bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA Binding Characteristics and Generation of Cytotoxic Lymphocytes against Peptides Derived from Oncogenic Proteins
Authors: Bertazzoni Carla , Marchesi Edoardo , Dermime Said , Ravagnani Fernando , Parmiani Giorgio , Gambacorti-Passerini Carlo 
Published: April 2018

Aims and background Structurally altered proteins (derived from chromosomal translocations or gene mutations) can be considered tumor specific antigens and represent an attractive target for a T-cell mediated response. T lymphocytes recognize antigens in the form of peptides bound to HLA-mole-cules. Materials and methods Peptides derived from oncogenic proteins were screened fro the presence of HLA binding motifs; actual binding were evaluated by HLA stabilization experiments using transfectants and specific anti-HLA antibodies. Specific lymphocytes were induced by in vitro peptide sensitization and screened by thymidine uptake or cellular cytotoxic assays. Results We identified peptides derived from EWS/FLI-1 fusion protein and from mutated K-RAS protein (encompassing respectively the fusion point and the mutation at position 12) that showed binding motif for HLA-Cw*0702 and HLA-A3 respectively. The actual binding of these peptides was analysed in a stabilization assay. We detected binding for the EWS/FLI-I peptide and for 5 RAS peptides (1 wild type and 4 mutated). The effect of temperature, β2-microglobulin (β2-m) and fetal calf serum (FCS) on the binding and the stability of the HLA/peptide complex was studied. A low temperature (26°C) increased the binding both in HLA-A3 and HLA-Cw*0702, while FCS reduced it. β2-m increased the binding to the HLA-A3 molecule but did not influence the binding to the HLA-Cw*0702. The stability of already formed complexed was somewhat different in the HLA-A3 and HLA-Cw*0702 system: both were more stable at 26°C than at 37°C but while the β2-m and FCS did not influence the stability of the HLA-A3/peptide complex, they seemed to cause opposite effects in the HLA-Cw*0702 system (β2-m stabilized and FCS destabilized the complex). Finally, we were able to generate a specific CD8+ CTL line against a K-RAS mutated peptide. Conclusions Although binding motifs and actual HLA binding can be detected in several cases, the generation of a cellular response is infrequent, confirming that HLA binding is necessary but not sufficient to obtain an in vitro response. Further optimization of culture conditions, type of Antigen Presenting Cells (APC), peptides, use of stabilizers like β2-m are still needed.
Role of Pamidronate Disodium in the Treatment of Metastatic Bone Disease
Authors: Ripamonti Carla , Fulfaro Fabio , Ticozzi Chiara , Casuccio Alessandra , De Conno Franco 
Published: April 2018

Aims and Background Bone metastases are a common feature of advanced neoplastic disease and are considered to be among the most frequent causes of pain and complications in oncologic patients. The main objective of the treatment of such patients is to control their symptoms and improve their quality of life. Pamidronate disodium is a second-generation bisphosphonate capable of inhibiting bone resorption (particularly osteoclast activity) without affecting bone reminerali-zation. After a brief introduction concerning the pathophysiology of bone metastases and neoplastic bone pain, we herein present data on the clinical pharmacology and toxicity of bisphosphonates in general, and pamidronate in particular. We conclude by reviewing the literature on the use of pamidronate in phase II and III trials involving patients with metastatic bone disease. Methods The paper is based on a review of articles published between 1984 and 1997 selected from the Cancerline and Medline databases. Results In the considered phase II and III studies involving patients with bone metastases (breast cancer and multiple myeloma in particular), pamidronate proved to be efficacious in reducing the incidence of pain and skeletal complications, decreasing the excretion of metabolic markers of bone resorption and improving the quality of life. Intravenous infusions of 60-90 mg over a period of 2 hr every 3-4 weeks did not cause any significant toxic effects and was easily managed. Conclusions Pamidronate is a bisphosphonate that is efficacious in the treatment of symptomatic bone metastases and can be considered an important therapeutic option in association with systemic treatments, radiotherapy and normal supportive care, especially in patients with breast cancer and multiple myeloma. Further randomized studies are necessary to confirm the positive preliminary results in other neoplasms, analyze the cost/benefit ratio of the treatment, and verify the possibility that, in addition to being used for palliative purposes, pamidronate may also prevent or delay the appearance of bone metastases.
Cancer Mortality by Urbanization and Proximity to the Sea Coast in Campania Region, Southern Italy
Authors: Bidoli Ettore , Franceschi Silvia , Montella Maurizio 
Published: April 2018

