according to the Kiel classification and the Working Formulation System. They represented 1.02% of all primary intracranial tumors of our series. The radiologic prediction appeared to be difficult: the suspicion was maximal when the absence of pathologic vessels at angiography occurred in a meningioma-like lesion at CT. Median survival was 4.53 months in the 16 cases who underwent surgery only versus 25.7 months in the 8 cases operated and irradiated with 40-60 Gy (p < 0.01). The prognosis of lymphomas of the CNS, even if radioresponsive tumors, remains poor. Most patients relapse after treatment, most often locally in the brain, with a variable frequency of spinal or systemic localization.
Malignant Melanoma of the Glans Penis in a Chronic Myeloid Leukemia Patient after Busulfan Therapy
Authors: Sparaventi Giovanni , Manna Annunziata , Muretto Pietro , Pazzaglia Carlo , Palazzi Mariangela , Porcellini Adolfo
Published: April 2018

There are many case reports of secondary neoplasms occurring after treatment with alkylating agents. A case of malignant melanoma of the glans penis in a chronic myeloid leukemia (CML) Ph'-positive patient after 13 years on busulfan treatment is described. Since neither impairment of immune status nor increased incidence of secondary neoplasm have hitherto been reported in CML, the suggestion that busulfan has a carcinogenetic effect is discussed.
Angiogenic Activity of Hyperplastic and Neoplastic Lymph Nodes
Authors: Pich Achille , Stramignoni Aldo , Navone Roberto , Lega Mauro , Gullino Pietro
Published: April 2018

Angiogenic capacity was tested in 14 non-Hodgkin's lymphomas, 7 Hodgkin's lymphomas and 15 cervical lymph nodes nonneoplastic but draining a territory with a laryngeal carcinoma. The objective was to find out whether different groups of lymphomas showed differences in their angiogenic capacity and to compare the ability to induce neovascularization of neoplastic lymphocytes. Frequency and intensity of the angiogenic response were similar for classes of lymphomas different for morphologic and immunologic characteristics. The presence of a carcinoma was sufficient to induce in tributary, nonmetastatic lymph nodes an angiogenic activity comparable to that known to characterize antigenically stimulated lymphocytes.
Applications of Biochemical Epidemiology in the Study of Human Carcinogenesis
Authors: Vineis Paolo , Caporaso Neil
Published: April 2018

The measurement of biochemical parameters in epidemiologic studies can contribute to a better understanding of mechanisms of chemical carcinogenesis. Through identification and quantitation of chemicals in tissues or body fluids or through markers of « effective dose » such as DNA adducts, mechanisms of cancer etiology and pathogenesis can be elucidated. Different approaches and the associated methodologic problems are discussed along with examples. As a comprehensive case study, the relationship between aromatic amine exposure and bladder cancer is considered in light of different biochemical aspects which could be the target of epidemiologic studies.
Anti-Melanoma Monoclonal Antibody 225-28S: Evaluation of Toxicity in Man
Authors: Cascinelli Natale , Attili Angelo , Belli Filiberto , Buraggi Gianluigi , Turrin Alberto , Gasparini Massimo , Terno Giovanni , Vaglini Maurizio
Published: April 2018

To investigate possible undesirable effects due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antibody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with 131I and F(ab')2 fragment with 131I, or 123I, or 111In or 99Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 μg, and the specific activity from 37.0 to 2116.4 MBq/mg. The total radioactivity injected varied from 25.9 to 891.7 MBq/mg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC, WBC, platelet count, serum creatinine, creatinine clearance, plasma electrolyte levels, serum proteins, albumin/globulin ratio, serum bilirubin, SGOT, SGPT, γGT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reactions. None of the aforementioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic.
Serum Beta2-Microglobulin in Malignant Lymphoproliferative Disorders
Authors: Melillo Lorella , Musto Pellegrino , Tomasi Paolo , Cascavilla Nicola , Bodenizza Carlo , Ladogana Saverio , Carotenuto Mario
Published: April 2018

Beta2-microglobulin (B2m) was measured on serum samples in 274 patients with acute and chronic lymphoproliferative disorders (85 non-Hodgkin lymphomas - NHL, 30 Hodgkin lymphomas - HL, 34 B-cell chronic lymphocytic leukemias - B-CLL, 8 Waldenström macro-globulinemias - WM, 76 multiple myelomas - MM, 31 acute lymphoblastic leukemias - ALL, 10 hairy cell leukemias - HCL). Two hundred and four patients were studied at the time of diagnosis, and results were correlated to clinical stage, and histologic subtype in NHL, immunoglobulin type in MM, and immunologic phenotype in ALL. Moreover, B2m was tested during and after chemo- and/or radiotherapy, and results were correlated to response, progression or relapse. Elevated pretreatment B2m values were found in widespread forms of NHL and HL, in patients with B symptoms and in the unfavorable histologic subgroups of NHL. Rapid falls in levels followed therapy institution. In B-CLL and in MM a close relationship between B2m and cell mass was found. A significant B2m level reduction followed treatment, whereas its increase could detect a relapse. In ALL, serum B2m was only slightly above the normal range. B2m seems to reflect the total burden of malignant cells mainly in MM and B-CLL; in other lymphoproliferative disorders it provides less prognostic information.
Mortality for Tracheal, Bronchial and Lung Cancer: Possibilities and Limits in Data Quality-Control
Authors: Guidi Enrica , Angelini Lauretta , Carletti Corrado , Cavazzini Luigi , Rausa Giuseppe
Published: April 2018

