bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staging gastrointestinal cancer as a precondition for multimodal treatment
Authors: Siewert J. R. , Sendler A. , Dittler H. J. , Fink U. , Höfler H. 
Published: October 2004

AbstractStaging gastrointestinal cancer is useful only if it has an impact on treatment. When applying modern multimodal therapies (i.e., neoadjuvant, adjuvant, or additive treatment), meticulous staging is mandatory. Preoperative staging should include all relevant prognostic factors. If possible, modern cellular biology‐related parameters should also be investigated, although their validity has not yet been analyzed properly. Using such modern techniques as endoluminal ultrasonography or video‐laparoscopy, a preoperative diagnostic accuracy of 85% can be achieved, providing a sound foundation for therapeutic decisions. Assessment by TNM staging (UICC) and surgical resection without residual tumor (UICC/R0) are crucial, as it has been shown by multivariate analyses that these factors have the most impact on prognosis. Postoperative staging is mainly done by pathohistologic evaluation of the surgical specimen. It is the basis for any postoperative adjuvant or additive therapy. In this paper the diagnostic methods and their validity are discussed in relation to the various gastrointestinal tumors.
Preoperative chemotherapy for unresectable gastric cancer
Authors: Wilke H. , Stahl M. , Fink U. , Meyer H‐J. , Siewert J. R. 
Published: October 2004

AbstractEven with extended surgery, including systematic lymphadenectomy of the lymph node compartment II, only half of the patients with locally advanced gastric cancer (LAGC), which comprises stages IIIA, IIIB, and IV, undergo a macroscopic and microscopic tumor‐free resection (i.e., R0 resection, according to UICC 1987/AICC 1988). An improvement of this situation is best accomplished by preoperative treatment modalities to increase the R0 resection rate and by preoperative and postoperative treatment to reduce local recurrences and distant metastases. For LAGC, which includes approximately two‐thirds of patients with locoregionally confined tumors, preoperative chemotherapy (CTx) represents a promising approach. Among a group of patients with surgically or clinically staged unresectable LAGC, approximately half underwent R0 resection after down‐staging induced by active modern CTx. The long‐term survival of these patients seems to be improved. Even in patients who had primarily unresectable tumors as defined by an explorative laparotomy, the long‐term survival was about 20% after preoperative CTx and subsequent surgery. Based on these experiences, randomized trials investigating preoperative CTx versus surgery alone are clearly needed to define whether such an approach has an impact on R0 resection rates and survival of patients with LAGC. Preconditions for such trials are clinical staging procedures, including endoscopic ultrasonography (T category) and surgical laparoscopy plus lavage (excluding peritoneal carcinomatosis), and a standardized surgical procedure.
Adjuvant treatment of gastric cancer
Authors: Macdonald John S. , Schnall Sandra F. 
Published: October 2004

AbstractAdenocarcinoma of the stomach represents a significant problem worldwide. The only known curative treatment of gastric cancer is complete surgical resection of the stomach tumor with surrounding lymph node‐bearing areas. However, as many as 50% to 90% of patients undergoing gastric tumor resection relapse and die of cancer. Adjuvant chemotherapy has been used to prevent recurrence of gastric cancer after surgical resection. Single agents including thiotepa and fluorodeoxyuridine have no benefit as adjuvant therapy. Likewise, combination chemotherapy including 5‐fluorouracil (5‐FU) plus methyl‐CCNU, 5‐FU plus Adriamycin plus mitomycin C (FAM), and mitomycin C plus 5‐FU plus cytosine arabinoside do not result in overall improved survival. Combined modality irradiation plus fluorinated pyrimidine, however, has resulted in long‐term survival of patients with known residual gastric cancer. The newest clinical trial in postoperative gastric cancer being performed in the United States will test 5‐FU plus leucovorin plus irradiation in a prospectively randomized study in patients with resected stage IB through stage IV stomach cancer. This surgical study, designed with excellent prospective quality control, is actively accruing patients and will be completed in 1.5 to 2.0 years.
Biology of human colon cancer metastasis
Authors: Gutman Mordechai , Fidler Isaiah J. 
Published: October 2004

