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 plasmalemmal relationship between metastases-forming leukemia cells and myeloid sinus endothelium during the transmural passage of the leukemia cells has been studied in rat bone marrow. After the myeloid vascular system was freed from normal circulating blood cells, the bone marrow was perfused with a suspension of leukemia cells derived from an ascites tumor. The bone marrow was then fixed by perfusion with double aldehyde with and without the addition of tannic acid. Leukemia cells were seen adhering to the adluminal aspect of the sinus endothelium and in all stages of endothelial penetration. The penetration of the sinus wall was independent of endothelial junctions; i.e., the transmural passage into the myeloid parenchyma was transcellular. At these sites, there were restricted areas of close plasmalemmal appositions of the two cell types where the intraplasmalemmal space was reduced to 2.3 nm. This space was interrupted by electron densities of 5 nm diameter and spaced 9 nm center to center. These close plasmalemmal appositions extended over distances ranging from 150 nm to 200 nm. It is suggested on the basis of the structural similarity that these heptalaminar complexes of close plasmalemmal apposition represent the structural equivalent of gap junctions and may be sites of intercellular communication requisite for transmural passage. When tannic acid was added to the fixative, there were extended areas of apparent fusion of the plasmalemmas of the two cell types, at the sites both of adhesion and of endothelial penetration. This fusion was limited to the outer leaflets of the two plasmalemmas, resulting in a single pentalaminar complex. These pentalaminar complexes extended over decidedly longer distances than the presumed gap junctions seen in the nontannic-acid-fixed material. The tannic acid material did not show the heptalaminar gap junction type of plasmalemmal apposition. It is believed likely that the tannic-acid-induced pentalaminar complexes may incorporate the smaller heptalaminar ones. The factors underlying the plasmalemmal configurational differences between the tannic acid and non-tannic-acid material remain undetermined.
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PMID:Endothelial attachment and plasmalemmal apposition in the transcellular movement of intravascular leukemic cells entering the myeloid parenchyma. 281 80

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.
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PMID:Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081. 365 56

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
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PMID:Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. 390 49

From January 1980 to August 1982 the Cancer and Leukemia Group B conducted a prospective randomized trial comparing chemoendocrine therapy with T-CAF (cyclophosphamide, adriamycin, and 5-fluorouracil plus tamoxifen) to CAF alone in postmenopausal women with advanced breast cancer. The patients were stratified by estrogen receptor (ER) status into three groups: ER-negative, ER-positive, ER-unknown. They were also stratified by dominant site of metastatic disease: visceral and other (osseous and/or soft tissue). A total of 246 eligible patients were enrolled in the study; 232 were evaluable and constitute the basis for this report. The study revealed that there was no difference in overall response frequency or response duration between T-CAF and CAF; there was no difference in response between T-CAF and CAF in ER-positive or in ER-negative patients; and there was no difference in response between T-CAF and CAF by dominant site of metastatic disease. The expected advantage of T-CAF over CAF, especially for ER-positive patients, was not observed.
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PMID:Chemoendocrine therapy vs chemotherapy alone for advanced breast cancer in postmenopausal women: preliminary report of a randomized study. 636 9

The Cancer and Leukemia Group B (CALGB) has conducted two recent trials of adjuvant chemotherapy in breast cancer patients found to have lymph node metastases after mastectomy. The first trial in 772 evaluable patients demonstrated an advantage of five drugs (CMFVP) over three drugs (CMF). This advantage is seen in the group of patients who have been followed the longest period of time (median 52 months). When the more recent entries are also included in the evaluation, the benefit is seen only in women with more than three positive nodes. The advantage of five drugs over three is seen first and most dramatically in those patients with the greatest burden of disease and only later, and less dramatically, appears in groups with fewer positive lymph nodes. The second trial examines the effects of two scheduling methods of CMFVP and the value of a non-cross-reacting drug combination during the second six months of a year of adjuvant therapy.
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PMID:Cancer and Leukemia Group B adjuvant chemotherapy trials in postmastectomy breast cancer patients. 636 59

