bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignancies and lung transplantation.
Authors: Perez Callejo David , Almagro Elena , Doger de Speville Bernard Gaston , Huelves Miriam , Ibeas Patricia , Lopez-Gonzalez Ana , Palka Magda , Ruiz-Valdepeñas Andrea , Mohr Raphael , Carreño MariCruz , Laporta Rosalia , Provencio Mariano 
Published: March 2020

e12015 Background: Malignacies rank fourth on the leading causes of death in recipients of solid organ transplantation. High-dose immunosuppression, infections with oncogenic viruses and the pre-transplant risk, mainly due to tobacco, make these patients more susceptible for developing cancer. In the present study we reviewed a collective of 50 patients with lung transplantation (LT) and cancer. Methods: Retrospective study of 503 lung transplant patients, performed at the Hospital Universitario Puerta de Hierro during 1993 and 2012. We included the following variables: date of birth, reason and date of transplantation, date of diagnosis of malignancy, histology and response to treatment, date and cause of exitus. The contrasts between proportions were performed using Chi-square test and survival curves using the product-limit method of Kaplan-Meier. Results: The 503 included transplant patients developed a total of 55 post-transplant malignancies in 50 patients. Four patients presented tumors already previous to the transplantation. The main underlying pathologies of the patient collective are idiopathic pulmonary fibrosis (50%), emphysema (30%) and cystic fibrosis (14%). Histology of the 55 post-transplant tumors: 18 skin cancer, 12 lung cancer, 8 gastrointestinal cancer, 6 Non-Hodgkin Lymphomas, 2 bladder cancer, 2 myelodysplastic syndromes, 2 sarcomas and 5 others. The mean age of diagnosis of malignancies is at 59 years (18-68). The mean time from transplantation to tumor diagnosis amounts 4 years (1-15). Of the 21 patients (42%) that have died until data collection, cancer was death cause in 15 (30%) Conclusions: Relying on our data, the majority of malignancies are skin and lung cancer and lymphoproliferative syndromes, attributing complications that should be considered in lung transplantation.
Identification and functional characterization of a novel MUTYH gene mutation.
Authors: McDonnell Kevin , Chemler Joseph A. , Marvin Monica L. , Stern Ralph H. , Raskin Leon , Sherman David H. , Gruber Stephen B. 
Published: March 2020

e12026 Background: Biallelic germline mutations in MUTYH result in the autosomal recessive syndrome of MUTYH associated polyposis (MAP).Three well-known, common mutations account for the vast majority of identifiable germline mutations, and serve as the basis for current genetic testing strategies. Comprehensive sequencing of MUTYH often identifies variants of uncertain pathologic significance, and studies to determine the pathogenicity of newly identified variants may offer valuable clinical information and mechanistic insights. In the present study we seek to describe the base-excision repair function of a novel MUTYH (p.C306W) mutation identified in a patient with multiple colon polyps and a family history of colon cancers. Methods: A 50 year old patient with >50 adenomas underwent clinical and laboratory evaluation to assess for germline genetic mutations. We performed Sanger sequencing of tumor and germline DNA together with targeted restriction enzyme digest of germline DNA and fragment DNA sequencing of the alleles. We prepared MUTYH proteins with protein liquid chromatography and assessed their mismatched adenine excision repair capacity employing a glycosylase assay. Results: Analysis of the patient's germline DNA revealed an absence of APC mutations, and the presence of the previously well characterized p.G396D MUTYH mutation as well as a novel p.C306W mutation. Targeted restriction enzyme digest demonstrated trans configuration of the p.G396D and p.C306W MUTYH mutations. Mismatched adenine excision functionality of wildtype MUTYH, known mutant controls p.G396D and p.Y179C, and putative mutant p.C306W were assessed in the glycosylase assay. Consistent with previous experimental observations, relative to wildtype MUTYH, the p.G396D and p.Y179C MUTYH mutants demonstrated attenuated adenine excision activities of 43% and 0%, respectively. Comparable to the activity of the pY179C mutant, the novel p.C306D mutant demonstrated 0% adenine excision activity. Subsequent tumor analysis demonstrated G:C to T:A transversion in the APC gene in somatic DNA derived from an adenoma. Conclusions: Experimental and clinical data demonstrate that p.C306D MUTYH is a pathogenic mutation contributing to the phenotype of MAP.
Spanish national hereditary pancreatic cancer registry (PanFAM).
Authors: Guillen-Ponce Carmen , Mocci Evelina , Earl Julie , Guerrero Carmen T , Calcedo Maria Celia , Salazar Maria Teresa , Molina-Garrido MJ , Marquez Mirari , Gonzalez Gordaliza Cristina , Vazquez Sequeiros Enrique , Custodio Ana , Real Francisco X , Malats Nuria , Carrato Alfredo 
Published: March 2020

