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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distinct geographic variation in the global incidence of nasopharyngeal carcinoma reflects a complex etiology involving viral, environmental, and genetic components. The high to intermediate rates observed in endemic areas contrast markedly with the uniformly low rates seen in much of the world. An interesting epidemiologic observation is the early peak in age-incidence curves observed in certain geographically disparate populations, suggestive of distinct causal entities and the possible exhaustion of susceptible individuals from the population at a certain age. The aim of this study was to systematically evaluate the age-incidence profiles of NPC worldwide on partitioning populations according to level of risk, in an effort to provide clues about the importance of early-in-life factors and genetic susceptibility. Using data from 23 high-quality population-based cancer registries for the period 1983-1997, a key finding was the consistent pattern of bimodality that emerged across low-risk populations, irrespective of geographic location. Continual increases in NPC risk by age up to a first peak in late adolescence/early adulthood (ages 15-24 years) were observed, followed by a second peak later in life (ages 65-79 years). No such early peak in NPC incidence by age group was evident among the high-risk populations studied. These findings are discussed according to existing lines of biological and epidemiologic evidence related to level of population risk, age at diagnosis, and histologic subtype. A modified model for NPC tumor development is proposed on the basis of these observations.
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PMID:Age-incidence curves of nasopharyngeal carcinoma worldwide: bimodality in low-risk populations and aetiologic implications. 1876 4

Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1/PD-L1 pathway could be involved in the establishment of persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1 expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically elevated. In addition, PD-1 expression was significantly higher on CD8+ T cells along with cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific CTLs in ATLL patients compared with ACs and control individuals. Primary ATLL cells in 21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not observed in cells from ACs. Finally, in functional studies, we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8+T-cell response. These observations suggest that the PD-1/PD-L1 pathway plays a role in fostering persistent HTLV-1 infections, which may further ATLL development and facilitate immune evasion by ATLL cells.
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PMID:PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. 1883 Feb 59

Epidemiological studies have shown that chronic work stress or unfavourable psychosocial work conditions are prospectively associated with different adverse health outcomes. The aim of the present cross-sectional study was to investigate the relationship between work-related chronic stress as well as exhaustion and a cumulative measure of physiological wear-and-tear called allostastic load (AL). AL could be a possible biological pathway for how chronic work stress and exhaustion lead to health impairments in the long run. As the teaching profession has been proposed to be a potentially high stressful occupation, chronic work stress (effort-reward-imbalance) and exhaustion were assessed in 104 female school teachers. AL was first analyzed according to McEwen's classical model comprised of ten parameters including cortisol, epinephrine and norepinephrine, dehydroepiandrosterone-sulphate (DHEA-S), waist/hip-ratio (WHR), glycosylated haemoglobin (HbA1c), high-density lipoprotein (HDL), total cholesterol/HDL-ratio, and systolic and diastolic blood pressure. Additionally it was extended to include tumor-necrosis-factor-alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen, D-dimer, percent-body-fat, triglycerides, and glucose levels. A substantial proportion of our sample was highly exhausted whereas relatively few teachers showed high effort-reward-imbalance. AL scores were significantly higher in women high on effort-reward-imbalance or suffering from exhaustion. Although all teachers had been in a good health status, chronic work stress as well as exhaustion appears to be associated with changes in a multi-system summary indicator of physiological risk.
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PMID:Chronic work stress and exhaustion is associated with higher allostastic load in female school teachers. 1895 Dec 44

Dendritic cell (DC) vaccines have emerged as a promising strategy to induce antitumoral cytotoxic T cells for the immunotherapy of cancer. The maturation state of DC is of critical importance for the success of vaccination, but the most effective mode of maturation is still a matter of debate. Whereas immature DC carry the risk of inducing tolerance, extensive stimulation of DC may lead to DC unresponsiveness and exhaustion. In this study, we investigated how short-term versus long-term DC activation with a Toll-like receptor 9 agonist influences DC phenotype and function. Murine DC were generated in the presence of the hematopoietic factor Flt3L (FL-DC) to obtain both myeloid and plasmacytoid DC subsets. Short activation of FL-DC for as little as 4 h induced fully functional DC that rapidly secreted IL-12p70 and IFN-alpha, expressed high levels of costimulatory and MHC molecules and efficiently presented antigen to CD4 and CD8 T cells. Furthermore, short-term activated FL-DC overcame immune suppression by regulatory T cells and acquired high migratory potential toward the chemokine CCL21 necessary for DC recruitment to lymph nodes. In addition, vaccination with short-term activated DC induced a strong cytotoxic T-cell response in vivo and led to the eradication of tumors. Thus, short-term activation of DC generates fully functional DC for tumor immunotherapy. These results may guide the design of new protocols for DC generation in order to develop more efficient DC-based tumor vaccines.
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PMID:Short-term activation induces multifunctional dendritic cells that generate potent antitumor T-cell responses in vivo. 1895 36

