Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the use of circulating human lactate dehydrogenase (LDH) as a tumor marker, growth and remission of human tumor lines SW480, HEp-2, and Clouser, implanted into female BALB/c athymic nude mice, were followed during therapy. Three types of therapy were used: X-radiation, cyclophosphamide, and diphtheria toxin. After therapy tumor sizes were measured with calipers and compared to changes in the levels of circulating human LDH. Changes in LDH levels paralleled changes in tumor size, but the enzyme fluctuations were more pronounced. Mice bearing intraperitoneally growing SW480 and HEp-2 tumors were effectively treated with diphtheria toxin, and the measurement of circulating LDH was examined as a parameter for gauging the effectiveness of chemotherapy on tumors that could not be visualized. Circulating human LDH can be used to detect intraperitoneal tumor growth and/or remission and to predict death of the animal due to the tumor.
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PMID:Monitoring the therapy of human tumor xenografts in nude mice by the use of lactate dehydrogenase. 28 69

In vitro lymphocyte function was evaluated in 61 patients with different clinical stages of malignant melanoma. Thirty-one of these patients had localized disease, 13 regional metastases, 10 distant lymph node or skin metastases, and 7 visceral metastases. Following immunization, in vitro lymphocyte reactivity to three antigens (diphtheria toxoid, tetanus toxoid and alpha-hemocyanin of Helix pomatia) was studied in the presence of autologous serum, in addition to lymphocyte reactivity to phytohemagglutinin (PHA). The relationship of these tests with the clinical stage and the subsequent course of the disease in a 6 months' observation period was determined. The patients with visceral metastases (7) had a lowered lymphocyte reactivity to PHA compared with controls and the patients with other stages, while they also had a low reactivity to the test antigens (only significantly lowered compared with patients with localized disease). All these patients showed tumor progression or died from metastatic disease. Between the other stages (54 patients) there was no difference in lymphocyte reactivity to the test antigens or PHA. No correlation between lymphocyte reactivity to PHA and the subsequent course of the disease could be demonstrated in these 54 patients. However, lymphocyte reactivity to the test antigens following immunization showed a definite correlation with the subsequent course. Sixty-four percent (9/14) of patients without any lymphocyte reactivity to the three antigens showed tumor recurrence or progression, against 3% (1/40) of patients with positive lymphocyte reactivity to one, two, or three antigens. A suppressive effect of autologous serum on lymphocyte reactivity could be found only in 1 of 20 patients with a low reactivity to PHA or antigens. It is concluded that defects in lymphocyte function are related to subsequent tumor growth in patients with malignant melanoma.
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PMID:Humoral and cell-mediated immune response in patients with malignant melanoma. I. In vitro lymphocyte reactivity to PHA and antigens following immunization. 117 27

Researchers at the National Institute of Immunology (NII) in New Delhi, India have studied 2 vaccines to control fertility: the human chorionic gonadotropin (hCG) vaccine and the gonadotropin releasing hormone (GnRH) vaccine. Animal studies of both vaccines do not indicate any side effects. These 2 vaccines are at the clinical trial stage. Phase II clinical trials of hCG vaccine uses the heterospecies dimer conjugated to tetanus toxoid, diphtheria toxoid, or cholera toxin chain B as carriers. The subjects include hyperfertile women with at least 2 living children. They receive 3 primary immunizations every 6 weeks then a booster immunization as needed. As of May 1991, women with titers of 50ng of hCG bioneutralization capacity/ml had experienced 179 pregnancy-free cycles, and their sexual activity surpasses that prior to receiving the vaccine. 1 study shows that the lung tumors in nude mice which have passive immunization with anti-alpha hCG antibodies necrotize when researchers implant lung tumor cells. Injection of antibodies at the same time of implantation of tumor cells inhibits lung tumor growth. NII researchers plan to conduct a clinical trial with a beta hCG vaccine conjugated with vaccinia in lung cancer patients. The GnRH vaccine has the potential to be effective in both men and women. A study in male rats using diphtheria toxoid as the GnRH vaccine carrier reveals that antibody titers rise, testosterone levels fall, weight of testis decreases, and the prostate disappears. NII has begun clinical trials with postpartum women and, as of April 1992, 20 women were enrolled and immunized at 2 centers in India. Similar research in monkeys does not show evidence of passage of GnRH antibodies through breast milk. GnRH vaccine research in prostate cancer patients demonstrates declining levels of testosterone, luteinizing hormone, and follicle stimulating hormone, shrinkage of the prostate, and clearance of urinary ducts.
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PMID:Vaccines for control of fertility and hormone dependent cancers. 161 3