Linkage of various archives (municipal, hospital, autopsy) has enabled the authors to reconstruct the flow of information regarding death due to tracheal, bronchial or lung cancer (TBL ca) for the population residing within the Municipality of Ferrara during the period 1983–1985. The authors subsequently attempted to verify the cause of death by performing quality controls on clinical charts, radiologic findings, cytohistologic examinations and autopsy findings. Analysis of the data obtained in this manner suggests that municipal records are more « accurate » than are hospital records. The authors likewise indicate the usefulness and importance of the autopsy for a correct diagnosis of cause of death.
Histopathological Characterization of a Novel Monoclonal Antibody, MLuC1, Reacting with Lung Carcinomas
Authors: Agresti Roberto , Alzani Rachele , Andreola Salvatore , Bedini Vittorio , Gianì Silvia , Menard Sylvie , Rilke Franco , Colnaghi Maria I.
Published: April 2018

A monoclonal antibody (MoAb), MLuC1, derived from the fusion of P3 - X63 - Ag 8 - U1 mouse myeloma cells with spleen cells from an HR mouse immunized with the carcinoma cell line SW626, was studied to define its reactivity profile on normal and neoplastic human tissues and its potential clinical applications in lung cancer. Evaluation of paraffin sections using the ABC immunoperoxidase method showed a « pan-epithelial » reactivity; a large majority of epithelial components of organs in the respiratory, digestive and urogenital systems (except liver, rectum and ovary) were immunostained. As regard to neoplastic tissues MLuC1 recognized 84 % of lung carcinomas (82 % of small cell, 100 % of squamous cell, 74 % of adenocarcinomas), 86 % of breast and 62 % of ovarian carcinomas. On the contrary, MLuC1 was non-reactive with the other normal and tumoral non-epithelial tissues. Due to its spectrum of reactivity this MoAb could be useful for different diagnostic purposes such as differential diagnosis and lung cancer cytology.
Evaluation of Pulmonary Toxicity Induced by Pepleomycin
Authors: Villani Fabrizio , Pizzini Lionella , Rossi Anna
Published: April 2018

Spirometric parameters and transfer lung factor for carbon monoxide (TLCO) were determined in 14 cancer patients treated with pepleomycin at the dose of 10 mg twice weekly up to the cumulative dose of 200 mg. Mean values recorded after completion of therapy did not significantly differ from those recorded before treatment. Three patients pretreated with bleomycin had a fall in TLCO of more than 20 % of pretreatment values. Three patients (2 of them pretreated with bleomycin) showed radiologic signs of pulmonary toxicity without instrumental signs of lung toxicity. In patients with no risk factors, no significant modifications in the tested parameters were observed after completion of therapy. These preliminary results suggest that, in the absence of risk factors, pepleomycin, may have no significant pulmonary toxicity at least up to the cumulative dose of 200 mg.
Non-Hodgkin's Lymphoma in the Elderly: A Retrospective Evaluation of Toxicity Related to Aggressive vs. Conservative Treatments
Authors: Tirelli Umberto , Zagonel Vittorina , Volpe Rachele , Trovo Mauro G. , Carbone Antonino
Published: April 2018

The outcome of 70 elderly patients aged 65 years or more (median, 71 years) with non-Hodgkin's lymphoma (NHL) treated between 1973 and 1981 with aggressive (AM) or conservative modalities (CM) was retrospectively evaluated. A significantly higher incidence of lethal and severe toxicity was observed in patients treated with AM than in those treated with CM (32 % vs 3 %, p < 0.01), with 10 % treatment related deaths in the AM group. Only 56 % of the deaths were attributed to NHL; other major causes were treatment-related deaths, infection and cardiac diseases. No significant difference in response and survival was found between AM and CM groups (complete remission rates were 35 % vs 42 %, and 10 year survival rates were 31 % vs 19 %, respectively), but the prevalence of stages III-IV in patients treated with AM makes these results meaningless. Prospective randomized trials with AM vs CM are clearly needed in elderly patients with advanced unfavorable NHL.
Morphologic, Immunologic, and Cytogenetic Characteristics of Secondary Acute Unclassifiable Leukemia in Hodgkin's Disease
Authors: Orazi Attilio , Cattoretti Giorgio , Sozzi Gabriella , Miozzo Monica , Polli Nicoletta , Delia Domenico , Viviani Simonetta , Negretti Elena , Porta Giuseppe Della , Rilke Franco
Published: April 2018

Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.
The Influence of Thyroid Hormones on Colony Growth of Peripheral CFU-GM from Normal and Leukemic Subjects
Authors: Notario Antonia , Torriani Alessandra , Bravi Marco , Broglia Marco , Borghi Giuseppe , Guerra Giovanni
Published: April 2018

In order to clarify the alterations of granuloblastic cells in chronic and acute myeloid leukemia, the colony growth behavior of cultured CFU-GM from the peripheral blood of normal and leukemic subjects was examined in basal conditions and after adding to the medium T3 or T4 and/or thioproline and/or flurbiprofen. These drugs had in previous investigations proved their ability to modify cellular receptors and the uptake of thyroid hormones. The study was carried out in semisolid (double agar layer) and liquid medium, utilizing the techniques described previously. Both thyroid hormones enhanced the colony growth from normal peripheral blood CFU-GM and the response was more evident with T4 than T3. The effect on leukemic CFU-GM (from CML and AML) was less clear, probably due to the presence in leukemic cells of a defect of cellular uptake and to the utilization of T3 and T4. Indeed, on addition to the culture medium of thioproline, which modifies membrane permeability, and of fluorbiprofen, which inhibits PGE synthesis, the colony number and growth from leukemic CFU increased considerably in accordance with the results of our previous studies on these substances showing that they are able to modify cellular receptors for thyroid and several other hormones.
An Attempt at Topical DNCB Immunomodulation in Advanced Malignant Melanoma
Authors: Budzanowska Elzbieta , Pawlicki Marek
Published: April 2018

Nineteen patients with malignant melanoma metastatic to the skin, subcutaneous tissue or lymph nodes were treated with DNCB applied to the lesion. None of the patients was amenable to any other form of treatment. During the 20-month follow-up, complete remission occurred in 3 patients and partial remission in 3 patients, 1 patient showed stabilization of the disease, and in the remaining 12 not even transient improvement was observed.
Alcohol-Related Cancers in Mediterranean Countries
Authors: Tuyns Albert J.
Published: April 2018

In most countries bordering the Mediterranean, alcohol ranks second to tobacco as a risk factor for cancer. It is directly implicated in cancer of the mouth, larynx, hypopharynx and esophagus. For all these cancers a dose-response relationship has been demonstrated as well as a combination with the effect of tobacco, the two effects being multiplicative. Alcohol is also responsible for liver cancer developing on alcoholic cirrhosis. In addition, it has been suggested that alcohol consumption may be related to an increased risk of breast cancer.
The Role of Diet History and Biologic Assays in the Study of « Diet and Breast Cancer »
Authors: Gerber Mariette , Richardson Sylvia , Cavallo Franco , Marubini Ettore , De Paulet Pierrette Crastes , De Paulet André Crastes , Pujol Henri
Published: April 2018

Nutritional factors related to breast cancer were investigated by means of a hospital-based case-control study in Milan (Italy) and Montpellier (France). Liposoluble vitamins, cholesterol and triglycerides were measured in blood samples taken from interviewed subjects (319 cases and 344 controls). In addition serum zinc and copper was assessed in the Italian samples and serum fatty acids and malonyl-di-aldehyde in the French samples. A significant difference was found between cases and controls in total fat and cholesterol intake in both populations, and in saturated fatty acid and mono-unsaturated fatty acid consumption in the French samples. No difference emerged in liposoluble vitamin consumption in both popula-tiosn nor in zinc and copper consumption in the Italian samples. A statistically significant higher serum level of cholesterol and plasma level of vitamin E was observed in cases compared to controls in both populations. The difference in plasma vitamin E was confirmed after adjustment on total cholesterol and triglycerides. Similarly, zinc serum level was higher in Italian cases than in Italian controls, while malonyl-di-aldehyde was lower in French cases than French controls. A multivariate analysis was performed after classification of cases and controls according to quantile distribution of controls. Nutrient consumption and relevant blood markers were directly or partially correlated in both populations. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio values for the highest quantiles are: Dietary cholesterol, OR = 1.9 (1.1-3.4); total dietary lipids, OR = 1.9 (1.0-3.4); plasma vitamin E, OR = 4.2 (1.9-9.0); serum zinc, OR=12.2 (5.4-27.7); serum malonyl-di-aldehyde, OR=0.56 (0.33-0.97).
Rome Women's Screening Study: Knowledge, Attitudes and Practices of Women regarding Screening for Breast and Cervical Cancer
Authors: Perucci Carlo A. , Rapiti Elisabetta , Davoli Marina , Lagorio Susanna , Arca Massimo , Miller Anthony B.
Published: April 2018

