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

Neoplastic meningitis (NM) occurs in approximately 8% of all cancer patients. To confirm a clinical impression that NM is relatively common in patients who undergo surgical resection of an isolated cerebellar metastasis (ICM), a retrospective study was performed. All patients who underwent a surgical resection of an isolated CNS metastasis at The Johns Hopkins Hospital between January 1991 and June 1993 were identified. Their charts, laboratory and pathologic data, radiologic studies, survival and cause of death were reviewed. A total of 66 patients were identified fifty-five patients underwent a surgical resection of a supratentorial metastasis while 11 patients (6 females and 5 males) underwent a surgical resection of an isolated cerebellar metastasis. The ages of patients with cerebellar metastases ranged from 23 to 74 years at the time of diagnosis with a median age of 49 years. All 11 patients had stable systemic disease and an excellent performance status. Five patients had tumors from lung, 2 from breast, and 4 from other sites. Each was expected to have a long survival. However, 4 of the 11 patients (36%) developed unequivocal NM at 1, 3, 6, and 7 months following surgical resection and all died within 1 month from the diagnosis of NM. Two patients had a positive CSF cytology and the other two had multiple enhancing leptomeningeal metastases on MRI. Two additional patients died of progressive neurological disease without evidence of local recurrence, yet were never formally evaluated for NM and two were lost to follow-up. Thus, the incidence of NM in this patient population is at least 36%. In the 55 patients who had resections of supratentorial metastases, only 1 patient (2%) developed NM. This study suggests that NM following surgical resection of an ICM may be common and may result in the premature demise of patients with excellent performance status, minimal systemic disease, and a reasonable life expectancy. Further studies are needed to determine if prophylactic intrathecal chemotherapy administered perioperatively could diminish the incidence of clinically apparent NM in this patient population.
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PMID:Neoplastic meningitis following surgical resection of isolated cerebellar metastasis: a potentially preventable complication. 904 83

We studied the effect of recombinant human macrophage-colony-stimulating factor (rhM-CSF) on the formation of lung and liver metastases following the i.v. injection of the B16 melanoma subline (B16 LiLu) into mice. When rhM-CSF was administered before the B16 inoculation, the number of tumor metastases decreased in the lung and liver. However, the administration of rhM-CSF after B16 inoculation did not produce an antimetastatic effect in the lung, but did in the liver, B16 cells labeled with 5-[125I]-iodo-2'-deoxyuridine (125I-dUrd) were injected and the arrest of tumor cell emboli was examined in the capillary beds of the lung and liver of mice treated with either vehicle or rhM-CSF. In both groups, there were the same numbers of B16 cells in both the lung and the liver 3 minutes after the B16 injection, and almost all tumor cells died within 24 h. However, the number of cells surviving in the lung was decreased in mice injected with rhM-CSF (37%). There was no difference in the number of cells in the livers of mice treated either with vehicle or rhM-CSF in the first 24 h after tumor cell injection. The administration of rhM-CSF increased NK 1.1+ cells in the mouse spleen and facilitated NK activity in vivo. At the same time, the administration of an anti-NK 1.1 antibody blocked the antimetastatic effect of rhM-CSF in the lung but not in the liver. The antibody was effective only when it was injected before the B16 inoculation. These results suggest that the antimetastatic effect of rhM-CSF in the lung was mediated by NK 1.1+ cells within 24 h of B16 injection. In contrast, the antimetastatic effect of rhM-CSF in the liver was mediated not only by NK 1.1+ cells but also by other antimetastatic systems such as macrophages.
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PMID:Antimetastatic effect of recombinant human macrophage-colony-stimulating factor against lung and liver metastatic B16 melanoma. 911 84

Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF1 (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells. Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice. After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis.
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PMID:Regulation of tumor antigen presentation by urocanic acid. 920 Apr 43

The prognosis of medulloblastoma in children less than 3 years old is usually considered to be rather poor. However, recent experiences with this type of tumour seem to indicate that survival in this specific subgroup of patients can be longer than expected. Nineteen infants with posterior fossa tumours treated by the authors in the period 1983-1994, all of them with symptoms presenting during the 1st year of life and all operated on before the end of the 2nd year of life, have been retrospectively analysed. Total tumour removal was achieved in 14 cases, subtotal in 1 and partial in 3. One subject underwent only a biopsy of the tumour. In 14 patients a CSF shunt was inserted. Chemotherapy was administered to 18 out of the 19 patients in the series. At the time of the study, 11 children had died (57.9%) and 8 were alive (42.1%; mean survival 86.5 months). One patient died of complications secondary to the surgical treatment. Three patients died because of local recurrence of the tumour after apparent total excision, death supervening 5, 12 and 18 months after the surgical treatment. A further 2 patients in whom total tumour removal had been performed died 3 and 17 months after surgery of local recurrence of the disease associated with regional metastases. Progression of the residual tumour, accompanied by metastatic dissemination in 3 cases, accounted for death in the other 5 patients who did not survive. Brain stem infiltration appeared to be the most significant adverse prognostic factor. All 8 long-term survivors had their tumour totally excised. Five of them underwent radiotherapy when at least 2 years old. On the basis of the results, the authors conclude that the current prognosis of infants with medullo-blastoma is not necessarily any worse than that of older children with the same disease and that chemotherapy can be particularly useful in this subgroup of patients, as shown by 3 long-term survivals obtained in children treated with this type of therapy only.
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PMID:Prognosis of medulloblastoma in infants. 929 75

