Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major goal of this study was to evaluate the effects of tumor necrosis factor-alpha (TNF-alpha), delivered as pGL1-TNF-alpha, on hematological variables, as well as C6 tumor growth in athymic mice treated with and without radiation. pGL1-TNF-alpha was administered intratumorally at low to high doses (15, 150 and 450 microg) in all three phases of this study. In phase A, pGL1-TNF-alpha expression within tumors was dose dependent and transient, with highest levels seen at 18 h after injection, whereas no TNF-alpha protein was detected in plasma. Low erythrocyte counts, hemoglobin, and hematocrit were associated with tumor presence, but the reduction in these variables was most striking in the group receiving 450 microg of pGL1-TNF-alpha, the group that also exhibited thrombocytopenia at 72 h. In phase B, treatment with pGL1-TNF-alpha at 15 or 150 microg resulted in the greatest degree of splenomegaly, increased spontaneous blastogenesis by splenocytes, and high leukocyte and lymphocyte numbers in the spleen. In these same two groups, flow cytometry analyses of spleen cells showed that high levels of natural killer (panNK+) cells, B (CD19+) lymphocytes, and cells expressing the CD71 and CD25 activation markers were present (p < 0.05). An enhancing effect was also noted in some of the measurements with parental plasmid p WS4 and tumor presence. In phase C, the slowest tumor progression was observed in the groups receiving 15 and 150 microg pGL1-TNF-alpha together with radiation; tumor volumes were 51 and 43% smaller, respectively, than for PBS-injected controls by the end of the study. Collectively, these results show that localized treatment with pGL1-TNF-alpha is hematologically nontoxic at low doses and support the premise that activation of lymphocytes may contribute to the antitumor effects of radiation against a highly aggressive brain tumor.
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PMID:Lymphocyte activation with localized pGL1-TNF-alpha gene therapy in a glioma model. 1181 46

Anthracyclines remain as the best drugs in the treatment of patients with aggressive malignant lymphoma in combination with other cytotoxic drugs. However, dose escalation is poorly tolerated and acute and late cardiac toxicity has limited the use of these compounds. Pegylated liposomal doxorubicin has been proven to be useful in some malignancies, without the presence of acute cardiac toxicity and with a good response rate in patients with relapsed/refractory lymphomas. We report the first study of this drug in combination chemotherapy in patients with previously untreated aggressive malignant lymphoma. Twenty consecutive patients with diagnosis of diffuse large-B-cell lymphoma, age < 18 yr to < 70 yr, without previous treatment, HIV-negative high and high-intermediate clinical risks were treated with the CHOP-Bleo regimen at standard doses, using pegylated-liposomal doxorubicin instead of doxorubicin, at 25 mg/m2 (3 patients), 30 mg/m2 (3 patients), and 35 mg/m2 (14 patients). Complete response was achieved in 17 cases (85%), with failure in 3 patients (15%). At a median follow-up of 18.1 mo, relapse has not been observed. Two patients died secondary to tumor progression. Toxicity was mild, only three episodes of granulocytopenia grade I were observed, and no mucositis, thrombocytopenia, or granulocitopenia grade > 2 was observed. Erythrodisestesias grade II was observed in one case and grade I in two cases. Cardiac function was normal before and 12 mo after chemotherapy. Pegylated liposomal doxorubicin appear as an promising drug in the treatment of patients with aggressive malignant lymphoma.
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PMID:Pegylated liposomal doxorubicin in combination chemotherapy in the treatment of previously untreated aggressive diffuse large-B-cell lymphoma. 1202 91

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.
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PMID:Intracaval and intracardiac metastatic nonseminomatous germ cell tumor: a rare cause of hemolytic anemia and thrombocytopenia. 1244 33

The aim of this study was to compare tolerance of a nitrosurea-based regime with 'standard' therapy of vincristine (VCR) and carboplatin for low-grade gliomas. Ten children with low-grade gliomas received second line therapy consisting of thioguanine, procarbazine, CCNU and vincristine (TPCV). Two groups were identified, i.e. patients who had either experienced significant toxicity with carboplatin (reaction group) or had re-growth of their tumor (re-growth group) following first line therapy. Patients were evaluated for toxicity. Data was available on nine patients. Patients in the reaction group completed a mean of 3 cycles of TPCV (range 2-4). One patient stopped after 2 cycles of TPCV due to tumor progression and died 3 months later and one remained on therapy at the time of analysis. Patients in the re-growth group received a mean of 5.5 cycles of TPCV (range 4-8). Treatment was discontinued in one patient after 4 cycles due to hematological toxicity, one experienced tumor progression after 4 cycles and one stopped after 6 cycles because of neurological toxicity. There was no difference in the incidence of grade 3/4 neutropenia or thrombocytopenia, transfusion requirements or delays in chemotherapy between TPCV and VCR/carboplatin in either group. There were no serious infections or toxic deaths. Seven of nine patients had stable disease at a mean of 13 months of follow up. TPCV therapy is a well-tolerated regime with comparable bone marrow toxicity to VCR/carboplatin. Significant disease stabilization was observed with TPCV and hence this regime may be used as second line therapy.
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PMID:Tolerance of nitrosurea-based multiagent chemotherapy regime for low-grade pediatric gliomas. 1289 35

