bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fluorescence in situ hybridization study of ETV6‐NTRK3 fusion gene in secretory breast carcinoma
Authors: Makretsov Nikita , He May , Hayes Malcolm , Chia Stephen , Horsman Doug E. , Sorensen Poul H. B. , Huntsman David G. 
Published: March 2004

AbstractThe translocation t(12;15)(p13;q25), in which the ETV6 gene from chromosome 12 is rearranged with the NTRK3 gene from chromosome 15, has recently been identified in secretory breast carcinoma (SBC). This fusion gene was initially described in congenital fibrosarcoma and congenital mesoblastic nephroma. The biological consequence of this translocation is the expression of a chimeric protein tyrosine kinase with potent transforming activity. To assess the frequency of t(12;15)(p13;q25) in breast cancer, we developed complementary probe sets (fusion and split‐apart probes) for the detection of this translocation by fluorescence in situ hybridization (FISH) in paraffin‐embedded, formalin‐fixed tissue sections. We tested four histologically confirmed cases of SBC for the presence of the ETV6‐NTRK3 gene fusion and then applied the FISH assay to tissue microarrays (TMAs) in order to screen 481 cases of formalin‐fixed, paraffin‐embedded invasive breast carcinomas of various histologic subtypes. Three of the four cases of SBC revealed fusion signals. Of the 481 cases in the TMAs, 202 gave signals of sufficient quality for screening by FISH, and only one case showed fusion signals in most or all of the tumor cells. On review of the histology of this case, SBC was confirmed. On the other hand, none of the fusion‐negative breast cancers revealed SBC histology. In all cases, the results from the fusion and split‐apart FISH assays for the ETV6‐NTRK3 fusion genes were concordant. Our data suggest that the ETV6‐NTRK3 fusion gene is a specific genetic alteration in SBC. © 2004 Wiley‐Liss, Inc.
Protective effect of alpha‐tocopherol in head and neck cancer radiation‐induced mucositis: A double‐blind randomized trial
Authors: Ferreira Paulo Renato , Fleck James Freitas , Diehl Ada , Barletta Daniela , Braga‐Filho Aroldo , Barletta Antonio , Ilha Ligia 
Published: March 2004

AbstractBackground.the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck.Methods.Fifty‐four patients with cancer of the oral cavity and oropharynx were randomly assigned to rinse the oral cavity in an oil solution containing either VE or placebo before every conventional fraction of 2 Gy and again 8 to 12 hours later during the 5 to 7 weeks of radiotherapy (RT).Results.Thirty‐six events/167 patient‐weeks (21.6%) and 54 events/161 patient‐weeks (33.5%) of symptomatic mucositis were observed in VE and placebo groups, respectively (p= .038). VE reduced the risk by 36%. Subjective data at the end of the treatment revealed that VE decreased pain grades 2 to 3 during RT (3 of 28 patients vs 14 of 26 patients,p= .0001). No significant influence was detected in survival.Conclusion.VE decreased the incidence of symptomatic oral radio‐induced mucositis in patients with cancer of the oropharynx and oral cavity. © 2004 Wiley Periodicals, Inc.Head Neck26:XXX–XXX, 2004
Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck
Authors: Koy Susanne , Hauses Martin , Appelt Hella , Friedrich Katrin , Schackert Hans K. , Eckelt Uwe 
Published: March 2004

AbstractBackground.ZAC/Lot1 is a previously identified candidate tumor suppressor gene. The gene maps to the human chromosome 6q24‐q25, a region frequently deleted in squamous cell carcinomas of the head and neck and other solid tumors.Methods.We have used a model of head and neck squamous cell carcinoma (HNSCC) and cell lines to analyze the role of the candidate tumor suppressor gene ZAC/Lot1 in oral carcinogenesis. We analyzed the expression in 11 cell lines, and we performed loss of heterozygosity (LOH)‐ and sequence analyses in 51 primary tumors.Results.Three (27.3%) of 11 cell lines showed a distinctly reduced expression of ZAC/Lot1 compared with expression levels of the gene in the normal oral mucosa. In addition, we analyzed 51 primary squamous cell carcinomas of the head and neck for LOH with seven microsatellite markers flanking ZAC/Lot1. We detected an average LOH rate of 31.4% in the region of interest. Sequence analysis revealed no mutations for the ZAC/Lot1 coding exons, including the exon/intron boundaries.Conclusions.These data could suggest a minimal role for ZAC/Lot1 in a subgroup of HNSCC tumors. © 2004 Wiley Periodicals, Inc. Head Neck 26: 338–344, 2004
Parathyroid hormone–related peptide as a cause of hypercalcemia in squamous cell carcinoma of the head and neck: A case presentation and subject review
Authors: Brawner J. Travis , Zitsch Robert P. 
Published: March 2004

