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1.
Br J Cancer ; 98(1): 77-9, 2008 Jan 15.
Article in English | MEDLINE | ID: mdl-18087272

ABSTRACT

Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a >or=35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR)+stable disease (P<0.0001) and survival (P=0.0002). Association of OR with survival was not significant. In multivariate survival analysis, >or=35% marker decline and radiological NP status were found as major determinants of prolonged survival with RR: 0.37 (P=0.01) and 0.63 (P=0.01), respectively. In advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional OR. CYFRA 21-1 >or=35% decline seems to be a reliable surrogate marker of treatment efficacy in terms of survival.


Subject(s)
Antigens, Neoplasm/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Keratins/blood , Lung Neoplasms/blood , Adenocarcinoma/blood , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adult , Aged , Carcinoma, Large Cell/blood , Carcinoma, Large Cell/drug therapy , Carcinoma, Large Cell/mortality , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Female , Humans , Keratin-19 , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Survival Rate , Treatment Outcome
2.
Eur Cytokine Netw ; 10(2): 205-10, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10400826

ABSTRACT

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.


Subject(s)
Cytokines/physiology , Gaucher Disease/physiopathology , Chemotaxis, Leukocyte , Child, Preschool , Cytokines/blood , Gaucher Disease/blood , Gaucher Disease/classification , Gaucher Disease/genetics , Gaucher Disease/immunology , Genotype , Humans , Hypergammaglobulinemia/etiology , Infant , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/blood , Interleukin-6/blood , Point Mutation , Receptors, Interleukin-2/blood , Severity of Illness Index , Sialoglycoproteins/blood , Solubility , Splenectomy , Tumor Necrosis Factor-alpha/analysis
3.
Eur J Haematol ; 62(2): 71-5, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10052708

ABSTRACT

Hairy cell leukemia (HCL) is a well recognized indolent B-cell lymphoproliferative disorder. HCL cell proliferation is regulated by growth factors and cytokines, of which tumor necrosis factor-alpha (TNF-alpha) may be one of the most important. The mechanism of TNF-alpha-induced HCL cell growth is mediated via 2 receptors, which are present in both cellular and soluble forms. In this study we determined the serum levels of TNF-alpha and their soluble receptors - sTNF-R60 and sTNF-R80 - in 23 HCL patients and correlated them with clinical parameters before and after therapy. Patients were classified according to their clinical status as either "active" at diagnosis or during relapse and "non-active" (responding to therapy with partial and complete remission). Most patients were treated with 2-CDA, following which serum levels of TNF-alpha, sTNF-R60 and sTNF-R80 were significantly decreased, particularly in CR. Significant differences in paired observation values were noted for TNF-alpha and sTNF-R80, indicating a good correlation with the clinical status of disease, but this was not the case for sTNF-R60 (coefficients of correlation between levels of TNF-alpha and sTNF-R80 and of TNF-alpha and sTNF-R60 were r = 0.85 and r= 0.64, respectively). These results suggest that decreases in both TNF-alpha and sTNF-R80 are indicative of response to treatment, while increased levels accompany active disease. Accordingly, we conclude that serum levels of the TNF family, as for the sIL-2R and IL-1 family, may also be used as sensitive markers for monitoring HCL status. Levels may be indicative of the clinical efficacy of therapy and can be used as an indicator of the presence of residual disease.


