Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nimustine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1994

Induced expression and subcellular localization of the Bcl-2 protein in cultured glioma cells.

It has recently been shown that the bcl-2 gene is involved in the growth and development of certain tumors by suppressing apoptosis. To explore the possible involvement of the Bcl-2 protein in gliomas, three human glioma cell lines (T98G, A172, and U251) were examined for the presence of this protein. It could be documented by confocal laser microscopy that the Bcl-2 protein was localized mainly in mitochondria and nuclear membrane of T98G cells. Flow cytometric analysis revealed that 71-87% of the cultured glioma cells expressed the Bcl-2 protein. Treatment of U251 cells with ACNU for 24 h induced increased Bcl-2 protein expression; induction was dose dependent. Exposure of T98G and A172 cells to ACNU did not affect their Bcl-2 protein levels. Southern blot analysis revealed no chromosomal translocation in the cells studied. These findings suggest that Bcl-2 protein overexpression in glioma cells may partly contribute to tumor growth and tolerance to chemotherapeutic agents.

Blotting, Southern↗
PubMed1994

[Chemotherapy of scirrhous gastric cancer].

Cancer chemotherapy plays a central role in the treatment of recurrent or unresectable scirrhous gastric cancers classified mainly as Borrmann type 4. Though we have no specifically effective drugs for scirrhous gastric cancer, 5-FU and its derivative, MMC, anthracyclines, CDDP, CQ and ACNU are known to be relatively effective single agents against this tumor. In an attempt to enhance the effect of single agents, several combined chemotherapy regimens have been devised and tested. These regimens included 5-FU + MMC, UFT + MMC, UFT + CDDP, MTX.5-FU, FAM, FAP, EAP and ELF regimen. At present, combined therapies using 5-FU and MTX or CDDP may be the most attractive of these combined regimens.

Adenocarcinoma, Scirrhous↗
PubMed1994

[Chemotherapy of brain tumors].

Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted.

Blood-Brain Barrier↗
PubMed1994

[Follow-up study of malignant astrocytomas showing complete response after initial treatment].

The prognosis for patients with malignant astrocytomas is still poor. The identification of groups of patients with good prognostic factors should be helpful in selecting the treatment strategies. In general, important prognostic factors are thought to be the extent of surgical resection required, age, performance status, duration of symptoms, location, and pathological tumor grade. The purpose of this present study is to evaluate the prognosis of patients with complete response (CR), that is, complete disappearance of the tumor mass in the contrast enhancement of computerized tomography (CT) scan after initial treatment. An additional purpose is to examine the effect of factors such as pathological tumor grade, location, age of patient, and the extent of surgical resection in achievement of CR. The subjects of the study were 81 patients with supratentorial malignant astrocytomas (45 males, 36 females) treated with surgical resection and radiochemotherapy in our division since 1980, and followed up for more than 5 years. There were 57 anaplastic astrocytomas (WHO grade III) and 24 glioblastomas (WHO grade IV). The extent of surgical resection and the response to the therapy were evaluated by CT scans. The Kaplan-Meier method was used in generating survival plots. Twenty-two cases (27%) showed CR at the end of the initial treatment, and the other 59 cases (73%) showed Non CR. Fifteen cases (26%) among 57 grade III patients and 7 cases (29%) among 24 grade IV patients showed CR. Tumor locations of CR cases were exclusively superficial with the exception of one case that involved deep structure. Average age of CR cases and Non CR cases were 34.4 and 49.7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMedDate not supplied

In vitro chemosensitivity test of malignant gliomas: clinical relevance of test results independent of adjuvant chemotherapy.

Tumor specimens of malignant human gliomas were processed in a colony forming assay (CFA, n = 70) and a metabolic test system (MTT-test, n = 49) for in-vitro chemosensitivity testing. The clinical data as well as the complete follow-up of these patients were obtained until their death or at least 2 years of survival. By means of multivariate statistical analysis we demonstrate that both test systems are not influenced by biometrical data of the patient of histopathological parameters of the tumor. According to the COX regression model the results of both assays are per se no prognostic factor when regarded independently of additional treatment. However, in 33 patients treated with either ACNU or BCNU, a prospective correlative trial clearly demonstrates a predictive value of the CFA in adjuvant chemotherapy of gliomas.

Carmustine↗
PubMed1993

[High-dose busulfan, VP-16 and ACNU therapy with stem cell transplantation for the treatment of children with acute leukemia].