A survey on knowledge, attitudes, and practice regarding breast and cervical cancer screening was conducted in Rome on a sample of women aged 18-64 years. Of the 793 interviewees, 31.9% had undergone at least one breast imaging examination; examinations were more frequent in women over 35 and in those familiar with breast self-examination and female pathophysiology. Seventy percent of the women had had at least one Pap smear. Women were classified as Pap smear underusers (26.0%), appropriate users (28.8%), and overusers (45.2%) as compared to standard screening recommendations, according to their age and their lifetime number of smears. Age over 35 was associated with both underuse and overuse. Such inappropriate screening patterns could be related in part to the fact that the women reported that their physicians recommendations for Pap smear frequency were once a year or more in 62%, and once every two or three years in only 2%.
Prognostic Impact of Early Detection of Contralateral Primary Breast Cancer
Authors: Ciatto Stefano , Ambrogetti Daniela , Bonardi Rita , Bravetti Patrizia , Del Turco Marco Rosselli
Published: April 2018

The authors report on a consecutive series of 175 contralateral metachronous breast cancers. Eighty-six cases detected in women self referring for cancer-related subjective symptoms were compared to 89 cases detected as asymptomatic at routine examination. Detection in the asymptomatic phase was associated with a more favorable stage, but no differences in survival rates were observed between asymptomatic or symptomatic cancers when survival was measured from the date of first cancer diagnosis, in order to adjust for lead time bias. The nodal status of the first or of the second cancer was the only variable of prognostic value on univariate analysis, whereas a significant association to prognosis was evidenced only for nodal status of the first cancer. The study suggests that routine clinico-mammographic check-up may achieve early detection of contralateral metachronous breast cancer in the asymptomatic phase, but this does not seem to have a relevant Impact on prognosis. The occurrence of a second primary breast cancer seems to be an indicator rather than a determinant of a worse prognosis.
Primary Non-Hodgkin Lymphomas of the Gastrointestinal Tract: Analysis of 41 Cases
Authors: Di Marco Adriano , Aitini Enrico , Rizzotti Aldo , Grandinetti Antonio , Campostrini Franco , Smerieri Franco
Published: April 2018

Forty-one patients suffering from primary non-Hodgkin lymphomas of the digestive tract have been observed over a period of 15 years. The primary sites were: the stomach in 27 cases, the small bowel in 8, the ileocecal region in 5, and the mesentery in 1. Patients were staged according to the modified Ann Arbor staging system proposed by Mushoff (20). Four kinds of management were employed: 1) surgery alone; 2) surgery and radiotherapy; 3) surgery, radiotherapy and chemotherapy; 4) surgery and chemotherapy. One patient was treated by chemotherapy alone. Radiotherapy was administered postoperatively and chemotherapy after or during radiotherapy. Generally, 2 opposed fields largely encompassing the tumor area and lomboaortic nodes if necessary, up to 25-30 Gy to the midline, were employed, with a booster dose up to 40-45 Gy to the involved area. Total abdominal irradiation was never employed. No clear difference emerged in survival rate nor in relapse-free survival among the four subgroups, but patients who underwent complete resection fared better than incompletely resected patients. However, these two subgroups were not homogeneous. A clear difference in survival rate did not emerge between patients treated or not with postoperative chemotherapy, whereas patients who relapsed after complete remission or those who never had complete remission had a poor prognosis.
Percutaneous Alcohol Injection of Portal Thrombosis in Hepatocellular Carcinoma: A New Possible Treatment
Authors: Livraghi Tito , Grigiori Walter , Mazziotti Alighieri , Sangalli Gabriele , Vettori Claudio
Published: April 2018

Hepatocellular carcinoma (HCC) with portal thrombosis is usually regarded as a contraindication for surgery and for percutaneous alcohol injection (PAI). For palliative purposes we used PAI in 4 patients with infiltrative HCC and segmental portal thrombosis. Ethanol, injected directly into the thrombus, diffused mostly along it. No complications emerged after 20 injections. In the first patient, who later a liver transplant, the thrombus was completely necrotic. In the other patients, biopsies yielded only necrotic material: in two cases, progression of the thrombus was stopped at 4 and 12 months of follow-up, and in one case the thrombus shrank and remained as such 13 months later. This preliminary experience might broaden the scope of treatment for HCC.
Recurrent Solitary Metastasis of Renal Cell Carcinoma in Skeletal Muscles
Authors: Merimsky Ofer , Levine Talia , Chaitchik Samario
Published: April 2018

Metastatic carcinoma to skeletal muscle is uncommon and may originate from breast, colon, lung, pancreas and other sources. Recurrent solitary metastases of renal cell carcinoma in the biceps femori and gluteus muscles are described in a 69 year-old man. The tendency of metastases to occur merely in muscles could not be explained in our case. The relative immunity of muscle to the metastatic process should be further investigated.
Sex Comparison of Heme Pathway in Rats Bearing Hepatic Tumors
Authors: De Calmanovici Rosa Wainstok , Cochón Adriana Cristina , Aldonatti Carmen , Cabral José Ricardo P. , De Viale Leonor Carmen San Martín
Published: April 2018

