bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Gene Copy Number Variations using a Method Based on Lab-on-a-Chip Technology
Authors: De Lellis Laura , Mammarella Sandra , Curia Maria Cristina , Veschi Serena , Mokini Zhirajr , Bassi Chiara , Sala Paola , Battista Pasquale , Mariani-Costantini Renato , Radice Paolo , Cama Alessandro 
Published: February 2018

Aims and Background Copy number variations (CNVs) contribute to genome variability and their pathogenic role is becoming evident in an increasing number of human disorders. Commercial assays for routine diagnosis of CNVs are available only for a fraction of known genomic rearrangements. Thus, it is important to develop flexible and cost-effective methods that can be adapted to the detection of CNVs of interest, both in research and clinical settings. Methods We describe a new multiplex PCR-based method for CNV analysis that exploits automated microfluidic capillary electrophoresis through lab-on-a-chip technology (LOC-CNV). We tested the reproducibility of the method and compared the results obtained by LOC-CNV with those obtained using previously validated semiquantitative assays such as multiplex ligation-dependent probe amplification (MLPA) and nonfluorescent multiplex PCR coupled to HPLC (NFMP-HPLC). Results The results obtained by LOC-CNV in control individuals and carriers of pathogenic MLH1 or BRCA1 genomic rearrangements (losses or gains) were concordant with those obtained by previously validated methods, indicating that LOC-CNV is a reliable method for the detection of genomic rearrangements. Conclusion Because of its advantages with respect to time, costs, easy adaptation of previously developed multiplex assays and flexibility in novel assay design, LOC-CNV may represent a practical option to evaluate relative copy number changes in genomic targets of interest, including those identified in genome-wide analyses.
Dichloroacetate Induces Different Rates of Cell Death in Cancer and Noncancer Cell Lines in Vitro
Authors: Washington Jovonia T , Quintyne Nicholas J 
Published: February 2018

Aims and Background The pyruvate mimetic dichloroacetate (DCA) has been shown to induce cell death in cancer cells. A number of studies in vitro and in vivo have suggested this molecule may serve as an anticancer agent, but some cells are resistant. Here we wanted to examine the effects of DCA on cancerous and noncancerous cells grown in culture for a prolonged period of exposure and at increasing concentrations. Methods Six cancer cell lines (A549, SK-HEP-1, HCT116, UPCI:SCC070, HeLa and MES-SA) and three noncancerous lines (RPE, GM03349B and HEK293) were exposed to 0.5 mM DCA for seven days and cell counts were taken every day to determine viability and cell cycle progression. The same cell lines were also exposed to higher doses of DCA up to 10 mM and viability was scored. Results Five cancer cell lines showed high levels of cell death early in the trial, but three of the lines showed a second delayed increase in cell death at later stages. HCT116 cells were unaffected by 0.5 mM DCA. GM03349B and RPE cells also died when treated with DCA. At high concentrations, all cell lines exhibited high rates of death. No specific cell cycle arrest of the cells was observed. Conclusion We found that there is considerable difference in the way cancer cells are affected by DCA. Some have populations that are highly resistant to treatment, while others have stronger rates of death only after prolonged exposure. We also found noncancerous cells are not all resistant to DCA, a significant finding that has not previously been observed in other in vitro DCA trials.
Histological Features and Treatment Approach of Trichoblastic Carcinomas: From a Case Report to a Review of the Literature
Authors: Laffay Lisa , Depaepe Lauriane , D'hombres Anne , Balme Brigitte , Thomas Luc , De Bari Berardino 
Published: February 2018

Background Trichoblastic carcinoma (or malignant trichoblastoma) is a rare malignant cancer of adnexal structures with morphological features that in some cases are reminiscent of a trichoblastoma. Trichoblastic carcinoma is underdiagnosed as it is a rather recent entity which is still not recognized as such by all pathologists. The differential diagnosis with basal cell carcinoma is often difficult to make and the optimal treatment has not yet been established. Case report We report the case of a 43-year-old patient who underwent surgical excision and adjuvant radiotherapy for a growing mass of 40 × 48 mm located in the lumbar right paraspinal skin. The pathological findings demonstrated a trichoblastic carcinoma. The clinicopathological profile, the histogenesis, and the difficulties related to the histopathological diagnosis and treatment of this rare entity are discussed in this article. Conclusion Although the published reports on this disease are few, surgery should be considered the standard therapeutic approach for trichoblastic carcinomas. Selected cases presenting clinical features of local aggressiveness can safely be treated with adjuvant irradiation to improve local control. However, acute and particularly late toxicities need to be taken into account in the decision.
A Case of Small Cell Carcinoma of the Prostate and Review of the Literature
Authors: Addeo Alfredo , Rinaldi Ciro , Panades Miguel 
Published: February 2018

