Top PDF Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

proliferation and is required for the generation and maintenance of memory T cells in vivo [24]. There is evidence that the frequency of T cells expressing CD27 increases gradually after ACT and may be associated with the long-term maintenance of a stable number of tumor-specific T cells in responding patients [25]. In this phase I clinical trial, the frequencies of both CD27+CD45RA+ and CD28+CD45RA+ cells increased signifi- cantly after culture and their population in transferred cells were about 60%. On the other hand, the frequency of CCR7+CD45RA+ cells, which were also expressed in less- differentiated T cells, did not change after culture for unknown reasons. The ratios of the less-differentiated phenotype T cells (i.e. CD27+CD45+, CD28+CD45RA+, and CCR7+CD45RA+ cells) in transferred cells differed greatly for each patient. A strong positive correlation was found between the ratios of CD27+CD45RA+ (r = 0.717, p = 0.037), CD28+CD45RA+ (r = 0.717, p = 0.037), CCR7+CD45RA+ (r = 0.733, p = 0.031) cells in transferred cells and those in PBMCs (before culture). It is necessary to improve upon or find new methods that can efficiently generate large numbers of less-differentiated T cells even in cases where there are few less-differentiated T cells. Consistent with previous reports [13], we found that stimulation with FN-CH296/anti-CD3 preferentially expanded CD8+ cells in this study. It is generally believed that the predominant tumoricidal effector mechanism is the cytotoxic killing effect of CD8 +
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Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small-Cell Lung Cancer: Results of a Phase IIB Clinical Trial.

Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small-Cell Lung Cancer: Results of a Phase IIB Clinical Trial.

The TUDD in a HRQOL score is defined as the interval between randomization and the date of the event, i.e. the date where the first significant deterioration in the HRQOL level of the patient was observed as compared to baseline HRQOL score, without any further significant improvement as compared to baseline HRQOL score [14]. Alive patients were censored at the time of the last fol- low-up if no definitive deterioration was observed before. Only patients with the baseline HRQOL score and at least one follow-up score or death were retained (modified intent to treat analysis). Each dimension was analysed. TUDD curves were calculated using the Kaplan-Meier estimation and were described using medians and 99%CI. As exploratory purpose only, TUDD curves were compared using the log-rank tests. The univariate Cox models were used to calculate the hazard ratio (HR) with a 99%CI. A subgroup analysis was also performed according to the level of aNK cells based on previous observed effect of aNK cells on OS. Variables investigated were gender (women vs. men), age (continuous variable), smoking habits (ceased vs. no vs. yes), PS (1 or more vs. 0), center (dichotomized according to the median of the distribution of patients included by center: 3 vs. >3) and the time to toxicity of grade 3–4 (time dependent variable). Variables with a univariate P-value  0.20 were eligible for the multivariate Cox analyses. Treatment arm and level of aNK cells subgroup (high vs. normal) were forced in multivariate Cox analyses. Their inter- action was also introduced and exploratory subgroup analyses were performed according to pre- treatment level of aNK cells based on previous observed effect of aNK cells on OS [13]. Finally, the same variables were introduced in each multivariate model for all HRQoL dimensions.
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Rev. Bras. Hematol. Hemoter.  vol.35 número5

Rev. Bras. Hematol. Hemoter. vol.35 número5

Background: Chronic obstructive pulmonary disease is a major inlammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without signiicant pulmonary ibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. Objective: This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells.
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Albumin and Neutrophil Combined Prognostic Grade as a New Prognostic Factor in Non-Small Cell Lung Cancer: Results from a Large Consecutive Cohort.

