Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of a clinical trial involving 599 patients with inoperable squamous cell, large cell anaplastic, and adenocarcinoma of the lung are summarized. Patients were randomized to initial therapy with Cytoxan (CTX) (cyclophosphamide), or to one of two schedules of Adriamycin (doxorubicin) 50, or 75 mg/m2 IV every three weeks, or to a combined regimen of ADR and CTX. Upon disease progression, CTX patients were randomized to one of the two ADR schedules, while ADR patients were randomly assigned to CTX alone, or in combination with Cisdiamminedichloroplatinum (Cis-Platinum) 15 mg/m2 IV every three weeks. No statistically significant response or survival differences were observed between the two dose schedules of Adriamycin for any of the cell types studied. The two dose levels did, however, differ with respect to toxicity. There were some response and survival differences among the various cell types in the comparison of low-dose Adriamycin and Cytoxan: (1) patients with adenocarcinoma treated with low-dose Adriamycin tended to survive longer (P = 0.04) than those treated with Cytoxan; and (2) patients with large cell carcinoma receiving Cytoxan experienced a greater tumor response rate than those receiving low dose Adriamycin (P = 0.03). Because of the difficulties involved in distinguishing these two cell types on pathologic examination, the evidence of apparent treatment differences should not be regarded as definitive. During the period when Adriamycin plus Cytoxan was open to patient entry 61 evaluable patients received that regimen, 21 received low-dose Adriamycin and 22 received Cytoxan. Because relatively few patients received the latter two regimens, comparisons of these treatments with Adriamycin plus Cytoxan lack statistical power. However, there is no suggestion in the available data that Adriamycin plus Cytoxan increased survival either in the overall population or in the subset of patients with squamous histology. Initial performance status, metastatic disease symptoms, primary disease symptoms, and weight loss were significantly correlated to survival time, and are recommended as stratification factors in future studies.
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PMID:Adriamycin and Cytoxan in the treatment of inoperable lung cancer. 630 71

Between 1976 and 1978 the Eastern Cooperative Oncology Group tested ten regimens in 415 patients with histologically documented, inoperable non-small cell bronchogenic carcinoma. Most patients were ambulatory (69%) and had extensive disease (69%). Patients were stratified by cell type: squamous cell carcinoma (SQ), large cell anaplastic carcinoma (LC), or adenocarcinoma (AD). Ineffective single agents (including cell types tested and percent complete and partial responses) were dactinomycin (SQ, 6%), dianhydrogalactitol (SQ, 0), ftorafur (AD and LC, 3%), and piperazinedione (AD and LC, 7%), Ineffective combination regimens included the contemporary standard regimen cyclophosphamide (CYT) plus CCNU (SQ, AD, and LC, 9%), methotrexate plus doxorubicin (ADR) plus CYT plus CCNU (MAC) (SQ and AD, 12%), and mitolactol plus ADR (AD and LC, 8%). When compared to CYT plus CCNU the following regimens demonstrated significant activity: CYT plus bleomycin plus cisplatin (SQ, 23%; P = 0.02) and ADR plus 5-FU plus cisplatin (AD and LC, 24%; P = 0.006). Mitomycin demonstrated marginal activity in squamous cell cancer (19%, P = 0.06). Neither "active" regimen improved survival although responders to any regimen had a significant prolongation of median survival (31.6 vs 15.7 weeks, P = 0.002). The MACC regimen, piperazinedione, and mitomycin were substantially more toxic than the two effective regimens, which were adequately tolerated. Ambulatory performance status, limited disease, and prior surgery were significant positive prognostic variables whereas prior radiation and pretreatment weight loss adversely affected response or survival.
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PMID:Chemotherapy for inoperable, non-small cell bronchogenic carcinoma: EST 2575, generation II. 702 58