e12033 Background: Inherited predisposition to Pancreatic Cancer (PC) corresponds 10% of all cases and includes members of families affected with hereditary cancer syndromes as Familial Pancreatic Cancer (FPC), Peutz-Jeghers, familial melanoma, hereditary breast and ovarian cancer, hereditary pancreatitis. An inherited predisposition in early onset PC (≤ 50 years) has also been suggested. We report preliminary data on PanFAM patients and screening of high risk individuals. Methods: PamFAM is a part of the European PANGEN PC case/control study of hereditary PC, co-ordinated by the Ramón y Cajal (RC) hospital and the Spanish National Cancer Research Center, with 16 participating hospitals. All families with clinical evidence of an inherited PC syndrome were recruited and multi-generational pedigrees were constructed. Cancer diagnoses were confirmed, when possible, by review of medical records. Blood samples and epidemiological data were collected for all participating family members. A screening program for early detection of PC, based on endoscopic ultrasound (EUS), CT and circulating tumour cells (CTCs) was offered to high risk individuals. Results: Of 505 Spanish PCs collected by PANGEN, 31 (~6%) were FPC cases; 18 (58%) revealed only PC and the remaining showed clustering with other tumor types, gastric cancer was the most common (13%). Among FPC families, 3 had 3 cases of PC and the remaining had 2 cases. The mean age of diagnosis was 67 years (range 47-85), 20 male and 11 female. Four FPCs were previously diagnosed with cancer (Hodgkin lymphoma, breast and prostate cancer) and 3 with acute pancreatitis. 37 PCs with no family history of cancer were diagnosed at the age of 50 years or earlier (mean 45, range 30-50), 18 male and 19 female. Other 27 eligible families were recruited by RyC hospital, 8 (30%) with FPC and 3 (11%) with PC ≤ 50 years. A cohort of 61 high risk individuals participes in the screening study: 3 had abnormal EUS, 1 a benign pancreatic node and 1 a renal angiolipoma; one young man had 2 CTCs. Conclusions: PanFAM is the first registry in Spain collecting hereditary PC cases and it represents an important resource to identify underlying gene defects and to the development of screening methods precursor lesions detection in high risk individuals.
Breast cancer detection among Irish BRCA1 and BRCA2 mutation carriers.
Authors: Walsh Elaine , Farrell Michael P. , Gallagher Fergal , Clarke Roisin , Nolan Carmel , Kennedy M. John , Daly Peter , McCaffrey John , Connolly Elizabeth M. , Boyle Terence , Kell Malcolm R. , O'Keefe Sylvia , Gallagher David J 
Published: March 2020

e12038 Background: High-risk breast cancer screening for BRCA1/2 mutations carriers with clinical breast exam, mammography and MRI have sensitivities approaching 100%. Even with intensive screening BRCA mutation carriers can present with self-detected interval cancers. We investigate screening practices and presentation among a cohort of Irish BRCA1/2 mutation carriers. Methods: Females with breast cancer belonging to kindreds now known to harbour BRCA1/2 mutations were retrospectively identified. Records were reviewed for BRCA mutation, demographics, breast cancer diagnosis, stage, histology and screening. We assessed screening modalities and whether breast cancers were diagnosed at screening or as interval cancers. Results: 53 cases of breast cancer were diagnosed from 1968-2010 among 53 Irish hereditary breast ovarian cancer kindreds. BRCA mutation status was unknown at time of diagnosis but subsequently confirmed. Detection method was identified in 50% of patients: 84% by clinical breast exam (CBE), 4% mammography, 4% MRI and 8% by a combination of CBE and mammography. Fifteen women (28%) developed second breast cancer; 9(60%) were undergoing screening, 2 were not and 27% were unknown. 22% were detected by CBE alone; 34% mammography; 22% a combination of mammography and CBE and 22% by MRI. In 41%, histology changed between first and second diagnosis. Two women developed a third breast cancer. In one, her second was an interval cancer despite being in a screening programme. Her third was radiologically detected. Conclusions: In this cohort of Irish BRCA1/2 mutation carriers almost 25% of second breast cancers were not detected by screening. 4% of cases were phenocopies and in 41% histology changed between first and second diagnosis. [Table: see text]
Rate of depressive episode in Peruvian oncologic outpatients.
Authors: Furuya Luis , Infanzon Erick , Venegas Diego 
Published: March 2020