The present study was undertaken to explore the effect of the presence of hepatic tumors induced by diethylnitrosamine (DENA) on the metabolic heme pathway, and to assess whether these tumors can modify the response of rats to the porphyrinogenic drug hexachlorobenzene (HCB) and whether the above mentioned effects occur to a greater extent in females than males. The results obtained showed that: a) Females were more susceptible to the hepatocarcinogenicity of DENA than males. b) Female normal and DENA treated rats were more susceptible than male rats to the porphyrinogenicity of HCB. c) The presence of hepatic DENA induced tumors could diminish basal hepatic ferrochelatase activity. d) Hepatic tumors could modify the response of animals to a porphyrinogenic drug such as HCB. Thus, both female and male DENA/HBC rats accumulated more porphyrins and showed a lower δ-aminolevulinate synthase and uroporphyrinogen I synthase induction than HCB rats. e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB.
In Vivo Effects of Multiple Cycles of Recombinant Interleukin-2 (IL2) on Peripheral Granulocyte-macrophage Hematopoietic Progenitors Circulating in the Blood of Cancer Patients
Authors: Gambacorti-Passerini Carlo , Hank Jacquelyn A , Borchert Agnes , Moore Karen , Malkovska Vera , Sondel Paul
Published: April 2018

The numbers of peripheral blood (PB) granulocyte-macrophage colony forming units (CFU-GM) were evaluated in five patients treated with multiple weekly cycles of recombinant interleukin-2 (IL2). A 4.5-12 fold increase in the number of CFU-GM was evident within 8 days after the beginning of the treatment. The maximal increase in the absolute numbers of CFU-GM/ml blood caused by the IL2 treatment, ranged from 14 to 57 times the baseline values and was reached after two or three cycles of IL2. IL2-activated PBMC, added in vitro to the PBMC of a normal donor did not modify the number of CFU-GM present in the donor PBMC. CFU-GM were also recovered from frozen samples of in vivo IL2-activated PBMC.
Interpreting Survival Differences and Trends
Authors: Berrino Franco , Micheli Andrea , Sant Milena , Capocaccia Riccardo
Published: April 2018

Since 1990 a concerted action between European population-based cancer registries (the EUROCARE project) has been carried out with the aims of establishing whether there are differences in cancer patient survival in Europe, and the reasons for such differences. Survival differences actually exist for cancer sites for which the stage of disease at diagnosis is the major prognostic factor (such as breast, stomach and colon cancer). However, for most cancer sites, survival increases over time and the survival rates of different countries tend to converge towards higher values. Interpreting survival differences and trends is not an easy task. Longer survival may be achieved by postponing death through better treatment or by anticipating diagnosis. However, an earlier diagnosis may or may not make a treatment more effective in postponing death. The computation of stage-specific or stage-adjusted survival is not sufficient for interpretation of survival differences, because staging procedures change over time and may vary in different hospitals and countries. In addition to an early diagnosis and more effective treatment, a number of factors may bias survival estimates. They may be classified into factors that can be controlled in the analysis (at least partially), such as mortality from other causes, demographic factors, epoch of diagnosis, different statistical methodology, and factors depending on the validity of cancer registry data, such as definition of the illness, exhaustiveness and quality of registration, completeness of follow-up, definition of the date of diagnosis, and definition of disease stage including the diagnostic procedure used to establish stage. To help disentangle the effects of early diagnosis and better treatment, several statistical approaches are being developed: multivariate analysis on relative survival data, new modeling analysis to separately estimate the proportion of cured patients and the length of survival for those patients destined to die, and the standardized collection of information on stage at diagnosis and staging procedures.
Variations in the Survival of Adult Cancer Patients in Italy
Authors: Gatta Gemma , Buiatti Eva , Conti Ettore , De Lisi Vincenzo , Falcini Fabio , Federico Massimo , Gafà Lorenzo , de Leon Maurizio Ponz , Vercelli Marina , Zanetti Roberto
Published: April 2018

Aims

As part of the ITACARE project, the present study analyzed and compared population-based data on the survival of adult cancer patients in Italy, according to sex, age, period of diagnosis and geographical area.

Methods

Nine Italian population-based cancer registries provided data on all their cancer patients (total 90,431 cases) followed for at least 5 years and diagnosed during the period 1978–1989. About 10% of the Italian population is covered by these registries. The data was analyzed by means of a multivariate model.

Results

The major findings were that there was a general improvement in 5-year relative survival over the study period (from 33% to 39%) and that there were significant differences in survival between different areas of the country, particularly for cancer sites which respond well to treatment. In general, the area covered by the Ragusa (Sicily) registry was characterized by significantly worse survival than other registry populations. Other important findings were that for all malignant cancer sites 5-year relative survival decreased with age from 50% for the youngest age class (15–44 years) to 27% for the oldest age class (75+ years) and that women have a better prognosis for most cancer sites (overall 5-year relative survival in women 48% vs 32% in men).