Subject(s)
2-Chloroadenosine/analogs & derivatives , Antimetabolites, Antineoplastic/therapeutic use , Biomarkers, Tumor , Deoxyadenosines/therapeutic use , Leukemia, Hairy Cell/blood , Receptors, Tumor Necrosis Factor/blood , Tumor Necrosis Factor-alpha/metabolism , 2-Chloroadenosine/therapeutic use , Humans , Leukemia, Hairy Cell/drug therapy , Leukemia, Hairy Cell/pathology , Neoplasm, Residual/blood , Prognosis
4.
Anticancer Res ; 19(4C): 3549-52, 1999.
Article in English | MEDLINE | ID: mdl-10629651

ABSTRACT

The prognostic value of the tumor markers CYFRA 21-1, tissue polypeptide specific antigen (TPS) and carcinoembryonic antigen (CEA) was investigated in three histologic subtypes of non-small cell lung cancer. Pretreatment serum marker levels were measured in 38 patients with adenocarcinoma (AC), in 43 patients with squamous cell carcinoma (SQC) and in 35 patients with large cell carcinoma (LCC). Univariate analysis in AC showed significant lower survival of patients with elevated levels of TPS, CYFRA 21-1 and CEA. In LCC, elevated levels of TPS and CEA were found to predict lower survival, while in SQC--only TPS was a predictor. A multivariate analysis of survival identified CEA (Relative Risk-5.5; p = 0.004), CYFRA 21-1 (RR-3.4; p = 0.008) and TPS (RR-3.0; p = 0.02) as independent prognostic factors in AC. In SQC, only TPS (RR-2.3; p = 0.03) was such a factor whereas in LC--none of the markers studied retained statistical significance. Thereafter, the combinations of the two strongest prognostic factors in the AC group--CEA and CYFRA 21-1 were explored to divide this group into subsets with different prognosis. In cases where both markers were positive, the relative risk of death was 10.5 times higher as compared to cases where both markers were negative (p = 0.002).


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/metabolism , Carcinoembryonic Antigen/blood , Carcinoma, Non-Small-Cell Lung/blood , Lung Neoplasms/blood , Peptides/blood , Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Large Cell/blood , Carcinoma, Large Cell/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/diagnosis , Female , Humans , Keratin-19 , Keratins , Lung Neoplasms/diagnosis , Male , Middle Aged , Multivariate Analysis , Prognosis , Risk , Survival Analysis , Time Factors
5.
Cancer Detect Prev ; 22(5): 416-21, 1998.
Article in English | MEDLINE | ID: mdl-9727622

ABSTRACT

Previously available serum tumor markers had a low clinical value in malignant pleural mesothelioma (MPM). The recently developed tissue polypeptide-specific antigen (TPS) and CYFRA 21-1 assays identify the soluble cytokeratin 18 and 19 fragments, respectively. In MPM these cytokeratins are expressed and may therefore be used as serum tumor markers. In this preliminary study, TPS and CYFRA 21-1 assays were evaluated to determine their potential for management of patients with MPM. Carcinoembryonic antigen (CEA) was evaluated as an additional marker. The study group consisted of 95 patients with benign lung and pleural diseases (BLPD), 14 patients with MPM, 41 patients with adenocarcinoma of lung (AC), and 40 patients with squamous cell carcinoma of lung (SQC). The utilized cutoff points corresponded to a 95% specificity for patients with BLPD. In MPM, TPS showed greater sensitivity (64.3%) than CYFRA 21-1 (50.0%), while CEA showed no sensitivity. In SQC, the marker CYFRA 21-1 had the highest sensitivity (52.5%), whereas in AC the most sensitive marker was CEA (56.1%). Significantly lower levels of CEA were found in MPM compared with BLPD (p < 0.001) or AC and SQC (p < 0.0001). Conversely, TPS levels in MPM were significantly higher than in SQC (p < 0.05). Close correlation of various individual pretreatment marker levels was observed only between TPS and CYFRA 21-1, both in MPM (r = 0.84; p < 0.001) and in non-small cell lung cancer (NSCLC) (r = 0.71; p < 0.001). In serial determinations of the markers during chemotherapy of MPM (n = 10), TPS and CYFRA 21-1 were shown to demonstrate more or less the same pattern of reactivity, although the changes in the TPS levels better reflected the clinical response to therapy. In conclusion, TPS seems to be a more sensitive marker than CYFRA 21-1.


