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)

Prostate cancer selectively metastasises to skeletal sites, where it normally produces osteoblastic lesions. This study investigated whether haematopoietic growth factors known to be present in the bone environment could be involved in the survival and proliferation of prostate skeletal metastases. To evaluate this hypothesis we investigated the effects of recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF), recombinant granulocyte colony-stimulating factor (rG-CSF), recombinant erythropoietin (rEPO) and recombinant interleukin-3 (rIL-3) on the growth of 3 human prostate cancer cell lines. Two hormone-insensitive cell lines, PC-3 and DU145, were significantly stimulated by rGM-CSF and rEPO in serum-free medium but their growth was unaffected by incubation with rIL-3 or rG-CSF. A hormone-sensitive cell line, LNCaP, was stimulated only by rGM-CSF. To investigate further the involvement of GM-CSF in prostate cancer, the presence of GM-CSF protein in the 3 prostate cancer cell lines was examined by immunohistochemistry, and analysis of cell line conditioned media was carried out by ELISA and Western blotting. These techniques demonstrated that GM-CSF-like material was produced by both DU145 and PC-3 cells but not by LNCaP. The results from ELISA found that media conditioned by DU145 and PC-3 cells contained 1.7 and 2.5 pg GM-CSF/micrograms protein, respectively, whereas no GM-CSF was detectable in the LNCaP conditioned media. Our results were also confirmed by Western blot analysis demonstrating one single band for DU145 and PC-3 conditioned media which co-migrated along with the standard rGM-CSF band. No bands were associated with the LNCaP conditioned media. The presence of GM-CSF gene transcripts in DU145 and PC-3 cells was established by reverse transcription and polymerase chain reaction of total RNA.
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PMID:Production and response of human prostate cancer cell lines to granulocyte macrophage-colony stimulating factor. 792 24

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to enter routine clinical practice, has aroused considerable interest due to its novel mechanism of action and its significant activity in metastatic breast cancer. Given this activity, it seemed logical to attempt to combine paclitaxel with doxorubicin, the other most active single agent in metastatic breast cancer. The Eastern Cooperative Oncology Group performed two trials investigating paclitaxel/doxorubicin combinations in patients with advanced breast cancer in an attempt to identify a tolerable dose and schedule of the combination. In the first trial, paclitaxel and doxorubicin were alternated every 3 weeks in doses of 200 mg/m2 and 75 mg/m2, respectively, for patients who had received no more than one prior chemotherapeutic regimen. Therapy was well tolerated in this setting. At these doses, paclitaxel induced more granulocytopenia and less thrombocytopenia than did doxorubicin. Objective responses (complete and partial responses) were seen in seven of 12 patients; two other patients had improved disease (relief of pain in bony metastases). A second limited-institution Eastern Cooperative Oncology Group trial evaluated paclitaxel and doxorubicin given in combination. In this phase I trial, doxorubicin was given as an intravenous push and paclitaxel as a 24-hour continuous infusion. The sequence of drug administration (D-->P or P-->D) was alternated both between and within patients, so that we might evaluate the effect of administration schedule on toxicity. Therapy was begun at an initial paclitaxel dose of 150 mg/m2 and an initial doxorubicin dose of 50 mg/m2 in six patients, with a subsequent six patients receiving 175 and 60 mg/m2, respectively, of paclitaxel and doxorubicin. In addition, patients received granulocyte colony-stimulating factor 5 micrograms/kg/d. While therapy at the initial dose level was well tolerated, dose-limiting mucositis was seen at the second dose level, although only when paclitaxel preceded doxorubicin. This suggests that sequence of drug administration in paclitaxel-based regimens may play an important role as a determinant of toxicity and (perhaps) efficacy, a finding similar to that seen when paclitaxel and cisplatin were combined in patients with ovarian cancer. Based on this study, we identified the sequence of doxorubicin (50 mg/m2) followed by paclitaxel (150 mg/m2) to be the maximum tolerated dose. This combination is currently being compared with paclitaxel alone and doxorubicin alone in patients with advanced breast cancer in an intergroup trial led by the Eastern Cooperative Oncology Group.
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PMID:Paclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience. 793 56

For more than 10 years, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Breast Cancer Site Group has focused primarily on trials of adjuvant therapy and of investigational new drugs (IND). Four trials of adjuvant therapy in node-positive women have been completed, are active, or are about to begin. Investigational new drug (IND) studies have included Phase II trials of intravenous and oral menagaril, 10-EDAM (edatrexate), taxotere, and mifepristone (RU-486) as well as a Phase I/II trial of 5-fluorouracil (5-FU), doxorubicin, and vinorelbine (FAN); a Phase I/II trial of 5-FU, leucovorin, doxorubicin, and vinorelbine (super-FAN), all as first-line therapy for metastatic disease; and a Phase III study of vinorelbine plus doxorubicin versus doxorubicin alone as first- or second-line metastatic therapy. A proposed study with the European Organization for Research and Treatment of Cancer in locally advanced breast cancer will compare a standard NCIC CTG regimen of cyclophosphamide, epirubicin, and 5-FU (CEF) with epirubicin and cyclophosphamide granulocyte colony-stimulating factor (G-CSF), a more dose-intensive regimen. In addition, NCIC CTG is preparing a pilot of CEF with G-CSF to examine whether a substantially more intensive dosage can be given without added toxicity. NCIC CTG will also enter patients into a currently active Cancer and Leukemia Group B/Southwest Oncology Group randomized trial of intensive therapy versus more intensive therapy with bone marrow support in women younger than age 60 with 10 or more positive nodes. It is believed that optimizing the combination and timing of adjuvant hormonal and chemotherapy, exploring dose intensive approaches, developing investigational new drugs, studying the role of biologics, and tumor banking in conjunction with clinical trials remain important approaches for the future.
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PMID:Clinical cooperative trials of the National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group. 803 51