Conclusions

The significant regional differences in survival may reflect unequal provision of care, particularly between northern-central Italy and the south. The reasons for the general survival improvement with time are not completely understood, whereas the marked overall sex difference is related to the fact that the commonest cancer in women (breast cancer) is eminently more treatable than the commonest malignancy in men (lung cancer). The unfavorable trend with increasing age may be due to increasing difficulty in applying complete therapy protocols as general health declines, sometimes in relation to an advanced cancer stage at diagnosis.
Diagnosis of Chromophobe Renal Cell Carcinoma by Chromosomal Analysis
Authors: Marras Susanna , Faa Gavino , Scarpa Roberto , Valdes Enrico , Vanni Roberta
Published: April 2018

Chromophobe renal cell carcinoma may pose a differential diagnostic problem by routine histologic examination because it may be misdiagnosed as another type of renal cancer with a totally different clinical behavior. A low DNA content as well as hypodiploidy seem to be associated with this renal tumor subtype. We report a case in which the cytogenetic report was of great value for a correct histologic diagnosis.
Down-Modulation of P210bcr/abl Induces Apoptosis/Differentiation in K562 Leukemic Blast Cells
Authors: Deora Arunkumar B. , Miranda Michelle B. , Rao S.G. Anand
Published: April 2018

Aims and background

K562 cells are growth factor independent and neither function as stem cells nor differentiate into functional end cells. They are blast cells. There is evidence that the constitutively expressed bcr-abl tyrosine kinase might be responsible for the maintenance of the blast state of CML cells. We have studied the effect of two tyrosine kinase inhibitors, quercetin and genistein, on K562 cells.

Methods

K562 cells were treated with quercetin/genistein for a period of 72 hrs and then subjected to staining for apoptosis and erythroid differentiation and Western blotting with c-abl and phosphotyrosine monoclonal antibodies.

Results

The IC50 value was found to be 9.2 μg/ml for quercetin and 11.8 μg/ml for genistein. Quercetin-treated cells did not show any differentiation but showed 68% apoptosis as compared to 7% in control. Genistein-treated cells showed 16% apoptosis and 15% erythroid differentiation. Quercetin reduced the level of p210 by 74% and its phosphotyrosine content by 67.6%. Genistein reduced p210 by 77.8% and its phosphotyrosine content by 16%.

Conclusion

Both quercetin and genistein are able to down-modulate the tyrosine kinase activity of p210 as well as bring about a decrease in the content of the protein with different effects: quercetin induced apoptosis while genistein brought about both differentiation and apoptosis.
Carcinoma of the Prostate: Brain Stem Metastasis as the Only Site of Spread
Authors: Salvati Maurizio , Cervoni Luigi
Published: April 2018

Aims and background

Metastasis to the brain from prostate carcinoma is a rare event; it is reported in less than 4% of postmortem examinations. The prevalence of cases detected antemortem is even smaller, and the prevalence of brain stem metastasis as the only site of metastasis has been reported in only two other cases.

Method

The authors present a third such case.

Results

A 55-year-old man, treated for an adenocarcinoma of the prostate (prostatectomy and radiotherapy), started to complain of facial expression disturbances and headaches 2 years later. Physicial examination showed a left VII cranial nerve palsy. MRI showed an enhancing mass in the pons. Total body CT was negative. The patient was treated with a course of whole-brain and brain stem radiotherapy following stereotactic biopsy. Four months after radiotherapy, the neurological symptoms had disappeared and the patient died of a myocardial infarct. The systemic disease was still clinically silent.

Conclusion

Our case involved only brain stem metastasis, probably implicating Batson's direct route of the paravertebral venous pathway.
Smoking in Italy, 1995
Authors: Pagano Romano , La Vecchia Carlo , Decarli Adriano
Published: April 2018

Aims and background

Patterns and trends in smoking habits are a major determinant of subsequent incidence and mortality for lung cancer, and other tobacco related neoplasms on a population level.

Methods and study design

Smoking prevalence in Italy was analyzed using data from the 1995 National Multipurpose Survey, conducted by the National Institute of Statistics (ISTAT) and based on a sample of 50,585 subjects (24,497 men and 26,088 women), aged 15 years or over, identified in strata of geographic area and size of the municipality in order to be representative of the general Italian population. Data on smoking were obtained through a self-administered questionnaire.

Results

Overall, 25.3% of Italians aged 15 years or over (34.1% of males, 17.1% of females) described themselves as current smokers, 20.5% (28.0% of males, 13.5% of females) as ex-smokers, and 54.2% (37.9% of males, 69.4% of females) as never smokers. Heavy current smokers (≥15 cigarettes per day) were 15.6% of males and 3.9% of females. Compared to previous surveys, reported smoking prevalence increased, mostly in the youngest age groups (15 to 24 years) in both sexes. However, the increase could be partly or largely attributable to the different modality of data collection (interview in previous surveys, self-administered questionnaire in the present survey), which may have reduced underreporting.

