Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 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

The aim of the present investigations was to study the effectiveness of a cytostatic drug (VCR) during different phases of tumor growth (1st, 7th, 14th days a.t.) and at the periphery and at the centre of the tumor (on the 14th day a.t.). Furthermore the inducement of a partial synchronization in the proliferation of tumor cells was attempted. It was found that the intensity of the cytostatic effect significantly decreased both with the passage of time after transplantation and within the tumor from the periphery to the centre. The changing cytostatic sensitivity probably is due to the diminishing vascular supply and the decreased rate of cell proliferation; especially the decline of the growth fraction. A partial synchronization of the proliferation of tumor cells could not be demonstrated.
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PMID:Age-dependent change of the effect of a cytostatic drug on the proliferation kinetics of a solid tumor of the mouse. 46 97

Graded doses of LSTPA or L1210 leukemia cells were injected ip or iv into fully compatible hosts or mice incompatible for Multiple Minor Histocompatibility Loci (MMHL). Three days later the animals were treated with single doses of BCNU, NM, DTIC and VCR. The results showed that NM and VCR could synergize with the weak anti-tumor immune responses of MMHL-histocompatible mice only upon ip injection of the tumor. If the same tumor has been injected iv, only BCNU could synergize with the host's antitumor response. On DTIC treatment, no synergistic effects were detectable for either route of tumor's challenge.
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PMID:[Experimental models of immunochemotherapeutic synergism: study of the influence of the treatment schedule]. 55 36

The series comprises 57 consecutive patients with Ewing's sarcoma admitted to the National Cancer Institute of Milan from 1965 to 1976. In 75% the diseas was confined to one bone, while in 25% multiple bone and/or visceral lesions were present. Patients with clinically localized tumor treated before 1971 with local therapy, showed a median disease-free survival of 5 months. After 1971, radiotherapy and/or surgery to local tumor was combined with multiple drug chemotherapy (ADM, VCR, CTX) and the projected median disease-free survival increased to 24+ months. In previously untreated patients with advanced tumor adriamycin, used as single drug, achieved an overall response rate of 73%. This is comparable to that achieved by a new combination including ADM, VCR, CTX, CCNU (75%). This multiple drug regimen is, however, expected to prolong the duration of response.
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PMID:Ten years experience with Ewing's sarcoma. 87 24

The development and application of the VCR-MTX-CF regimens for the treatment of osteogenic sarcoma have changed the biological behavior of the tumor. Recent results strongly project major advances for the future. Although the major effect of chemotherapy resides in the eradication of micrometastases, its application for treatment of the primary tumor may also be considered. However, careful experimental design and follow-up periods for several years will be required to determine the optimum approaches. For example, it is possible that the interaction between weekly VCR-MTX-CF and radiation therapy may assume increasing importance. Thus, with the effective application of VRC-MTX-CF, the management of osteogenic sarcoma has evolved into a multidisciplinary approach and future advances will be based on the collective judgement of specialists from many fields.
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PMID:Osteogenic sarcoma: state of the art with high-dose methotrexate treatment. 108 79

Using tumor-bearing mice as experimental animals, the survival rate, hematopoietic, heart, liver, kidney and immunological functions as indexes, Liu Wei Rehmannia Oral Liquid against the side-effect of drugs of anti-tumor chemotherapy (ADM, CTX, DDP, VCR and 5FU) were observed. The results showed that the survival rate in the treated group was significantly higher than that in control, the survival days were highly different (P < 0.01); the hemopoietic functions (HB, WBC, PL) in the treated group were higher also (P < 0.05 & P < 0.01); in the functions of heart, liver and kidney the treated group could protect the above-mentioned three organs (P < 0.01); in immune functions, the oral liquid could protect the NK and T-, B-Lymphocyte transformation, being inhibited by drugs of chemotherapy. In comparing with control group NK and T lymphocyte transformation were all significantly different (P < 0.01 & P < 0.05), while only 3 chemotherapy drugs were markedly different in B lymphocyte transformation (P < 0.05 & P < 0.01). The discussion indicated that Liu Wei Rehmannia Oral Liquid is effective in protecting the functions of hematopoiesis, immunity, heart, liver and kidney during chemotherapy, which provides an objective data for the clinical application.
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PMID:[Research on liu wei Rehmannia oral liquid against side-effect of drugs of anti-tumor chemotherapy]. 130 43

A 29-year-old-woman with recurrent cancer of rectum was treated with Etoposide, cis-platinum and external irradiation. Previous postoperative chemotherapies consisted of MMC, CPA, VCR and HCFU. Histologically, the tumor invaded in sheets and nests, and consisted of round to ovoid malignant cells with high nuclear/cytoplasmic and hyperchromatic nuclei with a coarse, clumped, or stippled chromatin pattern. Most cells demonstrated a positive reaction by Grimelius and NSE staining. Eight months after surgery, we switched to Etoposide cis-platinum and external irradiation, because of local recurrence. Etoposide (total 725 mg) and cis-platinum (total 100 mg) were injected into bilateral iliac artery and 60 Gy radiotherapy was performed. The patient showed a good response, and a complete response (CR) was evident for the following 42 months. Thus, Etoposide, Cis-platinum and radiotherapy are considered an effective combination therapy for a patient with small cell undifferentiated carcinoma.
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PMID:[A case of small cell undifferentiated carcinoma (SCUC) of the rectum treated with etoposide, cis-platinum and radiotherapy]. 133 27

A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5 microM in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the T/C by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.
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PMID:New triazine derivatives as potent modulators of multidrug resistance. 135 53

A 38-year-old male was admitted with edema of the neck and face. Chest X-ray revealed a mediastinal tumor. On chest CT and MRI, a tumor infiltrating the superior vena cava and bilateral brachiocephalic veins in the upper mediastinum was observed. Venography revealed obstruction of bilateral brachiocephalic veins. The tumor was diagnosed as thymoma by percutaneous biopsy, but since it was of stage III according to Masaoka's classification, complete extirpation was considered to be impossible. Preoperative chemotherapy with multiple drugs (CDDP, ADM, VCR, CPA) was administered. The superior vena cava syndrome resolved and the tumor diminished in size. Because of leukopenia, rhG-CSF was also used. The tumor infiltrated the left brachiocephalic vein; therefore, total resection and left brachiocephalic vein reconstruction were performed. Histopathological examination showed extensive, necrosis and fibrosis containing residual thymoma. Postoperatively, similar chemotherapy and cobalt irradiation (40 Gy) to the superior mediastinum were performed. We thus present a case of invasive thymoma which responded to preoperative chemotherapy.
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PMID:[A case of invasive thymoma responsive to preoperative chemotherapy]. 150 97

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
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PMID:[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. 163 23


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