{"title":"Intraportal and systemic allogeneic cell therapy in a murine model of hepatic metastatic breast cancer.","authors":"Soumya Panigrahi, Elena Yacovlev, Yael Gelfand, Lucia Schuger, Shimon Slavin, Shoshana Morecki","doi":"10.1080/13684730310001661","DOIUrl":"https://doi.org/10.1080/13684730310001661","url":null,"abstract":"<p><p>Allogeneic immunocompetent splenocytes were tested for their ability to exert a GVT effect in a murine model of liver metastasis. Mammary carcinoma cells originating from an H-2(d) mouse were inoculated through the PV of F(1) (H-2(d/b)) mice, to mimic clinical hepatic involvement in malignant disease. Cell therapy was given either locally (PV) or systemically by IV inoculation to test differential efficacy of the GVT effect, and the differential expression of GVHD symptoms induced by diverse routes of administration. Livers of mice treated with H-2(b) derived splenocytes given PV or IV remained tumor-free for at least 4 weeks following tumor inoculation. Furthermore, all secondary recipients of adoptively transferred (AT) liver cells were tumor-free for >300 days. In contrast, all livers of untreated control mice or mice treated with syngeneic splenocytes displayed tumor metastases as early as 2 weeks following tumor inoculation, and large local tumors developed in AT secondary recipients. Our data demonstrate the efficacy of allogeneic cell therapy, given either locally or systemically, in the eradication of liver metastases. However, diverse routes of cell therapy administration did not show any difference in the expression and outcome of GVHD.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 3","pages":"99-106"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310001661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22474500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topical platelet-derived growth factor in patients enhances wound closure in the absence of wound contraction.","authors":"H Paul Ehrlich, Bruce M Freedman","doi":"10.1080/13684730310001643","DOIUrl":"https://doi.org/10.1080/13684730310001643","url":null,"abstract":"<p><p>Recombinant human platelet-derived growth factor (PDGF) is reported to promote wound closure in problem wounds. The mechanism of PDGF enhancement of wound closure is not clear. Does PDGF enhance wound contraction, or re-epithelialization, or both? In four patients undergoing elective surgery, a full excision 5 cm(2) punch wound was made behind each ear. The left post-articular wound received daily PDGF in a gel and each right post-articular wound received placebo-gel daily. The placebo-treated wounds closed in 19.8 days, while the PDGF-treated wounds closed significantly faster, in 15.6 days, p=0.002. At Day 20, all healed wounds were processed for histology. PDGF-treated wounds showed granulation tissue beneath an uninterrupted epidermis. A fine birefringence pattern, consistent with granulation tissue, was found by polarized light microscopy. The control closed-wounds had a smaller area of granulation tissue under an intact epidermis and polarized light microscopy showed mostly normal dermis. The presence of intact dermis within the closed-wound site is the hallmark of wound contraction. Topical PDGF limits the role of wound contraction in wound closure. Control wounds healed by wound contraction, while PDGF-treated wounds close by re-epithelialization and filling in with scar.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 3","pages":"85-90"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310001643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22474586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vladislav Treska, Jitka Kocova, Ludmila Boudova, Petra Neprasova, Ondrej Topolcan, Ladislav Pecen, Zbynek Tonar
{"title":"Inflammation in the wall of abdominal aortic aneurysm and its role in the symptomatology of aneurysm.","authors":"Vladislav Treska, Jitka Kocova, Ludmila Boudova, Petra Neprasova, Ondrej Topolcan, Ladislav Pecen, Zbynek Tonar","doi":"10.1080/13684730310001652","DOIUrl":"https://doi.org/10.1080/13684730310001652","url":null,"abstract":"<p><p>Cytosol levels of cytokines [interleukins 1b, 6, 8 (IL-1b, 6, 8), tumor necrosis factor-alpha (TNF-alpha)] in aneurysm walls were evaluated in a prospective non-randomized study of 57 patients. The group was divided into two subgroups: Subgroup I (ruptured aneurysms, n=11) and Subgroup II (asymptomatic aneurysms, n=32). A control group