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)

Fifteen to 20 years ago, the natural history of HCC demonstrated approximately 1.5 months median survival after diagnosis with rare cases of one-year survival. Ten to 15 years ago, one shot intraarterial (IA) injection of mitomycin C (MMC) or doxorubicin (ADR) became the prevailing treatment and prolonged median survival to 3-5 months. Ten years ago, transcatheter arterial embolization was introduced and improved the survival rate dramatically. In the earlier period, TAE was performed with gelatin sponge (GS) plus ADR or MMC and showed shrinkage of HCC in the well-capsulated case. Combined use of Lipiodol (LPD) with anticancer drug and GS in later period showed further progress in antitumor response and survival. The one year survival rate obtained from our 100 cases was 53.8%, and the 2 year one was 36.5%. We speculate that the effective response of LPD plus drug to intrahepatic daughter nodules contributed to this improvement because we clarified the efflux of LPD to peripheral portal vein clinically and experimentally. Since the metastatic liver tumor originating from colon or gastric cancer is usually hypovascular and shows limited response to intra-arterial chemotherapy, a special device is needed for improvement. We introduced an S.C. implanted port for injection route and long-term intermittent IA combination therapy with ADR or MMC and degradable starch microspheres (DSM), which embolise arteries temporarily for 20-30 minutes. These new methods achieved a favorable response rate with better quality of life, and would be expected to prolong the life span of patients with metastatic liver tumor.
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PMID:[Recent progress in multidisciplinary treatment of hepatic cancer]. 254 1

A rare case is reported of pineal metastasis from lung cancer initially caused by neurological abnormalities of pineal tumor. A 70-year-old female suffering from headache and deterioration of consciousness for 1 week was admitted. She also had a tumor on both sides of her neck. On admission, neurological examination revealed disturbance of upward gaze, and CT scans showed hydrocephalus and pineal tumor. The tumor was seen as a slightly high density mass on non-contrast CT, and was homogeneously enhanced after administration of contrast material. Right V-P shunt and excision of the left neck tumor were performed at the same time. Pathological diagnosis of neck tumor was undifferentiated carcinoma metastasized to cervical lymph nodes. Extensive study was made, by bronchial fiberscope and biopsy, in order to find the origin of the malignancy and disclosed a small cell lung cancer of left lower lobe. The patient took radiation therapy for both the whole brain (60 Gy) and for the bilateral cervical regions (45 Gy). Two courses of chemotherapy using CDDP, ADR, VCR and CY were administered. Both the neck and the pineal tumors were markedly reduced in size at the termination of radiation therapy. However, she was readmitted 3 months later because of dyspnea. Chest X-P revealed enlargement of the left-lung tumor. She died on April 22, 1987. General autopsy disclosed invasive enlargement of left lung cancer, however, no remote metastasis was found. Examination of pineal region showed only necrotic pineal tissue, and no tumor cell was seen in either macroscopic or microscopic study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pineal metastatic tumor from lung cancer initially caused by neurological abnormalities of pineal body tumor]. 255 Aug 31

When a large amount of iodized oil (LPD) is selectively administered to targeted segments of the liver, the tumor vessels and sinusoids around the tumor are filled with LPD, subsequently regurgitating excessive LPD via the hepatic arterioportal communication into the portal branches surrounding the tumor. Segmental arterioportal chemoembolization in HCC with Doxorubicin-in-oil emulsion (DOE), which we named cement therapy, was performed in 18 patients with HCC. DOE was administered selectively into one segment division of Couinaud in ten patients, two segments in seven and three segments in one. Computed tomography and ultrasonography following the cement therapy revealed an overall response rate of 39%. The one-year cumulative survival rate was 80%, and that for three-years was 33%. Three cases underwent segmental hepatectomy and these specimens revealed total necrosis of the main tumor and whole daughter nodules, followed by various degrees of hepatic parenchymal infarction. This cement therapy realizes the simultaneous chemoembolization via the artery and portal vein, and was considered an effective treatment for extra-capsular infiltration and daughter nodules of HCC nourished by the portal vein blood flow. Limited administration of DOE to the targeted segments enables transarterial oily chemoembolization (TOCE) without any serious side effects.
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PMID:[Segmental arterio-portal chemo-embolization in hepatocellular carcinoma (cement therapy)]. 255 Dec 28