Albumin and Neutrophil Combined Prognostic Grade as a New Prognostic Factor in Non-Small Cell Lung Cancer: Results from a Large Consecutive Cohort.

significantly related to lung cancer survival. It has been reported systemic inflammation and nutritional status were closely related to NSCLC [7, 23]. The connection between inflammation and survival of NSCLC dates back to early of 21 century [24]. After decade years, mounting reports have provided solid evidence to prove prognostic value of systemic inflammation and nutritional status which can be easily quantified and reflected by peripheral neutrophil and serum albumin [13, 19]. In our study, we firstly took albumin and neutrophil together to evalu- ate whether the combination of them could present a better predictive value for NSCLC patients’ survival. Strikingly, we found ANPG not only was a strong independent predictor but also had a higher sensitivity than either of them.
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Luiz Henrique Araujo 1,2,a

Luiz Henrique Araujo 1,2,a

According to a survey sent to all RT services registered with the Sociedade Brasileira de Radioterapia (Brazilian Society of Radiotherapy), approximately 25% of all RT procedures are performed in lung cancer patients. Among these, approximately half are submitted to palliative treatment only, and very few are in early stages (I or II). Few centers have stereotactic body RT or stereotactic ablative RT to treat localized disease, only one of them providing care via the public health care system. Among the 13 centers that provide this technology, only 10 use it for lung cancer treatment. The preliminary experience (21 patients; mean age, 81 years) with stereotactic body RT in a private health care institution showed that the treatment was mostly recommended for elderly or clinically inoperable patients. With a median follow-up period of 12 months, local control was achieved in 95% of the patients, and the complication rate was very low. (61)
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Rev. Assoc. Med. Bras.  vol.58 número2

Rev. Assoc. Med. Bras. vol.58 número2

We agree that modainil certainly may be considered an option for treatment-associated cancer-related fatigue (chemotherapy or radiotherapy), and recent evidence rec- ommends its use in cases of severe fatigue and in patients with advanced disease 5-7 . However, evidence supporting

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Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

RAD51 G.C to be associated with a reduced RP incidence but a decreased OS. This is not contradictory, because our RP group included a large proportion of patients with mild/moderate RP (grade 1 and 2), which was not likely to have an impact on patients’ survival negatively. Furthermore, some other studies also did not find any association between RP grade and prognosis [35]. In this study, we were much interested in the finding that the influences of RAD51 2135G.C and XRCC2 R188H on overall survival were only evident in patients with RP. Several possibilities may explain these findings. First, irradiation of lung tissues induces immediate damage through intracellular protein denaturation, membrane disruption, and alterations of DNA. RP is largely a consequence of cellular DNA injury that appears in the second generation of cells [36]. The absence of RP may imply a low amount of DNA injury, which could result from an efficient DNA repair, whereas the presence of RP may indicate a high amount of DNA injury due to a suboptimal DNA repair. Therefore, it can be speculated that if the host cells have optimal DNA repair capacity, the activity of the entire HR machinery is less likely to be influenced by a single HR genetic polymorphism. On the contrary, if the DNA repair capacity is suboptimal, the subsequent changes in gene expression or activity resulting from functional SNPs may pose a substantial influence on the whole HR machinery. Second, RP per se is an inflammatory response to ionizing radiation, which triggers a large network of signaling events, including transient activation of pro-survival pathways such as the epidermal growth factor receptor (EGFR) pathway [37], and upregulation of a variety of cytokines, such as tumor necrosis factor alpha (TNF-a), interleukins, and transforming growth factor beta (TGF-b) [38,39,40]. Although many of these inflammatory responses are harmful to normal tissue, they confer a survival advantage of tumor cells and regulate cellular radiation response and DNA repair. Hence, the SNP-survival association could be more pronounced in the presence of RP. Additional mechanistic studies are needed to test these hypotheses.
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J. Pneumologia  vol.28 número3

J. Pneumologia vol.28 número3

Recent advances in genetics and molecular biology lead to the identification of genes and protein products overexpressed by tumors. Such products, called tumor markers, were previously used only as diagnostic and prognostic tools, but are currently being the target of extensive research, with growing evidence that some of them may have an important role in the development of new

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Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