Aim and background Small cell carcinoma of the prostate (SCCP) is a relatively rare entity, an aggressive tumor with a tendency to metastasize early. There is no standard chemotherapy regimen for SCCP. We report the case of a 67-year-old man with an initial diagnosis of prostate adenocarcinoma with bone metastases who subsequently developed a small cell carcinoma of the prostate with liver metastases. Methods and study design A review of this case and of the current literature was done with a view to highlighting the ideal approach to such an unusual tumor. Results and conclusion The patient was treated with carboplatin and etoposide and after 3 cycles achieved a good response. Unfortunately he developed massive pulmonary embolism which impeded the continuation of treatment and caused his death. By reviewing the literature we found there is no standard of care and new targeted therapies have failed to prove any benefit so far. It is mandatory to persevere in planning trials and exploring new drugs to improve the outcome of patients with SC-C P. It might also be worth creating a register for SCCP where data can be collected to coordinate the management of these patients and to establish better connections among cancer centers.
LDOC1 Gene Expression in Two Patients with Head and Neck Squamous Cell Carcinomas and Parkinson's Disease
Authors: Salemi Michele , Giuffrida Domenica , Giuffrida Maria C , Soma Pier Franco , Rolfo Alessandro , Cimino Laura , Condorelli Rosita A , Castiglione Roberto , La Vignera Sandro , Calogero Aldo E 
Published: February 2018

Introduction Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Risk factors for this cancer include tobacco and alcohol use, ultraviolet light exposure, and viral infection. Parkinson's disease is one of the most common neurodegenerative disorders, with a prevalence of 3% in persons over the age of 65 years. Apoptosis is a programmed cell death machinery pivotal for normal development, the establishment of highly organized neuronal circuitry, and the elimination of cancer cells. It has been suggested that increased expression of proapoptotic genes is associated with head tumors. One of these genes is the leucine zipper, down-regulated in cancer 1 (LDOC1) gene. Case report We report two interesting cases of a 79-year-old man and a 98-year-old woman, both with Parkinson's disease and well-differentiated multiple HNSCC, in whom we evaluated the possible differential expression of LDOC1. Results We found that LDOC1 gene expression was increased in both patients compared with three male and three female controls. Conclusions These findings suggest that apoptosis may play a pathogenetic role in HNSCC.
Intraoperative Radiotherapy during Kyphoplasty for Vertebral Metastases (Kypho-IORT): First Clinical Results
Authors: Reis Tina , Schneider Frank , Welzel Grit , Schmidt Renè , Bludau Frederic , Obertacke Udo , Wenz Frederik 
Published: February 2018

Aims and background Kyphoplasty is an effective procedure providing structural stability and pain alleviation in vertebral metastases. To prevent early regrowth, patients typically receive postoperative fractionated radiotherapy, which is associated with long treatment duration. Therefore, we established a new approach to deliver intraoperative radiotherapy during kyphoplasty to shorten the treatment time and reach structural stability and sterilization of the metastases (Kypho-IORT). Methods and study design For Kypho-IORT, a 50 kV X-ray source with a specially designed applicator was used. A radiation dose of 8 Gy in 5 mm distance was delivered. After radiation the device was removed and the kyphoplasty was completed according to the standard procedure. Since August 2009, 18 patients with instable or painful spinal metastases received Kypho-IORT. The median age was 63 years (range, 43–73). Results Kypho-IORT was successfully performed in 18 of 21 vertebral lesions (86%). No severe complications occurred during or early after IORT. The median pain score using a visual analogue scale decreased from 5/10 before the procedure to 2.5/10 at day 1 (P <0.001) and to 0/10 six weeks after the procedure (P = 0.001). Imaging studies were available for 15 of 18 patients. Stable disease within the irradiated vertebral body was seen in 14 patients (93%) and local progressive disease in one patient (7%). No re-irradiation due to local progressive disease or pain recurrence was necessary within the median follow-up of 4.5 months. Conclusions Kypho-IORT is well tolerated without severe side effects and provides fast improvement of pain. Although stable disease was seen in 93% of the patients, a longer follow-up is necessary to assess the effectiveness. A dose escalation study to establish the maximally tolerated dose has been initiated.
Daily On-Line Set-Up Correction in 3D-Conformal Radiotherapy: Is It Feasible?
Authors: Deodato Francesco , Cilla Savino , Gabriella Macchia , Massaccesi Mariangela , Ippolito Edy , Caravatta Luciana , Picardi Vincenzo , Romanella Michele , Di Falco Carlo , Bartollino Alessandra , Valentini Vincenzo , Cellini Numa , De Spirito Marco , Piermattei Angelo , Morganti Alessio G 
Published: February 2018