In the first phase of this study 34 patients with advanced pancreatic cancer have been treated either with gemcitabine/cisplatin or gemcitabine/5-fluorouracil (5FU)/leucovorin combination. (Gemzar: 900 mg/m2, Cisplatin: 20 mg/m2, 5-FU: 750 mg/m2). Treatments were continued till tumor progression. There was no difference observed between the two protocols in the clinical response rates (PR=65%). On the other hand, a significant difference was found between the two protocols regarding the side effects. In the case of gemcitabine/5-FU neutropenia, thrombocytopenia and anaemia (as well as nausea and vomiting) were much less frequent compared to gemcitabine/cisplatin combination. Based on these data the efficacy of gemcitabine/5-FU combination was evaluated in 99 stage III, T1-4, N1 and stage IV, T1-4, N0-1, M1 pancreatic cancer patients throughout 364 treatment cycles. OR was achieved in 10% while stable disease in 52% of the cases. The average survival period was 8.33 months while the time to progression was 5.75 months. Based on these data we recommend gemcitabine/5-FU/leucovorin combination for the treatment of advanced pancreatic cancer.
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PMID:[Experience with the treatment of advanced pancreatic cancer in Hungary]. 1297 69

In this report, we present a six-year-old male patient with partial intestinal obstruction due to refractory Non-Hodgkin's lymphoma (NHL) whose partial obstruction was successfully treated with Taxol(R) without any surgical intervention. Following an unsuccessful treatment attempt to treat his high-grade (stage 3) B-cell lymphoma with standard and second-line chemotherapy regimens he was started on radiotherapy and third line chemotherapy during which he was admitted with partial obstructive ileus as a result of tumor progression. Treatment was continued with Taxol(R) and resulted in total cure of the ileus with reduction of palpable tumor mass over 24 h without necessitating any surgery. Taxol(R) (200 mg/m (2)/week) was administered without any major side effects/toxicities for six courses. A control CT of the abdomen revealed a significant reduction in tumor size. After the next course, the patient developed severe thrombocytopenia that unfortunately did not resolve before the patient died as a result of further tumor growth and dissemination. Although there are studies that report response to Taxol(R) treatment in adult patients with refractory NHL, our review of the literature failed to demonstrate any report about the effectiveness of Taxol(R) in childhood NHL. In conclusion, our case may indicate that Taxol(R) can be effective and be administered safely in an outpatient setting in children with refractory NHL with the aim of prolonging the survival without sacrificing good quality of life. Studies on larger number of patients are needed to make a definitive conclusion about the value of Taxol(R) in refractory childhood NHL.
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PMID:Partial intestinal obstruction due to childhood refractory hon-Hodgkin's lymphoma, successfully treated with taxol. 1368 May

Gemcitabine (Gemzar) and paclitaxel exhibit good activity and good safety profiles when used alone and together in the treatment of advanced breast cancer. In a phase II trial, 45 patients with metastatic breast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 and paclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients (60.0%) had prior adjuvant therapy. Objective response was observed in 30 patients (objective response rate 66.7%, 95% confidence interval [CI] = 52%-71%), including complete response in 10 (22.2%) and partial response in 20 (44.4%). Median duration of response was 18 months (95% CI = 11-26.7 months), median time to tumor progression for the entire population was 11 months (95% CI = 7.1-18.7 months), median overall survival was 19 months (95% CI = 17.3-21.7 months), and the 1-year survival rate was 69%. Treatment was well tolerated, with grade 3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia were each observed in six patients (13.3%). No patient was discontinued from the study due to hematologic or nonhematologic toxicity. Thus, the gemcitabine/paclitaxel combination shows promising activity and tolerability when used as first-line treatment in advanced disease. The combination recently has been shown to be superior to paclitaxel alone as first-line treatment in anthracycline-pretreated advanced disease according to interim results of a phase III trial and it should be further evaluated in comparative trials in breast cancer.
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PMID:Gemcitabine/paclitaxel as first-line treatment of advanced breast cancer. 1476 1

