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1.
A. Cassone P. Marconi F. Bistoni E. Mattia G. Sbaraglia E. Garaci E. Bonmassar 《Cancer immunology, immunotherapy : CII》1981,10(4):181-190
Summary Chemical, ultrastructural, and immunoadjuvant properties of Candida albicans (CA) and of a number of its fractions have been characterized through the analysis of the antitumor activity of soluble and insoluble cell wall components.CD2F1 mice were inoculated IP with Moloney virus-induced lymphoma LSTRA and treated with bis-1-chloroethyl-nitrosurea (BCNU) on day +5 after tumor challenge. A significant increase of the antitumor efficacy of BCNU treatment was found in mice inoculated with CA as immunoadjuvant on days –14 and +1 (–14/+1 schedule) with respect to tumor challenge.However, no significant difference in survival time was found between mice treated with BCNU alone and those treated with BCNU plus either soluble mannan or glucan-protein fractions extracted from CA and administered according to –14/+1 or –7/+1 schedules. On the other hand, mice treated with BCNU plus the insoluble glucan fraction (wall ghosts) given on days –14/+1 or even on day –7 only (i.e., without boosting after tumor challenge) survived longer than animals treated with BCNU alone.The immunoadjuvant effect of CA and of other classic immunoadjuvants, such as BCG and Corynebacterium parvum, was completely abolished by total-body irradiation (400 R) given 5 h before the first administration of the agent on day –7 prior to tumor challenge.These results indicate that: (a) the minimal structure required for the expression of the immunoadjuvant effect of CA is the insoluble, -glucan component of the cell wall; (b) the soluble components of CA cell wall (i.e., mannan and glucan-protein) per se do not show any detectable immunoadjuvant effect in the present animal-tumor system; they may, however, modulate this effect, as shown by the fact that whole CA, but not the insoluble -glucan, needs a boosting injection for the expression of its immunoadjuvant properties; (c) the immunoadjuvanticity of CA is radiosensitive. 相似文献
2.
W. Den Otter J. W. De Groot H. F. J. Dullens 《Cancer immunology, immunotherapy : CII》1999,16(2):72-76
Summary DBA/2 mice were immunized against the syngeneic SL2 lymphoma by two or five injections with irradiated lymphoma cells given IP or SC, respectively. The antitumor efficacy induced in immunized mice was tested by (a) IP injection of the immunized mice with nonirradiated tumor cells and (b) transfer of the total immune peritoneal exudate, the cellular fraction only, or the cell-free fraction only, IP into tumor-bearing recipients, or (c) tumor neutralization tests (Winn assay). It was shown that immunized mice were able to reject 5×107 SL2 tumor cells (8 of 14 mice survived >100 days), while in most transfer experiments 2×105 SL2 cells could be eradicated. In the tumor neutralization experiments a number of 106 SL2 cells were eradicated. When the immune exudates were given before the inoculations of SL2 tumor cells the number of survivors increased significantly. Further, it was shown that the cellular fraction is the major contributor to the antitumor effect in the transfer experiments, since there was no significant difference in tumor eradication after injection of a complete immune exudate and after injection of the isolated cellular fraction. Injection of the noncellular fraction had no measurable antitumor effect. An increase in the number of injections with total peritoneal exudates from immunized mice did not result in an increase in tumor eradication in the tumor-bearing recipients.Extra stimulation (IP) of immunized mice with 104 nonirradiated cells 6 days after the last immunization resulted in an increase of the antitumor efficacy of these peritoneal exudates of these mice when collected 4–24 h after this stimulation. Extra stimulation with 106 irradiated cells had no measurable effect. 相似文献
3.