consisted of 14 kidney donors. Aortic walls were examined by immunohistochemistry and microscopy to detect inflammatory cells. More pronounced inflammatory changes and higher cytosol cytokine levels [IL6 (p<0.001), IL8 (p<0.0003) and TNFalpha (p<0.002)] were found in the walls of ruptured aneurysms than in the asymptomatic aneurysms. Immunohistochemically, most cells within the inflammatory infiltrates stained positively with the monoclonal antibody to the leucocyte common antigen (CD 45). The majority were of B-cell origin, which was demonstrated by positive staining with the monoclonal antibody L26 directed against the CD 20 antigen. These results show that an inflammatory process plays a significant role in patients with ruptured abdominal aortic aneurysms (AAA). A means of modifying the inflammatory process in the wall of AAAs might play an important role in preventing aneurysm rupture.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 3","pages":"91-7"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310001652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22474587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elaine G Rodrigues, A S Garofalo, Luiz R Travassos
{"title":"Endogenous accumulation of IFN-gamma in IFN-gamma-R(-/-) mice increases resistance to B16F10-Nex2 murine melanoma: a model for direct IFN-gamma anti-tumor cytotoxicity in vitro and in vivo.","authors":"Elaine G Rodrigues, A S Garofalo, Luiz R Travassos","doi":"10.1080/13684730310000121","DOIUrl":"10.1080/13684730310000121","url":null,"abstract":"<p><p>Syngeneic IFN-gamma(-/-) and IRF-1(-/-) mice are very sensitive to B16F10-Nex2 murine melanoma cells implanted subcutaneously. In contrast, IFN-gamma-R(-/-) (GRKO) mice are remarkably resistant to tumor development. Only 0-30% of these animals, challenged with a high dose of melanoma cells (5 x 10(5)), developed tumors at a late stage. The hypothesis of interferon gamma (IFN-gamma) accumulation and consequent cytotoxicity to implanted tumor cells was confirmed in vitro and ex vivo. IFN-gamma reduced tumor-cell growth in vitro in 60-81%, added alone or with LPS. Splenocytes and peritoneal macrophages from naïve GRKO mice activated with anti-CD3 and interleukin-12 (IL-12), respectively, accumulated IFN-gamma at levels 10-fold those of the wild-type. Supernatants of IL-12-activated macrophages from GRKO mice were toxic to B16F10-Nex2 cells, an effect reversible by anti-IFN-gamma antibody treatment. IL-12-activated macrophages from iNOS(-/-) mice were still highly cytotoxic to B16F10-Nex2 cells, but IL-12-activated macrophages from IFN-gamma-deficient mice were not inhibitory. In vivo, a single injection of anti-IFN-gamma antibody 18 h after tumor-cell challenge in GRKO mice rendered all animals susceptible to B16F10-Nex2 melanoma development. No tumors developed in the untreated GRKO mice during up to 45 days of observation. This model can be useful in understanding immune responses that involve IFN-gamma as a direct cytotoxic factor.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 3","pages":"107-16"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310000121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22474501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jørgen Agnholt, Keld Kaltoft, Niels O Jakobsen, Jens F Dahlerup
{"title":"T-cell vaccination in Crohn's disease: principles and presentation of the first two cases.","authors":"Jørgen Agnholt, Keld Kaltoft, Niels O Jakobsen, Jens F Dahlerup","doi":"10.1080/13684730310000130","DOIUrl":"https://doi.org/10.1080/13684730310000130","url":null,"abstract":"<p><p>In Crohn's disease (CD) CD4(+) T-cells producing tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important for disease progression. T-cell vaccination with such attenuated (gamma-irradiated) CD4(+) T cells may ameliorate the auto-reactive actions of Type-1 T cells through stimulation of interleukin-10 (IL-10)-producing regulatory T cells. This study aimed to propagate and use gut-derived type-1 CD4(+) T-cells for vaccination in CD. In a case study, two patients with CD-activity index (CDAI) >150 for >1 year were vaccinated with 800 x 10(6) attenuated autologous gut-derived CD4(+) T cells producing Type-1 cytokine -- grown in the presence of high concentrations of only IL-2 and IL-4. The T-cell vaccination was safe, causing only minor redness and tenderness at the injection sites. In Case 2, the treatment brought 3-years with active steroid-resistant CD into remission. CDAI dropped from 171 to 76, CD-endoscopic index of severity fell from 20 to eight and C-reactive protein reduced from 165 to 70 nmol/L. Case 1 received rescue infliximab (there was disease progression before sufficient quantities of cells were ready for the second vaccination). We concluded that it is possible to propagate T cells for autologous vaccination for CD and that treatment was safe. One patient, vaccinated according to the protocol, improved with sustained result for >1 year.