Subject(s)
Biomarkers, Tumor/metabolism , Keratins/metabolism , Mesothelioma/metabolism , Pleural Neoplasms/metabolism , Antigens, Neoplasm/metabolism , Carcinoembryonic Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Humans , Keratin-19 , Lung Neoplasms/metabolism , Peptides/metabolism
6.
Ann Otol Rhinol Laryngol ; 107(8): 713-6, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9716876

ABSTRACT

Inflammatory cytokines have been shown to play an important role in the pathogenesis of various inflammatory processes. In throat infections, intracellular inflammatory cytokines have been detected from the sites of inflammation. The present study aimed to evaluate serum cytokine levels of patients with throat infections and correlate them to the inflammatory parameters and type of inflammation. Significantly higher inflammatory cytokine levels (interleukin [IL]-6 > 7 pg/mL, IL-1 > 1 beta pg/mL, tumor necrosis factor alpha > 1 pg/mL) were detected in most of the patients as opposed to healthy controls. Clinical parameters of infection (fever > 38 degrees C, leukocytosis > 11,000 white blood cells per cubic millimeter, polymorphonuclear neutrophils > 75%) were significantly correlated with high levels of inflammatory cytokines: mainly IL-6 and tumor necrosis factor alpha, and to a lesser degree with IL-1 beta. No correlation, however, was found between the type of inflammation and cytokine levels. The present study indicates a role of inflammatory cytokines in the pathogenesis of throat infections and the need for an anti-inflammatory and anticytokine therapeutic approach.


Subject(s)
Cytokines/immunology , Tonsillitis/immunology , Adolescent , Adult , Child , Cytokines/blood , Female , Humans , Male , Middle Aged , Tonsillitis/blood
7.
Eur Cytokine Netw ; 9(1): 33-9, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9613675

ABSTRACT

Hairy cell leukemia (HCL) is a well-recognized chronic lymphoproliferative disorder of B cell lineage, which may be regulated by growth factors including cytokines and cytokine antagonists. Previous studies have shown a good correlation between circulating soluble interleukin-2 receptor (sIL-2R) levels and disease activity and response to therapy was always associated with a decrease in sIL-2R levels. The interleukin-1 (IL-1) family of agonists and antagonists may also be involved in the regulation of hematopoietic malignancies. In the present study, we evaluated members of the IL-1 family (IL-1beta, IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptors Type I and Type II (IL-1sRI and IL-1sRII) in 23 patients with HCL. Patients were classified according to the clinical state of their disease. Most were treated with 2-chloro-2'-deoxyadercosine (2-CDA) and treatment was associated with a significant decrease in the serum levels of sIL-2R, IL-1beta and IL-1sRII in patients achieving a complete or partial response. In contrast to the above, levels of IL-1Ra increased during response to treatment and clinical response to 2-CDA was associated with an increase of 122% in IL-1Ra levels, in parallel with a decrease of 63% in IL-1beta and 47% in IL-1sRII levels. These results suggest that the balance between IL-1beta, IL-2 and their soluble receptors or antagonists may be involved in the pathogenesis and immunoregulation of HCL. Serum levels of these cytokines may therefore be used to monitor therapeutic efficacy of therapy in HCL and to detect any residual disease.


Subject(s)
Interleukin-1/blood , Leukemia, Hairy Cell/blood , 2-Chloroadenosine/analogs & derivatives , 2-Chloroadenosine/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Deoxyadenosines/therapeutic use , Humans , Interleukin 1 Receptor Antagonist Protein , Leukemia, Hairy Cell/drug therapy , Receptors, Interleukin-1/blood , Receptors, Interleukin-1/drug effects , Receptors, Interleukin-1 Type II , Severity of Illness Index , Sialoglycoproteins/blood , Sialoglycoproteins/drug effects
8.
Cancer ; 82(10): 1850-9, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9587116