Aims and background The aim of this report was to investigate the feasibility in terms of treatment time prolongation of an on-line no-action level correction protocol, based on daily electronic portal image verification. Methods and study design The occupation of a linear accelerator (LINAC) delivering 3-D conformal treatments was monitored for two weeks (from Monday to Friday, 10 working days). An electronic portal image device I-View (Elekta, UK) was used for setup verification. Single-exposure portal images were acquired daily using the initial 8 monitor units delivered for each treatment field. Translational deviations of isocenter position larger than 5 mm or 7 mm, for radical or palliative treatments, respectively, were immediately corrected. In order to estimate the extra workload involved with the on-line protocol, the time required for isocenter check and table correction was specifically monitored. Results Forty-eight patients were treated. In all, 482 fractions had electronic portal images taken. Two hundred and forty-five setup corrections were made (50.8% of all fractions). The occupation of the LINAC lasted 106 h on the whole. Twelve h and 25 min (11.7% of LINAC occupation time) were spent for portal image verification and setup correction. On the average, 4.3 fractions per hour were carried out. Conclusions When used by trained therapists, ideally, portal imaging may be carried out before each fraction, requiring approximately 10% of LINAC occupation time.
The Burden of Rare Cancers in Italy: The Surveillance of Rare Cancers in Italy (RITA) Project
Authors:   The RITA working group, Trama Annalisa , Mallone Sandra , Ferretti Stefano , Meduri Francesca , Capocaccia Riccardo , Gatta Gemma 
Published: February 2018

Aims and background The project Surveillance of rare cancers in Italy (RITA) provides, for the first time, estimates of the burden of rare cancers in Italy based on the list of rare cancers proposed in collaboration with the European project Surveillance of Rare Cancers in Europe (RARECARE). Methods RITA analyzed data from Italian population-based cancer registries (CR). The period of diagnosis was 1988 to 2002, and vital status information was available up to December 31, 2003. Incidence rates were estimated for the period 1995–2002, survival for the years 2000–2002 (with the period method of Brenner), and complete prevalence at January 1, 2003. Results Rare cancers are those with an incidence <6/100,000/year. In Italy, every year there are 60,000 new diagnoses of rare cancers corresponding to 15% of all new cancer diagnoses. Five-year relative survival was on the average worse for rare cancers (53%) than for common cancers (73%). A total of 770,000 patients were living in Italy in 2008 with a diagnosis of a rare cancer, 22% of the total cancer prevalence. Conclusions Our estimates constitute a useful base for further research and support the idea that rare cancers are a public health problem that deserves attention. Centers of expertise for rare cancers that pool cases, expertise and resources could ensure an adequate clinical management for these diseases. Our data also showed that cancer registries are suitable sources of data to estimate incidence, prevalence and survival for rare cancers and should continue to monitoring rare cancers in Italy.
Mutational and Expressional Analyses of MYD88 Gene in Common Solid Cancers
Authors: Je Eun Mi , Kim Sung Soo , Yoo Nam Jin , Lee Sug Hyung 
Published: February 2018

Aims and background Myeloid differentiation primary response gene 88 (MYD88) is a protein involved in hematopoietic differentiation and innate immunity. Recent studies revealed MYD88 mutation in hematological malignancies and MYD88 overexpression in some solid cancers. The aim of this study was to see whether alterations of MYD88 protein expression and somatic mutation of MYD88 gene are features of common solid cancers. Methods We analyzed MYD88 mutation in 45 gastric, 45 colorectal, 45 breast, 45 hepatocellular, 45 prostate and 45 lung carcinomas by single-strand conformation polymorphism (SSCP). We also analyzed MYD88 protein expression in 60 gastric, 60 coloretal and 107 prostate carcinomas by immunohistochemistry. Results In the immunohistochemistry results, MYD88 protein was highly expressed in gastric (75%), colorectal (80%) and prostate (83%) cancers. However, MYD88 expression was significantly different among normal tissues (gastric: 58%, colon: 100%, prostate: 86%). MYD88 expression was significantly increased in gastric cancer cells compared with normal cells, whereas it was decreased in colorectal cancer cells compared with normal cells. There were no somatic mutations of the MYD88 gene in gastric, colorectal, breast, hepatocellular, prostate and lung carcinomas. Conclusions Our data indicate that MYD88 overexpression might be a feature of many solid cancers, but MYD88 expression in normal cells differs depending on the organs. The data suggest that a gain of MYD88 expression in gastric cancers might play a role in cancer pathogenesis by activating oncogenic functions of MYD88.
Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer
Authors: Montanari Marco , Fabbri Francesco , Rondini Ermanno , Frassineti Giovanni Luca , Mattioli Rodolfo , Carloni Silvia , Scarpi Emanuela , Zoli Wainer , Amadori Dino , Cruciani Giorgio 
Published: February 2018

