Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While structure-activity relationships for vinblastine (VLB), vincristine, deacetyl-VLB, and deacetyl-VLB amide (vindesine, VDS) in several tumor and leukemia models have been reported previously, the present study explores these relationships for a series of N-substituted vindesine analogues. These compounds were prepared from the reaction of deacetyl-VLB acid azide with the appropriate amines and were characterized by mass spectral analysis, 1H and 13C NMR spectra, electrometric titration, and infrared spectra. N-Alkylvindesines have reduced activity compared to that of VDS against the Gardner lymphosarcoma (GLS). N-beta-Hydroxyethyl-VDS surpasses vindesine in its activity against the Ridgway osteogenic sarcoma and the GLS, whereas against the B16 melanoma it is less active than VDS. N-beta-(4-Hydroxyphenethyl)-VDS, envisaged as a substrate for the enzyme tryosinase, was shown to be more active than VDS against the B16 melanoma but has only marginal activity against the GLS. In terms of collective antitumor activity against the model systems used, vindesine emerges as the congener with optimum qualities. Bis(N-ethylidenevindesine) disulfide, the first example of a bridged bisvindesine and comparable to VDS in its antitumor profile, shows evidence of activity against a P388/VCR leukemia strain known to be resistant to maytansine as well as to vincristine.
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PMID:Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted deacetylvinblastine amide (vindesine) sulfates. 43 Apr 77

218 patients examined for localized cancer of the extremities (50% benign, 50% malignant) are reported. The incidence is considered by sex and age. Demolition surgery was carried out in 35 patients and 27 locoregional treatment with antiblastics and radioactive isotopes was employed. Conservative surgery was used in 158. Operative mortality was less than 1% (2 cases out of 218) and did not reach 6% if amputations and disarticulations alone are considered. There were no deaths in cases submitted to radiochemotherapy and inguinocrural hymphadenectomy. The series includes a 15-years survival for giant-cell tumour of the femur treated with radioactive microsphores, an 11-years survival for a popliteal melanoma submitted to radiocolloid infiltration, a 9-year survival for femoral osteosarcoma for which hip disarticulation was carried out and a 4-year survival for a recurrent rhabdomyosarcoma of the hip operated by hemipelvectomy.
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PMID:[Methods of treatment of tumors of the soft parts and bones of the limbs and extremities. Analysis of case records]. 46 96

Screening for retinoic acid-binding protein (RABP) in experimental tumors revealed the presence of this protein in three mammary tumors, two metastatic colon tumors, B16 melanoma. Lewis lung carcinoma, Ridgway osteogenic sarcoma, and keratoacanthoma. RABP was below the limits of detection in two weakly metastatic colon tumors and in Sarcoma 180. After s.c. implantation of RABP-containing tumors into mice, this protein could be traced in the lungs due to pulmonary metastasis. Following implantation of Lewis lung tumors, RABP was detected in the lung on the 6th day. On the 15th day after implantation, RABP was present in lung and brain, but not in other tissues where this protein was normally lacking. In primary cultures of Lewis lung carcinoma, the lower limit for detection of RABP by sucrose gradient sedimentation technique corresponded to 0.12 mg protein that was extractable from 3 X 10(5) cells. Both chick embryo skin and rabbit ear skin extracts contained RABP; the level of cellular retinol-binding protein was high in chick embryo skin but only marginal in rabbit ear. The amounts of these proteins on chick embryo skin and rabbit ear skin correlate with the biological potency of retinol and retinoic acid, as observed by others.
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PMID:Retinoic acid-binding protein in experimental tumors and in tissues with metastatic tumor foci. 56 58