AbstractThe process of metastasis is highly selective and favors the survival and growth of a few subpopulations of cells that preexist within a heterogecous primary neoplasm. To produce metastases, tumor cells must succeed in invasion, embolization, survival in the circulation, arrest in a distant capillary bed, and extravasation into and multiplication in organ parenchyma. The outcome of this process depends on the interaction of metastatic cells with multiple host factors. To assess metastatic potential accurately, it is necessary to orthotopically implant human tumor cells recovered from surgical specimens into nude mice. This orthotopic implantation of tumor cells is invariably associated with trauma to the specific organ of implantation, which is followed by the processes of inflammation and repair. Tissue‐specific growth factors may be responsible for stimulation of tumor cells that possess specific surface receptors. Understanding the factors that regulate cancer metastasis should allow for the design of rational therapy.
Anal cancer: Multimodal therapy
Authors: Schlag P. M. , Hünerbein M. 
Published: October 2004

AbstractAnal cancer is a rare clinical entity which represents 1–2% of all gastrointestinal tract cancers. Due to the paucity of this malignancy it has been difficult to establish generally accepted guidelines for treatment, although various therapy modalities have been evaluated. For a long time radical surgery was the primary treatment for anal cancer and still about 30% of the patients undergo abdominoperineal rectotomy. However, recurrence rates of 20–40% have been observed after this multilating procedure. Therefore, other treatment options, including external or interstitial radiotherapy and chemotherapy, are used increasingly with the intention to preserve sphincter function. In the last years much interest has been addressed to multimodal therapy with radiation (50 Gy) and chemotherapy (5 fluouracil and mitomycin C). Presently radiochemotherapy appears to be the most efficient therapy in advanced anal cancer. Locoregional tumor control is obtained in 60–80% of the patients and there is evidence that radiochemotherapy can improve disease‐free survival. Despite considerable toxicity, radiochemotherapy should be recommended as primary therapy to most patients.
Parathyroid hormone‐related protein: Primary osteolytic factor produced by breast tumor cells in vitro?
Authors: Tabuenca Arnold , Mohan Subburaman , Garberoglio Carlos A. , Borgen Patrick I. , Rosol Thomas , Linkhart Thomas A. 
Published: October 2004

AbstractTumor cells in bone metastases are thought to induce bone resorption primarily by releasing paracrine factors. Parathyroid hormone related protein (PTHrp) has been proposed to mediate osteolytic activity of many tumors. PTHrp is produced by 40% to 60% of breast tumors and is elevated in the serum of up to 50% of patients with breast cancer metastases to bone. Most biologic processes in humans are heterogeneous in nature, so the purpose of this study was to investigate the hypothesis that paracrine factors other than PTHrp could mediate bone resorption by breast tumor cells. Serum‐free conditioned medium (CM) was collected from five human breast tumor cell lines and tested for bone resorption‐stimulating activity (BRSA) in mouse calvaria organ cultures. CM from all tumor cells studied produced significant bone resorption, comparable to that produced by 10 nM PTH. Small amounts of immunoreactive PTHrp (1.4–12.5 pM) were produced by all breast tumor cell lines. When tested in vitro, equivalent amounts of human PTHrp[1–36] did not produce significant bone resorption. Indomethacin (1 μM) significantly blocked BRSA by CM from all cell lines but did not decrease BRSA by PTHrp. In contrast PTHrp antibody (130 μg/ml) completely blocked BRSA by 1 nM PTHrp but did not modify BRSA by CM of breast tumor cells. The results of this study support the hypothesis that breast cancer cells release paracrine factors in vitro that stimulate bone resorption by a mechanism that is partially dependent on prostaglandin synthesis and at least in part different from that of PTHrp. These results suggest that breast tumor cells may produce osteolytic factors that are distinct from PTHrp and that may constitute a more significant portion of the osteolytic activity produced at sites of metastasis in bone, although additional in vivo studies are needed to test this hypothesis.
Pretransplant intrathymic inoculation of donor antigen combined with FK506 treatment: Prolongation of survival of cardiac, but not renal, allografts in rats
Authors: Motoyama Kentaro , Kamei Takafumi , Arima Takeshi , Ueki Masao , Hirano Tatsuya , Nakafusa Yuji , Tanaka Masao 
Published: October 2004

