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1.
Ana Maria Martins Kristin Lindstrom Sandra Obikawa Kyosen Maria Veronica Munoz-Rojas Nathan Thibault Lynda E. Polgreen 《BMC endocrine disorders》2018,18(1):83
Background
Mucopolysaccharidosis type I (MPS I) results in significant disease burden and early treatment is important for optimal outcomes. Recognition of short stature and growth failure as symptoms of MPS I among pediatric endocrinologists may lead to earlier diagnosis and treatment.Case presentation
A male patient first began experiencing hip pain at 5 years of age and was referred to an endocrinologist for short stature at age 7. Clinical history included recurrent respiratory infections, sleep apnea, moderate joint contractures, mild facial dysmorphic features, scoliosis, and umbilical hernia. Height was more than ??2 SD below the median at all time points. Growth velocity was below the 3rd percentile. Treatment for short stature included leuprolide acetate and recombinant human growth hormone. The patient was diagnosed with MPS I and began enzyme replacement therapy with laronidase at age 18.Conclusions
The case study patient had many symptoms of MPS I yet remained undiagnosed for 11 years after presenting with short stature. The appropriate path to MPS I diagnosis when patients present with short stature and/or growth failure plus one or more of the common signs of attenuated disease is described. Improved awareness regarding association of short stature and growth failure with attenuated MPS I is needed since early identification and treatment significantly decreases disease burden.2.
P. M. van der Zee H. J. Verberne J. H. Cornel O. Kamp F. M. van der Zant R. Bholasingh R. J. De Winter 《Netherlands heart journal》2011,19(7-8):324-330
Objective
To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS).Methods
A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician’s discretion.Results
524 patients were included. GRACE and TIMI risk scores were 75 (57–96) and 1 (0–2) in the rule-out ACS group, and 89 (74–107) and 2 (1–3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9–10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p?<?0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality.Conclusions
TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protocol. 相似文献3.
Pieter Stolk Harald E Heemstra Hubert GM Leufkens Brigitte Bloechl-Daum Eibert R Heerdink 《Orphanet journal of rare diseases》2009,4(1):1-7
Background
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment.Aim
To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV.Methods
We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant.Results
Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001).Conclusion
This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS. 相似文献5.
Ana Paula F Trombone Celio L Silva Luciana P Almeida Rogerio S Rosada Karla M Lima Constance Oliver Maria C Jamur Arlete AM Coelho-Castelo 《Genetic vaccines and therapy》2007,5(1):1-8
Background
Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of the mucopolysaccharidoses. The disease is caused by a deficiency of the lysosomal enzyme sulphamidase and results in the storage of the glycosaminoglycan (GAG), heparan sulphate. MPS IIIA is characterised by widespread storage and urinary excretion of heparan sulphate, and a progressive and eventually profound neurological course. Gene therapy is one of the few avenues of treatment that hold promise of a sustainable treatment for this disorder.Methods
The murine sulphamidase gene cDNA was cloned into a lentiviral vector and high-titre virus produced. Human MPS IIIA fibroblast cultures were transduced with the sulphamidase vector and analysed using molecular, enzymatic and metabolic assays. High-titre virus was intravenously injected into six 5-week old MPS IIIA mice. Three of these mice were pre-treated with hyperosmotic mannitol. The weight of animals was monitored and GAG content in urine samples was analysed by polyacrylamide gel electrophoresis.Results
Transduction of cultured MPS IIIA fibroblasts with the sulphamidase gene corrected both the enzymatic and metabolic defects. Sulphamidase secreted by gene-corrected cells was able to cross correct untransduced MPS IIIA cells. Urinary GAG was found to be greatly reduced in samples from mice receiving the vector compared to untreated MPS IIIA controls. In addition, the weight of treated mice became progressively normalised over the 6-months post-treatment.Conclusion
Lentiviral vectors appear promising vehicles for the development of gene therapy for MPS IIIA. 相似文献6.
Mucopolysaccharidosis type I (MPS I) arises from a deficiency in the α-L-iduronidase (IDUA) enzyme. Although the clinical spectrum in MPS I patients is continuous, it was possible to recognize 3 phenotypes reflecting the severity of symptoms, viz., the Hurler, Scheie and Hurler/Scheie syndromes. In this study, 10 unrelated Chinese MPS I families (nine Hurler and one Hurler/Scheie) were investigated, and 16 mutant alleles were identified. Three novel mutations in IDUA genes, one missense p.R363H (c.1088G > A) and two splice-site mutations (c.1190-1G > A and c.792+1G > T), were found. Notably, 45% (nine out of 20) and 30% (six out of 20) of the mutant alleles in the 10 families studied were c.1190-1G > A and c.792+1G > T, respectively. The novel missense mutation p.R363H was transiently expressed in CHO cells, and showed retention of 2.3% IDUA activity. Neither p.W402X nor p.Q70X associated with the Hurler phenotype, or even p.R89Q associated with the Scheie phenotype, was found in this group. Finally, it was noted that the Chinese MPS I patients proved to be characterized with a unique set of IDUA gene mutations, not only entirely different from those encountered among Europeans and Americans, but also apparently not even the same as those found in other Asian countries. 相似文献
7.