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 3","pages":"117-23"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310000130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22474502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Liebau, Harry Merk, Sebastian Schmidt, Christian Roesel, Christiaan Karreman, Johannes Bernd Prisack, Hans Bojar, Axel W A Baltzer
{"title":"Interleukin-12 and interleukin-18 change ICAM-I expression, and enhance natural killer cell mediated cytolysis of human osteosarcoma cells.","authors":"Christian Liebau, Harry Merk, Sebastian Schmidt, Christian Roesel, Christiaan Karreman, Johannes Bernd Prisack, Hans Bojar, Axel W A Baltzer","doi":"10.1080/13684730310001977","DOIUrl":"https://doi.org/10.1080/13684730310001977","url":null,"abstract":"<p><p>Cytokines play important roles in the expression of adhesion molecules and the function of anti-tumor effector cells in the immune system. In this study, the influence of interleukin-12 (IL-12) and IL-18 on the expression of ICAM-1 and natural killer (NK)-cell mediated lysis in a human osteosarcoma cell line (HOS) was evaluated. ICAM-I expression of HOS cells were analyzed by flow cytometry following treatment with IL-12, IL-18 or both, and in co-cultures with peripheral lymphocytes. NK-cell activation in response to IL-12 and IL-18 was investigated by selective flow cytometry using propidium iodide. ICAM-1 expression on HOS cells was significantly enhanced by IL-12, but only when co-cultured in cell-to-cell contact with peripheral lymphocytes. Antibodies to interferon-gamma abrogated this effect. If HOS cells and peripheral lymphocytes were separated in co-cultures, IL-18 could substitute for cell-to-cell contact, facilitating IL-12-mediated enhancement of ICAM-1. Addition of IL-18 also enhanced NK-mediated cytolysis of HOS cells. These findings demonstrate that IL-12 can enhance the expression of ICAM-1 in the presence of IFN-gamma and, with IL-18, enhances NK anti-tumor activity. Immunomodulation via cytokine therapy may lead to improved eradication of chemotherapy-resistant osteosarcomas.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 4","pages":"135-42"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730310001977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24112552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxygen-sensitive pro-inflammatory cytokines, apoptosis signaling and redox-responsive transcription factors in development and pathophysiology.","authors":"J. Haddad","doi":"10.1080/13684730216401","DOIUrl":"https://doi.org/10.1080/13684730216401","url":null,"abstract":"The transition from placental to pulmonary-based respiration causes a relative hyperoxic shift, or oxidative stress, which the perinatal developing-lung experiences during birth. Dynamic changes in pO2, therefore, constitute a potential signaling mechanism for the regulation of the expression/activation of reduction-oxidation (redox)-sensitive and O2-responsive transcription factors, apoptosis signaling and pro-inflammatory cytokines. The variation in deltaPO2, in particular, differentially regulates the compartmentalization and function of the transcription factors hypoxia-inducible factor-1alpha (HIF-1alpha) and nuclear factor-kappaB (NF-kappaB). In addition, O2-evoked regulation of HIF-1alpha and NF-kappaB is closely coupled with the intracellular redox state, such that modulating redox equilibrium affects their expression/activation. The differential regulation of HIF-1alpha and NF-kappaB in vitro is paralleled by O2- and redox-dependent pathways governing the regulation of these factors during the transition from placental to pulmonary-based respiration ex vivo. Furthermore, the birth transition period in vitro and ex vivo regulates apoptosis signaling pathways in a redox-dependent manner, consistent with NF-kappaB playing an anti-apoptotic function. An association is established between an oxidative stress condition and the augmentation of a pro-inflammatory state in pathophysiology, regulated by the O2- and redox-sensitive pleiotropic cytokines.