A prospective Phase II study of temozolomide (TMZ) was conducted in 16 patients with refractory meningioma. All patients had previously been treated with surgery and involved-field radiotherapy; however, no patient had prior chemotherapy. TMZ was administered orally for 42 consecutive days every 10 weeks. Grade 3 or greater TMZ-related toxicity included anemia (25%), fatigue (18.7%), neutropenia (37.5%), seizures (6.3%), and thrombocytopenia (18.7%). No patient demonstrated a neuroradiographic complete or partial response. Time to tumor progression ranged from 2.5 to 5.0 months (median 5.0 months); survival ranged from 4 to 9 months (median 7.5 months).
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PMID:Temozolomide for treatment-resistant recurrent meningioma. 1507 29

In the nearly 130 years since Trousseau first described migratory thrombophlebitis in cancer patients, thromboembolism has become a well-established presenting sign and complication of cancer. The coagulation system is activated in cancer and is further amplified by treatment with chemotherapy, radiation or surgery. Hypercoagulation is documented in virtually all cancer types, albeit at different rates, and is the second leading cause of death in cancer patients. The relationship between clotting activation and carcinogenesis supports the view of cancer as a hypercoagulable state and holds implications for the development of thrombosis, enhancement of tumor growth and risk of poor clinical outcomes. Although it is well recognized that cancer can activate the coagulation cascade, it is less well known that activation of the coagulation system may also support tumor progression. Additionally, platelet activation in cancer patients and its impact on tumor progression and metastasis further expand the role of the hemostatic system in malignancy. The problem of thrombosis in patients with metastatic diseases is a serious concern for clinicians. This review explores the mechanisms and clinical implications of coagulation and platelet activation in cancer. The prevention and treatment of venous thromboembolism in cancer will also be discussed by reviewing data from key clinical investigations. Finally, the emerging role of low-molecular-weight heparin as an antineoplastic agent will be explored. Warfarin and unfractionated heparin have been in clinical use for more than 50 years. Both are effective anticoagulants, but their use is associated with a number of impediments, including the need for intensive coagulation monitoring, wide variation in dose-response relationships, multiple drug interactions (in the case of warfarin), and serious immune-mediated thrombocytopenia (in the case of heparin). The introduction of low-molecular weight heparin advanced anticoagulation therapy by enhancing efficacy and eliminating the need for intensive coagulation monitoring. Fondaparinux, the first selective factor Xa inhibitor, represents yet another improvement in anticoagulation therapy. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Additionally, efficient inhibition of factor Xa activity impairs the activation of tissue factor/factor VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis, and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a number of orally active direct antithrombin and anti-factor Xa are in advanced clinical development for various thromboembolic disorders.
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PMID:Role of current and emerging antithrombotics in thrombosis and cancer. 1706 36

In the nearly 130 years since Trousseau first described migratory thrombophlebitis in cancer patients, thromboembolism has become a well-established presenting sign and complication of cancer. The coagulation system is activated in cancer and is further amplified by treatment with chemotherapy, radiation or surgery. Hypercoagulation is documented in virtually all cancer types, albeit at different rates, and is the second leading cause of death in cancer patients. The relationship between clotting activation and carcinogenesis supports the view of cancer as a hypercoagulable state and holds implications for the development of thrombosis, enhancement of tumor growth and risk of poor clinical outcomes. Although it is well recognized that cancer can activate the coagulation cascade, it is less well known that activation of the coagulation system may also support tumor progression. Additionally, platelet activation in cancer patients and its impact on tumor progression and metastasis further expand the role of the hemostatic system in malignancy. The problem of thrombosis in patients with metastatic diseases is a serious concern for clinicians. This review explores the mechanisms and clinical implications of coagulation and platelet activation in cancer. The prevention and treatment of venous thromboembolism in cancer will also be discussed by reviewing data from key clinical investigations. Finally, the emerging role of low-molecular-weight heparin as an antineoplastic agent will be explored. Warfarin and unfractionated heparin have been in clinical use for more than 50 years. Both are effective anticoagulants, but their use is associated with a number of impediments, including the need for intensive coagulation monitoring, wide variation in dose-response relationships, multiple drug interactions (in the case of warfarin), and serious immune-mediated thrombocytopenia (in the case of heparin). The introduction of low-molecular weight heparin advanced anticoagulation therapy by enhancing efficacy and eliminating the need for intensive coagulation monitoring. Fondaparinux, the first selective factor Xa inhibitor, represents yet another improvement in anticoagulation therapy. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Additionally, efficient inhibition of factor Xa activity impairs the activation of tissue factor/factor VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis, and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a number of orally active direct antithrombin and anti-factor Xa are in advanced clinical development for various thromboembolic disorders.
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PMID:Role of current and emerging antithrombotics in thrombosis and cancer. 1680 96


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