AbstractIt has been shown that pretransplant intrathymic injection of donor antigen prolongs rat cardiac allograft survival. The purpose of the present study was to evaluate whether co‐administration of FK506 could enhance the beneficial effect of intrathymic preimmunization; we also wished to clarify whether this combined treatment could be effective for renal allografts. Seven days prior to transplantation 5×107 donor splenocytes were injected into the thymus of LEW (RT11) recipients of WKA (RT1u) cardiac or renal allografts. Using a miniosmotic pump, FK506 was administered for 7 days before transplantation at a dose of 3 mg/kg/day. Whereas intrathymic injection of donor splenocytes or subcutaneous FK506 alone showed limited (15.2 days) or no (7.3 days) prolongation of cardiac allograft survival, the combined treatment with these two modalities synergistically prolonged the survival of the cardiac allograft (> 82.0 days). This combined treatment, however, failed to prolong renal allograft survival (8.4 days). Although donor‐specific prolongation of a second cardiac allograft was obtained in LEW rats with a well beating WKA heart, two of the three recipients ultimately rejected both first and second WKA cardiac allografts. Additionally, LEW rats with a long‐surviving WKA heart rejected a WKA renal allograft in a normal fashion. These data demonstrate a synergistic effect of intrathymic injection of donor splenocytes and subcutaneous FK506 on cardiac, but not renal, allograft survival and suggest that quantitative or qualitative differences of immunogenicity of kidney may contribute to the rejection of renal allografts.
Function of the sphincter of oddi in patients with juxtapapillary duodenal diverticula: Evaluation by intraoperative biliary manometry under a duodenal pressure load
Authors: Miyazaki Satoru , Sakamoto Tsuguo , Miyata Masahiko , Yamasaki Yoshio , Yamasaki Hajime , Kuwata Keiji 
Published: October 2004

AbstractThe purpose of this study was to elucidate the function of the sphincter of Oddi (SO) in patients with juxtapapillary duodenal diverticula (JDDs). The SO function was evaluated by intraoperative biliary manometry in three groups of patients. Group 1 consisted of nine patients with JDDs and a dilated common bile duct (CBD) (diameter > 10 mm). Group 2 consisted of six patients with JDDs and a normal‐sized CBD (diameter < 10 mm). Group 3 consisted of 26 patients without JDDs and with normal‐sized CBDs.In the absence of a duodenal pressure load, the patients in group 1 demonstrated a lower baseline SO pressure and lower resistance of the biliary outflow than patients in group 3. They also demonstrated a lower baseline SO pressure and shorter decay time (which represented terminal biliary ductal resistance) than patients in group 2. In the presence of a duodenal pressure load of 300 mm H2O, the patients in group 1 demonstrated a lower incidence of phasic SO contractions, a higher baseline SO pressure, and a higher resistance of the biliary outflow than group 2 and group 3 patients. The decay time in group 1 and group 2 patients was higher than that of group 3 patients. Based on these findings, we conclude that the SO function in patients with JDDs is impaired owing in part to long‐standing compression of the terminal biliary ductal system by a distended JDD associated with a rise in intraduodenal pressure in daily life.
Targeting the A site RNA of the Escherichia coli ribosomal 30 S subunit by 2′-O-methyl oligoribonucleotides: a quantitative equilibrium dialysis binding assay and differential effects of aminoglycoside antibiotics
Authors: ABELIAN Arthur , WALSH Andrew P. , LENTZEN Georg , ABOUL-ELA Fareed , GAIT Michael J. 
Published: October 2004

The bacterial ribosome comprises 30 S and 50 S ribonucleoprotein subunits, contains a number of binding sites for known antibiotics and is an attractive target for selection of novel antibacterial agents. On the 30 S subunit, for example, the A site (aminoacyl site) close to the 3′-end of 16 S rRNA is highly important in the decoding process. Binding by some aminoglycoside antibiotics to the A site leads to erroneous protein synthesis and is lethal for bacteria. We targeted the A site on purified 30 S ribosomal subunits from Escherichia coli with a set of overlapping, complementary OMe (2′-O-methyl) 10-mer oligoribonucleotides. An equilibrium dialysis technique was applied to measure dissociation constants of these oligonucleotides. We show that there is a single high-affinity region, spanning from A1493 to C1510 (Kd, 29–130 nM), flanked by two lower-affinity regions, within a span from U1485 to G1516 (Kd, 310–4300 nM). Unexpectedly, addition of the aminoglycoside antibiotic paromomycin (but not hygromycin B) caused a dose-dependent increase of up to 7.5-fold in the binding of the highest affinity 10-mer 1493 to 30 S subunits. Oligonucleotides containing residues complementary to A1492 and/or A1493 showed particularly marked stimulation of binding by paromomycin. The results are consistent with high-resolution structures of antibiotic binding to the A site and with greater accessibility of residues of A1492 and A1493 upon paromomycin binding. 10-mer 1493 binding is thus a probe of the conformational switch to the ‘closed’ conformation triggered by paromomycin that is implicated in the discrimination by 30 S subunits of cognate from non-cognate tRNA and the translational misreading caused by paromomycin. Finally, we show that OMe oligonucleotides targeted to the A site are moderately good inhibitors of in vitro translation and that there is a limited correlation of inhibition activity with binding strength to the A site.
Two related ARID family proteins are alternative subunits of human SWI/SNF complexes
Authors: WANG Xiaomei , NAGL Norman G. , WILSKER Deborah , VAN SCOY Michael , PACCHIONE Stephen , YACIUK Peter , DALLAS Peter B. , MORAN Elizabeth 
Published: October 2004