Twenty-nine patients with local-regional pelvic recurrences of malignant urothelial tumors were treated with combined intra-arterial and iv chemotherapy. 5-FU (1 g/m2) was infused daily for 5 days via bilateral percutaneously placed hypogastric catheters. Doxorubicin (25 mg/m2) was infused iv on Days 1 and 2 and mitomycin (5 mg/m2) was infused iv on Days 3 and 4 of each course. Seventeen patients (58%) demonstrated an objective decrease in the size of the pelvic mass. All four patients with one of the adenocarcinoma variants of malignant urothelial tumors responded to therapy, while the three patients with squamous transformation of a transitional cell carcinoma failed to respond. The median survival of the responding patients was significantly longer (52 weeks) than that of nonresponding patients (28 weeks) (P = 0.002). Patients with initial low-volume pelvic disease demonstrated durable control of local residual tumors, with four of six patients having negative repeat cystoscopic examinations.
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PMID:Management of pelvic complications of malignant urothelial tumors with combined intra-arterial and iv chemotherapy. 704 31

Doxorubicin was administered via peripheral vein to rabbits with or without VX-2 carcinoma and to rats with 13762 mammary adenocarcinoma. In rabbits, the doxorubicin tissue levels showed a decreasing order as follows: kidney, spleen, lung, heart, marrow, liver, gut, tumor, muscle, and fat. In rats, the order of doxorubicin concentration in organs from high to low appeared similar, except lung concentration was closer to spleen and kidney; and doxorubicin level in fat was higher than that in muscle. When different doses of doxorubicin were given, the tissue concentrations were proportional to the dose. At 24 hr after administration, the concentration of doxorubicin in liver was much higher in rats that received the drug injected directly into the hepatic artery or mesenteric-portal vein than in those that received the drug via the peripheral vein. In the discussions, our results in rats and rabbits were compared with what had been reported in the literature of tissue uptake studies in mice, dogs, and patients.
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PMID:Tissue disposition of doxorubicin in experimental animals. 708 94

The effects on DNA integrity of continuous (72-h) exposure of human MCF-7 breast adenocarcinoma cells to 50 nM doxorubicin (a concentration which can be maintained in the plasma by continuous infusion) were characterized by bisbenzimide spectrofluorophotometry, cell flow cytometry, agarose gel electrophoresis, and neutral elution. Spectrofluorophotometry and cell flow cytometry indicated the presence of DNA fragmentation, which was maximal at 24 h. Resolution of these fragments on agarose gels failed to demonstrate "laddered" oligosomal profiles. Neutral elution analysis at 24 h indicated that doxorubicin induced fragmentation of nascent, but not mature, double-stranded DNA. Drug-treated cells exhibited endoreduplication and significant shifts in cell cycle distribution, (i.e., increased G0/G1 and G2/M fractions and a markedly reduced S-phase fraction). These alterations occurred without inhibiting the incorporation of [3H]dThd into cellular DNA; in fact, both the rate and magnitude of [3H]dThd incorporation increased progressively. Doxorubicin also produced a sustained decline in c-myc mRNA levels that paralleled both growth arrest and induction of DNA fragmentation. Ultrastructural examination revealed morphological alterations consistent with the induction of differentiation (e.g., increased lipid content and mitochondrial density, appearance of tight junctions, and secretory ducts) and further suggested the possibility of autocatalysis (e.g., lipofuschin-containing vacuoles). A gradual decline in cell number was observed, with loss of approximately 35% of the cell population after 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of differentiation and growth arrest associated with nascent (nonoligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubicin. 794 87

An 87-year-old woman, who had been suffering from hypothyroidism and had been treated as an outpatient at our department since 1982, noticed left cervical swelling toward the end of November 1992. Because ultrasonic examination revealed a mass in her thyroid gland, she was admitted for a closer examination and additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of thyroid gland and the left cervical lymph node, performance of various examinations did not detected any other NHL lesions. Therefore, it was classified as stage II NHL according to the Ann Arbor classification. Laboratory data on admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count 10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free-T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism. In addition, stage IIa and IIc gastric cancers were detected by the examination with gastric endoscopy performed for stage classification. Both were adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy, polypectomy was performed. The polyps were diagnose histologically as moderately differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600 mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o. on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph node swelling disappeared, and shrinkage of the mass in the thyroid gland was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of elderly Hashimoto disease presenting malignant lymphoma, gastric cancer and colon cancer]. 829 59