Richard L. Wahl Barry S. Wilson Monica Liebert William H. Beierwaltes 《Cancer immunology, immunotherapy : CII》1987,24(3):221-224
Summary Nonspecific uptake of radiolabeled monoclonal antibodies in normal tissues is a significant problem for tumor imaging. A potential means of decreasing nonspecific antibody binding is to blockade nonspecific antibody binding sites by predosing with cold, nonspecific isotypematched antibody, before injecting specific antibody. Nontumor-specific murine monoclonal antibody LK2H10 (IgG1) or Ab-1 (IgG2a) was given i.v. at doses of 0 to 3.5 mg to nude mice with xenografts of human melanoma. These mice were then given i.v. 4 g of 131I anti-high molecular weight antigen of melanoma (HMWMAA) monoclonal antibody 763.24T (IgG1) or 225.28S (IgG2a), respectively. These mice were also given a tracer dose of 125I LK2H10 or Ab-1, respectively. Specific tumor uptake of anti-HMWMAA antibodies was see in all cases. No drop in tumor or nontumor uptake was demonstrated for either of the tumor-specific or nonspecific monoclonal antibodies due to nonspecific monoclonal antibody pretreatment. These data suggest that high doses of isotype-matched unlabeled nonspecific monoclonal antibody given before 131I tumor-specific monoclonal antibody, will not enhance tumor imaging.
Present address: Hybritech, San Diego, CA, USA 相似文献
4.
Edward D. Ball Kim E. Nichols Olive S. Pettengill George D. Sorenson Michael W. Fanger 《Cancer immunology, immunotherapy : CII》1986,22(3):211-216
Summary Interferon has been shown to enhance the ability of nonspecific cytotoxic mononuclear cells to lyse some, but not all, tumor cells. We have examined the effect of recombinant human gamma interferon (rIFN) on the cell-mediated cytolysis of tumor target cells derived from continuously cultured lines of small cell carcinoma of the lung (SCCL). Cells from the SCCL lines DMS 44, 53, 79, 92, and 406 were labeled with 51Cr and incubated with normal and rIFN-stimulated peripheral blood mononuclear cells for 18 h at 37 °C and tumor cell lysis estimated by measuring 51Cr release. Although cells from certain SCCL lines were good targets for cell mediated cytotoxicity, susceptibility to lysis was heterogenous among the different SCCL lines. DMS 406 and 79 were, on average, maximally lysed, while DMS 44, 53, and 92 showed less susceptibility to lysis by either control or rIFN-stimulated effector cells. In addition, although pretreatment with rIFN increased the cytolytic capacity of normal peripheral blood mononuclear cells from several different donors, preincubation of the tumor cell lines with rIFN resulted in inhibition of cytolysis mediated by both control and IFN-activated effector cells. These findings suggest that although rIFN may enhance cell-mediated lysis of SCCL tumor cells, it may also decrease susceptibility to lysis.This work was supported by Grants CA 37868, CA 31888, CA31918, CA33852, and AI 19053 awarded by the National Cancer Institute and Institute of Allergy and Infectious Diseases, DHHS. Statistical assistance was provided by Therese Stukel, biostatistician at the Norris Cotton Cancer Center, Hanover, H. H. and supported by Grant CA 23108 from the National Cancer Institute 相似文献
5.
Koji Adachi Paul Belser Hans Bender Derui Li Ulrich Rodeck Etty N. Benveniste David Woo Wolff H. Schmiegel Dorothee Herlyn 《Cancer immunology, immunotherapy : CII》1992,34(6):370-376
Summary Recombinant tumor necrosis factor (rTNF; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF- was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNF may be protein-synthesis-dependent. The dose of rTNF that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells.125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNF, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNF effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials,125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with125I-labeled mAb 425 and rTNF. 相似文献
6.
Osamu Kaneko Lucy Gong Jingli Zhang Johanna K. Hansen Raffit Hassan Byungkook Lee Mitchell Ho 《The Journal of biological chemistry》2009,284(6):3739-3749
Ovarian cancer and malignant mesothelioma frequently express both
mesothelin and CA125 (also known as MUC16) at high levels on the cell surface.
