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)

The effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and human recombinant interleukin 2 (IL2), on palpable intradermal (i.d.) bladder tumor were studied. The murine transitional cell carcinoma MBT-2 was used in C3H mice. IL2 was given intraperitoneally at 5,000 U/injection three times a day for 5 consecutive days beginning on day 10. LAK cells were generated in vitro from normal splenocytes: 10(7)-10(8) LAK cells were transferred intravenously on day 10 and, in some experiments, also on day 13. IL2 alone, LAK cells alone (total 8 x 10(7], and both in combination showed little or no influence on intradermally growing MBT-2 tumors. Cyclophosphamide was also combined with adoptive immunotherapy (IL2 and LAK). CY (100 mg/kg, i.p. on day 9 or 10) alone was able to suppress i.d. MBT-2 growth significantly. The combination treatment of IL2 and LAK cells with CY caused additional tumor growth suppression in a manner dependent on the total number of LAK cells transferred. The amount of the additional tumor growth suppression was, however, relatively small when compared with CY plus IL2-treated groups. In comparison, experimentally induced 3-day and 10-day pulmonary metastases of MBT-2 cells were treated by the same protocol of IL2 and LAK cells but without CY. IL2 alone reduced the number of gross metastatic nodules in the lung. The addition of LAK cells to the IL2 almost entirely eradicated the 3-day metastatic nodules but was less effective against the 10-day metastases. The data suggest that adoptive immunotherapy with IL2 and LAK cells mediates tumor regression of micrometastases at a selected organ (lung), but is ineffective against the same tumor growing in the skin or in gross metastatic nodules. Host immune suppression by CY was not beneficial in this model in creating a successful therapeutic effect of LAK cells and IL2.
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PMID:Ineffectiveness of adoptive chemoimmunotherapy with lymphokine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murine bladder cancer. 325 20

The tumor was found in the peritoneum of a 6-months old female NMRI-mouse. Histologically it can probably be classified as a less-differentiated reticulum-cell sarcoma (histiocytic sarcoma). Following ip. or sc. transplantation metastases were only in some cases found. After im. inoculation of tumor brei lungs, livers, kidneys, spleens and lymph nodes were free of metastases, as a bioassay revealed. The im. transplantation was the most suitable technique for chemotherapeutic experiments: It resulted in a 100% take rate and a relatively narrow and well reproducible death range; tumor size and life span of the animals could be used as therapeutic parameters. The tumor was highly sensible against the cytostatic drugs Cyclophosphamide, Doxorubicin and Vincristine. A moderate activity showed CCNU, Cis-DDP and Bleomycin, while DTIC and a novel Benzochinonguanylhydrazon-derivative only reversibly influenced the tumor growth and not the life time of the animals. Liposomally encapsulated Daunorubicin and Bleomycin had in general similar effectiveness as the drugs in its free form. Because of its high sensitivity against a lot of cytostatics with different mechanisms of action the tumor can be recommended for the screening of novel antineoplastic substances.
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PMID:Characterization of a new tumor in NMRI-mice suitable for chemotherapeutic experiments. 329 88

Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.
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PMID:Double alkylating agent therapy with ifosfamide and cyclophosphamide for advanced non-small cell lung cancer. From the Manchester Lung Tumour Group. 333 40

The case of a 36 year old patient in whom breast cancer was diagnosed in February 1983 is reported. At the time of the diagnosis bone metastases, were already present. Therapy was started on the basis of a FAC-regimen (Ftorofur-, Adriamycin-Cyclophosphamide), where after the patient developed clinical and laboratory signs of hepatic lesion. At the time of the first FAC-course the suspicion of viral hepatitis of cholestatic type was raised; HBsAg was consistently negative. In the 3rd week after completion of the second FAC-course clinical signs of cholestatic hepatitis with high fever and leucopenia of increasing severity were suggestive of drug-induced hepatitis. Cyclophosphamide was incriminated, therefore, this component was omitted from the subsequent FAC-course. Nevertheless, the clinical manifestations reappeared in a more pronounced form. This time, too steroids were administered, with beneficial effect. In view of the complaints pointed to bone-metastases further cytostatic treatment, Vepesid monotherapy was started, but after the first course the patient developed hepatitis and died. Necropsy revealed, in addition to extensive bone-metastases, microscopic signs of drug-induced hepatitis. The types of liver damage caused by the cytostatic agents used in this study are reviewed. No hepatitis has been reported in connection with these drugs (Adriamycin + Ftorofur or Vepesid) thus far. The diagnostic criteria of drug-induced hepatitis are outlined. It is pointed out that with the eves more extensive use of cytostatic therapy a growing incidence of this complication should be taken into account.
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PMID:Drug hepatitis of cholestatic type in association with a FAC-regimen for breast cancer. 344 15