p270 (ARID1A) is a member of the ARID family of DNA-binding proteins and a subunit of human SWI/SNF-related complexes, which use the energy generated by an integral ATPase subunit to remodel chromatin. ARID1B is an independent gene product with an open reading frame that is more than 60% identical with p270. We have generated monoclonal antibodies specific for either p270 or ARID1B to facilitate the investigation of ARID1B and its potential interaction with human SWI/SNF complexes in vivo. Immunocomplex analysis provides direct evidence that endogenous ARID1B is associated with SWI/SNF-related complexes and indicates that p270 and ARID1B, similar to the ATPase subunits BRG1 and hBRM, are alternative, mutually exclusive subunits of the complexes. The ARID-containing subunits are not specific to the ATPases. Each associates with both BRG1 and hBRM, thus increasing the number of distinct subunit combinations known to be present in cells. Analysis of the panels of cell lines indicates that ARID1B, similar to p270, has a broad tissue distribution. The ratio of p270/ARID1B in typical cells is approx. 3.5:1, and BRG1 is distributed proportionally between the two ARID subunits. Analysis of DNA-binding behaviour indicates that ARID1B binds DNA in a non-sequence-specific manner similar to p270.
Phosphorylation of androgen receptor isoforms
Authors: WONG Hao Yun , BURGHOORN Jan A. , van LEEUWEN Marije , de RUITER Petra E. , SCHIPPERS Esther , BLOK Leen J. , LI Ka Wan , DEKKER Henk L. , de JONG Luitzen , TRAPMAN Jan , GROOTEGOED J. Anton , BRINKMANN Albert O. 
Published: October 2004

Phosphorylation of the human AR (androgen receptor) is directly correlated with the appearance of at least three AR isoforms on an SDS/polyacrylamide gel. However, it is still not clear to what extent phosphorylation is involved in the occurrence of isoforms, which sites are phosphorylated and what are the functions of these phosphosites. The human AR was expressed in COS-1 cells and AR phosphorylation was studied further by mutational analyses and by using reversed-phase HPLC and MS. The reversed-phase HPLC elution pattern of the three isoforms revealed that Ser-650 was phosphorylated constitutively. After de novo synthesis, only Ser-650 was phosphorylated in the smallest isoform of 110 kDa and both Ser-650 and Ser-94 were phosphorylated in the second isoform of 112 kDa. The hormone-induced 114 kDa isoform shows an overall increase in phosphorylation of all the isolated peptides. The activities of the Ser–Ala substitution mutant S650A (Ser-650→Ala) was found to be identical with wild-type AR activation in four different cell lines and three different functional analyses, e.g. transactivation, N- and C-terminal-domain interaction and co-activation by transcriptional intermediary factor 2. This was also found for mutants S94A and S515A with respect to transactivation. However, the S515A mutation, which should eliminate phosphorylation of the potential mitogen-activated protein kinase site, Ser-515, resulted in an unphosphorylated form of the peptide containing Ser-650. This suggests that Ser-515 can modulate phosphorylation at another site. The present study shows that the AR isoform pattern from AR de novo synthesis is directly linked to differential phosphorylation of a distinct set of sites. After mutagenesis of these sites, no major change in functional activity of the AR was observed.
Intranasal antigen targeting to MHC class II molecules primes local IgA and serum IgG antibody responses in mice
Authors: SNIDER D. P. , UNDERDOWN B. J. , MCDERMOTT M. R. 
Published: October 2004