6 patients with solid tumours (4 malignant melanomas, one fibrosarcoma, one osteogenic sarcoma) received i.v. C. parvum alone or in combination therapy (radiotherapy, Levamisole and/or vitamin A). The single doses of C. parvum ranged from 5.0-7.5 mg/m2; No. of doses ranged from 1-8; interval between doses ranged from 2-140 days. 2 patients with malignant melanoma had no measurable disease, one of them (stage I) still has no evidence of disease. The patient with fibrosarcoma appeared to have a minor decrease in size of some of the lung metastases for a short time (ca 4 weeks), but soon progressed as well as the other 4 patients. Except for the one patients still having no evidence of disease the other 5 are dead of disease. Survival time did not appear to correlate either with systemic reaction to C. parvum or with No. of doses of C. parvum. The one minor response was observed in a patient receiving a total of 8 doses; but response was seen already after 3 doses, and progression occurred after 6 doses. So this change of lung metastases might have been unrelated to this therapy. Summarizing, there was no evident anti-tumour effect observed after i.v. C. parvum in these patients with solid tumours.
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PMID:First impressions of I.V. C. parvum in patients with solid tumours. 60 43

Resection of pulmonary metastases in osteogenic sarcoma has been reported by us to result in a five-year survival rate of 27 percent. A later report of surgical management of pulmonary metastases from all types of sarcomas showed a five-year survival rate of 26%. This report reviews the experience with 188 patients treated surgically for pulmonary metastasis from a variety of carcinomas, demonstrating that a similar rate of survival is obtainable by surgical excision of these metastases. A total of 188 patients underwent 242 thoractomies for metastatic pulmonary carcinomas. The most frequent sites of origin were the colon, melanoma, breast, and testicular carcinoma. Surgical treatment of these metastases is justified when the following criteria are adhered to: (1) primary site controlled or controllable; (2) no extrapulmonary metastatic sites demonstrable; (3) good surgical risk; and (4) no effective treatment available by nonsurgical means.
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PMID:Pulmonary resection in metastatic carcinoma. 62 May 76

If the study of tumor immunology is to have a profound impact on clinical medicine, certain hypotheses must be proven to be valid. First and foremost, it must be demonstrated that malignant tissue possesses antigenic substances (probably protein moieties) that are unique to that particular malignant process. In addition, these antigenic substances must be very similar in histologically similar tumors. Second, the host defense mechanisms must be capable of reacting to these tumor-associated antigens. The reaction is, of course, necessary in order to develop both diagnostic and therapeutic routes of application. The reaction of the immunologic system to these tumor-associated antigens could be monitored as an early serodiagnostic tool for subclinical cancer, and the cytotoxic reaction holds great promise as an immunotherapeutic tool. The essence of tumor immunologic research can thus be stated in the form of the following questions: 1. Do histologically similar cancers from identical primary sites share common tumor-associated antigens? 2. Does the immunologic system react to these antigens? 3. Can this reaction be assayed on one hand for serodiagnosis and augmented on the other for immunotherapy? Specific antigens have been found in animal tumors and have been divided into two classes: the viral induced tumors, which share common antigens when caused by the same viral agent, and carcinogen-induced tumors, which appear to have unique antigenic determinants for each tumor. In recent years a great many human tumors have been found to have tumor-associated antigens; these include colonic carcinoma, neuroblastoma, melanoma, soft tissue and osteogenic sarcoma, bladder carcinoma and Burkitt's lymphoma. This report includes evidence for the existence of such antigens in adenocarcinoma of the ovary and squamous cell carcinoma of the cervix. The laboratory evidence that has been presented would suggest that there are both a cell-mediated response and humoral response to the antigenic determinants of these two gynecologic cancers. It would appear that the mediated (lymphocyte) effect is considerably more cytotoxic and definitive than the humoral factors measured. In addition, the allogenic experiments would suggest strongly that indeed (at least with regard to these two cancers) histologically similar cancers from the same organ share common antigenic determinants. The identification and isolation of these tumor-associated antigens appears complex. The complexity is increased when one studies patients afflicted with these cancers for plasma carcinoembryonic antigens. This antigen, which was thought to be specific for adenocarcinoma of the colon, is found in the blood of a significant number of patients with adenocarcinoma of the ovary and squamous cell carcinoma of the cervix.
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PMID:Tumor-associated antigens in gynecologic cancer. 76 38

