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)

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.
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PMID:Thermoradiotherapy of recurrent malignant brain tumors. 131 81

A retrospective review covering a 9-year period revealed 113 patients who underwent 157 major bowel procedures during 130 operations performed solely by gynecologic oncology surgeons. Forty-eight percent of the operations were done for tumor cytoreduction, and 33% were performed for a bowel obstruction. Other indications included colostomy closure, fistula repair, resection for multiple enterotomies, temporary diversions, repair of perforated bowel, treatment for severe proctosigmoiditis, management of ureteral stricture, treatment for vulvar necrosis, and resection of an incidental small bowel tumor. Of the 157 procedures, 44% were colostomies, 32% were bowel resections with reanastomosis, 9% were urinary conduits, 6% were intestinal bypass procedures, 5% were colostomy closures, and 4% were ileostomies. Postoperative complications occurred in 32% of the 130 operations. These included wound infection, death, sepsis, fistula formation, urinary tract infection, unexplained febrile morbidity, anastomotic leakage, stomal infarction, adult respiratory distress syndrome, bowel obstruction, deep venous thrombosis, and wound hematoma. Four of the eight deaths were due to tumor progression, three were from sepsis, and one was from adult respiratory distress syndrome. Of the 130 operations, 89 (68%) were associated with no complications. These data support the concept that gynecologic oncology surgeons are able to perform intestinal operations as therapy for gynecologic malignancies with acceptable complication rates. Since a thorough understanding of the natural history of the cancer, familiarity with alternative therapeutic options, and knowledge of the prognosis are important in making operative decisions, and since gynecologic oncologists are technically capable of performing operations on the small bowel and colon, referral of patients with a primary or recurrent gynecologic malignancy or with a subsequent intestinal complication after initial therapy should be directed to the gynecologic oncologist whenever possible.
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PMID:Intestinal surgery performed on gynecologic cancer patients. 198 13

In a prospective multicenter study, 244 men with highly or moderately differentiated prostatic cancer in stage I, II or III (VACURG) were consecutively randomized to three groups of treatment: Group A (77 patients) received polyestradiol phosphate (Estradurin, Leo) 80 mg i.m. every fourth week + ethinyl estradiol (Etivex, Leo) 150 micrograms daily, group B (72 patients) estramustine phosphate (Estracyt, Leo) 280 mg twice daily, and group C (76 patients) no therapy. Only men without current or previous other malignancy and without cardiovascular disease were admitted to the study. After 4 1/2 years 125 of the 244 patients had left the study, 9 because of cancer progression (stage IV, VACURG). The most serious complications were cardiovascular, including ischemic heart disease, cardiac decompensation, cerebral ischemia and venous thromboembolism, which occurred in 24 patients from group A and 9 from group B as compared to only one patient in group C. The subgroup superficial or deep venous thrombosis comprised 11 group A and 2 group B patients. Estrogens (E + e) offered as palliative treatment to patients with non-generalized prostatic carcinoma is burdened with a high incidence of serious cardiovascular complications.
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PMID:Cardiovascular complications of estrogen therapy for nondisseminated prostatic carcinoma. A preliminary report from a randomized multicenter study. 352 68

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. 838 28

Between January 1991 and June 1995 we have operated on 19 patients (9 male, 10 female) with 22 skeletal metastases of the lower limb (19 femora, 3 tibiae) using a static interlocking nail. Closed intramedullary nailing without resection of the metastasis has been established as our standard procedure. We have stabilized 15 patients with advanced osteolysis and seven pathological fractures. Sixteen patients underwent postoperative local radiation therapy with 40 Gy. As intraoperative complications we have observed one fracture of an osteolysis and one death due to fat embolism. Postoperatively there were observed one seroma, one haematoma and one patient with non fatal pulmonary embolism following DVT. Two patients died within the first 30 postoperative days because of tumor progression. All patients surviving longer than 30 days could be mobilized under full weight-bearing. Morphine like analgetics for metastasis related pain were no longer needed. A secondary instability has not been observed within a mean survival time of 199 days (811 longest follow up). Closed intramedullary nailing in combination with postoperative local radiation therapy seems to be an appropriate and technically non demanding procedure to stabilize skeletal metastases of the lower limb in patients with a short or medium-term expectation of life.
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PMID:[Surgical management of bone metastases of the lower extremity with AO interlocking nail]. 902 56

Hemostatic disorders are frequently observed in patients with malignancy with a significant proportion developing thrombotic and/or hemorrhagic complications including disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), and thrombocytopenia. Together, these abnormalities are the second most common cause of mortality in cancer patients, which has led many investigators to try to unravel the pathogenesis of thromboembolic disease, in the eventuality that this will lead to novel therapeutic treatments. The plasminogen activation system is one pathway that has been consistently implicated in cancer. Its relevance to cancer extends from being responsible for many of the hemorrhagic episodes that occur in cancer patients to being fundamental to many, if not all of the molecular mechanisms that define tumor progression. Recent developments of clinical significance shall be reviewed with respect to the role of the plasminogen activation system in tumor growth and metastasis dissemination and in the thrombophilic state in the cancer patient.
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PMID:The role of the plasminogen activation system in cancer. 1035 86

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p < 0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p < 0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.
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PMID:Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study. 1084 93

Patients with cancer are frequently treated with anticoagulants, including heparins, to treat or to prevent thrombosis. Recent randomized trials that compared low molecular weight heparin to unfractionated heparin for the treatment of deep vein thrombosis have indicated that heparins affect survival of patients with cancer. Experimental studies support the hypothesis that cancer progression can be influenced by heparins, but results of these studies are not conclusive. Heparins are negatively charged polysaccharides that can bind to a wide range of proteins and molecules and affect their activity. As a consequence, heparins have a wide variety of biological activities other than their anticoagulant effects, which may interfere with the malignant process. In the present systematic review, we critically evaluate experimental studies in which heparins have been tested as anti-cancer drugs. All animal studies, published between 1960 and 1999, that report effects of heparins on growth of subcutaneously implanted tumors, spontaneous metastasis or experimentally induced metastasis are reviewed. In addition, we discuss mechanisms by which heparins potentially exert their activity on various steps in cancer progression and malignancy related processes. It is shown that heparins can affect proliferation, migration, and invasion of cancer cells in various ways and that heparins can interfere with adherence of cancer cells to vascular endothelium. Moreover, heparins can affect the immune system and have both inhibitory and stimulatory effects on angiogenesis. Because of the wide variety of activities of heparins, it is concluded that the ultimate effect of heparin treatment on cancer progression is uncertain.
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PMID:The complex effects of heparins on cancer progression and metastasis in experimental studies. 1117 40

A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.
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PMID:Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer. 1468 33

Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan.
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PMID:Thalidomide for the treatment of multiple myeloma. 1532 81


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