Three genome-wide association study (GWAS) identified susceptibility variants in the telo- merase reverse transcriptase (TERT) gene associated with lung cancer risk [5–7]. TERT en- codes the catalytic subunit of the telomerase ribonucleoprotein complex, which catalyzes the addition of telomeric repeats at the ends of chromosomes, thus plays a crucial role in maintain- ing genome integrity, controlling cell proliferation, and regulating tissue homeostasis [8,9]. Tel- omerase is generally believed to be critical in cancer initiation and progression. Telomerase activation is a pivotal prerequisite for cell immortalization [10]. It lacks activity in most normal human cells with limited proliferative ratio, whereas it is activated in >90% of cancerous cells, making them grow continuously [11,12]. TERT expression is also increased in cancers, and prognostic significance was demonstrated in many cancer types [13–16]. Besides, functional and mechanistic studies have suggested that TERT acts as a direct transcriptional regulator of oncogenic signaling pathways that not only modulate its own levels but also control the induc- tion of target genes critical for cell survival and cancer progression [8,17–20]. What is more, telomerase is reported to be the target of many kinds of anticancer agents, and both telomerase inhibition and telomere dysfunction have been demonstrated as a consequence of platinum treatment, suggesting the potential influence of TERT on treatment efficacy of platinum-based chemotherapy [21,22].
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Int. braz j urol.  vol.34 número6

Int. braz j urol. vol.34 número6

Surveillance - Six of our patients entered a surveillance protocol. Three of them relapsed. His- tological evaluation after orchiectomy had shown a pT 2 tumor with seminomatous and embryonal cell components in one of the relapsed patients. Despite regular follow-up, two years after primary diagnosis, retroperitoneal recurrence of the tumor was detected when the patient complained of lank pain and weight loss. Tumor markers were increased. At irst, the pa- tient refused any further imaging and therapy. After one year, the CT scan showed multiple metastases in the retroperitoneum and upper abdomen. Due to renal insufiency a carboplatin (instead of cisplatin) based chemotherapy was initiated. Nevertheless, a few days later the patient died of complications caused by the chemotherapy with renal failure and tumor lysis syndrome.
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Int. braz j urol.  vol.38 número6

Int. braz j urol. vol.38 número6

Objective: To perform a systematic review and meta-analysis of all randomized con- trolled trials comparing the effi cacy of Sipuleucel-T versus placebo for asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer (mCRPC). Materials ans Methods: Several databases were searched, including MEDLINE, EMBA- SE, LILACS, and CENTRAL. The endpoints were overall survival (OS), time to progres- sion (TTP) and side effects. We performed a meta-analysis (MA) of the published data. The results are expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their correspon- ding 95% confi dence intervals (CI 95%).
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Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer.

Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer.

malignant cells are thought to be derived from a common precursor cell, acquired genetic instability gives rise to subsequent generations expressing unique characteristics, such as activated oncogenes and tumor suppressor genes [14]. However, recent studies involving intratumoral genetic heterogeneity have gener- ated contradicting results. Gerlinger et al (2012) [15] reported marked intratumoral heterogeneity with respect to somatic mutations in driver and passenger genes, which may foster tumor adaption and therapeutic failure via Darwinian selection. Snuderl et al (2011) [16] reported stable coexistence of heterogeneous clones possessing different receptor tyrosine kinase amplification (EGFR, MET, and PDGFRA) within the same tumor. As a driver gene, EGFR was suggested to be associated with resistance to EGFR-TKIs when mutations in this gene exhibited intratumoral heterogeneity. Our recent study (2012) [17] also indicated that EGFR mutation shift deriving from chemotherpy may be related to the heterogeneity of intratumoral EGFR mutation and to different chemosensitivity levels of mutant and wild-type cells, In contrast, Yatabe et al (2011) [18] reported that EGFR heterogeneity occurred extremely rarely in lung adenocarcinoma. These authors speculated that the heterogeneity observed in previous studies was an artifact resulting either from a mutant allele-specific imbalance and heterogeneously distributed EGFR amplification or from a difference in EGFR mutation detection sensitivity across different methods.
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Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

3 Radzikowska E, Glaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20561 cases. Ann Oncol, 2002, 13(7): 1087-1093. 4 Paesmans M, Sculier JP, Libert G. Prognostic factors for survival in advanced

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Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.

Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.

could help overcoming the immune suppressive actions of the IDO-protein, which are otherwise a result of the early expression of IDO in maturing antigen-presenting cells. However, since IDO- Figure 7. IDOlong contains various T cell epitopes. (A) PMBC from seven patients (1 breast cancer patient and 6 melanoma patients) were analysed for responses against IDO194 (DTLLKALLEIASCLE (IDO194-208)) (grey bars), IDO200 (LLEIASCLEKALQVF (IDO200-214)) (white bars) and compared to IDOlong (black bars) by IFN-c ELISPOT assay. The average number of peptide-specific spots (after subtraction of spots without added peptide) was calculated per 5610 5 PBMC for each patient. PBMC were stimulated once with peptide before being plated at 5610 5 cells per well in duplicates either without or with the peptide. (B), CpG stimulate IDO-specific T cells. PBMC from a melanoma patient and a renal carcinoma patient were treated with either IL-2 or the TLR9 ligand CpG ODN in the presence of IL-2 for 14 days and, subsequently, examined for IDO-specific T cells by TNF-a ELISPOT. Hence, PBMC were plated at 5610 5 cells per well in duplicates either without or with the IDOlong peptide before and after cell
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Comparison of Photodynamic Therapy versus conventional antifungal therapy for the treatment of denture stomatitis: a randomized clinical trial

Comparison of Photodynamic Therapy versus conventional antifungal therapy for the treatment of denture stomatitis: a randomized clinical trial

In the present study, a higher percentage of clinical success was verified in the NYT group (53%) than in the PDT group (45%). Nystatin would have also reduced Candida cells on the tongue and buccal mucosa in patients from the NYT group, which could justify the higher percentage of success in this group. On the other hand, no antimicrobial treatment of the dentures was performed in this group, which could have con- tributed to the rate of clinical failure obtained (47%). The high rate of clinical failure observed in the PDT group (55%) might be attributed to the recolonization of the palatal mucosa after PDT by Candida cells from other sites of the mouth, such as tongue, particularly mid-dorsum, and buccal mucosa. In addi- tion, the clinical conditions in which PDT was performed, such as treatment time (three times a week for 15 days, a total of six sessions) and the parameters used (only one type and concentration of photosensitizer and light fluence) might also explain the rate of clinical failure observed in this group. A longer treatment period might achieve a better resolution of palatal inflammation. Further trials are necessary to evaluate the effect of additional parameters of PDT, such as other types and concentrations of photosensitizer and light fluences, in an endeavour to find a higher clinical success rate. In the present investigation, the clinical failure rates are not in agreement with the microbiological results obtained, i.e. a reduction in CFU/mL values was observed even in patients who showed no improvement in palatal inflammation. This cor- roborates the findings of Barbeau et al. [1], and Zomorodian et al. [8] who found no significant relationship between DS and number of yeast colonies. Furthermore, other reports have demonstrated that healthy denture wearers were also Candida carriers [3,6,22,28]. Although both treatments resulted in a sig- nificant reduction in values of CFU/mL from dentures and pal- ates in this study, and given that the aetiology of DS is multifactorial, a more effective treatment should be directed towards all aetiological factors involved in this pathology.
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Progress on treatment of uveal melanoma

Progress on treatment of uveal melanoma

4 Amanda YL Goh. Christopher J Layton. Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review. Clin Exp Ophthalmol 2016 ;44(6):509-519 5 Kalirai H, Dodson A, Faqir S, et al . Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer 2014 ;111(7):1373-1380 6 Landreville S, Agapova OA, Matatall KA,et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res 2012;18(2):408-416
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Carcinoma Urotelial da Bexiga e Via de Sinalização mTOR