Computed tomography has been found to be a more accurate diagnostic tool in the analysis of brain metastases than radionuclide scanning. Of 1,100 patients studied by CT scan, 57 showed evidence of intracerebral metastasis, and 14 showed evidence of hydrocephalus. Density levels below that of normal brain tissue were found in cases of metastases from the lung (13), breast (7), melanoma (4), kidney (3), lymphoma (3), and nasopharynx (1); levels above normal were found in cases of metastases from melanoma (8), lung (3), colon (3), chorionic carcinoma (2), osteogenic sarcoma (1), and kidney (1).
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PMID:Computed tomography in metastatic disease of the brain. 94

In parallel studies the effects of FHL1 and PNL on plated melanoma cells from cell lines and short-term cultures were compared. FHL showed more frequent and also stronger cytotoxic and/or growth-inhibiting effects than PNL. On melanoma target cells from cell lines both FHL and PNL showed more frequent and stronger cytotoxic and/or growth-inhibiting effects than on melanoma target cells from short-term cultures. In the individual donors the percentage of monocytes and EAC-rosette-forming cells in FHL was significantly higher than in PNL. A significant correlation was found between multiplication of the melanoma target cells during the period and an increased susceptibility towards lymphocytes from healthy donors. Melanoma target cells from cell lines were not more fragile, or more susceptible to unfavourable culture conditions than cells from short-term cultures, since non-lymphocytic "effector" cells showed much weaker cytotoxic and/or growth-inhibiting effects than lymphocytes from healthy donors. Cytotoxic effects of lymphocytes from healthy donors were also registered on target cells from a mammary carcinoma and an osteosarcoma cell line. No significant differences in the cytotoxic effects of lymphocytes from healthy donor were observed when tested on mycoplasma-contaminated melanoma cells and the same cells made mycoplasma-free. Mitomycin-C-treated lymphocytes retained their cytotoxic effects. Lymphocytes from a healthy donor tested on different occasions on the same melanoma cells from a short-term culture showed an incidental cytotoxic reaction.
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PMID:The influence of different isolation procedures and the use of target cells from melanoma cell lines and short-term cultures on the non-specific cytotoxic effects of lymphocytes from healthy donors. 105 13

N-(Phosphonacetyl)-L-aspartate (PALA) is an analog of the transition state for the aspartate transcarbamylase reaction and has been reported previously to be a potent and specific inhibitor of de novo pyrimidine nucleotide biosynthesis. It is now shown that PALA has considerable antitumor activity against certain transplantable tumors in mice. PALA, unlike other antimetabolites, was less effective against ascitic leukemias than against two solid tumors, B16 melanoma and Lewis lung carcinoma. Another solid tumor, Ridgway osteogenic sarcoma, which is sensitivie to many established chemotherapeutic agents, did not respond to PALA. Daily or intermittent treatment with PALA did not significantly increase the life-span of mice bearing i.p. leukemia L1210. The survival time of mice bearing i.p. P388 leukemia was prolonged by PALA treatment by up to 64%. In a number of experiments mice bearing i.p. B16 melanoma survived 77 to 86% longer than did controls when treated with PALA (490 mg/kg) on Days 1, 5, and 9. Lewis lung carcinoma, a tumor refractory to most established antineoplastic agents, was highly sensitive to PALA. Treatment on Days 1, 5, and 9 following s.c. implantation of Lewis lung carcinoma was curative to 50% of the mice. If treatment was delayed until s.c. Lewis lung tumors had reached about 500 mg, PALA neither cured the mice nor produced significant tumor regression. However, extensive delay of tumor growth and prolongation of survival were still observed.
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PMID:Antitumor activity of N-(phosphonacetyl)-L-aspartic acid, a transition-state inhibitor of aspartate transcarbamylase. 106 66

Contemporary clinical research is actively engaged at the conquest of residual neoplastic disease. The preliminary results of combined treatment modalities for osteogenic sarcoma, Ewing's sarcoma, rhabdomyosarcoma, breast cancer, malignant melanoma and Hodgkin's disease have shown a significant decrease in the incidence of distant metastases. In some neoplasias the decreased relapse rate was associated to improved survival. Since the problem of long-term carcinogenesis does exist, the use of prolonged adjuvant chemotherapy, at present moment, is best limited to patients at high risk of early relapse when treated only with local or local-regional modalities.
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PMID:Treatment of residual neoplastic disease in solid tumours. 106 17


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