W. Anné D. A. M. J. Theuns B. Schaer Y. Van Belle T. Szili-Torok T. Smith J. Res L. Jordaens 《Netherlands heart journal》2014,22(6):279-285
Background
The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial.Methods
We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60–70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons.Results
The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60–70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population.Conclusions
Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for implantation, since they strongly correlate with survival. 相似文献8.
Ester Simeone Giusy Gentilcore Diana Giannarelli Antonio M. Grimaldi Corrado Caracò Marcello Curvietto Assunta Esposito Miriam Paone Marco Palla Ernesta Cavalcanti Fabio Sandomenico Antonella Petrillo Gerardo Botti Franco Fulciniti Giuseppe Palmieri Paola Queirolo Paolo Marchetti Virginia Ferraresi Gaetana Rinaldi Maria Pia Pistillo Gennaro Ciliberto Nicola Mozzillo Paolo A. Ascierto 《Cancer immunology, immunotherapy : CII》2014,63(7):675-683
Background
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.Patients and methods
Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.Results
Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).Conclusion
Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required. 相似文献9.
Maria Sandbacka Mervi Halttunen Varpu Jokimaa Kristiina Aittomäki Hannele Laivuori 《Orphanet journal of rare diseases》2011,6(1):1-5
Background
Thymic epithelial tumours (thymoma and carcinoma) are exceptionally rare in children. We describe a national multicentre series with a view to illustrating their clinical behaviour and the results of treatment.Methods
From January 2000 all patients under 18 years of age diagnosed with "rare paediatric tumours" were centrally registered by the Italian centres participating in the TREP project (Tumori Rari in Età Pediatrica [Rare Tumours in Paediatric Age]). The clinical data of children with a thymic epithelial tumour registered as at December 2009 were analyzed for the purposes of the present study.Results
Our series comprised 4 patients with thymoma and 5 with carcinoma (4 males, 5 females; median age 12.4 years). The tumour masses were mainly large, exceeding 5 cm in largest diameter. Based on the Masaoka staging system, 3 patients were stage I, 1 was stage III, 1 was stage IVa and 4 were stage IVb. All 3 patients with stage I thymoma underwent complete tumour resection at diagnosis and were alive 22, 35 and 93 months after surgery. One patient with a thymoma metastasizing to the kidneys died rapidly due to respiratory failure. Thymic carcinomas were much more aggressive, infiltrating nearby organs (in 4 cases) and regional nodes (in 5), and spreading to the bone (in 3) and liver (in 1). All patients received multidrug chemotherapy (platinum derivatives + etoposide or other drugs) with evidence of tumour reduction in 3 cases. Two patients underwent partial tumour resection (after chemo-radiotherapy in one case) and 4 patients were given radiotherapy (45-54 Gy). All patients died of their disease.Conclusions
Children with thymomas completely resected at diagnosis have an excellent prognosis while thymic carcinomas behave aggressively and carry a poor prognosis despite multimodal treatment. 相似文献10.
Yamamoto Daigo Yamada Masanori Okugawa Homa Tanaka Kanji 《World journal of surgical oncology》2004,2(1):1-4
Background
Malignant pleural mesothelioma is a rare malignancy. The outcome remains poor despite complete surgical resection.Patients and methods
Eleven patients with histologicaly proven epithelial type malignant pleural mesothelioma undergoing extrapleural pneumonectomy with systemic chemotherapy and/or radiotherapy before and after surgical resection were retrospectively reviewed.Results
Ten out of 11 patients underwent complete surgical resection, of these 7 patients had stage I disease. Of these 7 patients, 5 are alive without any recurrence, a 2-year survival rate of 80% was observed in this group. There was no operative mortality or morbidity.Conclusion
Extrapleural pneumonectomy with perioperative adjuvant treatment is safe and effective procedure for epithelial type malignant pleural mesothelioma. 相似文献11.