We studied the effects of preimmunization with a synthetic carboxy-terminal peptide of the beta-subunit of human choriogonadotropin (hCG) conjugated to diphtheria toxoid on the growth of two tumor models, the transplantable Lewis lung carcinoma in C57BL/6J mice and the spontaneous mammary carcinoma in C3H/OuJ mice. Immunization with the conjugate prior to Lewis lung tumor implantation significantly (P less than 0.05) retarded the growth of tumors as measured by tumor weight 18 days following transplantation. The weights of Lewis lung tumors in animals preimmunized with the hCG immunogen were inversely correlated (r = 0.61) with the levels of circulating antibodies against human chorionic gonadotropin, whereas no statistical correlation was found between tumor weights and the levels of antibodies reactive to diphtheria toxoid. The number of conjugate-treated C3H/OuJ mice that developed mammary tumors was significantly (P less than 0.05) reduced compared to their vehicle-treated cohorts. Pretreatment with the synthetic muramyl dipeptide analog utilized as an adjuvant with both immunogens did not show any effect on the tumor growth in either tumor system.
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PMID:Effects of immunization against human choriogonadotropin on the growth of transplanted Lewis lung carcinoma and spontaneous mammary adenocarcinoma in mice. 348 61

Monoclonal antibodies were raised against the guinea pig line 10 (L10) hepatocarcinoma, and an IgG1-producing hybridoma (D3) was selected for further study. D3 is a true monoclonal antibody as demonstrated by two-dimensional gel electrophoresis. Radioimmunoassays on live cells revealed no cross-reactivity with normal tissues or with the line 1 hepatocarcinoma which was used as a control. Membrane immunofluorescence assays demonstrated similar specificity. Immunoperoxidase staining of cryostat sections of tumor and normal tissues of both adult animals and fetuses showed that the D3 monoclonal antibody reacted primarily with the L10 tumor, but some cross-reactivity with smooth muscle, placenta, fetal skeletal muscle, and fetal liver was also demonstrated. Radioimmunoprecipitation of detergent extracts of iodinated L10 cells showed that the antigen is present on the cell surface as a dimer of Mr 290,000 (unit size, Mr 148,000). Therapy studies with unconjugated D3 antibody demonstrated a minor dose-dependent effect on tumor growth. D3 antibody conjugated to the A chain of diphtheria toxin (10(-7) M) was cytotoxic to 100% of L10 cells in vitro. Animals treated with a single 1-mg i.v. injection of this immunoconjugate on Day 7 following the intradermal injection of 10(5) tumor cells demonstrated a highly significant inhibition of tumor growth compared to control animals and those treated with unconjugated antibody.
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PMID:Guinea pig line 10 hepatocarcinoma model: characterization of monoclonal antibody and in vivo effect of unconjugated antibody and antibody conjugated to diphtheria toxin A chain. 634 71

A monoclonal antibody directed against a cell surface chondroitin sulfate proteoglycan of human melanoma cells, 9.2.27, and its diphtheria toxin A chain (DTA) conjugate were investigated for their effects on in vitro protein synthesis and in vivo tumor growth of human melanoma cells. The 9.2.27 IgG and its DTA conjugate display similar serological activities against melanoma target cells but only the conjugate can induce consistent in vitro inhibition of protein synthesis and toxicity in M21 melanoma cells. However, both 9.2.27 IgG and its DTA conjugate effect significant suppression of M21 tumor growth in vivo in an immunotherapy model of a rapidly growing tumor in athymic nu/nu mice, suggesting that other host mechanisms may mediate monoclonal antibody-induced tumor suppression.
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PMID:Monoclonal antibody and an antibody-toxin conjugate to a cell surface proteoglycan of melanoma cells suppress in vivo tumor growth. 657 5

BRO human melanoma cells were prelabeled in vitro with [125I]5-iodo-2'-deoxyuridine ([125I]IdUrd) and inoculated into NIH-II nude mice ip, im, sc, or iv. Saline or diphtheria toxin (DT), which is selectively toxic to human cells compared to those of mice, was injected, and the loss of 125I from the animals was monitored daily with a whole-body gamma scintillation detector. For most of the inoculation sites DT accelerated the rate of 125I excretion and in all cases was cytotoxic for the inoculated cells as determined by host survival or measurement of visible tumor growth. Differences between the rates of 125I loss for DT-treated mice compared to untreated mice were most evident for cells inoculated ip or im. These results indicate that [125I]IdUrd prelabeling of human tumor cells inoculated in nude mice offers a rapid method for determination of cytotoxicity in vivo.
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PMID:Correlation of cytotoxicity with elimination of iodine-125 from nude mice inoculated with prelabeled human melanoma cells. 658 33

