pinecone/core-2020-05-10-deduplication huggingface dataset:
Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk
Estimating and explaining the effect of education and income on head and neck cancer risk : INHANCE consortium pooled analysis of 31 case-control studies from 27 countries

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region, and calendar time, and to explain the association in terms of behavioural risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2·50; 95%CI 2·02- 3·09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviours; and it remained elevated among never users of tobacco and non-drinkers (OR = 1·61; 95%CI 1·13 - 2·31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviours: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America, and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low vs high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioural risk factors for these cancers, and which varies across cancer sites, sexes, countries, and country income inequality levels. © 2014 Wiley Periodicals, Inc
Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor

Cataloged from PDF version of article.Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category. © 2014 UICC
Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level
Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions

At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the “missing heritability.
Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR?=?0.81; 95% CI: 0.72-0.92; p?=?0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR?=?1.19; 95% CI: 0.63-2.24; ptrend ?=?0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.Grant sponsor: Polish Ministry of Science and Higher Education; Grant number: NN402178334; Grant sponsors: Research Fund at Region Sjaelland, DK; Baden-Wurttemberg State Ministry of Science, Research and Arts; CRIS Foundatio
Reproductive history and breast cancer in a population of high fertility, Costa Rica, 1984-85

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1987The relationship between breast cancer and women's reproductive history in Costa Rica was analyzed using logistic regression methods on data from 171 breast cancer cases and 826 population-based controls aged 25–58 years. The risk of breast cancer in nulliparous women under age 45 was 3 times that for parous women in the same age group. Women over 44 years of age with a parity greater than 4 had a risk of breast cancer of 0.3 compared to women of the same age but with a parity of 1–4. Neither breast-feeding nor birth interval showed an overall association with breast cancer independent of parity. Women with early age at first birth had a lower relative risk of breast cancer than women aged 20–24 at first birth, but only in two subgroups—women aged 45 and over and women with parity 1–4. Women without a completed pregnancy in the last 20 years had an elevated relative risk. However, results are not conclusive because some information is probably distorted by recall errors. Declines in fertility rates in the 1960s and 1970s may result in an increase of 30% in breast cancer incidence in Costa Rica between 1980 and the year 2000, according to the relative risks found in this study. In contrast, the effect of childlessness will probably not produce significant changes in national breast cancer trends.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA
ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis

Abstract  \ud
The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigenI/intercellular adhesion molecule I (LFA-I/ICAM-I) interaction to CD3/TCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-I-or+ tumor cell lines as target cells and anti-CD3- or anti-LFA-I containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-I- melanoma-derived cell line lgR39 was relatively resistant to CD3-mediated lysis by both TCRαβ+ and TCRγdL+ CTL, when compared with ICAM-I+ cell lines. Induction of ICAM-I on the membrane of lgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptible to CD3-mediated lysis. Anti-ICAM-I MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-I was critical in the TNF-induced increase in susceptibility to lysis of lgR39 cells. CTL formed less efficient conjugates with the ICAM-I- cells as compared to ICAM-I+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-I- tumor cells by CTL were enhanced by the addition of anti-LFA-I containing heterocross-linked MAb, thereby mimicking the LFA-I/ICAM-I interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3-mediated lysis of ICAM-I- target cells by CTL without affecting their conjugate formation. Anti-LFA-I MAb added after conjugate formation still inhibited lysis of both ICAM-I+or- tumor cells. Taken together, these findings suggest that the LFA-I/ICAM-I interaction co-activates CD3/TCR-mediated lysis by CTL through both an enhanced CTL-target cell binding and the delivery of post-conjugate costimulatory signals
Pleiotropic actions of suramin on the proliferation of human breast-cancer cells in vitro

Suramin, a non‐specific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breast‐cancer cell lines in vitro. In complete growth medium, pleiotropic effects were observed with respect to cell proliferation, i.e. suramin is stimulatory at low concentrations and inhibitory at higher concentrations, for 4 of the 6 cell lines studied. The various cell lines showed marked differences with respect to the antiproliferative action of suramin, the Evsa‐T cells being by far the most sensitive ones. A suramin concentration of 100 μg/ml brought about a 100% stimulation of the proliferation of ZR/HERc cells, ZR 75.1 cells ectopically expressing a human epidermal growth factor receptor (EGF‐R) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for T‐47D and MDA‐MB‐231 cells. The non‐specificity of the action of suramin was established by the observation that suramin‐induced inhibition of cell proliferation could be abolished by insulin‐like growth factor‐1 (IGF‐I) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serum‐free conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the non‐specific nature of its action. The stimulatory effect of low concentrations of suramin on the proliferation of breast cancer cells may have important consequences for breast cancer patients treated with suramin. Copyrigh
A Polymerase-chain-reaction Assay for the Specific Identification of Transcripts Encoded by Individual Carcinoembryonic Antigen (CEA)-gene-family Members