Capabilities of computed tomography (CT) and magnetic resonance (MR) imaging in the diagnosis of cerebellopontine angle-petromastoid (CPA-PM) lesions were compared in 75 patients. CT and MR demonstrated 95.8% and 98.7% of the lesions, respectively. MR was often more helpful for characterization of neuromas, epidermoid cysts, exophytic gliomas, and vascular lesions, while CT was usually more informative for meningiomas, metastases, and tympanomastoid cholesteatomas. A specific diagnosis could be made with MR for most types of lesions through use of relaxation parameters and characteristic morphologic changes. Size, shape, location, and contour of the lesions, however, were generally more helpful for differential diagnosis than relaxation times. With the exception of metastatic lesions, cholesteatomas, and some meningiomas, MR was usually more helpful than CT in defining the full extent of the lesions and their relationships to contiguous structures. MR, because of its high accuracy in lesion detection, characterization, and localization, is a suitable primary diagnostic modality for evaluating patients with suspected CPA-PM lesions.
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PMID:Cerebellopontine angle-petromastoid mass lesions: comparative study of diagnosis with MR imaging and CT. 349 10

Ifosfamide (IFOS) 5 g/m2 and its parent analog Cyclophosphamide (CYCLO) 1.5 g/m2 were studied in a randomized phase II study, accruing 171 patients with advanced soft tissue sarcoma. Both drugs were administered as 24 hr infusions, every 3 weeks, with comcomitant Mesna 400 mg/m2 i.v. bolus 4 hourly X 9 doses. Twenty-four patients were ineligible and 12 were not evaluable. The groups were well matched for age, previous chemotherapy (42% of the total) or radiotherapy, the presence of distant metastases and performance status, but there were more females (59% vs. 45%) in the IFOS arm. Among the 68 evaluable patients receiving IFOS, there were 2 CR, 10 PR (overall response 18%), 27 SD and 29 PD. For CYCLO, the corresponding results in 67 patients were 1 CR, 4 PR (overall response 8%), 23 SD and 39 PD. Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively. Response rates were higher for females (20% vs. 5%, P = 0.01) and patients who had not received previous chemotherapy (19% vs. 4%, P = 0.01). Fourteen of the 17 responses came from a group of 43 females, who had not received previous chemotherapy, for whom the overall response rate was 37.5%. Remissions were noted in only 4 histological subtypes (centrally reviewed material), i.e., 5 of 17 synovial sarcomas, 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas. One of the 31 leiomyosarcomas responded to Cyclophosphamide. Durations of response did not differ significantly between the 2 arms--median 26, range 10-81+ weeks. Leucopenia was significantly more severe on CYCLO, particularly in patients who had received previous chemotherapy (P = 0.007). Serious infections occurred in approx. 7% of patients with no difference between the two drugs, although there was one toxic death on CYCLO. Nausea and vomiting were significantly worse on IFOS and alopecia, related in extent to dose, was seen in both arms. Other side-effects, such as hematuria or rises in serum creatinine and encephalopathy, were infrequent and mild. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy.
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PMID:Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas. 359 91

Both B16 melanoma and Lewis lung carcinoma growing in C57/Bl mice spontaneously metastasize to the lungs and other organs. When the tumors are grown in the mouse tail to a specific volume and amputated, the spontaneously disseminated tumor cells can then be independently treated. The effects of a single dose of cyclophosphamide (200 mg/kg), cis-platinum (6 mg/kg) and melphalan (10 mg/kg) on the appearance of pulmonary and other metastases were measured. The cis-platinum treatment was shown to reduce the number and incidence of metastases of both tumors at various times after treatment. The antimetastatic effectiveness of cis-platinum against these two tumors was increased when 2.4 mg/kg was administered each day for five consecutive days after amputation of the primary. Cyclophosphamide, when administered at two-thirds maximum tolerated dose, had a small promoting effect on the number and incidence of pulmonary metastases of Lewis lung carcinoma, whereas, applied in the same dose, it had efficacy in the treatment of disseminated B16 melanoma and inhibited appearance of both pulmonary and lymph-node metastases. When melphalan was administered in single- and multiple-dose regimens, the number and incidence of metastases of both tumors increased at various times after primary tumor amputation. These data suggest that melphalan can promote the growth of disseminated tumor cells in both the lungs and other sites and that some systemic chemotherapies may result in promotion instead of suppression of metastatic disease.
Clin Exp Metastasis 1987 Sep
PMID:The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice. 365 51

