pinecone/core-2020-05-10-deduplication huggingface dataset:
Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens

Intralesional administration of cultured dendritic cells (DCs) engineered to produce IL-12 by in vitro infection with recombinant adenovirus frequently displays eradicating efficacy against established subcutaneous tumors derived from the CT26 murine colon carcinoma cell line. The elicited response is mainly mediated by cytolytic T lymphocytes. In order to search for strategies that would enhance the efficacy of the therapeutic procedure against less immunogenic tumors, we moved onto malignancies derived from the inoculation of MC38 colon cancer cells that are less prone to undergo complete regression upon a single intratumoral injection of IL-12-secreting DCs. In this model, we found that repeated injections of such DCs, as opposed to a single injection, achieved better efficacy against both the injected and a distantly implanted tumor; that the use of semiallogeneic DCs that are mismatched in one MHC haplotype with the tumor host showed slightly better efficacy; and that the combination of this treatment with systemic injections of immunostimulatory anti-CD137 (4-1BB) monoclonal antibody achieved potent combined effects that correlated with the antitumor immune response measured in IFN-gamma ELISPOT assays. The elicited systemic immune response eradicates concomitant untreated lesions in most cases. Curative efficacy was also found against some tumors established for 2 weeks when these strategies were used in combination. These are preclinical pieces of evidence to be considered in order to enhance the therapeutic benefit of a strategy that is currently being tested in clinical trials. Supplementary Material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html
Prognostic value of soluble P-selectin levels in colorectal cancer

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC
Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer

In an attempt to identify tumor suppressor genes on chromosome 10 in non-small cell lung
cancers, we isolated 10 types of splicing variants of the HELLS/ SMARCA6 gene transcripts.
HELLS/SMARCA6 is a novel member of SNF2 family, which is implicated in cellular function like chromatin remodeling. Variant 1 was an alternatively spliced isoform containing
an insertion of a 44-ntd intronic sequence between exons 3 and 4, giving rise to a premature
termination of translation. The expression of the variant 1 was detected exclusively in the
lung cancer specimens (11 of 43 cases, 26%), but was not detected in corresponding normal tissues. D10S520 marker in the proximity of the HELLS/SMARCA6 gene showed prevalent allelic loss (41%) as compared with flanking markers (25-31%). These results suggest that loss of function of HELLS/SMARCA6 by allelic loss and aberrant proteins by tumor-specific exon creation may result in epigenetic deregulation, leading the lung cells to malignancy or its progression
Characterization of human PA2.26 antigen (T1α-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas

El pdf del artículo es la versión post-print.We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1α-2, podoplanin), a small mucin-type trans-membrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca2+-dependent cell-cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion. © 2004 Wiley-Liss, Inc.Funded by: Fondo de Investigaciones Sanitarias. Grant Numbers: FIS-01/1125, FIS-02/1025; Ministerio de Ciencia y Tecnología. Grant Number: SAF2001-2361; FIS and Fundación Carolina.Peer Reviewe
Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC(50) (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38
Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8

In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3beta in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion
Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study.

A protective effect of calcium and/or dairy products on colorectal cancer has been reported in epidemiological studies but the findings are considered inconsistent. In particular, it is unclear whether they act at a particular step of the adenoma-carcinoma sequence. To investigate the effect of dairy product consumption and dietary calcium, vitamin D and phosphorus intake on the adenoma-carcinoma sequence in the French E3N-EPIC prospective study. The population for the study of risk factors for adenomas was composed of 516 adenoma cases, including 175 high-risk adenomas, and of 4,804 polyp-free subjects confirmed by colonoscopy. The population for the colorectal cancer study was composed of 172 cases and 67,312 cancer-free subjects. Diet was assessed using a self-administered questionnaire completed at baseline. There was a trend of decreasing risk of both adenoma (ptrend=0.04) and cancer (ptrend=0.08) with increasing calcium intake, with RRs for adenoma and cancer of 0.80 (IC 95%=0.62-1.03) and 0.72 (95% CI=0.47-1.10), respectively, in the fourth quartile compared to the first. A protective effect of dairy products on adenoma (RRQ4 vs. Q1=0.80, 95% CI=0.62-1.05, ptrend=0.04) was observed and of milk consumption on colorectal cancer (RRQ4vs. Q1=0.54, 95% CI=0.33-0.89, ptrend=0.09), although the latter did not reach significance. Phosphorus intake also decreased the risk of adenoma (RRQ4 vs. Q1=0.70, 95% CI=0.54-0.90, ptrend=0.005). No vitamin D effect was identified. Our data support the hypothesis that calcium, dairy products and phosphorus exert a protective effect at certain steps of the adenoma-carcinoma sequence
Polymorphism of  Xeroderma Pigmentosum group G  and the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus

We investigated the effects of  XPG  His1104Asp polymorphism (rs17655) on the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus (SCCOLE). This population‐based case‐control study involves 611 new cases of lung cancer, 601 new cases of oropharyngeal, laryngeal and esophageal cancers, and 1,040 cancer‐free controls. The  XPG  polymorphism was assayed by PCR‐RFLP method for 497 lung cancer cases, 443 cases of oropharyngeal, laryngeal and esophageal cancers and 912 controls. Binary and polytomous unconditional logistic regression models were fitted to assess the main effects and the effect modifications between the polymorphism and environmental exposures. With the adjustment for potential confounders, the  XPG  Asp1104Asp genotype was inversely associated with lung cancer (odds ratio [OR] = 0.62, 95% confidence limits [CL] = 0.38, 1.0) and SCCOLE (OR = 0.47, 95% CL = 0.27, 0.82), with the combined His1104His and His1104Asp genotypes as the referent. With subjects having genotype Asp1104Asp and no tobacco smoking exposure as the common referent, the ORs on lung cancer were 13 (95% CL = 4.4, 37) for heavy tobacco smoking (>20 pack‐years), 1.9 (95% CL = 0.78, 4.5) for having at least one copy of 1104His, and 23 (95% CL = 9.5, 56) for the joint effect, respectively. Compared to non‐smokers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy smokers (>20 pack‐years) having at least one copy of 1104His was 8.0 (95% CL = 2.7, 24). Similarly, compared to non‐drinkers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy drinkers (≥3 drinks/day) with at least one copy of 1104His was 10 (95% CL = 2.7, 38). In conclusion, our study suggests that the  XPG  Asp1104Asp genotype may be associated with decreased susceptibility to lung cancer and SCCOLE. © 2005 Wiley‐Liss, Inc
Familial risk of colon and rectal cancer in Iceland: evidence for different etiologic factors?

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs
Anticancer activity of bovine lactoferricin and a cytolytic 9-mer peptide : from milk to cancer vaccine?

The papers of the thesis are not available in Munin:
<br>1. L.T. Eliassen, G. Berge, B. Sveinbjørnsson, L. Vorland, J.S. Svendsen,
Ø. Rekdal: 'Evidence for direct antitumor mechanism of action by bovine lactoferricin',  Anticancer Research (2002), 22:2703-2710 (International Institute of Anticancer Research - publisher's restriction). <a href=http://x-port-sfx.uio.no/sfx_ubto?ctx_enc=info%3Aofi%2Fenc%3AUTF-8&ctx_ver=Z39.88-2004&rft.issn=0250-7005>Check availablility</a>
<br>2. Liv Tone Eliassen, Gerd Berge, Arild Leknessund, Mari Wikman, Inger Lindin, Cecilie Løkke, Frida Ponthan, John Inge Johnsen, Baldur Sveinbjørnsson, Per Kogner, Trond Flægstad and Øystein Rekdal: 'The antimicrobial peptide, Lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo', International Journal of Cancer, Volume 119, Issue 3 (p 493-500) (Wiley - publisher's restriction). Available at <a href=http://dx.doi.org/10.1002/ijc.21886>http://dx.doi.org/10.1002/ijc.21886</a>
<br>3. Berge, G., Eliassen, L. T., Sveinbjørnsson, Bartnes, K. Ø. Rekdal:
'Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide' (Manuscript)Cationic antimicrobial peptides (CAPs) are found in many diverse species playing a part in the innate immune system. CAPs are important as antimicrobial agents in most organisms, being able to kill a wide range of bacteria as well as fungi, enveloped viruses and protozoa. Certain CAPs also exhibit direct cytotoxic activity against many different types of human cancer cells. Bovine lactoferricin (LfcinB) derived from the protein bovine lactoferrin found in cow milk has been the starting point for this thesis. LfcinB is a CAP which exhibits antimicrobial and antitumor activities. In the present work the main focus has been to explore the anticancer activity of LfcinB and the de novo designed peptide, LTX-302, which is a 9-mer cytolytic peptide optimalized from parental LfcinB.   
<br>We found that LfcinB kill cancer cells by necrosis due to a dual mechanism of the peptide on both the mitochondrial membranes and the plasma membranes. In vivo studies of the more active peptide, LTX-302, demonstrated a vaccinating effect against the murine A20 B-cell lymphoma in immunocompetent mice. Subcutaneously established tumors were treated with LTX-302 by intratumoral injection of the peptide and a majority of the tumors obtained complete regression upon LTX-302 treatment. The cured mice were found to be protected against a rechallenge with A20 cells, but not against Meth A sarcoma cells, indicating a specific immune response. The complete regression was T-cell dependent, and both CD4 and CD8 T-cells were required for the protection. These studies show that local treatment of cancer by a CAP can induce active immunization against the cancer, conferring a novel strategy for therapeutic vaccination against cancer
Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long-term survival in a randomized study

Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long-term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2-armed study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m2 day 1) and etoposide (120 mg/m2 days 1-3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease-free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 +/- 30.86 months. A significant difference in overall (p = 0.02) and disease-free (p = 0.0001) survival was observed between patients undergoing adjuvant chemotherapy vs. control group. Adjuvant chemotherapy significantly improved both overall (p = 0.02) and DFS (p = 0.003) of anatomically resected patients, but only the DFS (p = 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long-term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected
Intratumoural expression of TNF-R1 and EMAP-II in relation to response of patients treated with TNF-based isolated limb perfusion

Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical response. Tumour biopsies were taken before and after ILP of patients (n = 27) with advanced sarcoma or metastatic melanoma. Biopsies were randomly analysed by western blotting for proEMAP/EMAP-II and TNF-R1 expression. Appropriate melanoma biopsies were stained for EMAP-II, TNF-R1, CD31 and CD68. For melanomas we found that an up-regulation of EMAP-II, in contrast to proEMAP or TNF-R1, directly after ILP significantly correlated with a complete tumour response. No correlation was found for sarcoma patients. In a comparative analysis we found that the overall proEMAP and EMAP-II expression was higher in melanoma as compared to sarcoma cases and measurements in cell lines revealed high proEMAP expression by melanoma cells. We report high EMAP-II expression by endothelial cells and association with macrophages. In addition, macrophages are recruited to vessel-remnants after ILP. An upregulation of EMAP-II directly after ILP of melanoma patients correlates with and might predict a complete response to TNF-based ILP. The association of macrophages with EMAP-II expression and vascular damage suggests a role for EMAP-II in regulating the TNF-based anti-tumour effects observed with an ILP. Analysis of EMAP-II expression in melanoma biopsies should be implemented in the ILP procedure
Cancer incidence in eastern Libya: The first report from the Benghazi Cancer Registry, 2003

Cancer registration in Northern Africa is still limited and, until now, there have been no population-based data available for Libya. In this paper, we present the first data collected and analyzed by the Benghazi Cancer Registry. Registration was carried out by active data collection; the registry staff routinely visited all hospitals and pathological laboratories in eastern Libya (1.6 million inhabitants) and collected information from all death registration offices. A huge archive of prevalent cases was established before the 2003 data were collected. A total of 997 cases of primary cancers were registered among residents in 2003. The world age-standardized incidence rate for all sites combined (except non-melanoma skin) was 118 per 100,000 for men and 95 per 100,000 for women. The most frequently diagnosed malignancies in males were lung cancer (19%) and colorectal cancer (10%), followed by cancers of the head and neck (9%) and bladder (9%). Among females, they were breast cancer (26%), cancer of the colon and rectum (9%), uterus (7%) and non-Hodgkin lymphoma (5%). Our study provides data on cancer incidence in eastern Libya, and confirms that cancer incidence is much lower than in western countries. Moreover, observed patterns indicate that the incidence of many cancers, including those of the lung, breast, colon, rectum and bladder is quite different from previous estimates based on the data available from the neighboring countries. (c) 2006 Wiley-Liss, Inc