Aims and background The risk for several cancers is higher in urban than in rural areas. The gradient has seldom been studied in southern Europe. Patients and methods The geographical pattern of mortality for different cancers and all causes was studied in the Campania Region (about 5.6 million inhabitants), whose largest town is Naples. The key variables were residence in urban/rural and coastal/inland municipalities. Relative risks of death and corresponding 95% confidence intervals by residence were evaluated by means of Poisson log-linear regression models. Results Significantly increased mortality rates in urban compared to rural municipalities were found for several cancer causes of death. In particular, in both sexes, excesses in the order of 30-50% were observed for tobacco-related neoplasms (i.e., larynx, lung, and bladder) and cancers of the intestine, liver, brain, multiple myeloma and non-Hodgkin's lymphoma, in addition to all-cancer, and all-cause mortality. In females, specific excesses were also noticed for cancer of the gallbladder, pancreas, breast and uterus (corpus and cervix). Conversely, significantly decreased mortality rates in urban with respect to rural municipalities were observed for cancer of the oral cavity and pharynx in males. Coastal location and degree of urbanization were strongly correlated, thus showing similar associations with most causes of death. However, a significant excess of cancer of the pleura in males was restricted to coastal municipalities. Conclusions Anti-smoking campaigns, sanitation improvements, hepatitis B vaccination, and a decrease in obesity emerge as high priorities with respect to cancer control strategies in the Campania Region, particularly in overpopu-lated, underprivileged urban areas.
Does Long-Term Exposure to Gel-Filled Silicone Implants Increase the Risk of Relapse after Breast Cancer?
Authors: Petit Jean-Yves , Lê Monique , Rietjens Mario , Contesso Geneviève , Lehmann Andrée , Mouriesse Hélène 
Published: April 2018

Background An increased risk of cancer and autoimmune diseases associated with gel-filled silicone implants, debated by FDA experts since 1991, has given rise to a profusion of literature on the subject. However, such effects have not been adequately investigated in patients with breast cancer. In a previous report we compared 146 breast cancer patients with gel-filled silicone implants for breast reconstruction to 146 control patients in whom no reconstruction had been performed. The observed results were reassuring, as the evolution of the disease after 10 years was better in the reconstruction group than in the control group. We now report the end results of this study with a median follow-up of 13 years after the breast reconstruction (range, 10-20 years). Method The relative risks of detrimental events were estimated with Cox's Proportional Hazards Model, with stratification according to age at diagnosis. Results The risks of locoregional recurrences and distant metastasis were significantly lower in the BR group than in the control group. The risks of death, of a second breast cancer and of a second primary cancer at a site other than the breast were not significantly different between the two groups of patients. Conclusion Long-term follow-up of patients exposed to gel-filled silicone implants confirms the absence of detrimental effects after breast cancer. The power of our study is, however, below that required to detect a very slight increase in the risks studied.
Interleukin-2, Interferon-α and Interleukin-2 plus Interferon-α in Renal Cell Carcinoma. A Randomized Phase Ii Trial
Authors: Boccardo Francesco , Rubagotti Alessandra , Canobbio Luciano , Galligioni Enzo , Sorio Roberto , Lucenti Antonio , Cognetti Francesco , Ruggeri Enrico , Landonio Giuseppe , Baiocchi Claudia , Besana Carlo , Citterio Giovanni , De Rosa Marisa , Calabresi Federico 
Published: April 2018

Background The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC). Patients and methods In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rIL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 106 IU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-α at a daily dose of 6 x 106 IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity. Results Twenty-three percent (95% CI: ± 17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI: ± 11.9) and 9% (95% CI: ± 11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine, months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN. Conclusions Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.
Early Gastric Cancer: Diagnosis, Surgical Treatment and Follow-Up of 45 Cases
Authors: Sigon Roberto , Canzonieri Vincenzo , Cannizzaro Renato , Pasquotti Bruno , Cattelan Alessandro , Rossi Carlo , Carbone Antonino 
Published: April 2018

