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International Journal of Molecular... Nov 2003E-cadherin, an intercellular adhesion molecule, is important in cell growth and differentiation. Adhesion between cells is thought to decrease as cancers develop and...
E-cadherin, an intercellular adhesion molecule, is important in cell growth and differentiation. Adhesion between cells is thought to decrease as cancers develop and disseminate. Knowledge of the effect of cell adhesion on proliferation and chemosensitivity may help individualize cancer treatment. Lovo and MCF-7 cells, which express E-cadherin, and PC-3 cells, which do not, were used in this study. Proliferation and chemosensitivity were measured in two-dimensional (2-D) culture and three-dimensional (3-D) culture. Protein and mRNA expression of E-cadherin, catenin, and cyclin-dependent kinase inhibitors were determined. Growth of Lovo and MCF-7 but not PC-3 cells was markedly suppressed in 3-D relative to 2-D. MCF-7 cells express high levels for E-cadherin, catenin, and p27 in 3-D, but catenin and p27 expression was decreased by exposure to anti-E-cadherin neutralizing antibody. Chemosensitivity of PC-3 was similar in 2-D and 3-D, but chemosensitivity of Lovo and MCF-7 was less in 3-D than 2-D. Moreover, the presence of anti-E-cadherin antibody increased chemosensitivity of MCF-7 in 3-D. E-cadherin affected the regulation of cell proliferation and differentiation, and decreased chemosensitivity. Chemosensitivity of cancer is affected by the state of cell adhesion and expression of intercellular adhesion molecules. Consideration of intercellular adherence characteristics in different chemosensitivity tests is likely to improve their reliability.
Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cadherins; Cell Adhesion; Cell Cycle Proteins; Cell Division; Cell Line, Tumor; Cell Size; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinase Inhibitor p57; Cyclin-Dependent Kinases; Cyclins; Cytoskeletal Proteins; Doxorubicin; Drug Resistance, Neoplasm; Enzyme Inhibitors; Fluorouracil; Humans; Inhibitory Concentration 50; Mitolactol; Mitomycins; Nuclear Proteins; RNA, Messenger; Trans-Activators; Tumor Suppressor Proteins; alpha Catenin; beta Catenin
PubMed: 14532995
DOI: No ID Found -
Oncology 1975A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma.
Topics: Adenocarcinoma; Altretamine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Evaluation; Humans; Leukopenia; Lung Neoplasms; Middle Aged; Mitolactol; Nausea; Thrombocytopenia; Triazines; Vomiting
PubMed: 174041
DOI: 10.1159/000225036 -
Journal of Neurosurgery Dec 1984The authors have conducted a Phase II trial to evaluate orally administered dibromodulcitol in the treatment of 40 evaluable patients with recurrent medulloblastoma,...
The authors have conducted a Phase II trial to evaluate orally administered dibromodulcitol in the treatment of 40 evaluable patients with recurrent medulloblastoma, ependymoma, and malignant astrocytoma. Ten of 20 patients harboring medulloblastoma responded to therapy with a median time to tumor progression (MTP) of 40 weeks, and four of 20 patients had no sign of progression of disease 4 years after treatment was begun. The MTP for all 12 patients with ependymoma was 30 weeks. Nine of these 12 patients had stabilization of their disease with an MTP of 67 weeks; three of these 12 patients had no signs of progression for 1 to 3 years after treatment was begun. Of six patients harboring supratentorial gliomas, none responded to dibromodulcitol. Two patients, one with a primitive neuroectodermal tumor and the other with a metastatic carcinoma of the breast, had stabilization of disease for more than 4 and 2 years, respectively.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Child, Preschool; Dianhydrogalactitol; Drug Evaluation; Ependymoma; Female; Glioma; Humans; Male; Medulloblastoma; Middle Aged; Mitolactol; Neoplasm Recurrence, Local
PubMed: 6502234
DOI: 10.3171/jns.1984.61.6.1063 -