Jeong-In Baek Se-Kyung Oh Dong-Bin Kim Soo-Young Choi Un-Kyung Kim Kyu-Yup Lee Sang-Heun Lee 《Orphanet journal of rare diseases》2012,7(1):1-10
Background
Gaucher disease (GD) is due to deficiency of the glucocerebrosidase enzyme. It is panethnic, but its presentation reveals ethnicity-specific characteristics.Methods
We evaluated the distribution, and clinical and genetic characteristics of GD patients in the Iberian Peninsula (IP). We analysed geographical distribution, demographic, genetic and clinical data, age at diagnosis, type, and years of therapy in 436 GD patients from the IP.Results
The prevalence of GD was 1/149,000 inhabitants; 88.3% were type 1, 6.7% type 2, and 5.0% type 3. The mean age at diagnosis in type 1 was 28.7 years. A total of 72.7% were classified as having mild forms, 25.5% moderate, and 1.7% severe. Anemia and thrombocytopenia were present in 56% and 55%, respectively. Bone disease and hepatomegaly were reported in 62% and 68%, respectively, and were more likely in asplenic than in non-splenectomized patients. Sixty-nine mutant alleles were identified, and five mutations accounted for 75% of the GBA alleles. Several patients described in our series had interesting phenotypes. A total of 58.7% of patients had received enzyme replacement therapy and 12.6% were treated with miglustat.Conclusions
A broad spectrum of GBA mutations is present in the IP, with 98.2% of type 1 GD being mild and 23.0% never treated. These data highlight genetic and phenotypic heterogeneities among geographic populations. 相似文献12.
Kui Shen Yuan Qi Nan Song Chunqiao Tian Shara D Rice Michael J Gabrin Stacey L Brower William Fraser Symmans Joyce A O’Shaughnessy Frankie A Holmes Lina Asmar Lajos Pusztai 《BMC medical genomics》2012,5(1):1-8
Background
Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results.Discussion
We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality.Summary
The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants. 相似文献13.
Anna Maria Di Giacomo Luana Calabrò Riccardo Danielli Ester Fonsatti Erica Bertocci Isabella Pesce Carolina Fazio Ornella Cutaia Diana Giannarelli Clelia Miracco Maurizio Biagioli Maresa Altomonte Michele Maio 《Cancer immunology, immunotherapy : CII》2013,62(6):1021-1028
Background
Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.Methods
Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4+ and CD8+ T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.Results
Median overall survival among 27 patients was 9.6 months (95 % CI 3.2–16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS+ T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.Conclusions
Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS+ T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required. 相似文献14.
Dipti Talaulikar Bruce Shadbolt Jane E Dahlstrom Anne McDonald 《Journal of hematology & oncology》2009,2(1):1-9
Objective
Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective.Methods
Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment.Results
Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression.Conclusion
Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study. 相似文献15.
Steven De Vleeschouwer Hilko Ardon Frank Van Calenbergh Raf Sciot Guido Wilms Johannes van Loon Jan Goffin Stefaan Van Gool 《Cancer immunology, immunotherapy : CII》2012,61(11):2105-2112
Purpose
Adult patients with relapsed high-grade glioma are a very heterogenous group with, however, an invariably dismal prognosis. We stratified patients with relapsed high-grade glioma treated with re-operation and postoperative dendritic cell (DC) vaccination according to a simple recursive partitioning analysis (RPA) model to predict outcome.Patients and methods
Based on age, pathology, Karnofsky performance score, and mental status, 117 adult patients with relapsed malignant glioma, undergoing re-operation, and postoperative adjuvant dendritic cell (DC) vaccination were stratified into 4 classes. Kaplan–Meier survival estimates were generated for each class of this HGG-IMMUNO RPA model. Extent of resection was documented but not included in the prognostic model.Results
Kaplan–Meier overall survival estimates revealed significant (p?<?0.0001) differences among the 4 HGG-IMMUNO RPA classes. Long-term survivors, surviving more than 24?months after the re-operation and vaccination, are seen in 54.5, 26.7, 11.5, and 0?% for the classes I, II, III, and IV respectively.Conclusion
This HGG-IMMUNO RPA classification is able to predict overall survival in a large group of adult patients with a relapsed malignant glioma, treated with re-operation and postoperative adjuvant DC vaccination in the HGG-IMMUNO-2003 cohort comparison trial. The model appears useful for prognostic patient counseling for patients participating in DC vaccination trials. A substantial number of long-term survivors after relapse are seen in class I to III, but not in class IV patients. 相似文献16.