Aims and background The 5-year survival rate of early gastric cancer (EGC) is 85%-100% after “curative” resection, as compared to 20%-30% in advanced gastric cancer (AGC). Because of this relatively high cure rate, the interest in the diagnosis and therapy of EGC has been steadily increasing. The present study, based on 45 EGCs, is aimed at a critical evaluation of the diagnostic procedures and surgical options. Methods and results Forty-five patients with early gastric cancer (27 men and 18 women; median age, 62 years; range, 28-84) were diagnosed and operated on. They represented 22.5% of all patients with gastric cancer (200) treated in the period July 1987 to January 1998. Forty-one patients were from the northeastern part of Italy. The most frequent symptom was epigastric pain (84%). Barium upper gastrointestinal radiography findings were strongly suggestive of malignancy in 41 cases (91%). Preoperative histopathological diagnosis of adenocarcinoma was performed in 43 cases (95.5%). In two cases (4.5%) severe epithelial dysplasia (associated with ulcer) was the first diagnosis, but the final diagnosis on the basis of the resected specimens was a well differentiated adenocarcinoma. The primary surgical procedure included i) subtotal distal resection (37 cases) with Billroth II (33) and Billroth I (4) reconstructions; ii) total gastrectomy (3) for proximal neoplastic extension; iii) proximal gastric resection (2) for cardial cancer; iv) degastro-total gastrectomy (3) for cancer of the stump. Two patients, previously treated with conservative surgery, underwent degastro-total gastrectomy for neoplastic microfocal extension to the margin of resection and for early anastomotic recurrence, respectively. Mural infiltration was limited to the mucosa and submucosa in 27 and 18 cases, respectively. Lymph node metastases were found in three mucosal and five submucosal tumor cases, involving either the first or the second echelon. No operative deaths or postsurgical complications occurred in this series. In the follow-up period (median, 36 months; range, 3-120) four patients died due to other causes; one developed liver metastases, another developed oropharyngeal cancer and two died of biopsy-proven lung cancer without evidence of gastric cancer recurrence. Conclusions The clinical presentation of EGC is aspecific. Preoperative endoscopy with biopsy remains the most sensitive diagnostic procedure. For treatment, subtotal distal gastric resection with lymphadenectomy is the “gold standard” but in some instances total gastrectomy may be indicated. Accurate pathological examination establishes the depth of infiltration, as well as the superficial extension of tumors and the lymph node status. Although the prognosis of EGC is favorable, a medium-term follow-up should be planned.
Measurement of the Cost of Screening for Cervical Cancer in the District of Florence, Italy
Authors: Zappa Marco , Cecchini Silvia , Ciatto Stefano , Iossa Anna , Falini Patrizia , Mancini Maria , Paci Eugenio 
Published: April 2018

Aims and background To estimate the cost per woman examined and per CIN II or more severe lesion detected in a population-based cytologic screening program for cervical cancer prevention. An organized cytologic screening program has been ongoing in the Florence District since 1973, and a call-recall system using mail invitation has been ongoing since 1980. Smear reading and assessment of screening positives is centralized at the screening unit. Methods and study design All relevant resources (costs) consumed by the program were listed and measured. The unit cost per examined woman and per each CIN II or more severe lesion detected was estimated for each screening phase (recruitment, screening, assessment). Results The cost per examined woman was $24.60, whereas that per CIN II or more severe lesion detected was $13,600. Staff accounted for 80% of total amount. Conclusions Although the cost for a single procedure is low, the cost per detected lesion is quite remarkable due to the low detection rate in a population screened for a long time. Different approaches and longer interval screening tests are discussed.
Quality Control by Portal Film Analysis in Radiotherapy for Prostate Cancer: A Comparison between Two Different Institutions and Treatment Techniques
Authors: Italia Corrado , Fiorino Claudio , Ciocca Mario , Cattaneo Giovanni Mauro , Montanaro Paolo , Bolognesi Angelo , Lanceni Angelo , Reni Michele , Bonini Antonio , Modugno Antonio , Calandrino Riccardo , Valdagni Riccardo 
Published: April 2018