We examined the mobilization of blood monocytes (MO) with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) with regard to the in vitro generation of MO-derived tumor-cytotoxic macrophages (MAC) for use in adoptive immunotherapy of cancer patients. Eleven patients with progressing metastatic cancer received interferon (IFN)-gamma activated tumor-cytotoxic MAC generated in vitro from autologous MO with and without pretreatment with rhuGM-CSF. RhuGM-CSF was administered subcutaneously at 10 micrograms/kg for 7 days. RhuGM-CSF treatment and adoptive cell transfer were well tolerated, and no toxicity greater than WHO II degrees occurred. Fever was the most common side effect and was seen in all patients during rhuGM-CSF treatment and during 9 of 22 MAC therapies. Bone pain was noted in 5 of 11 patients during rhuGM-CSF therapy. RhuGM-CSF treatment led to a continuous increase in the white blood cell counts and the number of MO within the leukapheresis products. The mean number of transfused MAC was 0.9 x 10(9) without rhuGM-CSF pretreatment and 1.9 x 10(9) after rhuGM-CSF administration. The maximum number of MAC that could be generated was 7.3 x 10(9), but after a dose escalation protocol only up to 2.7 x 10(9) MAC were transfused. Cytotoxicity against U937 cells increased during MO to MAC differentiation, but was decreased in both MO and MAC on treatment with rhuGM-CSF. This study proves the feasibility of reinfusing MAC generated in vitro from rhuGM-CSF mobilized MO.
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PMID:Adoptive immunotherapy with tumor-cytotoxic macrophages derived from recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) mobilized peripheral blood monocytes. 933 43

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and systemic low dose rIL-2 effectively eradicates pulmonary metastases of the murine MCA-105 sarcoma. We described earlier that host CD8+ T cells are critical for tumor eradication and that successful treatment is associated with production of high levels of IFN-gamma and granulocyte/macrophage (GM)-CSF by donor TIL in vitro. Here, we propose the mechanism through which adoptively transferred Thy-1.1+ TIL induce a host antitumor response in congenic Thy-1.2+ tumor-bearing mice. Donor Thy-1.1+ TIL were detected at the tumor site 12 h after transfer. These Thy-1.1+ cells produced IFN-gamma and GM-CSF in situ. The percentage of Thy-1.1+ TIL at the tumor site increased up to 16.4 +/- 4.9% 24 h after transfer but decreased to undetectable levels thereafter. In contrast, the percentages of host cells producing IFN-gamma and GM-CSF continued to increase at the tumor site. These increases were significantly higher in TIL + rIL-2-treated mice compared with untreated mice and rIL-2-treated mice 48 h after TIL transfer. The appearance of IFN-gamma+ and GM-CSF+ cells was followed by a large influx of host CD4+, CD8+, and Thy-1.2+ TIL and eventually by tumor eradication. This response was tumor specific since TIL obtained from MCA-205 did not induce high levels of IFN-gamma and GM-CSF and did not induce tumor eradication of MCA-105 tumor. Coinjection of Thy-1.1+ TIL and anti-IFN-gamma or anti-GM-CSF mAb significantly inhibited antitumor efficacy of the TIL + rIL-2 treatment. We conclude that successful adoptive immunotherapy in this model is mediated through cytokine production by adoptively transferred TIL that induce a host T cell-dependent antitumor response.
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PMID:Successful adoptive cellular immunotherapy is dependent on induction of a host immune response triggered by cytokine (IFN-gamma and granulocyte/macrophage colony-stimulating factor) producing donor tumor-infiltrating lymphocytes. 955 89

Where a leptomeningeal carcinomatosis is clinically diagnosed, evidence should be provided of tumor cells in the CSF. Not necessarily in the first specimen, but in the course of the illness. The staining of the cells with the Pappenheim method generally provides sufficient information about the cells. The identification of cells in metastases of epithelial tumours is not difficult for anyone with some experience. Identifying cells from primary brain tumours - which however only rarely cause meningosis - can sometimes be more difficult. Attention should be paid to whether the cells occur in clusters or singly. However, extreme caution is called for. The cytological monitoring of the CSF is an essential part of chemotherapy or radiation treatment.
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PMID:Cytology of neoplastic meningosis. 969 61

