Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-seven patients with malignant gestational trophoblastic disease (GTD) were treated by the Gynecologic Oncology Unit of the Tygerberg Hospital, Parowvallei, RSA, between 1977 and 1986. Treatment was primarily with triple chemotherapy (MAC) followed by citrovorum factor. The total remission rate in the 23 patients with high risk malignant GTD was 78.3% but in the 16 patients categorized as poor prognosis metastatic disease the remission rate dropped to 68.8%. The third world background in the majority of our patients, the poor general health, and the language barrier indirectly influenced the management of these patients. Psychological problems were evident in 60.9% of our patients. This often resulted in poor patient compliance which adversely influenced the outcome of the disease.
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PMID:High risk malignant gestational trophoblastic disease: experience with triple chemotherapy (MAC) in Third World circumstances. 246 40

Between 1972 and 1986, 37 patients with lower genital tract malignancies were treated with intracavitary or interstitial brachytherapy. Thirteen patients presented with clear cell adenocarcinoma, 14 patients with embryonal rhabdomyosarcoma, 6 patients with endodermal sinus tumor, 3 patients with sarcoma, and 1 patient with an undifferentiated tumor. FIGO classification was: Stage I, 16%; Stage II, 47%; and Stage III, 37%. Treatment policy included initial exploratory laparotomy with lymph node biopsy and ovarian transposition, chemotherapy (except in clear cell adenocarcinoma) and/or external radiotherapy prior to interstitial brachytherapy. Chemotherapy consisted of a combination of VAC-Ad (V = vincristine, A = D actinomycin, C = cyclophosphamide, Ad = adriamycin) in rhabdomyosarcoma and sarcomas, and MAC-Ad (M = methotrexate) in endodermal sinus tumor. External radiotherapy was used in seven patients: in one to reduce a bulky clear cell adenocarcinoma (20 Gy) and in six for pelvic nodal involvement (45 Gy). Brachytherapy techniques depended on tumor site and extent, and on the anatomy of the patients. Vulvar tumors were implanted with iridium-192 wires by an afterloading plastic tube technique. Cervical and vaginal tumors were treated with individually tailored moulded vaginal applicators loaded with either cesium-137 or iridium-192, with or without interstitial implants by plastic tube or guide gutter technique. Computerized dosimetry allowed calculation of treatment volumes and doses delivered on the tumor and adjacent critical organs. The prescribed dose (including external radiotherapy) was 60-75 Gy with 1-3 brachytherapy applications of a low dose rate (0.2 Gy/hr). Six patients are dead: one from chemotherapy complication, three of metastases (two sarcomas, one endodermal sinus tumor) and two of pelvic failures and metastases (two clear cell adenocarcinoma). The overall disease free 5-year survival is 72%. Actuarial 5-year local control is 84%, but including salvage is 94%: three (two rhabdomyosarcoma, one clear cell adenocarcinoma) of the five local failures were salvaged by surgery, chemotherapy and/or brachytherapy. Metastases occurred in six patients, one (sarcoma) salvaged by chemotherapy and external radiotherapy. Complications requiring surgery occurred in five patients: two hydronephroses, one urethral stricture, one ileo-cecal obstruction, and one vesicovaginal fistula. Twelve of the 17 patients (71%) over 12 years of age are normally menstruating. Two patients have produced three normal children. This multidisciplinary management of lower gynecological tract tumors including brachytherapy is both conservative and effective.
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PMID:Conservative treatment for lower gynecological tract malignancies in children and adolescents: the Institut Gustave-Roussy experience. 277 54

From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.
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PMID:Poor prognosis metastatic gestational trophoblastic disease: experience with moderate dose methotrexate plus folinic acid rescue as initial therapy. 302 4

Can the mental adjustment of patients to cancer influence the course of their disease? This question is considered in a critical review of relevant studies. Salient problems in this field of research are identified and basic methodological requirements outlined. The few systematic, prospective investigations which meet these requirements show evidence for an association between mental adjustment to cancer and subsequent outcome in patients with 'early'--ie non-metastatic disease. The evidence, however, should be regarded as provisional rather than conclusive. A definitive answer will require further carefully controlled long-term follow-up studies. In such studies, a crucial methodological issue is the measurement of mental adjustment to cancer. Hitherto, this has been based solely on clinical assessments. The development of a new measure of mental adjustment to cancer is reported. The MAC scale is a 40-item self-rating questionnaire. Initial results based on a study of 235 patients with a variety of cancers indicate that the scale is acceptable to patients, easy to administer in busy oncology clinics, reliable and stable over time. Its validity as measured by spouses' ratings appears satisfactory. Further evaluation is required. These preliminary results suggest that the MAC scale is a suitable, easily replicable method of measuring adjustment to cancer in studies of large numbers of patients.
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PMID:Mental adjustment to cancer: its measurement and prognostic importance. 332 57