In order to strengthen the anti-leukemia effect, we developed a new conditioning regimen with high dose busulfan, VP-16 and ACNU (BVA) for cytoreduction before stem cell transplantation. Fourteen patients with refractory acute leukemia received allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) after conditioning with the BVA regimen, 7; allogeneic BMT, 1; syngeneic BMT, 6; PBSCT. # Seven patients were transplanted in the first complete remission, and 8 patients were in their second or third remission. Although total body irradiation or cyclophosphamide was not included in this regimen, engraftment was obtained in all cases. Two patients suffered relapse, and one patient died of cytomegalovirus interstitial pneumonitis (IP) 64 days after PBSCT. The other 11 patients are alive and free of disease at a median follow up time of 647 days (98-1235 days). Major regimen-related toxicity was pulmonary complications such as IP (3 cases) and pulmonary edema (2 cases). However, all patients recovered rapidly following steroid therapy. The results indicate that this conditioning regimen is highly effective for the treatment of childhood acute leukemia.

Acute Disease↗
PubMed1994

Artificial control of nuclear translocation of DNA repair methyltransferase.

We constructed a recombinant plasmid carrying a chimeric cDNA that encodes a fusion protein, ER:MGMT, composed of the ligand-binding domain of the human estrogen receptor and the human O6-methylguanine-DNA methyltransferase. By introducing this plasmid into the methyltransferase-deficient human cell line HeLa MR, a system was established in which nuclear translocation of the ER:MGMT fusion protein can be controlled by estrogen. On in situ immunostaining using anti-MGMT, the cytoplasm of ER:MGMT-carrying cells was preferentially stained and nuclear staining occurred only when the cells were exposed to estrogen. The estrogen-dependent nuclear translocation of ER:MGMT was confirmed by Western blotting analysis of fractionated cell extracts. The fusion protein was translocated into the nucleus within 1 h after estrogen treatment and remained there unless estrogen was removed. The methyltransferase activity of the fusion protein was as active as the authentic methyltransferase enzyme, regardless of the presence or absence of estrogen. The ER:MGMT-producing cells were sensitive to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in the absence of estrogen, and estrogen treatment rendered the cells as resistant to ACNU as the ordinary Mer+ cell line, HeLa S3, thereby indicating that translocation of the methyltransferase into the nucleus is a prerequisite for repair of the chromosomal DNA damaged by alkylating agents. Taking advantage of the artificial control of cellular localization of the fusion protein, we examined the timing of the nuclear translocation required to execute efficient DNA repair. We obtained evidence that the methyltransferase must repair the DNA damage as soon as the DNA is exposed to ACNU, in order to avoid cell cycle arrest at the G2 phase.

Amino Acid Sequence↗
PubMed1994

[Cytotoxic action of alkylating agents in human tumor cells and its relationship to apoptosis].

Various anticancer agents have been known to induce apoptosis in certain types of human tumor cells. The fact that a variety of agents, which attack different cellular targets, induce common apoptotic cell death suggests that the nature of initial damage is not directly involved in apoptosis. The mechanism by which a damage leads to apoptosis is not known. However, modulation of this process may affect the outcome of anticancer drug treatment. This article briefly reviewed the studies of endogenous as well as exogenous factors which modulate apoptosis, and then described the characteristics of cell death induced by alkylating agents. O6-Alkylguanine, a major cytotoxic DNA damage produced by simple alkylating agents, can be repaired by the cellular enzyme O6-methylguanine-DNA methyltransferase (MGMT). About one-fifth of human tumor cell strains lack the MGMT activity and termed as Mer- cells. Mer- cells are hypersensitive to alkylating agents like chloroethyl nitrosoureas (CNUs), compared with repair-proficient Mer+ cells. It is suggested that identification of a factor which suppresses the MGMT gene expression in CNU-resistant Mer+ cells, may enable us to convert these Mer+ cells to Mer- phenotype, thus resulting in much higher sensitivity of Mer+ cells to CNUs.

Alkylating Agents↗
PubMedDate not supplied

O6-methylguanine-DNA methyltransferase and human cancer chemotherapy.