ABSTRACT

BACKGROUND: Recently developed tissue polypeptide specific antigen (TPS) and CYFRA 21-1 assays determine the soluble cytokeratin 18 and 19 fragments, respectively, in serum. The authors compared the value of TPS, CYFRA 21-1, and carcinoembryonic antigen (CEA) for the diagnosis, staging, prognosis, and monitoring of patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The study included 85 patients with benign lung diseases and 94 patients with NSCLC. TPS, CYFRA 21-1, and CEA serum levels were measured with commercial kits. RESULTS: The following were demonstrated: 1) CYFRA 21-1 and TPS levels, but not CEA levels, differed significantly between NSCLC patients with operable disease (Stages I-IIIA) and those with inoperable disease (Stages IIIB-IV). 2) The correlation coefficient between CYFRA 21-1 and TPS increased with the progression of NSCLC from Stages I-IIIA (r = 0.41, P = 0.04) to Stages IIIB-IV (r = 0.70, P < 0.001). 3) Multivariate analysis identified TPS and CYFRA 21-1 as significant predictors of survival, with relative risks of 2.57 (P = 0.001) and 2.05 (P = 0.01), respectively. For cases in which both cytokeratin markers were positive, the relative risk was 6.4 (P < 0.0001) compared with cases in which both were negative. 4) For the group with inoperable disease, the combined use of TPS and CYFRA 21-1 allowed for the definition of 3 sets of patients with significantly different median survival times (14.3 months vs. 7.4 months vs. 2.6 months). 5) The percentages of marker evaluations concordant with results of clinical assessments of response to therapy were 75.0%, 72.2%, and 61.1% for CYFRA 21-1, TPS, and CEA, respectively. CONCLUSIONS: These findings suggest that, for NSCLC patients, CYFRA 21-1 and TPS are significant prognostic factors and effective monitors of therapy. The combined use of these cytokeratin markers may provide additional information for prognosis.


Subject(s)
Antigens, Neoplasm/analysis , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/immunology , Keratins/analysis , Lung Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Carcinoembryonic Antigen/analysis , Carcinoma, Non-Small-Cell Lung/pathology , Evaluation Studies as Topic , Female , Humans , Keratin-19 , Lung Neoplasms/pathology , Male , Middle Aged , Monitoring, Physiologic/methods , Neoplasm Staging , Peptides/analysis , Predictive Value of Tests , Prognosis , Prospective Studies
9.
Am J Med ; 104(1): 40-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9528718

ABSTRACT

BACKGROUND: Sepsis occurs following the presence of bacteria in the circulation and is associated with fever, hyperthermia, and hypotension. Hypophosphatemia develops in the early stages of sepsis. High levels of inflammatory cytokines also characterize early sepsis. AIM: The aim of the present study was to correlate hypophosphatemia with cytokines and cytokine receptor levels during early sepsis. We aimed to reestablish the results obtained from patients in an in vivo experimental model, in order to understand the mechanism of hypophosphatemia induction in early sepsis. METHODS: Ninety-nine patients were enrolled in this study and their clinical condition was classified as the presence of infection, sepsis, and bacterial growth in blood cultures. Phosphate levels and cytokine levels were recorded. In order to determine whether hypophosphatemia is correlated to the increased inflammatory cytokines, we injected normal mice with recombinant cytokines and studied their effect on phosphate levels. RESULTS: Our results revealed that 80% of the septic patients had hypophosphatemia associated with very high levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 and of soluble IL receptor (sIL)-2R and IL-6R, especially in those patients with positive blood cultures. Injection of IL-6, TNFalpha and IL-1beta in mice markedly decreased the phosphate serum levels. CONCLUSIONS: Significant associations were demonstrated between high levels of inflammatory cytokines and their receptors and between serum phosphate levels, especially in patients with positive blood culture. Our results point to a correlation between the high inflammatory cytokines levels and hypophosphatemia during early sepsis. Cytokine levels and hypophosphatemia may be included in sepsis evaluation and prognosis. Anticytokine strategies might, therefore, reverse hypophosphatemia and other parameters of sepsis.


