Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we ...evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features.
mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used.
RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk.
hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We describe the effects of stem cell factor (SCF) on the dendritic cell (DC) pathway and provide evidence for the existence of a post granulocyte-macrophage colony-forming unit (GM-CFU) DC ...progenitor. When employed with cytokines regulating DC development (tumor necrosis factor TNF + GM colony-stimulating factor GM-CSF), SCF increased the size of monocyte (mono) and mono-DC colonies arising from cord blood CD34+ progenitor cells. The overall plating efficiency of these colonies increased approximately threefold, as compared with growth in TNF + GM-CSF. Most (approximately 70%) of the CFUs were mono-DC CFU, and SCF did not alter the proportion of mono-DC CFU to mono-CFU obtained with TNF + GM-CSF alone. Proliferation, as measured by thymidine uptake and manual cell counts, at least doubled and occurred earlier (by day 4). In long-term cultures established with TNF + GM-CSF + SCF, high levels of proliferation were prolonged for up to three weeks. These were associated with extended DC development and the capacity to form 2 degree mono-DC colonies. There was no induction of polymorphonuclear (PMN) cells in 2 degree cultures treated with either GM-CSF, GM-CSF + SCF or GM-CSF + granulocyte CSF (G-CSF), implying that the DC progenitor being replated was post GM-CFU. DC progeny arising in the presence of SCF exhibited typical DC features including: the lack of nonspecific esterase and phagocytic activity, the presence of class II major histocompatibility complex (MHC) antigens, the absence of CD14 antigens, and the ability to induce a potent mixed leukocyte reaction. Thus, SCF augments DC growth from progenitor cells without altering the developmental commitment instituted by TNF + GM-CSF. This enhancement follows the same general mechanisms previously reported for SCF-mediated lineage enhancement, i.e., increased colony size, number and plating capacity.
WEHI-3B/NOVO is a cloned murine leukemia cell line selected for resistance to novobiocin that is cross-resistant to the cytotoxic action of etoposide (VP-16) and to a lesser extent to a variety of ...other topoisomerase II (topo II)-reactive drugs. We have reported previously (Cancer Res. 52: 2782-2790, 1992) that WEHI-3B/NOVO cells exhibit a pronounced decrease in VP-16 induced DNA-topo II cross-link formation compared to the parental WEHI-3B/S cell line in intact cells, in the absence of a significant difference in the P4 unknotting activity of topo II assayed in nuclear extracts. Because the pattern of cross-resistance was suggestive of a topo II-mediated mechanism, we have ascertained whether a change in topo II can account for the multidrug-resistant phenotype of WEHI-3B/NOVO cells. No differences existed between WEHI-3B/S and WEHI-3B/NOVO cells in topo II mRNA and protein levels, as well as in the amount of topo II associated with the nuclear matrix. Neither sensitive nor resistant cells expressed detectable levels of the MDR1 gene; however, VP-16 accumulation in WEHI-3B/NOVO cells was 3-4-fold less than that present in WEHI-3B/S cells, whereas doxorubicin accumulation was the same in both cell lines. Over the first 60 s, no difference existed in the rate of uptake of VP-16 between parental and resistant cells; however, beyond the first 60 s of incubation, 3HVP-16 accumulated to a greater extent in parental sensitive cells. Thus, an increased rate of efflux of VP-16 was responsible for the lower steady-state concentration of the drug in resistant cells. The efflux Km for VP-16 in WEHI-3B/NOVO cells was 254.7 microM and the Vmax was 10.4 pmol/s/10(7) cells. In the presence of the inhibitors of energy metabolism, sodium azide and deoxyglucose, the efflux of VP-16 was markedly inhibited; readdition of glucose restored the original efflux rate. Northern blot analyses using the human 10.1 probe for the 3'-terminal region of the multidrug-resistance protein (MRP) cDNA revealed a mRNA species of approximately 6 kb in WEHI-3B/NOVO cells but not in WEHI-3B/S cells. Overexpression was associated with amplification of the cognate gene. To ascertain whether the overexpressed gene in WEHI-3B/NOVO cells was the murine MRP or a different member of the same superfamily of ATP-binding ABC cassette transporters, a 341-bp MRP cDNA probe was generated from a murine genomic library.
Due to the elevated levels of hematopoietically active cytokines such as tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GMCSF) in rheumatoid arthritis (RA) serum ...and synovium, the increased bone marrow activity in RA, and the effectiveness of GMCSF in mobilizing progenitor cell release from the bone marrow into the periphery, we hypothesized that hematopoietic progenitors are altered in the peripheral blood (PB) of patients with RA.