Two cases of primary extragonadal germ cell tumor of retroperitoneal origin are reported. One was a 26-year-old man complaining of back pain. He had a large retroperitoneal tumor with lung, liver and supraclavicular lymph node metastases. He was referred to us after being treated for malignant lymphoma. The serum AFP, beta-subunit of human chorionic gonadotropin (hCG-beta), CEA and CA-19-9 were elevated. The retroperitoneal disease was treated surgically and with radiotherapy. The pathological diagnosis was that of embryonal carcinoma and teratoma. The lung, liver and supraclavicular lymph node metastases disappeared completely after two courses of cisplatin-based chemotherapy. While further chemotherapy was postponed due to myelosuppression, the disease relapsed and was resistant to subsequent therapy. The patient died twelve months after he first saw us. The second case was that of a 36-year-old man complaining of edematous legs and external genitalia. He had an extensive retroperitoneal tumor with multiple pulmonary metastases. The serum AFP level was high. Suspected of having an extragonadal germ cell tumor, he was referred to us promptly. Cisplatin-based chemotherapy coupled with resection of residual retroperitoneal and pulmonary disease resulted in complete remission. The pathological diagnosis was that of possible embryonal carcinoma. Further chemotherapy was given as scheduled, using granulocyte colony-stimulating factor. The patient has been in complete remission for two years. The chemotherapeutic regimen and surgical policy in the treatment of the two patients were essentially same. Early diagnosis, adequate initial therapy and the use of granulocyte colony-stimulating factor may be relevant to the favorable prognosis in the latter case.
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PMID:Extragonadal germ cell tumor of retroperitoneal origin: report of two cases. 812 21

A murine tumor model showing metastases to lymph nodes (LN) was established by intradermally implanting highly metastatic MM48 tumor cells (2 x 10(6)) in C3H/HeN mice. We were searching for the most effective immunochemotherapeutic modality to treat this metastatic tumor. The combination therapy with chemotherapeutics, granulocyte colony-stimulating factor (G-CSF) and OK-432 on Days 8-11 was found to be remarkably effective, making the solid tumor disappear in more than half of the treated mice, though all of them eventually died of LN metastasis, as all the control mice did. Then an attempt was made to cure the mice from such fatal metastatic tumors with combined immunochemotherapy prior to surgical resection on Day 14. The combination therapy with chemotherapeutics, G-CSF and OK-432 more strongly inhibited the metastases then, and more than 85% of the mice survived. When the survivors were rechallenged with MM48 tumor cells, all of them rejected and survived without recurrences and metastases, indicating the acquirement of specific immunity. It is expected that this preoperative immunochemotherapy may be clinically useful for the treatment of malignant neoplasms.
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PMID:The inhibitory effect of preoperative immunochemotherapy on the lymph node metastasis of murine MM48 tumor. 853 Feb 55

A 67-yr-old woman who underwent total thyroidectomy 32 yr ago developed accelerated hyperthyroidism after injection of iodinated contrast media to evaluate a left hemipelvis mass. The patient was managed with propylthiouracil, beta-blockers and digoxin. Whole-body 201TI and 131I scans demonstrated a functioning metastasis in the left hemipelvis where biopsy revealed a well differentiated follicular thyroid carcinoma. Palliative external beam radiotherapy was administered. The patient then received radioiodine treatment with granulocyte colony-stimulating factor to minimize bone marrow toxicity. Clinically significant thyrotoxicosis occurring in metastatic thyroid carcinoma is rare and results from abnormal ectopic thyroidal tissue iodine metabolism. Iodide-containing medications and contrast media should be avoided in patients with functioning thyroid metastases to prevent abrupt increases in circulating thyroid hormone levels.
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PMID:Accelerated thyrotoxicosis induced by iodinated contrast media in metastatic differentiated thyroid carcinoma. 879 Feb 12

The effects of exogenous and endogenous granulocyte colony-stimulating factor (G-CSF) on invasion by cancer cells were studied, using lung cancer cell lines that produce G-CSF (NCI-H157) and lines that do not (PC-9 and NCI-H23). The invasive capacity of NCI-H157 cells was 26- to 27-fold higher than that of PC-9 and NCI-H23 cells. The invasiveness of PC-9 cells was stimulated by exogenous G-CSF, while that of NCI-H157 cells was not. Antibodies against G-CSF blocked the stimulation of PC-9 cell invasiveness by exogenous G-CSF. Anti G-CSF antibodies also inhibited invasion by NCI-H157 cells in the absence of exogenous G-CSF. These results suggest that endogenous and exogenous G-CSF both stimulate invasion by lung cancer cells.
Clin Exp Metastasis 1996 Sep
PMID:Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro. 887 9

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.
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PMID:Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor. 893 53

Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.
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PMID:Paclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study. 894 6

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.
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PMID:Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. 897 90


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