Carcinoma Urotelial da Bexiga e Via de Sinalização mTOR

Bladder carcinoma is the fifth most common malignancy, accounting for about 3.2% of all cancers worldwide. Its pathogenesis involves somatic genetic changes induced by environmental carcinogens such as tobacco, aromatic amines or arsenic. Despite the characterization established risk factors, carcinoma of the bladder is still an important epidemiologic problem whose incidence continues to increase every year. Carcinogenesis may occur through activation of protooncogenes or through loss of tu- mor suppressor genes, both of which have been documented in urothelial carcinoma (CUB). CUB, the most common form of bladder carcinoma, is divided into noninvasive and invasive with non-invasive lesions divided into low and high grade. Despite frequente reccurences, these injuries often have a low risk of progression to invasive disease and a generally favorable prognosis. In contrast, the invasive subtipe of CUB is characterized as being an aggressive disease, often with a reduced 5-year survival, de- spite treatment with adjuvant chemotherapy and radical cystectomy. Although its sur- gical and chemotherapeutic strategies have evolved, survival in invasive and metastatic disease showed no significant improvements in the last decades, since the introduction of BCG in the 1970s and in the 1980s MVAC. In this context there is an urgent need for new therapeutic targets.
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Rev. Assoc. Med. Bras.  vol.63 número7

Rev. Assoc. Med. Bras. vol.63 número7

D ESCRIPTION OF EVIDENCE COLLECTION METHOD Through the elaboration of six relevant clinical questions related to the proposed theme, we sought to present the main evidence regarding safety, toxicity and effectiveness of radiosurgery in the treatment of CNS metastases. The study population consisted of male and female patients of all ages, with metastatic CNS cancer independent of histological type and presence or absence of comor- bidities. For this, a systematic review of the literature was carried out in primary scientific databases (Medline – PubMed; Embase – Elsevier; Lilacs – Bireme; Cochrane Library – Record of Controlled Trials). All articles avail- able through Thursday, April 2, 2015 were considered. The search strategy used in Medline searches is described in Appendix 1. The articles were selected based on criti- cal evaluation, seeking the best evidence available. The
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PDF PT Jornal Brasileiro de Pneumologia 4 5 portugues

PDF PT Jornal Brasileiro de Pneumologia 4 5 portugues

2 . Assistant Professor of Medicine & Oncology, Mount Sinai Comprehen- sive Cancer Center, Miami, USA, Investigador Principal do Comitê Respiratório do Cancer Leukemia Group B (CALGB), USA. Endereço para correspondência – Mauro Zukin, COI – Clínicas Onco- lógicas Integradas, Av. das Américas, 4.666, unidade 322 – 22631- 004 – Rio de Janeiro, RJ, Brasil. E-mail: maurozukin@cmb.com.br. Recebido para publicação em 24/2/97. Reapresentado em 24/ 7/97. Aprovado, após revisão, em 12/8/97.

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Rev. CEFAC  vol.17 número2

Rev. CEFAC vol.17 número2

14. Pereira JA, Girvent M, Sancho JJ, Parada C, Sitges-Serra A. Prevalence of long term upper aerodigestive symptoms after umcomplicated bilateral thyroidectomy. Surgery. 2003;133:318-22. 15. Sugueno, LA. Voz e deglutição de pacientes com e sem mobilidade laríngea após tireoidectomia [tese]. São Paulo: Faculdade de Medicina; 2008. 16. Taïeb D, Baumstarck-Barrau K, Sebag F, Fortanier C, De Micco C, Loundou A et al. Heath- related quality of life in thyroid cancer patients following radioiodine ablation. Health Quality Life Outcomes 2011;9:3.
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