SUMMARYCovalent conjugates of hen egg lysozyme (HEL) and anti‐major histocompatibility complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice intranasally. Three weeks after intranasal (IN) priming, mice responded rapidly to IN challenge with a mixture of HEL and cholera toxin (CT), by producing large titres of anti‐HEL IgA and IgG1 antibody in serum, and IgA antibody in nasal secretions. No secondary response to HEL plus CT occurred in mice that received no priming or mice primed with HEL alone. The secondary serum IgG antibody response was dominated by the IgG1 subclass. HEL combined with CT adjuvant worked much better than HEL alone in producing the secondary response. Control conjugates, containing an IgG isotype‐matched mAb without specificity for mouse tissues, provided poor priming. Mice expressing MHC class II molecules, to which the anti‐MHC II mAb cou ld not bind, produced a weak antibody response compared with those that expressed the appropriate MHC class II molecule. Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract.
Increased adjuvant efficacy in stimulation of antibody responses after macrophage elimination in vivo
Authors: LEENAARS P. P. A. M. , SAVELKOUL H. F. J. , HENDRIKSEN C. F. M. , VAN ROOIJEN N. , CLAASSEN E. 
Published: October 2004

SUMMARYTo investigate whether macrophages influence the efficacy of adjuvants, we locally eliminated lymph node macrophages with dichloromethylene diphosphonate containing‐liposomes before primary immunization. After macrophage elimination, animals were immunized with a soluble antigen (TNP–KLH; 2,4,6‐trinitrophenyl–keyhole limpet haemocyanin) either in phosphate‐buffered saline (PBS), in complete Freund's adjuvant (CFA), or in Specol. Specol is a water‐in‐oil emulsion, considered to be less aggressive than CFA, but equally effective. A secondary immunization followed with TNP–KLH. In vivo macrophage elimination before Specol/TNP–KLH immunization resulted in increased adjuvant efficacy as measured by (primary) antibody responses. This suggests that the activity of Specol is not primarily mediated through macrophages but rather through other antigen‐presenting cell types (e.g. dendritic cells, B cells, fibroblasts). The overall quality of produced antibodies, in terms of isotype distribution and affinity maturation, remained the same. After primary injection, CFA/TNP–KLH immunization resulted in significantly higher antibody responses in macrophage‐depleted animals and antibody responses did not increase significantly after secondary immunization. However, a booster effect was found when macrophages were not eliminated before CFA/TNP–KLH immunization, suggesting that the presence of macrophages during the first weeks of the primary immune response is essential for the induction of an effective secondary response in CFA immunizations. In conclusion, macrophage depletion before immunization with a soluble T‐cell‐dependent antigen combined with Specol may enhance specific antibody responses without changing the isotype or affinity of the antibodies.
Nitric oxide increased interleukin‐4 expression in T lymphocytes
Authors: CHANG R.‐H. , LIN FENG M.‐H. , LIU W.‐H. , LAI M.‐Z. 
Published: October 2004

SUMMARYNitric oxide (NO) is a regulator of many biological functions including T helper 1 (Th1)/T helper 2 cells balance. It has been demonstrated that NO inhibits the secretion of interleukin‐2 (IL‐2) and interferon‐γ on Th1 cells. Here we showed that, in addition to the suppression of IL‐2 production, NO‐generating agents sodium nitroprusside (SNP) and S‐nitroso‐N‐acetylpenicillamine (SNAP) increased the secretion of IL‐4 both in Th2 clones and EL4 T cells. The additive effect was dependent on the dose of SNP and SNAP. Augmentation of IL‐4 production was detected with 1 μM SNP, and up to threefold increase in IL‐4 secretion could be observed with higher concentrations of SNP/SNAP. NO also weakly increased the activation of IL‐4 promoter. In contrast, NO markedly inhibited the induction of IL‐2 promoter, which could account for most of the reduction in IL‐2 production. Analysis of the transcriptional elements on IL‐2 and IL‐4 promoters revealed a selective inactivation of NF‐κB and NF‐AT. It is suggested that despite the complex feedback network regulating NO production, the enhanced IL‐4 expression would lead to the expansion of Th2 cells once NO is generated.