Since 1987, 14 patients (10 colorectal, 3 gastric and 1 lung cancer) with unresectable liver metastases received intra-arterial infusion chemo-embolization therapy using implantable infusion port. All patients had more than one lesion in bilateral lobe (H2 and H3). Infusion catheters were placed in the proper hepatic artery through the gastroduodenal artery on laparotomy. Infusion ports were implanted in the subcutaneous tissue of the abdominal wall. Various kinds of chemotherapeutic agents such as MMC, ADR, THP-ADR, CDDP and 5-FU were injected with embolization material (DSM or Lipiodol), every 1 to 4 weeks at the outpatient clinic. Among 10 cases of H2 grade metastases, 1 CR and 3 PR (40% clinical response) were obtained. However, all 4 cases of H3 grade were judged PD. All patients except one with H2 grade metastases are still alive, but 3 out of 4 with H3 grade died within 7 to 11 months. Catheter occlusion was observed in 4 cases for 3 to 7 months. Infection around the port occurred in 1 patient. A patient with metastatic liver cancer was treated by intermittent bolus injection with MMC and DSM. Partial response was confirmed by CT and tumor markers. Histological response was demonstrated in the specimen obtained at partial hepatectomy. It is concluded that this treatment is variable to prolong the survival of patients with H2 grade metastatic liver cancer, together with maintenance of the quality of life.
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PMID:[Chemo-embolization therapy of unresectable liver metastases using implantable infusion port]. 255 Dec 30

Chronic lymphocytic leukemia is a neoplastic disease in which drug resistance invariably occurs. We have studied the uptake and interaction with molecular targets of two drugs, chlorambucil and adriamycin, in CLL lymphocytes and CHO cell lines. Resistance does not appear related to uptake for either drug. Exposure to CLB causes DNA cross-links in the sensitive but not in the resistant cell line. The GSH content of B-CLL lymphocytes is depleted after a 20-hr incubation. An inability to maintain its GSH content may contribute to this cell's vulnerability to CLB. The resistance of CLL lymphocytes to ADR may be related to the undetectable levels of its target enzyme DNA topoisomerase II. Future approaches may involve study of novel anthracyclines, DNA topoisomerase I inhibitors and the development of in vitro predictive tests.
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PMID:Studies on drug resistance in chronic lymphocytic leukemia. 256 Dec 48

The aim of this study was to find out whether only resistant cells of the "multidrug-resistant" phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dnr) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabino-side-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multi-drug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210ctx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.
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PMID:Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein. 256 99

In order to study the mechanism of etoposide (VP-16) resistance in human tumor cells and to assess the role of P-170 glycoprotein in VP-16 accumulation, we have examined the uptake and efflux of VP-16 in both sensitive and multidrug-resistant MCF-7 human breast and HL60 human promyelocytic leukemia cells. The drug-resistant cells, MCF-7/ADR and HL60/ADR, were selected for resistance to adriamycin and were 200- to 250-fold resistant to VP-16. Whereas MCF-7/ADR cells overexpress the P-170 glycoprotein and show the multidrug-resistant phenotype, HL60/ADR cells do not overexpress the P-170 glycoprotein. Although there was a 2-fold decrease in accumulation of VP-16 in MCF-7/ADR cells, this decrease did not correlate with a 250-fold resistance to the drug. VP-16 efflux was rapid and almost complete from MCF-7 cell lines and it was decreased at 4 degrees. Further, there was a significant increase in VP-16 accumulation in the MCF-7/ADR cells in the presence of glucose-free medium supplemented with sodium azide. However, no change in the pattern of VP-16 efflux was observed. Under these conditions, addition of glucose caused release of VP-16 from MCF-7/ADR cells, suggesting energy-dependent modifications in the drug binding. Coincubation of vincristine with VP-16 also increased the drug accumulation and decreased the rate of efflux of VP-16 in both sensitive and resistant MCF-7 cells, suggesting that vincristine and VP-16 may compete for similar binding and efflux mechanisms in these cell lines. In contrast, daunorubicin increased VP-16 accumulation only in the sensitive MCF-7 cell line, whereas the efflux rate of VP-16 was not significantly changed in either cell line. HL60 sensitive cells accumulated 4- to 5-fold more VP-16 than the resistant subline. Both sensitive and resistant cells showed an important noneffluxable pool of the drug, 3-fold larger for sensitive cells (79 +/- 12 versus 25 +/- 2 pmol of VP-16/mg of protein, for sensitive and resistant cells, respectively). The efflux of VP-16 was temperature dependent only in sensitive cells. VP-16 accumulation in HL60/ADR cells was increased in glucose-free medium supplemented with sodium azide; however, the noneffluxable pool of VP-16 was not significantly changed. In contrast, although these conditions had no effect on the drug accumulation in the parental line, they caused a decrease in the noneffluxable pool of VP-16, suggesting an energy-dependent binding and retention of VP-16.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of differential drug uptake, efflux, and binding of etoposide in sensitive and resistant human tumor cell lines: implications for the mechanisms of drug resistance. 256 28