Subject(s)
Cytokines/blood , Hypophosphatemia/immunology , Hypophosphatemia/microbiology , Infections/immunology , Receptors, Cytokine/blood , Sepsis/immunology , Humans , Incidence , Infections/complications , Interleukin-2/blood , Interleukin-6/blood , Interleukin-8/blood , Prevalence , Sepsis/complications , Tumor Necrosis Factor-alpha/metabolism
10.
Cytokine ; 10(12): 977-83, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10049522

ABSTRACT

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.


Subject(s)
Breast Neoplasms/immunology , Breast Neoplasms/therapy , Cytokines/biosynthesis , Interferon-beta/therapeutic use , Interferon-gamma/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Combined Modality Therapy , Female , Humans , Interferon-gamma/metabolism , Interleukin-1/metabolism , Megestrol Acetate/therapeutic use , Prognosis , Receptors, Estrogen/metabolism , Receptors, Interleukin-2/metabolism , Recombinant Proteins , Tamoxifen/therapeutic use
11.
Fertil Steril ; 67(2): 261-5, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9022600

ABSTRACT

OBJECTIVE: To assess the potential involvement of vascular endothelial growth factor in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). DESIGN: A controlled clinical study that followed the kinetics of vascular endothelial growth factor in the plasma of patients with severe OHSS from the time of admission to the hospital and until clinical resolution. SETTING: Women hospitalized with severe OHSS in a tertiary medical center. PATIENT(S): Seven patients with severe OHSS after ovulation induction for IVF and seven controls who had received a similar ovulation induction regimen and did not develop the OHSS. INTERVENTION(S): Three blood samples were obtained from each OHSS patient: upon hospitalization for severe OHSS, when significant clinical improvement was evident, and on the first follow-up visit after the patients' discharge. Ascitic fluid was obtained from all OHSS patients by therapeutic paracentesis during the active phase of the syndrome. Blood samples were drawn from the control patients 4 to 6 days after ET. All samples were assayed for vascular endothelial growth factor levels, hematocrit, E2 levels, and white blood cell count. MAIN OUTCOME MEASURE(S): Vascular endothelial growth factor levels were assayed by ELISA. Estradiol was determined by RIA. RESULT(S): Compared with the controls, high levels of vascular endothelial growth factor were detected in the plasma of all patients admitted for severe OHSS. Levels dropped significantly along with clinical improvement, reaching minimum values after complete resolution. A statistically significant correlation was found between plasma vascular endothelial growth factor levels and certain biologic characteristics of OHSS and of capillary leakage such as leukocytosis and increased hematocrit. Ascitic fluid obtained from the study patients also contained high vascular endothelial growth factor levels. CONCLUSION(S): These findings suggest the involvement of vascular endothelial growth factor in the pathogenesis of capillary leakage in the OHSS.


Subject(s)
Endothelial Growth Factors/blood , Lymphokines/blood , Ovarian Hyperstimulation Syndrome/blood , Ovarian Hyperstimulation Syndrome/physiopathology , Adult , Ascitic Fluid/metabolism , Capillary Permeability , Endothelial Growth Factors/metabolism , Female , Hematocrit , Humans , Kinetics , Leukocyte Count , Lymphokines/metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
12.
Hum Reprod ; 11(7): 1381-6, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8671471