The amount of elongation factor 2 (EF-2) associated with different ribosomal fractions (mono- and polyribosomes) isolated from a methylcholanthrene-induced sarcoma is estimated during tumor growth (exponential and plateau phase of growth). Direct EF-2 quantification is obtained by a modification of the method of the diphtheria toxin-catalyzed transfer of (14C)ADP-ribose from (14C)NAD+ to the enzyme. Data reported show that the amount of EF-2 associated with the monoribosomal fraction changes during tumor growth, and particularly, that this amount increases when the tumor cells enter into the plateau phase. In contrast, the EF-2 content of the polyribosomal fraction does not change during the different phases of tumor growth. Data also show that the amount of EF-2 bound to the monoribosomal fraction isolated from tumor cells is significantly and constantly lower than that of the corresponding fraction isolated from reticulocytes or hepatocytes. Moreover the tumor monoribosomes generated by the polyribosome breakdown induced by the "starvation" procedure did not show significant changes in their EF-2 content with respect to monoribosomes isolated from tumor cells maintained in physiological conditions. Besides, tumor monoribosomes generated by the polyribosome breakdown induced by puromycin or by running-off treatment exhibit a relevant increase of the EF-2 content. In these conditions the amount of EF-2 associated with the monoribosomes is similar to that associated with the monoribosomes of control cells (hepatocytes and reticulocytes). Results are discussed in view of a possible regulative role of the EF-2 enzyme in the ribosomal cycle of eukaryotic cells.
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PMID:Association of elongation factor 2 with ribosomes during growth of a murine ascitic tumor. 685 May 53

Targeted protein toxins are a new class of reagents with the potential for great tumor selectivity and cytotoxic potency. Two such compounds were studied: 1) Tf-CRM107, a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107); and 2) 454A12-rRA, a conjugate of a monoclonal antibody (454A12) to the human Tf receptor and recombinant ricin A chain (rRA). Both compounds are potent and specific in killing human glioblastoma cell lines in vitro. The authors investigated the activity of these reagents administered intratumorally against solid U251 MG human gliomas in vivo. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were randomly assigned to be treated with 100-microliters intratumoral injections of Tf-CRM107 (10 micrograms) or 454A12-rRA (10 micrograms), equimolar doses of CRM107 (4.3 micrograms), 454A12 antibody (7.5 micrograms), or rRA (1.5 micrograms), or phosphate-buffered saline (PBS) every 2 days for a total of four doses. Tumor volume and animal weight were assessed by a blinded observer before each treatment and biweekly for 30 days after initiating therapy. With Tf-CRM107 administration, tumor regression of greater than 95% occurred by Day 14 (p < 0.01) and tumors did not recur by Day 30. Treatment with 454A12-rRA caused a 30% decrease in tumor volume by Day 14 (p < 0.01). Treatment with equimolar doses of the unconjugated targeted protein toxin components CRM107, 454A12, or rRA caused significant U251 MG tumor growth inhibition, but the effects were less potent than the antitumor effects of the conjugates. This study also characterized the dose-response effect of Tf-CRM107 on tumor growth and tumor weight on Day 30. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were treated with 100-microliters intratumoral injections of 10, 1.0, or 0.1 microgram of Tf-CRM107 or PBS every 2 days for a total of four doses. All three doses of Tf-CRM107 significantly inhibited tumor growth by Day 14 (p < 0.01) and at Day 30 (p < 0.05), with a significant dose-response relationship. This study demonstrated in vivo efficacy of the targeted toxins Tf-CRM107 and 454A12-rRA against a human glioma. With intratumoral administration, the effect of Tf-CRM107 was tumor-specific and in some animals curative. Regional therapy with these potent tumor-specific agents using direct intratumoral infusion should limit systemic toxicity and may be efficacious against brain tumors.
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PMID:Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. 811 65

Previously, we reported that experimental i.p. administration of fusogenic liposomes containing fragment A of diphtheria toxin (DTA) completely regressed ascites tumors without any severe side effects. In this study, we examined the therapeutic effects of intratumor injection of fusogenic liposomes using ddY mice implanted with Sarcoma-180 (S-180) cells intradermally. Intratumor injections of fusogenic liposomes containing DTA significantly inhibited the tumor growth as assessed by the relative mean tumor volume, and by the survival time of mice. No therapeutic effects were observed when simple liposomes containing DTA or empty fusogenic liposomes were administered. Using [3H]inulin encapsulated in fusogenic liposomes as a marker, we demonstrated that fusogenic liposomes delivered their contents into the solid tumor cells about 15 times more efficiently than simple liposomes. These results suggest that intratumor administration of fusogenic liposomes containing DTA is a highly effective approach to the local treatment of solid tumors.
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PMID:Intratumor administration of fusogenic liposomes containing fragment A of diphtheria toxin suppresses tumor growth. 862 Apr 55


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