The interaction between mesothelin and CA125 may facilitate the implantation
and peritoneal spread of tumors by cell adhesion, whereas the detailed nature
of this interaction is still unknown. Here, we used truncated mutagenesis and
alanine replacement techniques to identify a binding site on mesothelin for
CA125. We examined the molecular interaction by Western blot overlay assays
and further quantitatively analyzed by enzyme-linked immunosorbent assay. We
also evaluated the binding on cancer cells by flow cytometry. We identified
the region (296–359) consisting of 64 amino acids at the N-terminal of
cell surface mesothelin as the minimum fragment for complete binding activity
to CA125. We found that substitution of tyrosine 318 with an alanine abolished
CA125 binding. Replacement of tryptophan 321 and glutamic acid 324 with
alanine could partially decrease binding to CA125, whereas mutation of
histidine 354 had no effect. These results indicate that a
conformation-sensitive structure of the region (296–359) is required and
sufficient for the binding of mesothelin to CA125. In addition, we have shown
that a single chain monoclonal antibody (SS1) recognizes this CA125-binding
domain and blocks the mesothelin-CA125 interaction on cancer cells. The
identified CA125-binding domain significantly inhibits cancer cell adhesion
and merits evaluation as a new therapeutic agent for preventing or treating
peritoneal malignant tumors.Ovarian cancer largely is confined to the peritoneal cavity for much of its
natural history (1). Peritoneal
mesothelioma is a highly invasive tumor originating from the mesothelial
linings of the peritoneum (2).
The development of effective drug regimens against ovarian cancer and
mesothelioma has proven extremely difficult.Mesothelin was first identified in 1992 by the monoclonal antibody
(mAb)2 K1 that was
generated by the immunization of mice with human ovarian carcinoma (OVCAR-3)
cells (3). The mesothelin gene
encodes a 71-kDa precursor protein that is processed to a 40-kDa protein
termed mesothelin, which is a glycosylphosphatidylinositol (GPI)-anchored
glycoprotein present on the cell surface
(4). Mesothelin is a
differentiation antigen that is present on a restricted set of normal adult
tissues such as the mesothelium. In contrast, it is overexpressed in a variety
of cancers including mesothelioma, ovarian cancer, and pancreatic cancer
(5). In addition, mesothelin is
also expressed on the surface of non-small cell lung cancer cells
(6,
7), especially most lung
adenocarcinomas (8).We and others have shown that mesothelin is shed from tumor cells
(9,
10), and antibodies specific
for mesothelin are elevated in the sera of patients with mesothelioma and
ovarian cancer (11). Shed
serum mesothelin has been approved by the United States Food and Drug
Administration (FDA) as a new diagnostic biomarker in mesothelioma. In a Phase
I clinical study of an intrapleural interferon-β gene transfer using an
adenoviral vector in patients with mesotheliomas, we found that antitumor
immune responses targeting mesothelin were elicited in several patients
(12). A recent study indicated
that anti-mesothelin antibodies and circulating mesothelin relate to the
clinical state in ovarian cancer patients
(13). Pastan and colleagues
(14) developed an immunotoxin
(SS1P) with a Fv for mesothelin. Two Phase I clinical trials were completed at
the National Cancer Institute (National Institutes of Health, Bethesda, MD)
and there was sufficient antitumor activity of SS1P to justify a Phase II
trial. A chimeric antibody containing the mouse SS1 Fv for mesothelin was also
developed and is currently examined in a Phase I clinical trial for ovarian
cancer, mesothelioma, pancreatic cancer, and non-small cell lung cancer
(15).Mucins are heavily glycosylated proteins found in the mucus layer or at the
cell surface of many epitheliums
(16). There are two
structurally distinct families of mucins, secreted and membrane-bound forms.