ABSTRACT

The objective of this study was to follow the kinetics of four inflammatory cytokines in the plasma and ascitic fluid of seven patients who developed severe ovarian hyperstimulation syndrome (OHSS) after induction of ovulation for in-vitro fertilization. Blood samples were obtained from these patients at three different times: upon hospitalization; when significant clinical improvement was evident; and after complete resolution. Samples were analysed for interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). Ascitic fluid was obtained by therapeutic paracentesis from all study patients during the active phase and analysed for these cytokines. Two control groups were available: the first included 15 women undergoing controlled ovarian stimulation for in-vitro fertilization without developing OHSS, while the second consisted of 25 healthy women not undergoing ovulation induction or any other medical treatment. High concentrations of IL-1, IL-6 and TNF-alpha were detected in all individuals upon admission for severe OHSS. Concentrations dropped significantly along with clinical improvement, reaching normal values after complete resolution. A statistically significant correlation was found between plasma cytokine concentrations and certain biological characteristics of the syndrome such as leukocytosis, increased haematocrit, and elevated plasma 17-beta-oestradiol concentrations. Ascitic fluid obtained from the study patients contained high IL-6 and IL-8 concentrations, while other cytokines were unaltered. These results suggest close association between inflammatory cytokines and the pathophysiology of the ovarian hyperstimulation syndrome.


Subject(s)
Cytokines/blood , Inflammation Mediators/blood , Ovarian Hyperstimulation Syndrome/blood , Ovarian Hyperstimulation Syndrome/immunology , Adult , Ascitic Fluid/immunology , Case-Control Studies , Female , Fertilization in Vitro , Humans , Interleukin-1/blood , Interleukin-1/metabolism , Interleukin-6/blood , Interleukin-6/metabolism , Interleukin-8/blood , Interleukin-8/metabolism , Kinetics , Ovarian Hyperstimulation Syndrome/etiology , Ovulation Induction/adverse effects , Pleural Effusion/immunology , Tumor Necrosis Factor-alpha/metabolism
13.
Transplantation ; 60(9): 943-8, 1995 Nov 15.
Article in English | MEDLINE | ID: mdl-7491698

ABSTRACT

Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR). Seven of the patients underwent BMT from siblings (6 matched and 1 mismatched), 4 patients received bone marrow from other family members (3 mismatched and 1 matched), and 1 patient underwent HLA-matched unrelated BMT. Nine of 12 had a sex-mismatched BMT and 5/12 had an ABO-mismatched BMT. Nine of 12 underwent T cell-depleted (Campath anti-CDw52 moAb) BMT. Rejection was defined as marrow hypoplasia with a peripheral white blood cell count < 0.5 x 10(9)/L 21 days after BMT, in conjunction with the absence of donor cells by polymerase chain reaction analysis using a sex-mismatched probe and/or a tumor-specific probe (BCR/ABL). Twenty-five patients who underwent uneventful BMT with no GR served as controls. The levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) were evaluated by a high sensitive RIA or an enzyme immunoassay. The levels of TNF and IL-6 were found to be higher in 10/12 and 7/7 evaluated GR patients, respectively, as compared with controls (P < 0.05). The level of IL-1 was high only in 2/12 patients. TNF elevation occurred in all patients immediately after GR. TNF and IL-6 levels were significantly higher for patients with early rejection (< 35 days after BMT) as compared with patients with late rejection (> 35 days after BMT) (P < 0.049 and P < 0.006, respectively). Eight patients engrafted after the second transplant (2 only transient). All 6 patients with stable engraftment are alive (4 with basic disease), while the 4 patients who did not engraft and the 2 patients with only transient engraftment died. In the 6 patients with no engraftment or only transient engraftment, the elevated TNF levels remained high; in the 6 patients who had stable engraftment after retransplant, TNF levels, but not IL-6 levels, decreased. In conclusion, a majority of the patients with GR displayed high levels of inflammatory cytokines (TNF and IL-6). Dysregulation of inflammatory cytokines may be involved in the pathogenesis of GR.