Conclusions

The data of the 1995 National Household Survey confirmed previous patterns of smoking in Italy, i.e., a higher smoking prevalence in less educated, southern Italian males, and in more educated, northern Italian females. These figures reflect therefore the importance of the social and cultural correlates of smoking. Moreover, the stability in smoking prevalence over the last few years reflects the absence of any organized and structured intervention on a legislation and public health level on the smoking issue in Italy.
Squamous Cell Carcinoma of the Lacrimal Drainage System: Case Report and Literature Review
Authors: De Stefani Antonella , Lerda Walter , Usai Antonio , Cavalot Andrea , Riella Paola , Bussi Mario
Published: April 2018

Aims and background

Epithelial malignant tumors of the lacrimal drainage system are rare. The most prevalent type is squamous cell carcinoma. These tumors generally present with aspecific symptoms suggestive of chronic dacryocystitis, with the result that diagnosis and treatment are often delayed.

Methods and study design

We present the case of a patient with a squamous cell carcinoma of the lacrimal ducts and discuss the clinical and pathological features of these neoplasms, together with diagnostic and therapeutic strategies according to the data available in the literature.

Results and conclusion

The diagnostic and therapeutic approach to this kind of rare tumors has to be planned carefully. Radiographic examination of all masses arising in the medial canthus is essential. Dacryocystography allows the identification of space-occupying tumors in the lacrimal sac. Computed tomography and magnetic resonance imaging provide the most useful information about the extent of the neoplasm and its relationship with surrounding bone structures and soft tissues. Histological examination of a biopsy sample obtained by standard dacryocystectomy is essential to confirm the diagnosis. The treatment of choice is primarily surgical, consisting of complete resection with long-term follow-up. A number of surgical procedures have been described, which are more or less aggressive depending on the extension of the tumor. Radiotherapy is indicated when bone or lymphatic invasion is evident, and when neoplastic cells are present in the resection margins. Radiotherapy alone is not considered a treatment of choice, but only a palliative option in selected cases. The follow-up data available in the literature are incomplete. In most of the literature reports, relapse occurs in 50% of patients within 5 years.
Extramedullary Plasmacytoma in a Patient with Aids: Report of a Case and Review of the Literature
Authors: Vallisa Daniele , Pagani Leonardo , Bertè Raffaella , Civardi Giuseppe , Viale Pierluigi , Paties Carlo , Cavanna Luigi
Published: April 2018

Human immunodeficiency virus (HIV) is likely to play a role in the onset of plasma cell tumors (PCT). In fact, HIV could be involved in plasmacytomagenesis in several ways: it has the ability to lessen the immunosurveillance to such a degree as to impair the immune response against tumor cell growth. This decreased immunosurveillance could further facilitate the transforming malignant role of possible Epstein-Barr virus (EBV) infection occurring in this setting. Lastly, a murine retrovirus has been shown to be able to accelerate plasmacytomagenesis in mice, thus indicating that these viruses may be directly involved in the onset of PCT. According to cases previously reported in the literature, the clinical features of this case of HIV-associated PCT were more aggressive and the survival was shorter than expected for PCT cases in the general population. Further, the pattern of alteration of gam-maglobulinemia differed in this setting. These alterations strongly suggest a direct role of HIV in PCT. Further in-depth investigations are therefore warranted to elucidate this issue.
Role of P53 Mutations in the Radiosensitivity Status of Tumor Cells
Authors: Chiarugi Vincenzo , Magnelli Lucia , Cinelli Marina
Published: April 2018

Wild-type p53 is involved in cellular response to DNA damage including cell cycle control, DNA repair and activation of apoptosis. Accumulation of p53 protein following DNA damage may initiate the apoptotic process, resulting in cell death. DNA damage induced by radiation is an example of apoptotic stimulus involving p53. Regulation of apoptosis by p53 can occur through transcriptional regulation of pro-apoptotic (e.g. bax) and anti-apoptotic (e.g. bel-2) factors. Although wild-type p53 usually sensitizes cells to radiation therapy, p53 mutations have a variable effect on radiation response. For example p53 mutations in bone or breast tumors have been found to be associated with resistance to chemotherapeutic drugs or ionizing radiation. Mutated p53 has has been reported to increase sensitivity to radiation and drugs in colorectal and bladder tumors. The present brief commentary tries to find an explanation at molecular level of these conflicting results.
The Role of Radiotherapy in the Treatment of Carcinoma of the Prostate: A Survey of Clinical Practices in Lombardy, Italy, by the Airo-Lombardia Cooperative Group
Authors: Villa Sergio , Bertoni Filippo , Bossi Alberto , Caraffini Bruno , Corbella Franco , Di Lorenzo Innocenzo , Italia Corrado , Leoni Mario , Nava Simona , Sarti Enrico , Vavassori Vittorio , Villa Eugenio , Palazzi Mauro
Published: April 2018

Aims and background

We report the results of a survey performed in 1994 by the AIRO-Lombardia Cooperative Group, on the clinical patterns of radiation treatment for prostatic carcinoma in Lombardy, Italy, involving all radiotherapy centers serving an overall local population of about 8,800,000 people.