Flow cytometry assisted cell surface analysis was employed to compare the distribution of myeloid (CD34+CD33+), B lymphoid (CD34+CD10+), and erythroid (CD34+CD71+) committed progenitor cell subsets in the PB of healthy controls and patients with RA. Since RA and Sjogren's syndrome (SS) are related autoimmune disorders, primary SS PB was also investigated.
Only those patients with RA exhibiting clinically active disease (RA-A) demonstrated increases in myeloid and B lymphoid progenitor cell subsets. Growth of RA-A progenitors in cytokines promoting myelopoiesis (GMCSF, TNF, stem cell factor) produced increased monocyte and dendritic cell progeny, in support of the flow cytometry data. Lineage committed (CD34+CD38+) progenitors were increased in SS PB (p <0.03). However, these did not correlate with either the myeloid, erythroid, or B lymphoid lineages.
Distinct alterations in the distribution of PB progenitors are present in RA and primary SS. Since progenitor cells retain a proliferative capacity, their infiltration into the synovial/glandular environment may contribute to the accumulation of inflammatory cells within these sites. We propose that PB progenitors enter the diseased microenvironment through similar mechanisms as mature hematopoietic elements.
Stress urinary incontinence (SUI) has been reported to have a negative impact on sexual relations in up to 68% of women. The effect of suburethral sling on sexual functioning has been studies, but ...the results are still inhomogeneous. This study was undertaken to assess the effect of the transvaginal tension free vaginal tape (TVT), transvaginal tension free vaginal tape - obturate (TVT-O) and minisling procedures (SIS) on sexual function and to also evaluate the male experience respect to sexual activity before and after surgery of partners of women underwent surgery.
We enrolled 150 patients underwent a TVT/TVT-O or SIS for female stress urinary incontinence. All patients enrolled were invited to fill out the Female Sexual Function Index (FSFI) Questionnaire, before surgery and 12 months after surgery. We also evaluate the male experience, through questionnaire, respect to sexual activity before and after surgery of female partner.
At month 12, the mean follow-up FSFI total score in SIS group improved from baseline 22.7±3.83 to 26.2±4.01 (P=0.001), in the TVT group from baseline 22.5±4.11 to 28.5±3.87 (P=0.001) and in the TVT-O group from baseline 23.5±4.48 to 27.7±3.68. The male questionnaires reported an improvement of the sexual function of 84% for TVT group, 82.9% for SIS group and 80,9% for TVT-O group.
In our present study, patients underwent TVT, TVT-O or SIS showed comparable significant improvement of sexual function after sling procedure as evaluated by FSFI.
A vaccination campaign against HBV was undertaken by the Division of Neonatal Pathology at the Hospital of Trapani from 1984 to 1989 with the aim of reducing morbidity and mortality rates due to HBV. ...6,849 women were studied in order of HBV diagnosis. Seventy-four of these (1.08%) were HBsAg positive, and 4/74 were HBeAg positive. Seventy-two high-risk newborns underwent passive immunoprophylaxis and a vaccination cycle. Antibody titres demonstrated the effectiveness of therapy in 95.1% of subjects.
Flanders Marine Institute and its consortium of experts on non-indigenous species conduct an ongoing effort to collect and maintain a list of alien species with documented established populations in ...the Belgian part of the North Sea and its adjacent estuaries. The list strives to include all currently known non-indigenous and cryptogenic species registered in salt and brackish environments in the Belgian part of the North Sea, the Belgian coastal zone and adjacent estuaries (Yser, Scheldt, Ostend Sluicedock). The discovery of America (1492) marked by a strong increase in trans-Atlantic shipping is set as the historical baseline of this assessment. This effort scrutinizes intentional and unintentional introductions by man or other vectors. Alien species for which there is no evidence of resident populations are not included in the list, nor are species that are limited to the fresh water environment. Newly registered species as a consequence of (expected) naturally induced migrations are also excluded. This initiative aims at providing a freely available online source of information on non-indigenous species and its associated network of experts for this study area. This includes definitions, information sheets and background literature, by species, and further links to European and international initiatives. Each information sheet describes the life cycle and ecology of the species, the introduction pathways and distribution, the possible effects or impacts of the species on its environment and potential mitigation measures. Pictures and a fully documented reference list - all available at the VLIZ library - represent an important added-value.http://www.vliz.be/NL/Cijfers_Beleid/Niet_inheemse (Dutch)
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