CA125 (also known as MUC16) was first identified in 1981 by OC125, a mAb that
had been developed from mice immunized with human ovarian cancer cells
(17). The first cDNA clones
were reported in 2001 (18,
19). CA125 is a very large
membrane-bound cell surface mucin, with an average molecular mass between 2.5
and 5 million daltons. It is also heavily glycosylated with both
O-linked and N-linked oligosaccharides
(20). The peptide backbone of
CA125 is composed of the N-terminal region, extensive Ser/Thr/Pro-rich tandem
repeats (TR) with 156 amino acids each with both N- and
O-glycosylations, a SEA domain with high levels of
O-glycosylation and a C-terminal region with a short cytoplasmic tail
(19). The SEA domain was first
identified as a module commonly found in sea urchin sperm protein,
enterokinase and agrin (21,
22). The significance of the
SEA domain in CA125 is not clear.CA125 was originally used as a biomarker in ovarian cancer due to its high
expression in ovarian carcinomas and that it is shed into the serum
(23). A majority (88%) of
mesotheliomas are also CA125 positive on the cell membrane
(24). It was shown that 25% of
peritoneal mesotheliomas have high CA125 expression
(25). The intensity of CA125
membranous expression is indistinguishable between ovarian carcinomas and
peritoneal mesotheliomas. Gene expression analysis using the SAGE tag data
base has shown that mesothelioma has the second highest co-expression of CA125
and mesothelin after ovarian cancer
(26). Rump and colleagues
(26) have shown that
mesothelin binds to CA125 and that this interaction may mediate cell adhesion.
Scholler et al. (27)
recently showed that CA125/mesothelin-dependent cell attachment could be
blocked with anti-CA125 antibodies. Because mesothelin is present on
peritoneal mesothelium, there may be an important role for the
mesothelin-CA125 interaction in the tumorigenesis of ovarian cancer and
mesothelioma in the peritoneal cavity. The mesothelin binding site on CA125
may lie within the 156-amino acid TR units, indicating multimeric binding of
mesothelin to CA125. It has been found that the extraordinarily abundant
N-glycans on CA125, presumably in the TR region, are required for
binding to both glycosylated and non-glycosylated mesothelin
(28).Here, we identified the binding site of CA125 on mesothelin by use of
truncated mutagenesis and alanine replacement approaches. We measured binding
qualitatively by Western blot overlay assays and quantitatively by
enzyme-linked immunosorbent assay (ELISA). We also evaluated the interaction
of CA125 and mesothelin on cancer cells by flow cytometry. Furthermore, we
have shown that a single chain mAb (SS1) recognized the CA125-binding domain
and blocked the mesothelin-CA125 interaction on cancer cells. The identified
CA125-binding domain-Fc fusion protein also significantly inhibited cancer
cell adhesion. Our results suggest that conformation-sensitive structures of
the region (296–359) are required and sufficient for specific binding of
mesothelin to CA125. The domain proteins or the antibodies that block the
mesothelin-CA125 interaction merit evaluation as new therapeutic agents in
treating peritoneal malignant tumors. 相似文献
7.
Siegfried Matzku 《Cancer immunology, immunotherapy : CII》1984,17(2):106-111
Summary The survival of cloned variants of the BSp73 tumor differing in susceptibility to natural killer (NK) and macrophage-mediated cytotoxicity in vitro was evaluated in syngeneic animals. The cytocidal effect was assayed by whole-body determination of (125I)5-iodo-2-deoxyuridine (125IUdR) retention in intact animals and in animals depleted of phagocytes and/or radiation-sensitive lymphocytes. The following results were obtained: (1) In the peritoneal cavity, survival of the susceptible tumor cells (variant AS) was significantly higher in rats pretreated with radiation and silica than in untreated rats. (2) Cold target competition, response modification by C. parvum, and correlation of label excretion with survival of animals supported the notion that excretion rates of radioactivity were in fact determined by natural cytotoxicity in vivo. (3) Tumor cells resistant to natural cytotoxicity in vitro (variant ASML) were nevertheless killed in vivo (IP) by NK cells and macrophages. (4) Additional elements of tumor cell destruction were active upon IV injection of both AS- and ASML-derived cells, since rapid label excretion was observed irrespective of irradiation and silica treatment or addition of excess unlabeled competitor cells.The apparent increase in susceptibility of ASML cells in vivo might be due to a shift in phenotype induced by microenvironmental factors. No evidence was gained that differences in metastatic capacity exhibited by the variants might relate to differential action of natural cytotoxicity on these cells. 相似文献
8.