Subject(s)
Bone Marrow Transplantation/immunology , Cytokines/blood , Graft Rejection/immunology , ABO Blood-Group System , Adolescent , Adult , Blood Group Incompatibility , Child , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/therapy , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Histocompatibility Testing , Humans , Interleukin-1/blood , Interleukin-3/therapeutic use , Interleukin-6/blood , Lymphocyte Depletion , Male , Middle Aged , Reference Values , T-Lymphocytes , Time Factors , Tissue Donors , Tumor Necrosis Factor-alpha/analysis , Whole-Body Irradiation
14.
Leuk Lymphoma ; 17(1-2): 169-73, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7773155

ABSTRACT

Cytokines play a key role in the pathogenesis of chronic Graft versus Host Disease (cGVHD) and various studies have shown abberant production of cytokines by immune cells from GVHD patients. Based on these findings and others showing that high TNF levels precede the development of GVHD, we evaluated inflammatory cytokine levels following BMT and during the development of cGVHD. In this study, patients undergoing bone marrow transplantation (BMT) who consequently developed chronic GVHD were analyzed as to their cytokine production during cGVHD and this was correlated with their clinical manifestations. A positive correlation was found between the severity as well as the number of major clinical complications and high levels of inflammatory cytokines (IL-1 beta IL-6 and TNF alpha) compared to control patients or to normal donors. Patients undergoing BMT who did not develop GVHD, did not produce high levels of IL-1 beta IL-6 or TNF. High levels of cytokines may be used as a tool for assessing novel therapeutic modalities and response to GVHD treatment.


Subject(s)
Cytokines/biosynthesis , Graft vs Host Disease/metabolism , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Child , Child, Preschool , Chronic Disease , Cytokines/blood , Female , Graft vs Host Disease/blood , Graft vs Host Disease/etiology , Humans , Interleukin-1/blood , Male , Reference Values
15.
Article in English | MEDLINE | ID: mdl-8562579

ABSTRACT

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.


Subject(s)
Interleukin-1/blood , Interleukin-1/cerebrospinal fluid , Receptors, Interleukin-2/metabolism , Schizophrenia/blood , Schizophrenia/cerebrospinal fluid , Adult , Antipsychotic Agents/therapeutic use , Female , Humans , Interleukin-2/blood , Interleukin-2/cerebrospinal fluid , Interleukin-6/blood , Interleukin-6/cerebrospinal fluid , Lithium/therapeutic use , Male , Middle Aged , Psychiatric Status Rating Scales , Schizophrenia/drug therapy , Tumor Necrosis Factor-alpha/cerebrospinal fluid
16.
Tsitologiia ; 36(2): 182-8, 1994.
Article in Russian | MEDLINE | ID: mdl-7809967

ABSTRACT

By sequential selection for a resistance to a short-term heating at 45 degrees C, two independent clones, CHSR5 and CHSR6, have been isolated from ovarian cells of the Chinese hamster (CHO-K1). A subline CHO-A40, capable of proliferation at 40 degrees C, has been obtained as mass culture by culturing CHO-K1 cells for 2 months at 40 degrees C. The lines obtained have no cross-resistance to the temperature used in their selection: the CHSR5 and CHSR6 cells are not capable of reproduction at 40 degrees C, while the CHO cells do not survive over a 60 min heating at 45 degrees C. This bears evidence that mechanisms, underlying the cell resistance under different thermal regimens used, may be different. The heat resistant sublines maintain their heat resistance for 6 months of cultivation at 37 degrees C. The acquisition of heat resistance by cells correlates with their high primary resistance, and with their resistance to colchicine and actinomycin D.


Subject(s)
Hot Temperature , Animals , CHO Cells , Cell Separation , Clone Cells , Colchicine/pharmacology , Cricetinae , Cricetulus , Dactinomycin/pharmacology , Drug Resistance , Female , Phenotype , Time Factors
17.
Leuk Lymphoma ; 14 Suppl 1: 33-9, 1994.
Article in English | MEDLINE | ID: mdl-7820051

ABSTRACT

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder of the B cell lineage. In the search for specific markers with prognostic significance we evaluated the clinical value of IL-1 beta and sIL-2R levels in HCL patients. HCL patients (25) were classified according to their clinical status as "active", "non active" disease or partial or complete remission and response treatment. We found a good correlation between IL-1 beta or IL-2R levels and disease activity: improved clinical status or response to different therapies were associated with decreasing IL-1 beta or sIL-2R levels. In contrast, lack of response to therapy or disease progression was reflected in increases in both IL-1 beta and sIL-2R levels. In some patients increases of both cytokines preceded clinical symptoms. In conclusion our results show that IL-1 beta and s-IL-2R levels may be used as reliable markers for monitoring HCL activity, assessing response to treatment and predicting early progression of disease.


