Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Balb/c mice were exposed to fresh smoke, equivalent to 30 high-tar filtered cigarettes/day, for 83 wk or less. After groups of mice were subjected to 56, 64, 72, and 80 wk of tobacco smoke (TS) exposure, serum antibody responses to both T-dependent and T-independent antigens, numbers of plaque-forming cells, spleen cell and lymph node PHA responses, and systemic clearance of normal and opsonised antigen were investigated. Aged TS-exposed mice showed some deterioration of immune responsiveness with age, but results varied; in extreme old age the immunological responsiveness of TS-exposed mice was similar to that of age-matched controls. In addition, groups of mice inoculated with fibrosarcoma cells after 78 wk TS-exposure did not show significantly greater susceptibility to the early development of pulmonary metastases.
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PMID:Effects of chronic tobacco smoke exposure on immune responses in aged mice. 727 26

Comprehensive immune function by integrated score was assessed in 158 operable, 55 inoperable, and 52 metastatic breast cancer patients relative to 107 healthy controls. The score was derived from in vivo response to PPD and DNCB and in vitro lymphocyte stimulation by PPD and PHA. Proportion of E-RFC was significantly lower in patients than in controls but was not found to correlate directly with the above functional criteria. Fifty-one percent of the patients with early, operable tumors were shown to be at least partially immunosuppressed by integrated score achievement vs. 11% of controls. This proportion rises to 68% of inoperable and 89% of metastatic patients. Quantitative analysis by graded response revealed an additional, significant degree of immune impairment in the respective patient groups by all testing parameters. Depression of immune function in operable patients was not related to age nor influenced by surgery. Immunocompetence of patients with mammary dysplasia did not differ from controls. Increasing size of primary tumor (T) was not found to be matched by progressive degree of immunosuppression, excepting that associated with large T4 tumors. Patients with lymph node involvement (N+) were not significantly immunologically inferior to those without (N0) where the larger operable T2-3) tumors are concerned. In the smallest, T1 tumors, nodal involvement (N+) is accompanied by remarkable immunosuppression relative to T1N0 cases. This finding suggests a pre-existing immune defect inherent in T1N+ patients. It supports the hypothesis that the immunosuppression associated with early breast cancer is primary, patient related. Secondary tumor-induced depression of immune response characterizes advanced and metastatic human breast cancer.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. II. Further evidence of initial immune impairment by integrated assessment effect of nodal involvement (N) and of primary tumor size (T). 737 Sep 52

The prognostic significance of immunocompetence determined at diagnosis was analyzed in 158 operable breast cancer patients followed for 3--6 years, in terms of disease recurrence and of length of disease-free period (DFP) and in 52 patients with metastatic disease in terms of length of survival. In vitro lymphocyte stimulation by PPD and PHA were of higher predictive value with respect to probability of disease recurrence than in vivo cutaneous reactivity to PPD and DNCB. Conversely, length of DFP and of survival were found to correlate better with in vivo than within vitro parameters. Absolute number of peripheral blood lymphocytes (PBL) and percent of E-rosette-forming cells (E-RFC) proved devoid of prognostic value. Prognostic separation was best brought out upon analysis by integrated score of immunocompetence, comprising the four functional parameters. Probability of disease recurrence was 0.43 for all operable patients, as calculated by actuarial method 48 months postoperatively; it was 0.26 for optimal and 0.61 for suboptimal responders (P less than 0.0001). Separate analysis of Stage 1 (N0) and Stage II (N+) patients revealed prognostic segregation within each stage: probability of recurrence in Stage I was 0.06 for optimal vs. 0.41 for suboptimal responders (P less than 0.001) and in Stage II it was 0.45 vs. 0.79, respectively (P less than 0.01). These findings may prove valuable for a more selective patient allocation for post-mastectomy adjuvant therapy. Length of DFP was found inversely proportional to initial immunocompetence, with a mean of 23.5 months for good responders and 12.8 months for poor responders (P less than 0.01). Length of survival of metastatic patients was found to correlate with initial (pretreatment) levels of immunocompetence, mean survival being 29.5 months for those with preserved immune function and 12.3 months for the immunosuppressed (P less than 0.001). It was concluded that initial immunocompetence, determined by parameters of cell-mediated immunity, shows strong prognostic association with the subsequently observed course of human breast cancer.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. III. Prognostic significance of initial level of immunocompetence in early and advanced disease. 737 Sep 53

Twenty one patients with advanced metastatic cancer of various types received 30 mg of Bestatin daily per os as a single treatment for several weeks. It was observed that the blood lymphocyte counts remained unchanged but the frequency of SRBC rosette forming cells increased and the frequency of lymphocytes possessing receptors for the Fc-part of IgG became normalized after two weeks of treatment. The frequency of lymphocytes possessing receptors for C'3 was not changed. The natural killer activity of peripheral lymphocytes for K562 and Chang cells increased but the PPD stimulation of the lymphocytes was not altered. A slight, but significant increase of the PHA stimulation of lymphocytes was observed after 4-7 weeks of Bestatin treatment. It is concluded that Bestatin is a nontoxic drug which changes the cellular composition as well as certain immunological functions of human lymphocytes.
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PMID:Changes of the blood lymphocyte population in cancer patients treated with bestatin, a new immunomodulator. A phase I study. 747 May 79

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.
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PMID:Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies. 788 44