Y Guo DN Tukaye WJ Wu X Zhu M Book W Tan SP Jones G Rokosh S Narumiya Q Li R Bolli 《PloS one》2012,7(7):e41178
Background
Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear.Objective
To determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion.Methods
COX-2 knockout (KO) mice (COX-2−/−), prostacyclin receptor KO (IP−/−) mice, and respective wildtype (WT, COX-2+/+ and IP+/+) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30-min O/24 h R.Results
There were no significant differences in infarct size (IS) between non-preconditioned (non-PC) COX-2+/+, COX-2−/−, IP+/+, and IP−/− mice, indicating that neither COX-2 nor IP modulates IS in the absence of PC. When COX-2−/− or IP−/− mice were preconditioned, IS was not reduced, indicating that the protection of late PC was completely abrogated by deletion of either the COX-2 or the IP gene. Administration of the IP selective antagonist, RO3244794 to C57BL6/J (B6) mice 30 min prior to the 30-min O had no effect on IS. When B6 mice were preconditioned 24 h prior to the 30-min O, IS was markedly reduced; however, the protection of late PC was completely abrogated by pretreatment of RO3244794.Conclusions
This is the first study to demonstrate that targeted disruption of the COX-2 gene completely abrogates the infarct-sparing effect of late PC, and that the IP, downstream of the COX-2/prostanoid pathway, is a key mediator of the late PC. These results provide unequivocal molecular genetic evidence for an essential role of the COX-2/PGI2 receptor axis in the cardioprotection afforded by the late PC. 相似文献9.
Tsuji N Nishikori S Iwabe O Matsumoto S Shiraki K Miyasaka H Takagi M Miyamoto K Hirata K 《Planta》2005,222(1):181-191
Genes encoding phytochelatin (PC) synthase have been found in higher plants, fission yeast and worm. Recently, kinetic and mutagenic analyses of recombinant PC synthase have been revealing the molecular mechanisms underlying PC synthesis, however, a conclusive model has not been established. To clarify the mechanism of PC synthase found in eukaryotes, we have compared the two-step reactions catalyzed by the prokaryotic Nostoc PC synthase (NsPCS) and the eukaryotic Arabidopsis PC synthase (AtPCS1). Comparative analysis shows that in the first step of PC synthesis corresponding to the cleavage of -glutamylcysteine (-EC) from glutathione (GSH), free GSH or PCs acts as a donor molecule to supply a -EC unit for elongation of the PC chain, and heavy metal ions are required to carry out the cleavage. Furthermore, functional analyses of various mutants of NsPCS and AtPCS1, selected by comparing the sequences of NsPCS and AtPCS1, indicate that the N-terminal region (residues 1–221) in AtPCS1 is the catalytic domain, and in this region, the Cys56 residue is associated with the PC synthesis reaction. These results enable us to propose an advanced model of PC synthesis, describing substrate specificity, heavy metal requirement, and the active site in the enzyme. 相似文献
10.
Hisataka Kobavashi Harumi Sakahara Tsuneo Saga Makoto Hosono Makoto Shirato Hidetoshi Kanda Kaichiro Ishibashi Takeshi Watanabe Keigo Endo Isamu Ishiwata Junji Konishi 《Cancer immunology, immunotherapy : CII》1993,37(3):143-149
Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA 125, but the epitope it recognizes is different from that of monoclonal antibody OC125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (l) and light-chain () constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with125I,111In or99mTc demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the125I-labeled or99mTc-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with131I,111In or99mTc is promising for the radioimmunoimaging of ovarian cancer. 相似文献
11.
Background
Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients'' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.Methods and Findings
Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm3 and 3,610.14 mm3 for CA125 and between 0.21 mm3 and 131.51 mm3 for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm3 and 1.52 × 106 mm3 for CA125 and between 27 mm3 and 3.45 × 105 mm3 for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.Conclusions
This study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable tumor sizes for novel proteomic biomarker assays if sufficient physiologic data for the biomarker are available. The model may address the potential and limitations of tumor biomarkers, help prioritize biomarkers, and guide investments into early cancer detection research efforts. 相似文献12.