Aims and background Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy. Methods Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. Results Median patient age was 69 years (range, 52–83) and median baseline PSA concentration was 120 ng/mL (range, 5.35–4350). Sixteen (29.6%) patients had measurable lesions. Objective or PSA responses (>50% reduction) were observed in 8 (14.8%) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1–2) and infrequent, with grade 3–4 neutropenia in 12.9% of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7%) and fatigue and stomatitis in 1 case (1.9%). No drug-related serious adverse events were reported. Conclusions Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.
Second Malignancies following Breast Cancer Treatment: A Case-Control Study Based on the Peridose Methodology. ALLEGRO Project (Task 5.4)
Authors: Orecchia Roberto , Jereczek-Fossa Barbara A , Rondi Elena , Bossi-Zanetti Isa , Meaglia Ilaria , Luraschi Rosa , Leonardi Maria Cristina , Rotmensz Nicole , Botteri Edoardo , Fodor Cristiana , Cecconi Agnese , Morra Anna , Lazzari Roberta , Ferrari Annamaria , Cattani Federica , Galimberti Viviana , Luini Alberto , Veronesi Paolo , Zurrida Stefano , Magrini Stefano , Doerr Wolfgang , Humble Nicole , Trott Klaus R , Ottolenghi Andrea , Smyth Vere , Veronesi Umberto 
Published: February 2018

Aims and background To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. Material and study design A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose. Results 195 second cancers were registered (0.019% of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was −3.15 cGy (range, −15.8 cGy and +2.7 cGy). Conclusions The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.
Proteomic analysis shows down-regulations of cytoplasmic carbonic anhydrases, CAI and CAII, are early events of colorectal carcinogenesis but are not correlated with lymph node metastasis
Authors: Wang Ning , Chen Yang , Han Yuchen , Zhao Yue , Liu Yu , Guo Kejian , Jiang Yi 
Published: February 2018

Aim The aim of the study was to screen the markedly down-regulated proteins in colorectal cancer and analyze their relationship to carcinogenesis, cancer progression and pathological aspects. Methods Proteomic analysis was preformed on six fresh colorectal cancer tissues and paired normal colorectal mucosa by two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Two markedly down-regulated proteins among the proteins, of which the expressions were significantly decreased in colorectal cancer compared to normal mucosa, were confirmed by Western Blot in 12 colorectal cancers. Their relationship to carcinogenesis, cancer progression and pathological aspects of colorectal cancer were analyzed in 64 colorectal cancer and paired normal mucosa, 27 benign polyps, and 20 lymph node metastases by immunohistochemistry. Results Two-dimensional differential gel electrophoresis analysis showed there were 2 protein spots, of which the average abundances decreased 3.62 and 3.76 fold in colorectal cancer compared to normal mucosa, respectively. They were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as carbonic anhydrase I and II (CAI and CAII). Validation by Western Blot in 12 colorectal cancers showed there were significantly different expressions of CAI and CAII between colorectal cancer and normal mucosa (P = 0.002 and 0.027, respectively). Immunohistochemistry analysis indicated the expression of CAI and CAII was decreased from normal mucosa to benign polyps, and to colorectal cancer stepwise significantly (P <0.05). However, there were no differences in their expressions between lymph node metastasis and colorectal cancer (P >0.05). There were decreasing trends of CAI and CAII expressions from well to poor differentiation and from stage I or II to stage III or IV, but they were not statistically significant (P >0.05). Conclusions CAI and CAII are necessary enzymes of the colorectum for their normal function. Down-regulations of CAI and CAII are early events of colorectum carcinogenesis. They have no correlations with lymph node metastasis.