AbstractBackground.Serum levels of parathyroid hormone–related peptide (PTHrP) can be elevated with malignancy and cause hypercalcemia, which has been associated with a poor prognosis.Methods.We present a case of supraglottic squamous cell carcinoma with elevated serum PTHrP and hypercalcemia. The patient was acutely managed with intravenous fluids, furosemide, and zoledronic acid and then underwent a total laryngectomy and modified radical neck dissection.Results.The patient remains disease free and normocalcemic.Conclusion.Curative treatment for patients with head and neck cancer should not be withheld solely on the basis of humoral hypecalcemia of malignancy. © 2004 Wiley Periodicals, Inc. Head Neck 26: 382–384, 2004
Different ties for different needs: Recruitment practices of entrepreneurial firms at different developmental phases
Authors: Leung Aegean 
Published: March 2004

AbstractEntrepreneurial firms face significant challenges in attracting and acquiring needed human resources. That is,
in addition to difficulties associated with resource constraints and organization legitimacy, the requirements for
“person‐organization fit” change substantially as these firms transit from start‐up to
growth phase. This study examines how entrepreneurial firms tap evolving social network ties in order to address
“needs‐and‐fits” issues across different developmental stages of the firm. The findings
go beyond what “strength of weak ties” and “structural hole” theories would suggest, and
highlight the persistent use of strong and direct ties across developmental phases. © 2004
Wiley Periodicals, Inc.
Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood
Authors: Menu‐Branthomme Axelle , Rubino Carole , Shamsaldin Akhtar , Hawkins Michael M. , Grimaud Emmanuel , Dondon Marie‐Gabrielle , Hardiman Claire , Vassal Gilles , Campbell Sarah , Panis Xavier , Daly‐Schveitzer Nicolas , Lagrange Jean‐Leon , Zucker Jean‐Michel , Chavaudra Jean , Hartman Olivier , de Vathaire Florent 
Published: March 2004

AbstractSoft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3‐year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case‐control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow‐up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34–89)). The SIR was 113 (95% CI: 62–185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2–125) after chemotherapy alone (1 STS) and 19 (95%CI: 3–60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case‐control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended. © 2004 Wiley‐Liss, Inc.
Identification of five chromosomal regions involved in predisposition to melanoma by genome‐wide scan in the MeLiM swine model
Authors: Geffrotin Claudine , Crechet Françoise , Le Roy Pascale , Le Chalony Catherine , Leplat Jean‐Jacques , Iannuccelli Nathalie , Barbosa Angela , Renard Christine , Gruand Joseph , Milan Denis , Horak Vratislav , Tricaud Yves , Bouet Stéphan , Franck Michel , Frelat Gérard , Vincent‐Naulleau Silvia 
Published: March 2004

AbstractIn human familial melanoma, 3 risk susceptibility genes are already known, CDKN2A, CDK4 and MC1R. However, various observations suggest that other melanoma susceptibility genes have not yet been identified. To search for new susceptibility loci, we used the MeLiM swine as an animal model of hereditary melanoma to perform a genome scan for linkage to melanoma. Founders of the affected MeLiM stock were crossed with each other and with healthy Duroc pigs, generating MeLiM, F1 and backcross families. As we had previously excluded the MeLiM CDKN2A gene, we paid special attention to CDK4 and MC1R, as well as to other candidates such as BRAF and the SLA complex, mapping them on the swine radiation hybrid map and/or isolating close microsatellite markers to introduce them into the genome scan. The results revealed, first, that swine melanoma was inherited as an autosomal dominant trait with incomplete penetrance, preferably in black animals. Second, 4 chromosomal regions potentially involved in melanoma susceptibility were identified on Sus Scrofa chromosomes (SSC) 1, 2, 7 and 8, respectively, in intervals 44–103, 1.9–18, 59–73 and 47–62 cM. A fifth region close to MC1R was revealed on SSC 6 by analyzing an individual marker located at position 7.5 cM. Lastly, CDK4 and BRAF were unlikely to be melanoma susceptibility genes in the MeLiM swine model. The 3 regions on SSC 1, 6 and 7, respectively, have counterparts on human chromosomes (HSA) 9p, 16q and 6p, harboring melanoma candidate loci. The 2 others, on SSC 2 and 8, have counterparts on HSA 11 and 4, which might therefore be of interest for human studies. © 2004 Wiley‐Liss, Inc.
Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats
Authors: Vallebona Paola Sinibaldi , Rasi Guido , Pierimarchi Pasquale , Bernard Paola , Guarino Enrico , Guadagni Fiorella , Garaci Enrico 
Published: March 2004