e12043 Background: Depression in Lima, Peru has a prevalence rate of 6.7% and lifetime prevalence of 19%. The relationship between depression and cancer has been widely studied, affects approximately 15% to 25% of cancer patients. However, there is little research in latin population. We report the results of evaluate the frequency of depressive disorder in Peruvian oncologic outpatients and describe clinical and epidemiological features Methods: A descriptive transversal study was performed to 70 patients that attended to oncology clinic at the Hospital Nacional Cayetano Heredia. Data was collected through a survey that included a clinical demographic record and the spanish version – ICD 10 of the Mini International Neuropsychiatric Interview for the diagnosis of depressive episode. Results: The 52% of the participants were females. The mean age was 57 years (18- 83 y) Breast cancer (21%) and lymphoma non Hodgkin (21%) were the most common types of cancer. The mean period from diagnosis was 5 month. The frequency of depressive episode was 21.4%. The 33.3% of women with breast cancer had depression, while patients with NHL had only 13.3% of frequency. We founded two factors with statistically significant association: poor financial status (p =0.041) and advance clinical stages (III and IV) (p = 0.026; OR: 6.8) Conclusions: The frequency of depressive episode was similar to other reports in the literature, the poor financial status and advanced stage are most associated with depression in our population
Association of gliomas and BRCA 1 germline mutation: A possible linkage.
Authors: Frenay Marc , Met Domestici Marie Amelie , Berthet Pascaline , Burel-Vandenbos Fanny , Vennin Philippe , Sobol Hagay , Lebrun Christine , Mari Véronique 
Published: March 2020

e12502 Background: Gliomas are known to occur in association with several well-defined hereditary tumor syndromes such as NF1 and NF2, tuberous sclerosis, Li Fraumeni syndrom and Turcot syndrome. In addition, familial clustering of glioma in absence of these tumor syndrome have also been described. Methods: We have already reported the case of a 35 years old man who was diagnosed with an oligodendroglioma. Familial history reported 3 ovarian cancers at the first degree. Genetic testing had shown the BRCA1 exonic deletion c.3819del GTAAA, p. 1241 ter. (Patient 1 ) We collected 2 more cases of patients diagnosed with glioma and carrying BRCA1 mutation, whom have been seen by other physicians in an other hospital. Results: The second patient is a 59-year-old woman diagnosed with a glioblastoma with important oligodendroglioma differenciation (Patient 2). She was 43 at the time of diagnosis. At the age of 54, she developed a bilateral breast cancer. Moreover, the pedigree revealed a familial history of 4 breast cancers at the first degree. Genetic testing had shown the BRCA1 exonic substitution c.181T>G, p.Cys61Gly. The third patient is a 40-year -old woman diagnosed with an intra medullar pilocytic astrocytoma (Patient 3). This tumour is not usual which allows to keep in mind the genetic procedure. Beforehand, she had been diagnosed with a breast cancer at the age of 36. The pedigree revealed 6 breast cancers among the family and thus, BRCA analysis had been performed and showed the BRCA 1 exonic substitution c.3403 C>T, p.Gln 1135 X. Consequently, the patient had a prophylactic ovarian surgery at the age of 37 and contralateral prophylactic mastectomy at the age of 40. Interestingly, P1 had a BRCA1 deletion whereas P2 and P3 had BRCA1 substitution. On the other hand, P1 and P3 had Exon 11 mutation that both resulted in a truncated protein. Whereas, P2 had an exon 5 missens mutation. Conclusions: No specific association has been reported between BRCA1 mutation and glial tumor occurrence. These cases point out a possible relationship between BRCA1 germline mutation and glioma occurrence such as the relevance of familial history screening in glioma patients. Further investigations are needed to identify a disease-causing locus by genetic linkage analysis.
Meningeal hemangiopericitoma (HPC): Treatment outcome in a retrospective series in a single institution.
Authors: Muggeri Alejandro Daniel , CALABRESE BERNADETTE , Cerrato Sebastian , Cervio Andres , Diez Blanca D. 
Published: March 2020