Increased growth of tumor metastases has been reported after primary tumor excision in animal models. Postulated mechanisms for this phenomenon include circulating suppressor factors secreted by the primary tumor, tumor manipulation during surgical excision, and limiting nutritional factors which are consumed by both primary and metastatic tumors. To study this phenomenon, Lewis/Wistar rats with subcutaneous mammary adenocarcinoma implants (MAC-33) were randomized to receive either a standard protein diet (22.0% protein, 4.20 kcal/g) or a protein-depleted diet (0.03% protein, 4.27 kcal/g) ad lib per os. Twenty-one days after tumor inoculation, half of the animals in each dietary group underwent primary tumor excision. Control animals underwent sham excision on the flank contralateral to the tumor and physical manipulation of the primary tumor. At sacrifice 35 days after tumor inoculation, a significant increase in regional metastasis (axillary lymph nodes) and distant metastasis (lungs) occurred after primary tumor excision in animals receiving the standard protein diet. No increase in regional or distant metastases were found in animals receiving the protein-depleted diet after tumor excision. Serum was collected from animals given the standard protein diet following tumor or sham excision and added to MAC-33 tumor cell cultures for in vitro determination of tumor cell proliferation. [H3]Thymidine incorporation by MAC-33 cells in vitro was significantly suppressed by serum from tumor-bearing animals. These results imply that the biologic mechanism mediating this phenomenon is a circulating suppressor factor of tumor metastasis which is produced in tumor-bearing animals receiving standard protein (but not protein-depleted) diets.
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PMID:Inhibition of tumor metastasis by a circulating suppressor factor. 841 85

Five children with congenital-infantile fibrosarcoma are analyzed. The tumor was found at birth in four children: in one patient it was recognized at the age of 7 months. In three children the tumor affected the lower extremity. In one patient the inguinal region was the primary site, in another the abdominal wall. The morphology was that of a highly cellular spindle cell sarcoma with cells arranged in a fascicular pattern. Variations of this common pattern such as a cartwheel arrangement, and foci of small oval cells were observed. The immunohistochemistry revealed positivity of vimentin in four investigated tumors and muscle specific actin in three. Desmin, sarcomeric actin and myoglobin were all negative. There were scattered cells positive with KP1 (CD68), MAC 387, and in one case, with factor XIIIa antibodies which were considered to be reactive rather than tumor cells. The flow cytometry study showed DNA content in three tumors within diploid range; one tumor was hyperdiploid with the DNA index 1.2. Three children are disease-free from nine to 21 years after the diagnosis. One of them had the tumor preoperatively irradiated, and the subsequent histological examination revealed an almost complete tumor necrosis. In one patient there were six recurrences (treated by surgery only), and the child is well 25 months after the last recurrence. In one child the disease had an unusually aggressive course, and the patient died of widespread metastases to the lungs, lymph nodes and bones.
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PMID:Congenital-infantile fibrosarcoma: a clinicopathological study of five patients entered on the Prague children's tumor registry. 889 21

Methotrexate produced the first remission in leukemia and the first cure of a solid tumor, choriocarcinoma. Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid. Methotrexate also directly inhibits the folate-dependent enzymes of de novo purine and thymidylate synthesis. Resistance to methotrexate may develop as a result of elevated DHFR activity or defective transport of methotrexate into malignant cells. Increased DHFR enzyme levels may also result from amplification of the DHFR gene, which is now clinically significant in selected patients. Methotrexate is an active drug in the first-line treatment of gestational trophoblastic disease (GTD) and in metastatic squamous cell carcinoma of the cervix. Since the introduction of methotrexate chemotherapy for malignant GTD, most hospitals have reported almost 100% cure rates for patients with nonmetastatic disease using single-agent regimens. Patients with low-risk metastatic disease have been treated with methotrexate and folinic acid and over 50% complete remission rates have been reported. Patients with metastatic GTD who had one or more high-risk factors benefited from initial multiagent chemotherapy, rather than waiting for acquisition of drug-resistance to single-agent therapy to start multiagent treatment. Using multiagent combination chemotherapy such as MAC (methotrexate, actinomycin D, cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin D and cyclophosphamide, vincristine), most investigators have reported remission in approximately 60 to 80% of patients with high-risk metastatic GTD. Although the role of chemotherapy in carcinoma of the cervix has been limited for several reasons, trial of combination chemotherapy including methotrexate has been reported. However, it is still impossible to draw definite conclusions as to whether methotrexate combined with another clearly active drug may yield a superior response rate and survival.
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PMID:[Methotrexate in gynecologic oncology]. 897 93

Expression of a number of antigens associated with small cell lung cancer (SCLC) have been proposed as a marker of malignancy and the diagnostic tool for the staging procedures and important prognostic factor. Since the bone marrow (BM) was described as a frequent site for SCLC metastases, we have decided to assess clinical importance of cancer cells detection in BM, using immunofluorescence with MAC-1, MAC-31, NSE and anti-Fucosyl-GM1 (PF3) antibodies. The group of 32 patients with SCLC was assessed using our panel of antibodies. Control group consisted of 5 patients with other malignancies (3 patients with malignant lymphoma, 1 with chronic lymphocytic leukaemia and 1 with non-SCLC). The study revealed no correlation between the expression of SCLC markers in patients BM and the cancer treatment outcome measured as a response for treatment, time to progression, and survival time, and no significant difference was found between the patients and control group.
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PMID:[The use of monoclonal antibodies in the detection of small cell lung cancer metastases in bone marrow]. 1048 25

The anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg(-1), intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg(-1), i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and beta-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action.
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PMID:In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. 1060 28

A rare pattern of colon cancer recurrence is presented. A 63-year-old man underwent surgical resection after diagnosis of colon cancer. The postsurgical-pathologic examination showed a stage II colon cancer (MAC B2). Six courses of adjuvant chemotherapy (Mayo protocol) were started within four weeks of surgery. During follow-up, serial serum carcinoembryonic antigen levels became progressively elevated in an otherwise asymptomatic patient who showed no signs of recurrence in any of the conventional imaging tests performed (chest X-ray, abdominal ultrasound, and abdominal CT-scan). Positive findings suggesting lymph node mediastinal metastases were present in the PET scan. Surgical resection and pathologic examination demonstrated metastases of colon adenocarcinoma.
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PMID:[PET detection of recurring rectal adenocarcinoma in an unusual location. Case report]. 1086 60


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