Aims and background Accuracy and reproducibility of patient setup during radiotherapy for prostate cancer were investigated in two different Institutions (A and B), within their Quality Assurance programs. The purpose of the study was to evaluate and compare setup accuracy and reproducibility in Institutions A and B, which adopt different patient positioning and treatment techniques for prostate irradiation. Materials and methods A retrospective analysis of portal localization films taken during the treatment course was performed: 30 and 21 patients in Institutes A and B, respectively, entered the study. In Institute A, patients were treated in a prone position, utilizing an individualized immobilization cast (either an alpha cradle or a heat and vacuum-formed cellulose acetate cast) with an open table top and individual abdominal wall compressor to minimize small bowel irradiation; a 5-field conformal technique was used. In Institute B, patients were treated in a supine position without any immobilization device; a 6-field BEV-based technique (conformal only for patients treated with a radical aim) was adopted. A total of 598 portal films (420 from Institute A and 178 from Institute B) were analyzed. The mean number of films per patient was 12 (range, 4-29). Systematic and random setup errors were estimated utilizing the statistical method suggested by Bijhold et al. (1992). Results When patients with a mean (systematic) error larger than 5, 8 and 10 mm in craniocaudal, lateral and posterior-anterior directions, respectively, were compared, no statistically significant difference between the two groups was observed. Similarly, when comparing portal films, a significant difference ( P <0.01) appeared only in the craniocaudal direction (errors > 5 mm: Institute A = 24%; Institute B = 11%). In both Institutes, the SD of random and systematic error distribution ranged from 1.8 to 4.2 mm, with a small prevalence of systematic errors. Only for craniocaudal shifts in Institute A was the random error larger than the systematic error, and it was significantly worse than in Institute B (1 SD, 4.2 mm in Institute A vs 1.8 mm in Institute B). Conclusions Setup errors observed in Institutes A and B were similar and in accord with data reported in the literature. In Institute B, satisfactory geometrical treatment quality was achieved without patient immobilization. In Institute A, the goal of minimizing small bowel irradiation and prostate motion through the aforementioned technique, which makes patient position less comfortable, did not seem to considerably increase daily setup uncertainty.
La Risonanza Magnetica Del Carcinoma Pancreatico
Authors: Pavone Paolo , Laghi Andrea , Catalano Carlo , Panebianco Valeria , Pediconi Federica , Fabiano Sebastiano , Passariello Roberto 
Published: April 2018

The role of MR imaging in the assessment of pancreatic adenocarcinoma is in identification, characterization and staging of the neoplastic lesion. Technique optimization is required in order to obtain high qualities images competitive with spiral CT. The choice of imaging protocol is strictly related to the available equipment as well as fast imaging capabilities. Contrast-enhanced study using breath-hold sequences is required if working at high field strength with high gradient performance; on mid-low field strength nonbreath-hold acquisition techniques, using respiratory compensation techniques, can be implemented. The use of fat saturation pulses may increase the sensitivity of MR in detecting pancreatic lesions. Other advantages of MR imaging are represented by the availability of additional noninvasive techniques for the evaluation of the biliary tree (MR-cholangiopancreatography) and splanchnic vessels (MR-angiography). Lesion identification is based on Tlw sequences where the lesion appears hypointense compared with the surrounding pancreas; increased lesion-pancreas contrast is obtained when fat suppression is used. On dynamic studies following gadolinium injection, pancreatic tumors are hypovascular compared with surrounding normal pancreatic gland. Problems in correctly defining the size of the lesions may be encountered in patients presenting with inflammatory changes of the pancreatic parenchyma surrounding the carcinoma (epineoplastic pancreatitis). For lesion characterization MRI is not able to characterize focal pancreatic lesions, allowing a differential diagnosis between pancreatic cancer and focal hypertrophic chronic pancreatitis. Even the use of MR-cholangiopancreatography is not helpful for characterizing focal pancreatic masses. MR imaging is accurate in local staging (assessment of peripan-creatic fat infiltration) thanks to the higher contrast resolution, but in vascular staging and in the evaluation of lymphn-odal involvement it suffers the same limitations as computed tomography. Future perspectives are represented by the use of magnetic resonance angiography for the evaluation of vascular encasement and the use of specific contrast agents for lymphadenopathy. Identification of hepatic metastases with MRI has been proven to be high, with sensitivity and specificity comparable to CT. The use of liver-specific contrast agents (either positive or negative) is becoming almost routine and it is proving to further improve the diagnostic value of MRI.
I Marcatori Tumorali Nella Diagnosi Del Carcinoma Pancreatico
Authors: Cappelli Gino , Paladini Sergio , D'Agata Alberino 
Published: April 2018

The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The ganglio-sides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a “triplet” of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an “integrated” use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of ra-diochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.