e12511 Background: HPC is a rare malignant tumor with a high proclivity toward recurrence and metastasis. Methods: The purpose of this study was to analyse retrospectively a series of eighteen patients with HPC treated between January 1992 and Oct 2011 with respect to clinical presentation, treatment results and long-term follow-up outcomes.Survival rate and PFS were analyzed by Kaplan-Meier method, with the use of two-sided log-rank test statistics Results: Twelve were females with a median age of 44.5 years (21-62). In 17 the tumor was intracranial, in one in the spinal cord. Median follow-up was 75,5 months (4 -314). Eight underwent gross total resection (GTR) and 2 of them received adjuvant radiotherapy. Ten had subtotal resection (STR) and 2 of them received RT. Three of 6 with GTR without RT relapsed. All patients with STR suffered local progression (2 after RT). Five developed systemic metastases after reiterate surgical resection (more than 3); three of them are alive with disease after further treatment at 11, 18 and 28 month. The median progression free survival (PFS) was 42,5 months (4-264), with 2 and 5-year PFS rates of 88% and 27% respectively. The 2, 5 and 10-year survival rates was 100, 93 and 81% respectively. All patients with GTR are alive (median follow-up: 60,5 months, range 30-125) and 3 of 10 patients with STR died (median follow-up: 81,5 months, range 4-314). Conclusions: When safe and feasible, GTR should be pursued as an initial surgical strategy to maximize overall survival. Adjuvant RT may show promise in preventing tumor progression in GTR patients. In metastatic disease long term survival could be achieved. The lack of a standard of care for HPC patients makes it especially important to do a complete workup, especially among patients presenting with recurrent HPC.
Once-daily oral afatinib (A) combined with pemetrexed (P) in patients (pts) with advanced solid tumors: A phase I dose escalation trial.
Authors: Chu Quincy , Sangha Randeep , Hotte Sebastien J. , Deng Qiqi , Gyorffy Steve , Chand Vikram K. , Hirte Hal W. 
Published: March 2020

e13011 Background: A is an oral, irreversible, ErbB Family Blocker with single-agent activity in a variety of solid tumors. Preclinical studies have demonstrated additive antitumor effects when combining A or erlotinib with P in non-small cell lung cancer cell lines with sensitizing or resistant EGFR mutations. We hypothesized that once-daily A given with P would be safe and feasible in pts with advanced solid tumors. Methods: This Phase I trial was a standard 3+3 dose escalation design where A was administered orally at a starting dose of 30 mg/day on days 2–21 and combined with IV P (500 mg/m2) on Day 1 of a 21-day cycle. A was increased by 10 mg for each successive cohort until determination of the MTD, defined as the dose of A below which ≥2 of six pts experienced dose-limiting toxicity (DLT) in Cycle 1. MTD cohort was expanded to 18 pts and incidence and severity of AEs were graded according to CTCAE v3.0. Pts were treated to a maximum of 6 cycles with the option for A monotherapy thereafter. Results: 23 pts with advanced tumors were treated: 10 males, 13 females, ECOG 0/1/2 (30%/65%/4%), median age 58 yrs, and 57% received ≥3 prior chemotherapies. In Cycle 1, treatment-related DLTs were observed in six pts; two pts of three treated at 40 mg/day A dose and four pts of 20 treated at the MTD of 30 mg/day A dose. A and P were well tolerated, with the most frequent treatment-related AEs being diarrhea (91%; of which 86% were grade 1–2), stomatitis (65%) and rash (61%). Pts received a median of 2 cycles of treatment; five pts received >4 cycles, including one patient with serous ovarian cancer who continues on trial treatment beyond 14 months. Best response of 21 available pts included two partial responses, 14 with stable disease, and three with progressive disease. Detailed response and PK data will be further analyzed. Conclusions: In pts with relapsed or refractory advanced solid tumors, oral A at 30 mg/day combined with standard dose P (500 mg/m2) administered on Day 1 of a 21-day cycle, had an acceptable safety and tolerability profile. The study is currently evaluating an intercalated schedule of A on Days 2–6 with P based on preclinical synergy thought to arise from cell-cycle pharmacodynamic separation of A and P.
Proposal for a credentials-based clinical trials system.
Authors: Burke Lillian P. 
Published: March 2020