Greater than 50% of patients with esophageal carcinoma are found to be incurable at the time of diagnosis, leaving only palliative options. Self-expanding metal stents (SEMs) are effective for relieving symptoms and complications associated with esophageal carcinoma and improving quality of life. We undertook a retrospective analysis to evaluate the experience of palliative esophageal stenting for symptomatic malignant dysphagia in our institution over a period of 7 years. Between January 1999 and January 2006, 126 patients who received SEMs for malignant dysphagia were identified using an upper gastrointestinal specialist nurse clinician database. Data were obtained from patient case notes, endoscopy, histopathology, radiology, and external agency databases. Of the 126 identified, 36 patients were excluded from the analysis. A number of variables including age, sex, presenting complaints, type of stent, indications of stenting, success or failure of stent insertion, survival rate, and complication rate were analyzed. Of the 90 patients, 55 (61%) were male and 35 (39%) were female. The mean age of patients was 70.79 (range 40-97) years. The predominant presenting complaints were dysphagia (n = 81) and weight loss (n = 48). The indication for stenting was worsening dysphagia in all patients. Tumors were confined to the distal esophagus and esophagogastric junction in 73 patients (81%), and the mid-esophagus in 17 (19%). Adenocarcinoma was identified in 61 patients (67.8%) and squamous cell carcinoma in 29 (32.2%). Stenting numbers were comparable in endoscopic and radiologic groups (47 vs. 43), with successful stent deployment in 89 patients. The 7- and 30-day mortality was 9% (n = 8) and 28% (n = 25), respectively. Comparable numbers of early deaths were seen in both radiologic (n = 13) and endoscopic (n = 12) groups. Causes of early inpatient death included hemorrhage (n = 5), pneumonia (n = 7), exhaustion (n = 2), cardiac causes (n = 3), perforation (n = 1), and sepsis (n = 1). The number of patients with complications was 41 (45.6%), 25 in the surgical group and 15 in the radiologic group; the difference was not significant (P = 0.13). The mean survival time was 92.5 (0-638) days and median survival time was 61 days. A subgroup of patients with complete dysphagia (score 4) gained a mean survival of 59 days. Those patients receiving adjuvant chemotherapy or radiotherapy survived significantly longer than those receiving stenting alone (152.8 days vs. 71.8 days). There is no significant difference in complications or survival when using endoscopic or radiologic methods to deploy SEMs in patients with inoperable esophageal cancer. Mortality is low; however, the morbidity rate is significant. Patients receiving adjuvant chemotherapy or radiotherapy, in addition to stenting, survived significantly longer than those with a stent only.
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PMID:Outcome of palliative esophageal stenting for malignant dysphagia: a retrospective analysis. 1930 13

Stress can activate tumor-suppressive mechanisms, causing the loss of adult stem cell function with age. In this issue of Cell Stem Cell and in Nature, Castilho et al. (2009) and Harrison et al. (2009) highlight the importance of mTOR signaling in stem cell exhaustion and mammalian aging, respectively.
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PMID:Growth signaling at the nexus of stem cell life and death. 1973 40

Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent expressing Wnt1 in an epidermal compartment that includes the epithelial stem cells. Surprisingly, Wnt caused the rapid growth of the hair follicles, but this was followed by epithelial cell senescence, disappearance of the epidermal stem cell compartment, and progressive hair loss. Although Wnt1 induced the activation of beta-catenin and the mTOR pathway, both hair follicle hyperproliferation and stem cell exhaustion were strictly dependent on mTOR function. These findings suggest that whereas activation of beta-catenin contributes to tumor growth, epithelial stem cells may be endowed with a protective mechanism that results in cell senescence upon the persistent stimulation of proliferative pathways that activate mTOR, ultimately suppressing tumor formation.
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PMID:mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. 1973 30