In order to investigate the involvement of Protein Kinase C (PKC) in the signal transduction mechanisms related to intrinsic chemoresistance, two cellular clones were isolated from LoVo/WT colon adenocarcinoma cell line and their cytogenetic pattern was studied: LoVo C1.7 was intrinsically resistant to Doxorubicin while LoVo C1.5 showed the same resistance index as the mixed parental cell population. Two PKC isoforms, immunologically identified as beta and alpha PKC, were isolated from the cytosolic fraction of all cell types and one single peak of alpha PKC was obtained from the particulate fraction. Resistant LoVo C1.7 cells showed a significant increase of PKC activity; preincubation with H-7 induced PKC inhibition and reversal of drug resistance. These data suggest that in our cell system the identified calcium-dependent PKC subtypes can play a role in the mechanisms of intrinsic resistance.
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PMID:Analysis of calcium-dependent protein kinase-C isoenzymes in intrinsically resistant cloned lines of LoVo cells: reversal of resistance by kinase inhibitor 1-(5-isoquinolinylsulfonyl) 2-methylpiperazine. 839 71

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a "curative" intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P < 0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P < 0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival.
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PMID:Pre-, peri-, and postoperative chemotherapy for breast cancer: is one better than the other? 862 97

CI-994 [aka: acetyldinaline; PD 123654; 4-acetylamino-N-(2'aminophenyl)-benzamide] (Figure 1) is a novel antitumor agent with a unique mechanism of action. It is the acetylated metabolite of dinaline, a compound previously identified as having cytotoxic and cytostatic activity against several murine and human xenograft tumor models. CI-994 had activity against 8/8 solid tumors tested (log cell kills at the highest non-toxic dose): pancreatic ductal adenocarcinoma #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7); mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the human prostate carcinoma LNCaP (1.2). CI-994 had the same spectrum of activity in vivo as dinaline. It also behaved similarly in schedule comparison/toxicity trials. Prolonged administration with lower drug doses was more effective than short-term therapy at higher individual doses. If doses were kept between 40 and 60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days of administration. The maximum tolerated total dose was also increased with smaller individual doses administered for prolonged intervals. Clinical Phase I trials are ongoing with this agent.
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PMID:Preclinical antitumor activity of CI-994. 915 69

Doxorubicin shows a wide spectrum of activities in solid tumors, especially against breast carcinoma. The aim of this study was to examine if doxorubicin, when given at lower concentrations than applied in clinic, may induce changes in treated cells. With this purpose we developed human breast adenocarcinoma SK-BR-3 cell line resistant to doxorubicin. The sensitivity of these cells to doxorubicin and to some other cytostatics used in cancer treatment was determined by colorimetric MTT assay. Some parameters which may be of importance as prognostic factors in treatment of breast cancer were analyzed as well. The expression of genes involved in mitotic signal pathway (EGF, TGF alpha, EGF-R, erbB-2, erbB-3, c-myc and c-H-ras) was determined immunocytochemically. The concentrations of cathepsins were determined using quantitative immunoreactive assays (cathepsins B and L) or immunoradiometric assay (cathepsin D). The results revealed that even low doses of doxorubicin can induce numerous changes in treated cells: they become resistant to doxorubicin, and cross-resistant to several other cytostatics. The expression of the above mentioned genes involved in mitotic signal transduction, as well as cathepsins D and L, was similar in both parental and doxorubicin treated cells.
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PMID:Characterization of human breast adenocarcinoma SK-BR-3 cells resistant to doxorubicin. 937 56


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