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 1 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730216401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59837073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Amino acids 67 and 68 of transforming growth factor-beta regulate binding to a glycosyl phosphatidyl inositol-linked membrane protein on vascular endothelial cells.","authors":"K. Zhang, D. Polga, S. Salzman, J. Burmester","doi":"10.1080/13684730216399","DOIUrl":"https://doi.org/10.1080/13684730216399","url":null,"abstract":"Transforming growth factor-beta (TGF-beta) is a multifunctional growth and differentiation factor that affects almost all cells. Although equipotent in many cases, the three isoforms of TGF-beta (-beta1, -beta2, -beta3) have several important isoform specific activities. For example, TGF-beta2 binds with higher affinity to a 60 kDa cell-surface glycosyl phosphatidylinositol (GPI)-linked protein, expressed on vascular endothelial cells. We used chimeric TGF-beta proteins, in which selected regions of TGF-beta1 had been exchanged for the corresponding region of TGF-beta2, to demonstrate that amino acids 67 and 68 regulate binding of TGF-beta to this protein. Exchange of amino acids 67 and 68 of TGF-beta1 into TGF-beta2 resulted in a protein similar in affinity to TGF-beta1 for binding to the GPI-linked protein. In contrast, exchange of only amino acid 67 of TGF-beta1 into TGF-beta2, or exchange of only amino acid 68 of TGF-beta1 into TGF-beta2, resulted in a protein with affinity similar to that of TGF-beta2. This suggests that the coordinated change of Gln and His of TGF-beta1 to Thr and Ile at positions 67 and 68 alters the specificity of TGF-beta. Amino acids 67 and 68 are part of a surface-exposed alpha-helix that forms a projection away from the center of the TGF-beta molecule and is accessible for receptor binding.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 1 1","pages":"25-30"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730216399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59837023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Markowicz, J. Walewski, K. Zajda, P. Wiechno, H. Skurzak, J. Giermek, A. Gajkowska, M. Krzakowski, T. Pienkowski
{"title":"Recovery of dendritic cell counts and function in peripheral blood of cancer patients after chemotherapy.","authors":"S. Markowicz, J. Walewski, K. Zajda, P. Wiechno, H. Skurzak, J. Giermek, A. Gajkowska, M. Krzakowski, T. Pienkowski","doi":"10.1080/13684730216404","DOIUrl":"https://doi.org/10.1080/13684730216404","url":null,"abstract":"Dendritic cell (DC) counts and function were assayed in peripheral blood of lymphoma and solid tumor patients before and after chemotherapy. The DC counts declined significantly within the first week from the start of chemotherapy, recovered in the second week, and exceeded the baseline values in the third week. DC recovery was usually similar after the first and after the last cycle of chemotherapy. DC1 and DC2 subsets followed the pattern of reconstitution found for the DC population as a whole. Monocytes and granulocytes recovered 1-2 weeks later than DC. The primary proliferative response to keyhole lympet hemocyanin (KLH), totally DC-dependent, declined within the first week from the start of chemotherapy, and in the majority of patients (including those initially unresponsive) recovered along with DC counts. The recovered responsiveness to KLH, but not to anti-CD3 antibody, disappeared at the end of chemotherapy in lymphoma and some solid tumor patients. Prolonged depletion of CD4+ T cells could contribute to the loss of responsiveness in lymphoma patients receiving multiple cycles of chemotherapy. However, in some solid tumor patients, the reactivity to KLH was absent, despite the reconstitution of both DC and CD4+ T-cell counts. Our data show that numerical reconstitution of DC is not necessarily accompanied by functional recovery. The early recovery of DC should be considered while designing protocols for DC collection for immunotherapy.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"7 1 1","pages":"15-24"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730216404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59837115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}