e13012 Background: Molecular subtyping has identified drugable targets in many cancers; yet, often only a small proportion of cancers are affected by any specific alteration. This results in small patient subgroups, even for common cancers such as lung cancer. Agents such as imatinib and crizotinib have shown dramatic clinical efficacy but others with promise, e.g., PARP inhibitors, have difficulty in obtaining trial resources despite scientific rationale and support from both patients and physicians. Rare malignancies are not studied. The current clinical trials system makes it expensive to open a trial for rare cancers as reimbursement occurs only when patients are entered, leading to high costs per patient. Methods: Critical requirements for clinical trials in patient subgroups were identified and a system proposed to address these needs. Results: Requirements are: patient safety, oversight, data and biospecimen management, accurate imaging and dosing of drugs and radiation, pharmacy accountability, and efficiency. Regulations emphasize errors of commission while ignoring ethical issues related to failure to study rare cancers (i.e., errors of omission). A trials system that can address these concerns is proposed and is based on the well-established privileging system at hospitals. Physicians and others (e.g., nurses, data managers, pathology and radiology departments) would be credentialed to participate in trials depending on the skills required, e.g., PIs might be credentialed by study type/procedure (e.g., first in Man; phase I; phase I/II trials, or only phase IV; pharmacokinetic studies; Whipple procedures; sentinel node biopsies, biospecimen collection). Protocols could access this network only after rigorous review by a panel of experts. When a patient with a rare cancer/subtype is diagnosed, the PI would download the protocol from the internet and put the patient on study if the PI/institution met required credentials. Local IRBs would sign off on privileges, investigate complaints and monitor adherence to guidelines. Conclusions: A credential-based system might allow safe trials for rare patient groups although substantial regulatory issues would need to be addressed.
Selecting peptides for breast cancer treatment.
Authors: Suarez Eloah Rabello , Nader Helena Bonciani , Pinhal Maria Aparecida Silva , Del Giglio Auro 
Published: March 2020

e13016 Background: HER2 is a member of epidermal growth factor family of receptors that is an essential mediator of cell proliferation and differentiation. In breast cancer patients, HER2 overexpression is associated with aggressive disease, chemo and hormone therapy resistance and poor prognosis. Currently, a HER2 specific monoclonal antibody, trastuzumab, is in use as a treatment for these breast cancer cases; however, there are many reports of resistance to this treatment. As an alternative we have selected specific peptides to HER2 using a phage display technology. Methods: A cyclic 7 aminoacids random peptide library had been panned using an external domain of recombinant HER2. After each round of binding assays, peptides were sequenced and two were selected. Cellular viability, migration and apoptosis/necrosis induced by these peptides were evaluated using SKBR3 cells. Confocal microscopy was used to determine the peptides co-localization with acidic vesicles and heparan sulfate. Western blotting was performed to evaluated some cell signalling pathways induced by these peptides. Results: The peptides were able to reduce the cell viability and migration around 50% alone and 85% in association. Tavelorb was able to induce apoptosis/ necrosis in 70% of SKBR3 cells and when associated with Hercid, the effect has increased to 90%. These peptides co-localize with acidic vesicles around 40-50%. The peptides and trastuzumab co-localized with heparan sulfate around 70%. The association between Hercid and Tavelorb inhibits Akt (pSer473) and the proteins enrolled in this pathway, as GSK3 and the transcription factor c-myc, however Akt inhibition is not dependent of PTEN. In addition, this peptides decreases BCL-XL, and MCL-1, while enhance Bax. The most important effect of this peptides is the reduction in β-catenin expression. Interestingly, p53 is downregulated in the presence of trastuzumab showing a mechanism by some tumors could be resistant to this therapy. Conclusions: The association of peptides has a very effective antitumoral effect in vitro, and their action seems to be HS dependent. The data propose a potential use of these peptides as a future alternative for breast cancer treatment. Supported by FAPESP, CNPq, CAPES.