Kristin L. M. Boylan Kate Geschwind Joseph S. Koopmeiners Melissa A. Geller Timothy K. Starr Amy P. N. Skubitz 《Clinical proteomics》2017,14(1):34
Background
Currently, there are no FDA approved screening tools for detecting early stage ovarian cancer in the general population. Development of a biomarker-based assay for early detection would significantly improve the survival of ovarian cancer patients.Methods
We used a multiplex approach to identify protein biomarkers for detecting early stage ovarian cancer. This new technology (Proseek® Multiplex Oncology Plates) can simultaneously measure the expression of 92 proteins in serum based on a proximity extension assay. We analyzed serum samples from 81 women representing healthy, benign pathology, early, and advanced stage serous ovarian cancer patients.Results
Principle component analysis and unsupervised hierarchical clustering separated patients into cancer versus non-cancer subgroups. Data from the Proseek® plate for CA125 levels exhibited a strong correlation with current clinical assays for CA125 (correlation coefficient of 0.89, 95% CI 0.83, 0.93). CA125 and HE4 were present at very low levels in healthy controls and benign cases, while higher levels were found in early stage cases, with highest levels found in the advanced stage cases. Overall, significant trends were observed for 38 of the 92 proteins (p < 0.001), many of which are novel candidate serum biomarkers for ovarian cancer. The area under the ROC curve (AUC) for CA125 was 0.98 and the AUC for HE4 was 0.85 when comparing early stage ovarian cancer versus healthy controls. In total, 23 proteins had an estimated AUC of 0.7 or greater. Using a naïve Bayes classifier that combined 12 proteins, we improved the sensitivity corresponding to 95% specificity from 93 to 95% when compared to CA125 alone. Although small, a 2% increase would have a significant effect on the number of women correctly identified when screening a large population.Conclusions
These data demonstrate that the Proseek® technology can replicate the results established by conventional clinical assays for known biomarkers, identify new candidate biomarkers, and improve the sensitivity and specificity of CA125 alone. Additional studies using a larger cohort of patients will allow for validation of these biomarkers and lead to the development of a screening tool for detecting early stage ovarian cancer in the general population.13.
G. Mark Kollmorgen Don C. Cox Jerald J. Killion John L. Cantrell William A. Sansing 《Cancer immunology, immunotherapy : CII》1976,1(4):239-244
Summary EL4 lymphoma was grown as an ascitic tumor in the peritoneal cavity of C57Bl/6 mice. Animals with different tumor burdens (either 107 or 109 cells) were treated with a single intraperitoneal injection of BCNU using doses from 20–40 mg/kg. Response as measured by mean survival time and percent survival was dependent on tumor burden and dose of drug. The objective of chemotherapy was to increase the mean survival time, but not the percent survival, in order to evaluate the therapeutic effect of reovirus. Mice were given 108, 109, or 1010 Pfu of reovirus at various times with respect to chemotherapy. The number of mice cured after treatment with both BCNU and reovirus was significantly greater compared to mice treated with BCNU only. Mice cured with combination therapy developed tumor-specific immunity as measured by cytotoxic lymphocytes and serum, and resistance to a lethal tumor challenge.
The Abbreviations used are: BCNU: 1,3-bis-(2-chloroethyl)-1-nitrosourea; Saline: 0.9% NaCl solution; MEM: minimal essential medium; Pfu: plaque-forming units; FCS: fetal calf serum; BME: basal eagle's medium; SSC: sodium citrate-sodium chloride 相似文献
14.