Human chorionic gonadotropin (hCG) is a glycoprotein of which sugar chains are considered to show structural changes with malignancy. To study the sugar chain heterogeneity of urinary hCG in patients with gynecological disease, we employed serial lectin affinity chromatography (LAC) using concanavalin A (Con A) and phytohemagglutinin-E (PHA-E) which can separate N-glycoside-linked sugar chains, and Jacalin lectin which is specific for O-glycoside-linked sugar chains. The proportion of hCG which did not bind to Con A was clearly higher in patients with cervical cancer than in healthy pregnant women. The complex-type sugar chains bearing bisecting (beta 1-4) N-acetylglucosamine which bound to PHA-E increased in the early stage of cervical cancer, and tri- and tetra-antennary complex type sugar chains also increased in the advanced stages. In addition, the Jacalin-bound hCG increased significantly along with the stage of the cancer, especially in advanced cervical cancer with distant metastases. Taken together, these results show that alteration in sugar chain structures of hCG reflect the advanced stage of cervical cancer.
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PMID:Sugar chain heterogeneity of human urinary chorionic gonadotropin determined by serial lectin affinity chromatography: difference between benign and malignant disease. 793 72

NIH3T3 cells transfected with an activated Ha-ras oncogene were treated with L-PHA, the leukoagglutinin from red kidney beans. Cell lines resistant to L-PHA-mediated cytotoxicity were isolated and found to contain reduced levels of L-PHA-binding oligosaccharides. The levels of N-acetylglucosaminyltransferase V, the enzyme responsible for the initiation of the beta 1-6 branch, were reduced in L-PHA-resistant cells. Tumorigenicity in nude mice was unchanged by the change in oligosaccharide expression, but the ability to form lung tumors after intravenous injection was significantly reduced. These results demonstrate that the ability of NIH3T3 cells transfected with an activated Ha-ras oncogene to form lung tumors after intravenous injection into nude mice is reduced in all six L-PHA selected cell lines containing a reduction in beta 1-6 branched Asn-linked oligosaccharides.
Clin Exp Metastasis 1994 Jan
PMID:Tumor cell surface beta 1-6 branched oligosaccharides and lung metastasis. 828 20

During a fifteen-month period, 15 patients with progressive adenocarcinoma of the prostate (CaP) were treated with transrectal microwave hyperthermia (TRHT). There were 5 Stage T4 and 11 Stage T3 patients including 6 patients with skeletal metastases. Nine of the patients had severe and 6 had moderately severe signs and symptoms of CaP. TRHT was given six times at 2,450 MHz with temperature controlled at 43.5 degrees for thirty minutes. Cell-mediated immunity tests were performed before TRHT and at two, four, and six months post-therapy. The results of these tests were compared with those of 15 patients with benign prostatic hyperplasia (BPH) treated with the same TRHT and with 30 untreated normal volunteers. TRHT was well tolerated with mild acute toxicity noted in 3 patients (20%). Of the 15 patients treated, 2 (13%) showed scintigraphic evidence of regression of bone metastases. Five patients survived more than five years since treatment, and in 3 patients there was no evidence of CaP. A decrease of marked or moderate degree in signs and symptoms of CaP was noted in 8 patients (53%). The results of cell-mediated immunity tests were of interest. The 15 CaP patients prior to TRHT had lower OKT4/OKT8 ratio, lower PHA transformation index, and lower Con-A induced T-cell suppressor activity as compared with the 15 BPH patients and 30 healthy volunteers, who had normal immune parameters (p < 0.01). Following TRHT there was a significant increase in the monitored immune parameters noted in the 15 CaP patients (p < 0.01). This immune stimulation peaked at two months and gradually decreased to near pretreatment levels at six months. In the 15 BPH patients post-TRHT changes in immune tests were less apparent. The results of this small study, if confirmed, could be of clinical importance in patients with advanced prostate cancer.
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PMID:Transrectal hyperthermia as palliative treatment for advanced adenocarcinoma of prostate and studies of cell-mediated immunity. 851 90

The expression of -GlcNAc beta 1-6Man-(beta 1-6) branched oligosaccharides in carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with beta 1-6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the stroma adjacent to the carcinomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly including their ability to escape macrophage recognition.
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PMID:Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: possible association with the metastatic potential. 890 72

We have completed a phase I study to test feasibility and toxicity of immunotherapy of hepatic metastases from colorectal carcinoma by direct gene transfer of HLA-B7, a MHC class I gene. Eligible patients were HLA-B7 negative, immunocompetent by PHA lymphocyte stimulation and had at least two measurable hepatic lesions on CT scan for measurement of response of the injected lesion, as well as evaluation of possible distant response. Under ultrasonographic guidance the hepatic lesions were injected with Allovectin-7, a liposomal vector containing the combination of the HLA-B7 gene with beta 2-microglobulin formulated with the lipid DMRIE-DOPE. Eligible patients were injected on two schedules. On the first schedule patients received an injection on day 1 and the injected lesion was biopsied to determine transfection every 2 weeks for 8 weeks. Doses were escalated from 10 micrograms to 50 micrograms to 250 micrograms with three patients treated at each level. The second schedule included multiple injections of 10 micrograms. Three patients received injections on days 1 and 15. Three patients received injections on days 1, 15 and 29. A total of 15 patients have completed treatment. The plasmid DNA was detected in 14 of 15 patients (93%) by PCR. In five of 15 patients (33%) mRNA was also detected. The HLA-B7 protein was detected in five of eight patients (63%) by immunohistochemistry and in seven of 14 patients (50%) tested by fluorescence activated cell sorting (FACS) analysis. There has been no serious toxicity directly attributable to allovectin-7. Our results suggest that liposomal gene transfer by direct injection is feasible and non-toxic. Further studies will be necessary in order to establish the therapeutic efficacy.
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PMID:Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7. 927 18


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