AbstractIn previous studies, the antigen CSH‐275 (RTNKEASIC) was found expressed in tissue specimens from colorectal cancer but not in normal colonic mucosa. It was also naturally expressed in the DHD‐K12 experimental colorectal cancer in BDIX rats. In this study, we describe the effect of vaccination with the synthetic nonapeptide CSH‐275 in preventing tumor growth in a model closely mimicking the clinical situation of liver metastases, after surgical resection of primary colorectal cancer. A vaccination protocol using CSH‐275, conjugated with complete or incomplete Freund's adjuvant, was carried out to determine the effect in preventing the progression of liver metastases induced by DHD‐K12 cells injected in the splenic vein (preventive vaccine). An additional vaccination procedure was carried out to determine the effect on s.c. tumor growth (therapeutic vaccine). A significant improvement in survival along with the prevention of liver metastases formation and reduced growth of s.c. tumor were observed. CSH‐275 vaccination resulted in a significant increase in CTL activity against autologous DHD‐K12 cells in DHD‐K12 tumor‐bearing rats and the generation of a CTL response against DHD‐K12 cells in DHD‐K12 naive rats. Vaccination also induced massive infiltration of CD8+ cells in tumor. These results demonstrate that CSH‐275 is a new molecular target for colorectal cancer immunotherapy; it is also an excellent candidate for preclinical studies because it is naturally expressed on tumors in a fully competent syngeneic animal, which reproduces the clinical pattern of cancer progression. © 2004 Wiley‐Liss, Inc.
Inhaled particles and lung cancer, part B: Paradigms and risk assessment
Authors: Borm Paul J.A. , Schins Roel P.F. , Albrecht Catrin 
Published: March 2004

AbstractPoorly soluble particles of low toxicity (PSP), such as CB, TiO2and coal mine dust, have been demonstrated to cause lung cancer in rodents, being most pronounced in rats. Adequate epidemiologic studies do not clearly indicate increased lung cancer rates in humans exposed to such particles. This has caused controversial positions in regulatory decisions on PSP on different levels. The present review discusses the current paradigms in rodent particle carcinogenicity, i.e., (i) role of particle overload and of persistent inflammation and (ii) fibrosis as an intermediate step in particle‐induced lung cancer with regard to human risk assessment. Fibrosis, which is usually considered a precursor of lung cancer in humans, was not related to lung tumors in an animal study using 6 different particles, each at 3 dosages. Lung tumors after both inhalation and intratracheal instillation of PSP are related to particle surface dose, which forwards hazard assessment at surface‐based nonoverload concentrations and a standard setting using surface as an exposure metric. The scarce data available on humans do not support the overload concept but suggest a role for persistent lung inflammation. Differences in antioxidant protection between different rodent species correlate with susceptibility to PSP‐induced carcinogenicity and support the need for detailed studies on antioxidant response in humans. Apart from such bridging studies, further focus is also needed on surface chemistry and modifications in relation to their adverse biologic effects. © 2004 Wiley‐Liss, Inc.
Improving efficacy of interleukin‐12‐transfected dendritic cells injected into murine colon cancer with anti‐CD137 monoclonal antibodies and alloantigens
Authors: Tirapu Iñigo , Arina Ainhoa , Mazzolini Guillermo , Duarte Marina , Alfaro Carlos , Feijoo Esperanza , Qian Cheng , Chen Lieping , Prieto Jesus , Melero Ignacio 
Published: March 2004

AbstractIntralesional 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 cytolitic 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‐γ 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 aricle can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html. © 2004 Wiley‐Liss, Inc.
Highly efficient DNA incorporation of intratumourally injected [125I]iododeoxyuridine under thymidine synthesis blocking in human glioblastoma xenografts
Authors: Buchegger Franz , Adamer Florence , Schaffland Andreas Oliver , Kosinski Marek , Grannavel Carine , Dupertuis Yves Marc , de Tribolet Nicolas , Mach Jean‐Pierre , Delaloye Angelika Bischof 
Published: March 2004