Production of tumor necrosis factor α and interferon γ in interleukin-2-treated melanoma patients: Correlation with clinical toxicity 总被引:1,自引:0,他引:1
James S. Economou Mary Hoban Jeffrey D. Lee Richard Essner Stephen Swisher William McBride Dave B. Hoon Donald L. Morton 《Cancer immunology, immunotherapy : CII》1991,34(1):49-52
Summary Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose-limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor (TNF) and interferon (IFN). We measured the serum levels of TNF and IFN in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 × 106 IU or 12 × 106 IU Cetus IL-2/m2 by i. v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNF and IFN levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFN levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNF production, however, were not predictable and did not correlate with either IFN or toxicity. Some patients had modest increases in TNF production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNF in IL-2 cancer patients, which do not correlate well with toxicity.This work was supported by NIH Grants CA 50 780 (J. E.) and CA 29 605, CA 12 582 (D. L. M.) and the U. C. Tobacco-Related Disease Research Program RT-62 (J. E.). J. E. is the recipient of an NCI Clinical Investigator Award (KO8-01360) and is a Dorothy and Leonard Straus Scholar at UCLA 相似文献
15.
M. C. Fioretti A. Circolo R. Bianchi P. Merletti-Rivosecchi E. Bonmassar 《Cancer immunology, immunotherapy : CII》1980,9(3):145-152
Summary The present study was undertaken to explore the possible interaction between tumor immunity and antineoplastic agents at the brain level in murine lymphoma models. Host immunity against intracerebral lymphoma graft was directed against tumor-associated histocompatibility antigens, using an appropriate design of genetic distance between host and tumor. It was revealed that primary graft response against lymphoma cells can be demonstrated in the central nervous system. Immunochemotherapy synergism can occur at the mouse brain level, when allogeneic lymphomas are inoculated intracerebrally and the recipient hosts are treated with antineoplastic agents capable of crossing the blood-brain-barrier.Supported by C.N.R. Italia-USA Contract: n. 79.02381.65
Abbreviations used: ADM = Adriamycin BBB = Blood-brain-barrier BCNU = 1,3-bis-(2 chloroethyl)-1-nitrosourea Cy = Cyclophosphamide CNS = Central nervous system D/T = Dead mice over total animals tested DTIC = 5(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide HTHI = Host tumor histoincompatibility IC = Intracerebrally MMHL = Multiple minor histocompatible loci MST = Median survival time in days NS = Not significant NT = Not tested TAHA = Tumor-associated histocompatibility antigens TATA = Tumor-associated transplantation antigens 相似文献
16.
We have previously reported that four tRNAs of Drosophila melanogaster randomly labeled with iodine-125 hybridize in part to the 56EF region of polytene chromosomes where 5S RNA genes occur. In the presence of a 100-fold excess of unlabeled 5S RNA no hybridization of randomly labeled 125I-tRNAAsp
2 occurred at 56EF although hybridization elsewhere was not affected. In addition, tRNAAsp
2 labeled by introducing 125I-5-iodocytidylyl residues into the 3-CCA end with tRNA nucleotidyl transferase did not hybridize to 56EF but did hybridize to its other sites. The hybridization of tRNALys
2, tRNAGly
3 and tRNAMet
3 at 56EF was not eliminated by a 25 to 100-fold excess of unlabeled 5S RNA. When these tRNAs were labeled at the -CCA terminus they hybridized to 56EF as well as to their other sites with the exception that terminally labeled tRNALys
2 no longer hybridized to 62A. The hybridization of the latter three species of tRNA to the region of the 5S genes, amongst other sites, is confirmed. The previously observed hybridization of tRNAAsp
2 in this region appears to have been due to contamination of the tRNA sample with traces of material derived from 5S RNA. 相似文献
17.
In an effort to generate an A.CA mouse expressing Ed, the Ead gene has been introduced into A. CA mice which lack the major histocompatibility complex (MHC) class II E molecule. Flow cytometric analysis shows cell surface expression of the E chain on lymphocytes and macrophages in the transgenic mice. Analysis of T-cell receptor (Tcr) genes deleted in some E-expressing mouse strains demonstrates that T cells expressingTcrb-VS are partially deleted in these transgenic mice while those expressingTcrb-V8 andTcrb-11 are not. In addition, the expressed Ed chain can promote Mycoplasma arthriditis mitogen (MAM)-induced T-cell proliferation. The expression of the Ea chain, presumably as an Aß
fEd heterodimer, can alter the peripheral T-cell repertoire and T-cell reactivity to a microbial superantigen. 相似文献
18.