Although there has been initial success with some types of immunotherapy, such as adoptive cellular therapy and monoclonal antibody therapy for cancer, the experience with therapeutic cancer vaccines has been much less encouraging. Almost all randomized phase III trials testing therapeutic cancer vaccines have failed to meet their end points. There are several potential explanations for this, ranging from factors related to the clinical trial design and the vaccine itself. Perhaps the most important are host-related factors. Specifically, progression and metastases of many cancers are associated with induction of multiple cancer-specific immune-inhibitory pathways. These inhibitory pathways include induction of T-cell anergy through dendritic cell dysfunction, release of immunosuppressive cytokines, T-cell exhaustion through inhibitory T-cell signaling and T regulatory cell-mediated tumor-specific immune suppression. All of these pathways have been shown to be operational in patients with melanoma. To enhance the activity of therapeutic cancer vaccines, these immunosupressive pathways need to be addressed and reversed. A number of new immunomodulatory reagents that are able to interfere with some of these pathways are now being assessed in the clinic. Sanofi Pasteur designed a clinical trial in patients with advanced or metastatic melanoma that is intended to both induce tumor-specific T-cell responses and modulate or reverse some of the immune suppression pathways that the melanoma has induced. To accomplish this, the recently optimized ALVAC melanoma multi-antigen vaccine is administered with high doses of IFN-alpha. Clinical trial parameters have also been optimized to enhance the likelihood of inducing and documenting antitumor activity. Success with other therapeutic cancer vaccine approaches will likely require similar approaches in which promising immunogenic vaccines are integrated with biologically and clinically active immunomodulatory reagents.
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PMID:Strategies to enhance the therapeutic activity of cancer vaccines: using melanoma as a model. 1976 43

Olfactory neuroblastoma (esthesioneuroblastoma) is a rare neoplasm of the olfactory epithelium in the upper nasal cavity. Here, we report the case of a 69-year-old man who presented with massive progression of a metastatic esthesioneuroblastoma after endonasal resection, functional neck dissection, and radiotherapy of local and distant tumor relapses. After exhaustion of all conventional therapeutic options, we initiated treatment with the oral multityrosinekinase inhibitor sunitinib mesylate. Using this drug, significant improvement of clinical symptoms, disease stabilization, and recovery from Karnofsky index of 40% to 70% could be achieved in the absence of significant adverse drug effects. The patient died 15 months after initiation of sunitinib therapy due to complications of a traumatic femoral neck fracture without evidence of tumor progression. Immunohistochemical analysis of tumor tissue specimens obtained at initial surgery revealed ample expression of platelet-derived growth factor receptor (PDGFR)-b on stromal and endothelial cells. Sunitinib should be considered for palliative therapy of advanced esthesioneuroblastoma.
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PMID:Disease stabilization of progressive olfactory neuroblastoma (esthesioneuroblastoma) under treatment with sunitinib mesylate. 1982 Aug 99

Natural killer (NK) cells contribute to the graft-versus-leukemia effect after allogeneic stem cell transplantation. However, the efficacy of NK cell-mediated tumor cell lysis is limited due to target cell resistance, and target cell-induced apoptosis (TiA) was proposed to contribute to differences in susceptibility to NK cells. Here we analyzed the effects of target cells on the apoptosis of cytokine-activated NK cells in vitro. We found no association of target cell susceptibility and TiA of NK cells in an array of human and murine target-effector cell combinations. Incubation of NK cells with caspase inhibitors blocked TiA incompletely, indicating that TiA is partly based on caspase-independent mechanisms. Modulating NK cell susceptibility against TiA by caspase inhibition did not influence cytotoxic efficacy. Furthermore, we found cytotoxic potential of NK cells to be markedly decreased following first target cell contact. Exhaustion of NK cell activity by first target cell contact was, however, not mediated by TiA. In addition, we found no relevant TiA by lymphoma cell lines against activated murine NK cells. We conclude that TiA represents only a minor factor of target cell resistance against NK cell-mediated cytolysis.
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PMID:Relevance of target cell-induced apoptosis as mechanism of resistance against natural killer cells. 1982 23


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