A 47-year-old man was admitted with a cough on January 4, 1986. A chest X-ray film showed a mass shadow in the left lower lung, which was revealed to be a bronchogenic cyst by CT scanning and ultrasonography. Thoracotomy was performed on March 3, 1986 because cytologic tests on the fluid in the cyst suggested malignancy. A cyst, two tumors on the diaphragm and pleural thickening were revealed. Microscopic examination showed a benign bronchogenic cyst and a mixed-type malignant mesothelioma. In spite of chemotherapy (ADR, Cis-DPP, 5-fluorouracil) and immunotherapy (OK-432, PSK), the pleural thickening progressed, as was demonstrated by CT scanning and ultrasonography. Although cardiac tamponade due to invasion by the malignant mesothelioma developed, this was improved by cardiocentesis. The patient died of pneumonia on March 28, 1987. We studied the concentration of mineral fibers in lung and tumor tissues of this case by Energy Dispersive X-ray Analyser because asbestos or non-asbestos inorganic fibers might cause malignant mesothelioma. This case of malignant pleural mesothelioma accompanied by a bronchogenic cyst is very rare.
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PMID:[A case of malignant pleural mesothelioma with infectious bronchogenic cyst]. 258 7

This study was carried out to evaluate whether the preoperative levels of serum glycoproteins (CEA, SCC, TPA, IAP, ACT, ASP and sialic acid) and HLA antigens (class I and II) could be potential aids in the selection of suitable gastric and esophageal cancer patients for postoperative adjuvant immunotherapy of PSK. Gastric cancer patients underwent gastrectomy and received postoperative adjuvant chemotherapy (MMC, FT and ADR) with or without PSK. One hundred and forty esophageal cancer patients in cooperative study groups (organizing chairman; Dr. Hiroshi Satoh) underwent esophagectomy and received postoperative adjuvant radiotherapy and chemotherapy (FT, BLM) with or without PSK. The efficacy of PSK was recognized in the patients with normal levels of all glycoproteins in gastric cancer, and with normal levels of CEA or SCC or TPA and abnormal levels of one or more APRs in both gastric and esophageal cancer, and with positive HLA-B40 antigen. The combination of tumor-associated factors, such as CEA, SCC and TPA and various non-specific reactants such as APRs was useful as a prognostic indicator. In addition, some of HLA antigens were also valuable. The pretreatment levels of glycoproteins and HLA antigens have potential aids in the selection of patients with gastric and esophageal cancer for PSK treatment.
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PMID:[Clinical effects of PSK on esophageal and gastric cancer patients and usefulness of serum levels of glycoproteins and HLA antigens as prognostic indicators]. 258 37

A kinetic study of plasma concentration of Doxorubicin (Adriamycin) was performed in 25 cases of malignant melanoma of the extremity with malignant adenopathy, treated with the same dose (20 mg per m2). Drug concentration was measured using a radioimmunoassay, with good intra-assay and inter-assay reproducibility. The kinetic analysis used the multiple compartmental method and a simulation of the plasma curves. Adriamycin injected intravenously quickly leaves the plasma into an exchangeable compartment with a slow plasma return and subsequent prolonged mean duration of the plasma half life at a low concentration. Thus, the intravenous perfusion results in a high plasma concentration only during the time of infusion. After intra arterial injection proximal to the tumor, a fraction variable (average 35%) is not released back into the circulation, or released very slowly. This local sequestration (important in terms of local concentration) explains the efficiency and the potential local toxicity of this method of administration. The rapid release of about 70% of the drug into the plasma, with kinetics similar to that observed after intravenous infusion, allows for no significant reduction of systemic toxicity.
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PMID:Kinetics of adriamycin injected proximal to a tumor: a comparative study between venous and arterial injections. 258 5


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