Since there was no position for a full-time pediatric hematologist, Dr. Wolff practiced general pediatrics for 10 years while he volunteered as director of the hematology clinic at the Babies Hospital. He was appointed full-time Director of Pediatric Hematology in 1959. His early clinical studies were concerned with treatment of erythroblastosis fetalis and use of frequent transfusions and desferroxamine in children with thalassemia. The combined tumor clinic at the Babies Hospital, established in 1952, was one of the first to use the multidisciplinary approach to treatment of the child with cancer. In 1957, the Children's Leukemia Group A, later called the Children's Cancer Study Group, was established by Dr. Joseph Burchenal. Dr. Wolff was one of the first members. This group led to the establishment of various national intergroup committees for clinical study of cancers in children. In 1954, Farber began to use dactinomycin for treatment of Wilms' tumor. At first this drug was used only for treatment of metastatic tumors, but later it was also used to prevent metastases. Subsequently, other childhood tumors were found to be amenable to chemotherapy.
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PMID:Dr. James A. Wolff. III. First pediatric hematologist at Babies Hospital. 639 33

A randomized study of 264 children and adults with previously untreated localized Ewing's sarcoma of bone was undertaken between 1973 and 1978 by 83 institutions of three national study groups: Children's Cancer Study Group, Southwest Oncology Group, and Cancer and Leukemia Group B. The Intergroup Study was designed to determine if the addition of adriamycin (ADR) or bilateral pulmonary radiotherapy (RT) to vincristine, dactinomycin, and cyclophosphamide (VAC therapy) would improve survival and reduce local recurrences and metastases. All patients received RT to the primary lesion, and the survival rate after 3 years was 65%. The most effective treatment regimen was VAC plus ADR; 74% of the patients were free of disease at 2 years. The lengths of disease-free status and survival of patients treated with VAC plus ADR or VAC plus RT did not differ. However, both regimens were significantly superior to treatment with VAC alone. The addition of ADR or bilateral pulmonary RT to VAC was highly advantageous to patients with nonpelvic primaries. Bone and lung were the major sites of distant relapse, but the addition of bilateral pulmonary RT showed no advantage over that of ADR in reducing the occurrence of lung metastases. These recent results should eliminate some of the pessimism that has accompanied a diagnosis of Ewing's sarcoma, although distant metastases continued to be a major reason for failure in the control of this tumor. Survival of these patients can be improved through well-controlled clinical trials designed to determine optimal adjuvant chemotherapy and treatment of the primary lesion.
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PMID:Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: an Intergroup Study. 702 93

The analysis was undertaken to determine if the time to progression and survival for women with breast cancer treated with high-dose chemotherapy after a conventional-dose induction therapy differs significantly for women younger and older than 40 years of age. All patients treated in phase II or III protocols of high-dose chemotherapy for breast cancer are included in this analysis. Women were treated on one of six protocols: four sequential phase II protocols for metastatic breast cancer involving cyclophosphamide at a dose of 6000 mg/m2, thiotepa at 500 mg/m2, and carboplatin at 800 mg/m2 (CTCb) chemotherapy; one phase II study of CTCb chemotherapy for stage III or inflammatory breast cancer; and a Cancer and Leukemia Group B phase III study of cyclophosphamide, carmustine, and cisplatin for women with more than 10 involved lymph nodes after primary therapy. Eligibility criteria for the patients with metastatic disease included histologically documented breast cancer, at least a partial response to conventional dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m2, and physiologic age of 18-55 years. Patients with inadequate renal, hepatic, pulmonary, and cardiac function or tumor involvement of marrow or central nervous system were excluded. Of 99 registered patients, three (3%) died of toxicity. There were no toxic deaths in protocols for stage II and III disease, and to date none of these patients have relapsed. Thus, there are no differences by age for these studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy: analysis by age. 752 31

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

Immune T cells recognize peptide antigens presented to them within self-MHC molecules. Thus auto-tumor reactive lymphocyte populations can be generated. Antigenic expression can be modified and intensified and reactive lymphocyte populations can be expanded. Active immunization of the tumor-bearing human host can induce immune reactions of tumor rejection strength. Frequently, micrometastases can be eliminated and occasionally partial or complete remissions of gross metastases can be induced.
Leukemia 1994 Apr
PMID:Human cancer vaccines. 815 91


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