Subject(s)
Biomarkers, Tumor/blood , Interleukin-1/blood , Leukemia, Hairy Cell/blood , Leukemia, Hairy Cell/pathology , Receptors, Interleukin-2/metabolism , Disease Progression , Humans , Solubility
18.
Tsitologiia ; 33(12): 54-8, 1991.
Article in Russian | MEDLINE | ID: mdl-1841458

ABSTRACT

The ability of the mouse neuroblastoma cell line NTR to proliferate at 40 degrees C correlates with the position of the temperature optimum of protein kinases A and C activities in the region of higher temperatures compared to those for cells of the original line N18AI, and with higher thermostability of protein kinase A after its heating at various elevated temperatures. The found changes in protein kinases A and C in the cells of NTR line mean that the selection of variants, capable of growing at elevated temperatures, is accompanied with conformational protein changes.


Subject(s)
Genetic Variation/physiology , Hot Temperature , Neuroblastoma/enzymology , Protein Kinase C/metabolism , Protein Kinases/metabolism , Temperature , Animals , Cell Line , Enzyme Stability , Mice , Neuroblastoma/genetics , Tumor Cells, Cultured/enzymology
19.
Vestn Khir Im I I Grek ; 144(6): 99-105, 1990 Jun.
Article in Russian | MEDLINE | ID: mdl-2175519

ABSTRACT

Under study was the dynamics of functional properties of leukocytes of healthy people and patients after UV-irradiation of their blood, mixing the UV-irradiated and non-irradiated blood. It was shown that UV-irradiation and mixing the irradiated and non-irradiated blood facilitated the liberation of bactericidal cation proteins of leukocytes, higher expression of membrane receptors, growth factors, activation of reparation of DNA after its injury by gamma-rays. It proves the role of immediate activation of leukocytes of the circulating blood in trigger mechanisms of effects of autotransfusion of UV-irradiated blood.


Subject(s)
Blood Transfusion, Autologous , Blood/radiation effects , Leukocytes/radiation effects , Ultraviolet Rays , Cell Membrane/radiation effects , Cell Membrane/ultrastructure , DNA/radiation effects , DNA/ultrastructure , Humans , In Vitro Techniques , Leukocytes/immunology , Leukocytes/ultrastructure , Phagocytosis/radiation effects
20.
Mol Gen Mikrobiol Virusol ; (5): 20-4, 1990 May.
Article in Russian | MEDLINE | ID: mdl-2199826

ABSTRACT

The recombinant plasmid DNA YEp secl-v-sis was constructed. This plasmid was able to code for the synthesis and secretion into the cultural medium of the protein-product of oncogene v-sis. Transcription, copy number and stability of the plasmid DNA were studied under the conditions of galactose induction. The v-sis protein was determined by gel electrophoresis and immunoblotting methods and assayed for cell-proliferation activity in the mammalian cell culture.


Subject(s)
Oncogenes , Retroviridae Proteins, Oncogenic/biosynthesis , Saccharomyces cerevisiae/genetics , Transforming Growth Factors/biosynthesis , Amino Acid Sequence , Base Sequence , Cloning, Molecular , Molecular Sequence Data , Nucleic Acid Hybridization , Oncogene Proteins v-sis , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Restriction Mapping , Retroviridae Proteins, Oncogenic/genetics , Retroviridae Proteins, Oncogenic/metabolism , Transforming Growth Factors/genetics , Transforming Growth Factors/metabolism
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