T. Smith P. F. van Dessel D. A. M. J. Theuns A. Muskens-Heemskerk R. T. van Domburg A. A. Wilde L. Jordaens 《Netherlands heart journal》2011,19(10):405-411
Background
The benefit of implantable defibrillators (ICDs) for primary prevention remains debated. We analysed the implications of prophylactic ICD implantation according to the guidelines in 2 tertiary hospitals, and made a healthcare utilisation inventory.Methods
The cohort consisted of all consecutive patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) receiving a primary prophylactic ICD in a contemporary setting (2004–2008). Follow-up was obtained from hospital databases, and mortality checked at the civil registry. Additional data came from questionnaires sent to general practitioners.Results
There were no demographic differences between the 2 centres; one had proportionally more CAD patients and more resynchronisation therapy (CRT-D). The 587 patients were followed over a median of 28 months, and 50 (8.5%) patients died. Appropriate ICD intervention occurred in 123 patients (21%). There was a small difference in intervention-free survival between the 2 centres. The questionnaires revealed 338 hospital admissions in 52% of the responders. Device-related admissions happened on 68 occasions, in 49/276 responders. The most frequently reported ICD-related admission was due to shocks (20/49 patients); for other cardiac problems it was mainly heart failure (52/99). Additional outpatient visits occurred in 19%.Conclusion
Over a median follow-up of 2 years, one fifth of prophylactic ICD patients receive appropriate interventions. A substantial group undergoes readmission and additional visits. The high number of admissions points to a very ill population. Overall mortality was 8.5%. The 2 centres employed a similar procedure with respect to patient selection. One centre used more CRT-D, and observed more appropriate ICD interventions. 相似文献17.
Background
Elevated pre-operative neutrophil: lymphocyte ratio (NLR) has been identified as a predictor of survival in patients with hepatocellular and colorectal cancer. The aim of this study was to examine the prognostic value of an elevated preoperative NLR following resection for oesophageal cancer.Methods
Patients who underwent resection for oesophageal carcinoma from June 1997 to September 2007 were identified from a local cancer database. Data on demographics, conventional prognostic markers, laboratory analyses including blood count results, and histopathology were collected and analysed.Results
A total of 294 patients were identified with a median age at diagnosis of 65.2 (IQR 59-72) years. The median pre-operative time of blood sample collection was three days (IQR 1-8). The median neutrophil count was 64.2 × 10-9/litre, median lymphocyte count 23.9 × 10-9/litre, whilst the NLR was 2.69 (IQR 1.95-4.02). NLR did not prove to be a significant predictor of number of involved lymph nodes (Cox regression, p = 0.754), disease recurrence (p = 0.288) or death (Cox regression, p = 0.374). Furthermore, survival time was not significantly different between patients with high (≥ 3.5) or low (< 3.5) NLR (p = 0.49).Conclusion
Preoperative NLR does not appear to offer useful predictive ability for outcome, disease-free and overall survival following oesophageal cancer resection. 相似文献18.
Surasak Phuphanich Christopher J. Wheeler Jeremy D. Rudnick Mia Mazer HongQian Wang Miriam A. Nuño Jaime E. Richardson Xuemo Fan Jianfei Ji Ray M. Chu James G. Bender Elma S. Hawkins Chirag G. Patil Keith L. Black John S. Yu 《Cancer immunology, immunotherapy : CII》2013,62(1):125-135
Background
This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107).Methods
TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals.Results
Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months.Conclusions
Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors. 相似文献19.
Sander Kelderman Bianca Heemskerk Harm van Tinteren Rob R. H. van den Brom Geke A. P. Hospers Alfonsus J. M. van den Eertwegh Ellen W. Kapiteijn Jan Willem B. de Groot Patricia Soetekouw Rob L. Jansen Edward Fiets Andrew J. S. Furness Alexandra Renn Marcin Krzystanek Zoltan Szallasi Paul Lorigan Martin E. Gore Ton N. M. Schumacher John B. A. G. Haanen James M. G. Larkin Christian U. Blank 《Cancer immunology, immunotherapy : CII》2014,63(5):449-458
Introduction
Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a ‘real world’ population of patients treated with ipilimumab to identify markers for treatment benefit.Methods
Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.Results
A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.Conclusion
In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy. 相似文献20.
Einar Osland Vik-Mo Marta Nyakas Birthe Viftrup Mikkelsen Morten Carstens Moe Paulina Due-Tønnesen Else Marit Inderberg Suso Stein Sæbøe-Larssen Cecilie Sandberg Jan E. Brinchmann Eirik Helseth Anne-Marie Rasmussen Knut Lote Steinar Aamdal Gustav Gaudernack Gunnar Kvalheim Iver A. Langmoen 《Cancer immunology, immunotherapy : CII》2013,62(9):1499-1509