Methods

A questionnaire was sent to all 13 radiotherapy centers throughout Lombardy, asking for demographic and treatment details concerning the local population of patients with a localized (T1-4, N0-1, M0) carcinoma of the prostate treated with radiotherapy; 12 centers responded, making the basis for the present report.

Results

Analysis of collected data showed that in Lombardy: a) approximately 400 patients per year are irradiated for a localized carcinoma of the prostate, accounting for less than 30% of the total expected number of patients with this disease presentation; b) a complete staging (with PSA, transrectal ultrasonography, abdomino-pelvic CT or MRI scan and total-body bone scan) is performed in over 95% of patients before initiating radiotherapy; c) significant differences exist between radiotherapy centers as regards treatment planning and delivery.

Conclusions

An urgent need exists for implementing procedures aimed at standardizing radiotherapy procedures within Lombardy.
Ifosfamide Bolus Followed by Five Days Continuous Infusion in Extensively Pretreated Patients with Advanced Breast Cancer: A Phase II Study
Authors: Bisagni Giancarlo , Boni Corrado , Manenti Anna Lucia , Moretti Gabriella , Rondini Ermanno , Sassi Maurizio , Zadro Alvise , Savoldi Luisa
Published: April 2018

Purpose

A phase II study with ifosfamide in pretreated patients with advanced breast cancer was performed to determine the objective response rate, the toxicity and the feasibility of the regimen.

Methods & study design

Patients enrolled had advanced breast cancer pretreated with at least one previous regimen of chemotherapy for advanced disease. Treatment consisted of ifosfamide infused at a dose of 2 g/m2 iv in 4 hrs followed by ifosfamide, 8 g/m2 iv in 120 hrs in ambulatory treatment, using a portable external pump system. The total dose of ifosfamide was 10 g/m2; mesna (4 g/m2 iv) was administered mixed with ifosfamide in 120 hrs Cycles were repeated every 3 weeks. Three patients were pretreated with neoadjuvant and 15 with adjuvant chemotherapy. All patients were treated for advanced disease (median number of regimens, 1; range, 1-3): 21 with the cyclophosphamide-containing regimen and 15 with adryamicin. Sixteen patients received one or more lines of endocrine therapy. Fifteen patients had dominant site in viscera, 6 in bone, and only one in soft tissue; 17 patients had more than one site of disease.

Results

Twenty-two patients were enrolled and all were assessable for response and toxicity. A partial response was reached in 5 patients (23%; 95% confidence limits 5% to 60%). Hematologic toxicity was the dose-limiting side effect; grade 4 leukopenia occurred in 10 patients (46%).

Conclusions

Considering the response rate obtained in our series of intensively pretreated patients, the results seem to indicate that the regimen is active and could be included among the possible options in the treatment of patients with refractory, poor-prognosis, advanced breast carcinoma.
Pilot Study of Daily Ifosfamide 1 g/m2 Until Grade III Granulocytopenia as Second-Line Chemotherapy for Anthracycline-Pretreated Advanced Soft Tissue Sarcoma
Authors: Babović Nada , Jelic Svetislav , Milanović Nenad , Matković Suzana
Published: April 2018

Background and aims

Second-line chemotherapy regimens for advanced soft tissue sarcomas after treatment failure or tumor relapse following anthracyclines are still investigational. The aim of the present study was to assess the activity of ifosfamide with a new schedule for patients with advanced soft tissue sarcoma failing to achieve remission or relapsing following anthracycline-containing regimens; it was attempted to individualize dosages and prevent excessive toxicity.

Study design

A second-line chemotherapy regimen of ifosfamide 1 g/m2 daily, with drug withdrawal until the next cycle upon appearance of grade III granulocytopenia, was administered to 21 patients with advanced soft tissue sarcoma. All patients failed to achieve remission or relapsed following a first-line high-dose anthracycline regimen (epirubicin 180 mg/m2 or zorubicin 600 mg/m2 per cycle). The cycles were repeated every four weeks.

Results

The median number of cycles applied was three (range, 1-15). The ifosfamide dosage reached was 4-13 g/m2 per cycle, median 5 g/m2. A complete response was achieved in 1/21 patient (5%), no partial responses were observed, 4/21 patients (20%) had stable disease, and 16/21 (75%) had progressive disease. No difference in response and stable disease rates was observed between responders and non-re-sponders to first-line chemotherapy. No difference in the ifosfamide dose reached was noted between patients receiving second-line chemotherapy directly following first-line therapy and those with a time interval between first- and second-line chemotherapy. The granulocytopenia grade III nadir lasted for a median of one day (range, 1-3) and other toxicities including hematological toxicity were mild and infrequent.

Conclusions

In view of the swift regeneration from grade III granulocytopenia, continuation of the study with granulocytopenia grade IV as a limiting factor for ifosfamide dose escalation seems feasible, with the prospect of better efficacy without excessive toxicity.