We determined whether tumor cells consistently generating granulocyte/macrophage colony- stimulating factor (GM-CSF) can recruit and activate macrophages to generate angiostatin and, hence, inhibit the growth of distant metastasis. Two murine melanoma lines, B16-F10 (syngeneic to C57BL/6 mice) and K-1735 (syngeneic to C3H/HeN mice), were engineered to produce GM-CSF. High GM-CSF (>1 ng/10(6) cells)- and low GM-CSF (<10 pg/10(6) cells)-producing clones were identified. Parental, low, and high GM-CSF-producing cells were injected subcutaneously into syngeneic and into nude mice. Parental and low-producing cells produced rapidly growing tumors, whereas the high-producing cells produced slow-growing tumors. Macrophage density inversely correlated with tumorigenicity and directly correlated with steady state levels of macrophage metalloelastase (MME) mRNA. B16 and K-1735 subcutaneous (s.c.) tumors producing high levels of GM-CSF significantly suppressed lung metastasis of 3LL, UV-2237 fibrosarcoma, K-1735 M2, and B16-F10 cells, but parental or low-producing tumors did not. The level of angiostatin in the serum directly correlated with the production of GM-CSF by the s.c. tumors. Macrophages incubated with medium conditioned by GM-CSF- producing B16 or K-1735 cells had higher MME activity and generated fourfold more angiostatin than control counterparts. These data provide direct evidence that GM-CSF released from a primary tumor can upregulate angiostatin production and suppress growth of metastases.
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PMID:Angiostatin-mediated suppression of cancer metastases by primary neoplasms engineered to produce granulocyte/macrophage colony-stimulating factor. 970 57

Twenty patients with metastatic colorectal carcinoma were treated with a single infusion (400 mg) of a mouse monoclonal antibody (IgG2a) against the tumor-associated antigen CO 17-1A and with a daily injection of granulocyte macrophage colony-stimulating factor (GM-CSF) for 10 days. The cycle was repeated every month. Metastases from 5 of the 20 patients biopsied on days 1 and 10 of the first two treatment cycles were studied by immunohistochemistry. During treatment, neutrophils, monocytes, and T lymphocytes increased concordantly in the tumor as in the blood of the individual patient. Macrophages (CD68) and CD8+ T cells infiltrated the tumor glands and displayed TIA-1-reactive cytotoxic granules. Neutrophils were seen mainly in areas of necrosis. Activated (HLA-DR+) CD4+ T cells were usually abundant in the stroma. During treatment, few natural killer cells were found in the tumor, contrary to the marked increase seen in blood. Our observations indicate that GM-CSF markedly recruited activated, tumor-infiltrating leukocytes, possibly representing antibody-dependent cellular cytotoxicity and cytotoxic T effector cells. The notion that combined antibody and GM-CSF therapy may also promote a T-cell antitumor response is further supported and advocated by our findings. The study lends further support to combining GM-CSF with monoclonal antibody-based therapy.
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PMID:Immunopathology of metastases in patients of colorectal carcinoma treated with monoclonal antibody 17-1A and granulocyte macrophage colony-stimulating factor. 971 20

High levels of plasminogen activator inhibitor-1 (PAI-1) in tissue extracts have been associated with poor prognosis in many epithelial cancers. Ovarian cancers contain a higher concentration of PAI-1 than benign ovarian tumors or normal ovaries. Reports, however, on the prognostic value of PAI-1 content in ovarian cancers have been conflicting. We used immunohistochemistry to study the primary and metastatic tissues from 131 epithelial ovarian cancer cases. This group has been previously characterized for the expression of urokinase (uPA), uPA receptor, PAI-2 and macrophage colony-stimulating factor (CSF-1). The intensity and extent of staining for PAI-1 in the tumor epithelium was scored. Kaplan-Meier curves of survival were compared using the log-rank test. The Cox regression model was utilized for multivariate analysis. Approximately 50% of the primary tumors and metastases expressed PAI-1. Among invasive stages III and IV patients, those whose primary tumors expressed PAI-1 had a shorter overall survival. The combination of strong expression of PAI-1 and expression of uPA was a highly significant factor for short disease-free and overall survival. Similar results were seen with the combination of high PAI-1 and low PAI-2 expression. Strong PAI-1 expression was significantly associated with expression of uPA receptor or CSF-I in the tumor epithelium, but not with standard clinical parameters, and was an independent prognostic factor for poor survival on multivariate analysis. Our results show that PAI-1 expression in the primary tumor epithelium is an independent poor prognostic factor for survival, underscoring the tumor protective role of PAI-1 in ovarian cancer biology.
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PMID:Plasminogen activator inhibitor-1 is an independent poor prognostic factor for survival in advanced stage epithelial ovarian cancer patients. 976 Nov 11


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