Carcinoembryonic antigen (CEA) is a tumor marker that belongs to a family of closely related molecules with variable expression patterns. We have developed sets of oligonucleotide primers for the specific amplification of transcripts from individual CEA-family members using the reverse transcriptase/ polymerase chain reaction (RT/PCR). Specific primer sets were designed for CEA, non-specific cross-reacting antigen (NCA), biliary glycoprotein (BGP), carcinoembryonic antigen gene-family members 1, 6 and 7 (CGMI, CGM6 and CGM7), and one set for all pregnancy-specific glycoprotein (PSG) transcripts. Primers were first tested for their specificity against individual cDNA clones and product-hybridization with internal, transcript-specific oligonucleotides. Total RNA from 12 brain and 63 gynecological tumors were then tested for expression of CEA-related transcripts. None were found in tumors located in the brain, including various mesenchymal and neuro-epithelial tumors. CEA and NCA transcripts were, however, present in an adenocarcinoma located in the nasal sinuses. In ovarian mucinous adenocarcinomas, we always found co-expression of CEA and NCA transcripts, and occasionally BGP mRNA. CEA-related transcripts were also found in some serous, endometrioid and clear-cell ovarian carcinomas. CEA, NCA and BGP transcripts were present in endometrial carcinomas of the uterus and cervical carcinomas, whereas uterine leiomyomas were completely negative. No transcripts were found from CGM 1, CGM6, CGM7 or from PSG genes in any of the tumors tested. The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies.
Prognostic factors in renal-cell carcinoma: Immunohistochemical detection of p53 protein versus clinico-pathological parameters

Immunoreactivity forp53 protein was assessed in 100 cases of primary renal-cell carcinoma (RCC). The results were correlated with clinical survival data (follow-up 24 to 84 months: mean: 39 months) and with clinico-pathological parameters, including nuclear grade, tumour stage, cell type, tumour architecture and tumour diameter. In all, 32% of the tumours were p53-positive; there was no difference in survival between p53-positive and -negative cases. Similarly, p53 expression did not correlate with any of the clinico-pathological parameters mentioned. Nuclear grade (grade 1 + 2 vs. grade 3 + 4) had a striking impact on prognosis and so, to a lesser extent, did tumour stage and the occurrence of a spindle-cell component. The immunohistochemical detection of p53 in RCC is not of prognostic value. The estimation of nuclear grade, however is a major predictor of prognosis
Role of tumor-derived fibroblasts in the growth of primary cultures of human breast-cancer cells: Effects of epidermal growth factor and the somatostatin analogue octreotide

In the present study we have investigated the role of human breast-cancer-derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co-culture system, using Transwell tissue-culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co-culture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17β-estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promoting compounds, are responsible for the growth-promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts, in one culture the fibroblasts significantly inhibited epithelial tumor-cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co-cultured with epithelial cells
Inhibition of bispecific monoclonal antibody (bsAb)-targeted cytolysis by human anti-mouse antibodies in ovarian carcinoma patients treated with bsAb-targeted activated T-lymphocytes

T lymphocytes of 8 patients with ovarian cancer were targeted to the tumor cells using F(ab')2 fragments of a bispecific monoclonal antibody (bsAb), specific for CD3 (a component of the T lymphocyte receptor for antigen) and for the folate receptor MOv 18 (overexpressed by ovarian carcinoma cells) as part of a phase l/II study. Phase I (days 0 to 3) consisted of increasing intraperitoneal (i.p.) numbers (106−109) of bsAbtargeted T lymphocytes plus lowdose interleukin-2 (IL-2). Phase II (days 6 to 13, and 27 to 33) consisted of daily i.p. infusions of 109 targeted T lymphocytes, 2 mg soluble bsAb, and lowdose IL-2. Using enzymelinked immunosorbent assays (ELISA), human antimouse antibodies (HAMA) were detected in all patients: in the serum from day 13 onwards and in the peritoneal fluid from day 20 onwards. A significant proportion of the HAMA appeared to be directed against the idiotypes of the bsAb specific for CD3 and MOv18, as suggested by (I) the clearly higher ELISA titers against OC/TR bsAb as compared to those against a monoclonal antibody (MAb) with unrelated specificity, and (2) failure to abrogate the capacity of peritoneal fluid containing HAMA to block the binding of OC/TR bsAb to MOv18+ or CD3+ cells by absorption of human antimouse IgG-framework antibodies in peritoneal fluid to immobilized mouse IgG. The OC/TR-targeted cytolysis of the MOv18+ ovarian carcinoma cell line lgrov-1 by autologous T lymphocytes was inhibited by peritoneal fluid samples containing relatively high HAMA titers. Such inhibitory activity was never detected at the start of phase II, but coincided with the last series of i.p. infusions of targeted T lymphocytes in 2 patients
Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components

The high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating normal urothelium and outgrowth of transformed urothelial cells, we recently developed an in vitro co-cultivation model. With this model system we studied the effects of growth factors and extracellular-matrix components on the intra-epithelial expansion of human T24 bladder-carcinoma cells in primary mouse-bladder explants. Exposure of the cultures to acidic fibroblast growth factor (aFGF) and laminin led to a dramatic increase in the number of invasive T24 cells into the primary urothelium. Epidermal growth factor (EGF) and collagen types I and IV counteracted the infiltration of individual T24 cells. EGF, aFGF, laminin and collagen types I and IV did not directly affect the migration and proliferation of T24 cells. Apparently, the efficacy of invasion of transformed urothelial cells into primary urothelium is not only dependent on the intrinsic characteristics of the transformed cells, but can be influenced to a considerable extent by exogenous components exerting their influence on the normal urothelium. The clinical relevance of this observation needs to be studied further