Takeshi Todoroki Souichiro Murata Yuji Nakagawa Nobuhiro Ohkohchi Yukio Morishita 《International Seminars in Surgical Oncology : ISSO》2006,3(1):22
Background
Tumor spread beyond the peritoneal cavity in cases of papillary serous adenocarcinoma of the unknown primary (CUP) is a rare late event and carries a poor prognosis.Case presentation
A 71-year-old female was referred to our hospital because of a large right inguinal tumor with biopsy evidence of carcinoma as well as an elevated serum CA125 (cancer antigen 125). She underwent complete resection of the right inguinal tumor and multiple pelvic tumors, which involved the rectum, ovary and uterus. Pathological examination revealed the tumors to be metastases of a papillary serous adenocarcinoma with a psammoma body of CUP. On the 28th postoperative day, newly developed asymptomatic small left inguinal node metastases in the setting of a normal CA125 level were removed. Four and a half years after the primary resection, the CA125 level increased again and newly developed asymptomatic metastases were found in the right deep inguinal nodes and extirpated at that time. All surgical resections followed the modified FAM (5FU, Adriamycin; ADM, MMC) regimen, including protracted dairy oral administration of UFT or 5'-FDUR, Cimetidine and PSK (protein-bound polysaccharide K) as an immunomodulator or biological response modifier in conjunction with intermittent one-day continuous infusion (ADM+MMC) or intermittent single bolus injection of ADM+MMC. At present, the patient has been living in good health for almost 7 years with no evidence of relapse.Conclusion
Aggressive resection surgery followed by effective adjuvant chemotherapy is necessary for surviving long time without relapse of poorly prognostic patients with metastases outside of the abdominal cavity from peritoneal papillary serous adenocarcinomas.19.
D Humphrey A Tsukamoto-Adey O M Witte R Fox L Jerabek I L Weissman 《Journal of immunology (Baltimore, Md. : 1950)》1979,123(1):412-418
Moloney lymphomas and Moloney sarcomas share strong tumor antigens. In this report we analyze the cell-surface antigens on a Balb/c Moloney lymphoma, LSTRA, using hyperimmune sarcoma regressor sera (alphaMo) as a primary reagent. We also use heterologous anti-viral p30 and gp70 sera for a direct analysis of virion protein antigens on the LSTRA surface. Using radiolabeled alphaMo-binding assays, we demonstrate that LSTRA tumor antigens detected by these sera are all Moloney viral antigens; approximately 1/3 of these antigenic determinants are expressed on the intact virus, and the other determinants are revealed by detergent lysis of the virus. The major viral antigens expressed on the LSTRA cell surface are viral env gene products, whereas gag gene products are only sparsely represented. We conclude that alphaMo sera detect almost exclusively viral antigens on LSTRA cells, and these antigens are almost exclusively virion env gene products. 相似文献
20.
Daniel Johnston 《Cellular and molecular neurobiology》1981,1(1):41-55
The passive electrical cable properties of CA3 pyramidal neurons from guinea pig hippocampal slices were investigated by applying current steps and recording the voltage transients from 25 CA3 neurons, using a single intracellular microelectrode and a 3-kHz time-share system. Two independent methods were used for estimating the equivalent electrotonic length of the dendrites, L, and the dendritic to somatic conductance ratio, . The first method is similar to that used by Gorman and Mirolli (1972) and gave an average L of 0.96; the average was 2.44. The second method is derived here for the first time and assumes a finite-length cable with lumped soma. It is an exact solution for L and , using the slopes and intercepts of the first two peeled exponentials. The average L was 0.94; the average was 1.51. The results, using both methods, are in close agreement. The average membrane time constant for all 25 CA3 neurons was 23.6 ms, suggesting a large (23,600 cm2) average membrane resistivity. It is concluded that CA3 neurons are electronically short.This work was supported by Grants NS 11535 and NS 15772 from the National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, U.S. Public Health Service. 相似文献