AbstractIntratumoural (i.t.) injection of radio‐iododeoxyuridine (IdUrd), a thymidine (dThd) analogue, is envisaged for targeted Auger electron‐ or beta‐radiation therapy of glioblastoma. Here, biodistribution of [125I]IdUrd was evaluated 5 hr after i.t. injection in subcutaneous human glioblastoma xenografts LN229 after different intravenous (i.v.) pretreatments with fluorodeoxyuridine (FdUrd). FdUrd is known to block de novo dThd synthesis, thus favouring DNA incorporation of radio‐IdUrd. Results showed that pretreatment with 2 mg/kg FdUrd i.v. in 2 fractions 0.5 hr and 1 hr before injection of radio‐IdUrd resulted in a mean tumour uptake of 19.8% of injected dose (% ID), representing 65.3% ID/g for tumours of approx. 0.35 g. Tumour uptake of radio‐IdUrd in non‐pretreated mice was only 4.1% ID. Very low uptake was observed in normal nondividing and dividing tissues with a maximum concentration of 2.9% ID/g measured in spleen. Pretreatment with a higher dose of FdUrd of 10 mg/kg prolonged the increased tumour uptake of radio‐IdUrd up to 5 hr. A competition experiment was performed in FdUrd pretreated mice using i.t. co‐injection of excess dThd that resulted in very low tumour retention of [125I]IdUrd. DNA isolation experiments showed that in the mean >95% of tumour 125I activity was incorporated in DNA. In conclusion, these results show that close to 20% ID of radio‐IdUrd injected i.t. was incorporated in tumour DNA after i.v. pretreatment with clinically relevant doses of FdUrd and that this approach may be further exploited for diffusion and therapy studies with Auger electron‐ and/or beta‐radiation‐emitting radio‐IdUrd. © 2004 Wiley‐Liss, Inc.
Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin‐β1
Authors: Cai Jie , Peng Xuejun , Nelson Kevin D. , Eberhart Robert , Smith George M. 
Published: March 2004

AbstractThe success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4‐cm gap in the rat sciatic nerve. Adult female Sprague–Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L‐lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti‐calcitonin gene‐related peptide‐positive axons, but not RMDO95‐positive axons compared with nonfilament‐containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 247–258, 2004
In vivo behavior and mechanical stability of surface‐modified titanium implants by plasma spray coating and chemical treatments
Authors: Lee Baek‐Hee , Kim Jung Kyu , Kim Young Do , Choi Kuiwon , Lee Kyu Hwan 
Published: March 2004

AbstractThe geometric design and chemical compositions of an implant surface may have an important part in affecting early implant stabilization and influencing tissue healing. In this study, in vivo behavior and mechanical stability in implants of three surface designs, which were smooth surface (SS), rough titanium (Ti) surface by plasma spray coating (PSC), and alkali‐ and heat‐treated (AHT) Ti surface after plasma spray coating, were compared by histological and mechanical analyses. Surface morphologies of the implants were observed by optical microscopy and scanning electron microscopy. Chemical compositional surface changes were investigated by energy dispersive spectroscopy. The implants were inserted transversely in a dog thighbone and evaluated at 4 weeks of healing. At 4 weeks of healing after implantation in bone, the healing tissue was more extensively integrated with an AHT implant than with the implants of smooth (SS) and/or rough Ti surfaces (PSC). The bone bonding strength (pull‐out force) between living bone and implant was observed by a universal testing machine. At 4 weeks' healing after implant placement in bone, the pull‐out forces of the SS, PSC, and AHT implants were 235 (±34.25), 710 (±142.25), and 823 (±152.22) N, respectively. Histological and mechanical data demonstrate that appropriate surface design selection can improve early bone growth and induce an acceleration of the healing response, thereby improving the potential for implant osseointegration. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 279–285, 2004
Quantification of inflammatory cellular responses using real‐time polymerase chain reaction
Authors: Bailey LeeAnn O. , Washburn Newell R. , Simon Carl G. , Chan Edward S. , Wang Francis W. 
Published: March 2004

AbstractThe introduction of tissue engineering strategies for the repair and replacement of human body components extends the application and importance of biomaterials. Implanted biomaterials frequently evoke inflammatory responses that are complex and not well understood at present. The goals of this work were to develop improved measurement methods for the quantification of cellular inflammatory responses to biomaterials and obtain data that lead to an enhanced understanding of the ways in which the body responds to the introduction of biomaterials. To evaluate the biocompatibility of materials, we established a system that allows for the analysis and quantitation of cellular inflammatory responses in vitro. In this study, the inflammatory responses of murine macrophages (RAW 264.7) were analyzed. The cells were incubated with polymethylmethacrylate (PMMA) microspheres in the presence and absence of lipopolysaccharide (LPS) at 8 and 18 h. The analysis of the genetic material obtained from the cells was quantitated using real‐time reverse transcription polymerase chain reaction (RT‐PCR). The cell populations treated with LPS or PMMA microspheres singly resulted in an elevation of cytokine levels compared to the untreated control. LPS resulted in a 258‐fold increase, while PMMA resulted in an 87.9‐fold increase at 8 h. RAW 264.7 cells incubated with LPS and PMMA particles demonstrated a synergistic effect by producing a marked increase in the level of cytokine expression, 336‐fold greater than that of the untreated control at 8 h. Fluorescence microscopy studies that assessed cellular viability were also performed and are consistent with the RT‐PCR results. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 305–313, 2004