Journal of Clinical Oncology : Official... Jan 1986Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy with dibromodulcitol, doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies with respect to response rates, time to treatment failure (TTF), and survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in 42/97 patients and less than 5 ng/mL in the remaining patients. Patients with elevated pretreatment CEA levels were more likely to be estrogen receptor (ER) positive (P = .006), to have prolonged disease-free intervals (P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases, and to have multiple sites of metastatic disease (P = .004). Pretreatment CEA levels did not significantly predict for overall response rates, TTF, or survival; nonetheless, those patients with low pretreatment CEA levels had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA levels during therapy revealed a number of interesting patterns. During the first 4 months of treatment, serial CEA levels in responding patients either (1) progressively declined (15/29 women with elevated pretreatment CEA levels), or (2) initially rose significantly (mean, 243% of pretreatment value) and then declined (14/29 women with elevated pretreatment CEA levels). Peak CEA levels in the latter patients were seen 27 to 135 days following initiation of cytotoxic therapy. In some patients the initial increase in the CEA level was incorrectly interpreted as evidence of impending disease progression. CEA levels frequently increased around the time of clinical disease progression. However, rising CEA levels rarely provided a clinically meaningful lead time before the appearance of other clinical evidence of disease progression. These data suggest that routine pretreatment and monthly serial CEA levels in metastatic breast cancer patients have minimal use in clinical practice. Two further noteworthy findings were observed in this prospective study. First, patients with an unknown ER status had a prolonged median survival when compared with patients with ER positive or negative tumors; this appeared to be related to prolonged disease-free intervals in ER unknown patients. Second, two case of secondary acute leukemia were seen in patients treated with continuous DAVTH therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoembryonic Antigen; Clinical Laboratory Techniques; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Fluoxymesterone; Follow-Up Studies; Humans; Methotrexate; Mitolactol; Neoplasm Metastasis; Prednisone; Prognosis; Prospective Studies; Random Allocation; Tamoxifen; Vincristine
PubMed: 3510282
DOI: 10.1200/JCO.1986.4.1.46 -
Cancer Treatment Reviews Dec 1982
Review
Topics: Breast Neoplasms; Doxorubicin; Drug Therapy, Combination; Female; Humans; Mitolactol; Vincristine
PubMed: 6762921
DOI: 10.1016/s0305-7372(82)80040-6 -
Annals of Oncology : Official Journal... Nov 1992
Metastatic breast cancer: higher versus low dose maintenance treatment when only a partial response or a no change status is obtained following doxorubicin induction treatment. An Eastern Cooperative Oncology Group study.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Fluoxymesterone; Humans; Methotrexate; Mitolactol; Neoplasm Recurrence, Local; Prednisone; Prospective Studies; Remission Induction; Survival Rate; Tamoxifen
PubMed: 1450067
DOI: 10.1093/oxfordjournals.annonc.a058337 -
Cancer Oct 1984Utilizing multivariate logistic regression statistical analysis, the authors evaluated prognostic features associated with achievement of complete remission (CR) and...
Utilizing multivariate logistic regression statistical analysis, the authors evaluated prognostic features associated with achievement of complete remission (CR) and remission and survival duration in acute myelogenous leukemia (AML). These clinical variables were analyzed in 77 consecutive adult patients who underwent 108 courses of remission induction therapy with daunomycin, cytosine arabinoside, and 6-thioguanine (DAT) chemotherapy for newly diagnosed and first relapse of AML. Eight patients had developed leukemia in the setting of other malignant or immunologic diseases (therapy-linked AML) and 69 patients had not (primary AML). Sixty-three percent of patients with primary AML achieved CR with median remission and survival durations of 11 and 24 months, respectively. Significant unfavorable predictive features for achievement of CR were splenomegaly, and elevated leukocyte count or serum alkaline phosphatase levels. Patients who had leukocyte counts of less than or equal to 10,000/mm3 at diagnosis or less than or equal to 40,000/mm3 at the start of therapy, and those who received greater than 120 mg/m2 of daunomycin had significantly longer remissions and survival than those who did not. Fifty-seven percent of patients in first relapse also achieved CR; however, relative to first remissions, second remission durations were significantly shorter (median, 4.6 months). Sixty-two percent of patients with therapy-linked AML achieved CR, but remission durations (median, 2.8 months) were significantly shorter than first remissions of primary AML patients. These data identify clinical features associated with increased risk of failure to achieve CR and potential for short remission duration and survival. Alternative forms of therapy should be considered for such high-risk patients.
Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Mitolactol; Prognosis; Regression Analysis; Splenomegaly; Tamoxifen; Time Factors
PubMed: 6592033
DOI: 10.1002/1097-0142(19841015)54:8<1672::aid-cncr2820540831>3.0.co;2-f -
Journal of Clinical Oncology : Official... Jan 1994To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
PURPOSE
To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer.
MATERIALS AND METHODS
One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse.
RESULTS
Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant.
CONCLUSION
Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Logistic Models; Middle Aged; Mitolactol; Neoplasm Metastasis; Remission Induction; Survival Analysis; Tamoxifen; Treatment Outcome; Vincristine
PubMed: 8270982
DOI: 10.1200/JCO.1994.12.1.45 -
Chinese Medical Journal Nov 2009Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and...
BACKGROUND
Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and LRP is indefinite. The aim of this study was to investigate the effects of down-regulation of survivin on LRP expressions and the reversal of chemoresistances in HCC both in vitro and in vivo.
METHODS
The expressions of survivin were detected by RT-PCR and Western blotting in HCC cell line SMMC-7721 and SMMC-7721/ADM. The sensitivities of these two cell lines to ADM were evaluated by MTT assays. SiRNA which targeted survivin was transfected into SMMC-7721/ADM cells, then the sensitivity of SMMC-7721/ADM cells to ADM and the expressions of survivin and LRP were detected respectively. SMMC-7721/ADM cells were transplanted subcutaneously into nude mice to establish xenograft tumors. Antitumor activities of RNA interference (RNAi) targeting survivin, various doses of ADM and combination therapies were observed respectively. Possible toxicities were evaluated. LRP expression changes were tested. Student's t test was used for evaluating statistical significance.
RESULTS
The expressions of survivin in SMMC-7721/ADM cell line showed significant elevation compared to those in SMMC-7721 cell line (P < 0.05). Positive siRNA down-regulated the expressions of survivin significantly (P < 0.05). SiRNA targeting survivin could sensitize SMMC-7721/ADM cells to ADM and down-regulate the expressions of LRP significantly (P < 0.05). Growths of the tumors were significantly inhibited in positive siRNA group as compared with those in the control group from the 8th day (P < 0.05). Combination therapies caused significant tumor inhibitions compared with tumors of nude mice in the other three groups respectively (P < 0.05). No toxicities were found in nude mice treated by siRNA and combination therapies. The expressions of LRP were markedly reduced in tumors treated with siRNA targeting survivin (P < 0.05).
CONCLUSIONS
Down regulation of survivin gene by RNAi can increase chemosensitivity of HCC both in vitro and in vivo. The reversal of drug resistance may be reduced through the inhibitions of LRP.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Doxorubicin; Drug Resistance, Neoplasm; Humans; Inhibitor of Apoptosis Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins; Mitolactol; Mitomycins; RNA Interference; RNA, Small Interfering; Reverse Transcriptase Polymerase Chain Reaction; Survivin; Vault Ribonucleoprotein Particles; Xenograft Model Antitumor Assays
PubMed: 19951584
DOI: No ID Found -
Advances in Enzyme Regulation 1976
Review
Topics: Animals; Antineoplastic Agents; Carbohydrates; Dose-Response Relationship, Drug; Glucosamine; Hematopoiesis; Humans; Mannitol; Mannomustine; Mitobronitol; Mitolactol; Structure-Activity Relationship
PubMed: 788476
DOI: 10.1016/0065-2571(76)90019-4