Adolescent and young adult patients with pelvic sarcomas continue to have a poor prognosis with standard combination chemotherapy and local irradiation. In addition to a significant risk of local failure, these patients are at high risk for systemic relapse. Twenty-three consecutive patients with Ewing's sarcoma, alveolar rhabdomyosarcoma, undifferentiated sarcoma, or malignant peripheral neuroepithelioma originating in the pelvis were treated with short, intensive combined modality therapy. This approach integrates 5 cycles of VADRIAC chemotherapy (Vincristine, Adriamycin, Cyclophosphamide) with high dose irradiation to the primary lesion (55-60 Gy) and sites of gross metastatic disease (45-50 Gy). Following achievement of a complete response, intensification therapy consisting of total body irradiation (TBI) (8.0 Gy), high dose VADRIAC chemotherapy, and autologous bone marow transplantation is given. All therapy is completed within 6-7 months. No maintenance chemotherapy is given; no surgery is intended. Of the twenty-three patients with pelvic sarcomas treated on this combined modality protocol, 22 achieved a complete remission. Local control was achieved and maintained in all twenty-three patients. With a median follow-up of 21 months since initiation of treatment, there have been nine relapses (all systemic). Seven relapses occurred among the thirteen patients who presented with overt metastatic disease and the other two relapses were among the ten patients with localized disease at presentation. All seven metastatic patients who relapsed have died, whereas both of the relapsed localized patients remain alive. Acute and late toxicities have been acceptable using this aggressive combined modality approach. Induction chemotherapy had a significant impact on reduction of the typically large (greater than 10 cm diameter) soft tissue mass associated with these pelvic tumors, thus facilitating achievement of local control by high dose irradiation. Of 18 patients with measureable soft tissue tumor, all experienced a partial response (greater than 50% reduction in size) following the initial two cycles of chemotherapy given prior to local irradiation. In conclusion, this short, intensive chemoradiotherapeutic regimen is highly effective in controlling the primary lesion (100% local control) and inducing a complete response in a high proportion (96%) of these high risk pediatric and young adult patients with pelvic sarcomas. The role of TBI as "systemic" adjuvant therapy to control micrometastatic disease is discussed as still under investigation.
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PMID:Treatment of pelvic sarcomas in adolescents and young adults with intensive combined modality therapy. 367 16

Three chemotherapeutic agents, methotrexate, cyclophosphamide and cis-diamminedichloro-platinum (cis-platinum), were examined for their effectiveness against metastases in a murine transitional cell carcinoma model. Systemic treatment of the drugs was applied against a MBT-2 derived subline which generates 100% incidence of lung metastases in C3H mice by five weeks. The drugs were examined for their effect against the number of metastases, incidence of metastasis and size of the subcutaneously implanted primary tumor. All three compounds significantly reduced both the number of lung metastases and the incidence when compared to untreated animals. None of the agents proved 100% effective against metastatic tumors. These results suggest the existence of a chemotherapeutic resistant population of metastatic cells. Administration of methotrexate and cis-platinum effectively reduced the size of the primary tumor as compared to untreated animals. Cyclophosphamide did not significantly affect primary tumor size. The response of the antineoplastic agents against the metastatic tumor cells indicates that the L3F2 metastatic cell line is an effective model to study agents against metastatic bladder cancer.
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PMID:The efficacy of chemotherapeutic agents against murine bladder metastasis. 368 79

The transplantable mouse pancreas cancer cell line (MPC-83) has been established for two years, and transplanted serially into Kunming strain (KM) mice subcutaneously for 55 generations on Feb. 11, 1985. The transplantability rate in KM, BALB/C and Swiss mice was 100%. The tumor cells of some passages were stored in liquid nitrogen, and their revival was fine. It is the first transplantable pancreas cancer cell line ever established in China. The primary tumor was derived from a spontaneous pancreas cancer of a outbred male KM mouse. It was a poor-differentiated pancreatic acinar cell cancer. The transplanted tumors from all generations were similar to the primary one in both histology and histochemistry. The esterase staining was positive. By electron-microscopy, the zymogen granules were seen in the cytoplasm of its 1st, 25th and 33rd passages. The chromosome numbers in 28th, 32nd and 35th passages were hypertriploid with a modal number of 60 to 69, and some abnormal submetacentric chromosomes could be seen. The mean survival time of the tumor-bearing mice was 22 days. Metastases could be found in the lung (80%), sometimes in pancreas, omentum and other abdominal organs nearby with bloody cancerous ascites (10.5%). The fat necrosis might be noted around the tumor. These phenomena were similar to the clinical characteristics of human pancreas cancer. The preliminary therapeutic test shows that MPC-83 is sensitive to anticancer drugs such as 5-FU, Cyclophosphamide and cis-platin. This modal may be used for study of pancreas cancer, the mechanism of metastasis and antimetastatic agents of tumor, basic research and anticancer drugs.
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PMID:[Transplantable mouse pancreatic acinar cancer cell line (MPC-83) and its characteristics]. 373 17


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