Two kinds of human tumor cell strains having different activity of O6-methylguanine-DNA methyltransferase (O6-MT) were transplanted into nude mice. Mice were then injected intraperitoneally (i.p.) with the bifunctional agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride(ACNU). The tumors with low O6-MT activity were quickly suppressed or cured. This result suggests that some tumors, if determined to have low O6-MT activity, might be cured if the host is treated with ACNU. This observation may open a new approach to experimental cancer chemotherapy. Treatment with ACNU of experimental animals bearing HeLaMR tumors (which have low O6-MT activity and are Mer-), resulted in the regression of the tumors or their disappearance. In animals bearing HeLaS3 tumors (which have high O6-MT activity and are Mer+) the tumors were hyperplastic.

Animals↗
PubMed1993

[Intensive 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) and cryopreserved autologous bone marrow transplantation].

High-dose ACNU followed by autologous bone marrow transplantation was administered alone or together with other agents such as cyclophosphamide, dacarbazine, carboquone or/and VP-16. The starting dose of ACNU was 200 mg/m2, with gradual escalation up to 400 mg/m2. Median duration of granulocytes of less than 100/mm3 and platelets of less than 30,000/mm3 was 4.5 days (range; 0-9) and 10.5 days (range; 0-43), respectively. Bacteremia occurred in 4 cases, but no case of pneumonia was encountered. Heart failure possibly due to the cyclophosphamide was noted in one case with arrhythmia. Out of 13 cases with measurable diseases, three patients with Hodgkin's disease, two patients with diffuse lymphoma, and one patient with follicular lymphoma attained a complete response. Partial response was obtained in two patients with non-Hodgkin's lymphoma. Two patients with melanoma and one with acute nonlymphocytic leukemia without measurable disease still remain disease-free.

Adult↗
PubMedDate not supplied

Modulation of O6-methylguanine-DNA methyltransferase-mediated 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea resistance by O6-benzylguanine in vitro and in vivo.

Our previous studies have indicated that O6-methyl-guanine-DNA methyltransferase (MGMT) is a key factor determining tumor cellular resistance to 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). This study describes the modulation of MGMT-mediated ACNU resistance by O6-benzylguanine pretreatment. The ACNU sensitivity of MGMT proficient human tumor HeLa S3, SMMC-7721, and Cc801 cells in tissue culture was markly enhanced by 10 mm O6-benzylguanine, and a correlation between the extent of enhancement and the level of MGMT activities was observed. A single i.p. injection of 100 mg/kg of O6-benzylguanine caused a complete inhibition of MGMT activities in HeLa S3 tumor xenografts and combination of O6-benzylguanine with ACNU (7.5 mg/kg) significantly inhibited HeLa S3 tumor growth. The results demonstrated that O6-benzylguanine could be used as a potential adjuvant in combination chemotherapy with ACNU to treat MGMT proficient tumors.

Animals↗
PubMed1993

[Intra-arterial ACNU, CDDP chemotherapy for brain metastases from lung cancer: comparison of cases with and without intra-arterial mannitol infusion].

To assess whether therapeutic efficacy is related to intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for brain metastases from lung cancer, clinical results of patients with and without IA mannitol infusion were compared. Thirty-nine patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B). There were 22 patients in group A and 17 in group B. During radiotherapy, ACNU and CDDP, at a dose of 100 mg/body, were given through the common carotid artery at a rate of 20 mg/min. In group A, 50 ml of 20% mannitol was injected intra-arterially at a rate of 50 ml/min immediately prior to the injection of chemotherapeutic agents. Major complications, such as seizure and neurotoxicity, were not observed. Complete response (disappearance of enhanced tumor mass) was obtained in 72% of group A and in 67% of group B. The median time to tumor progression was 40 weeks for group A and 22 weeks for group B. The median survival time (MST) was 45 weeks for group A and 30 weeks for group B. The survival time was significantly longer in group A as compared to group B (p < 0.05). When the patients who died of failure of vital organ systems other than brain complications were excluded in calculating the survival time, the MST was 69 weeks for 11 patients of group A and 34 weeks for 7 patients of group B. These data suggest that an effort to increase drug delivery to the brain tumor may indeed lengthen the survival time of patients with brain metastases from lung cancer.

Adult↗
PubMed1993

[Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patients with brain tumor].

In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtained by intraarterial infusion of 18.5 MBq of 99mTc-HMPAO. Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supraor infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99mTc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99mTc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99mTc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99mTc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherapy.

Adolescent↗
PubMed1993

Identification of cellular defect in UVS1, a UV-sensitive Chinese hamster ovary mutant cell line.

UVS1 is an intermediately UV-sensitive Chinese hamster ovary mutant originally isolated by its hypersensitivity to an anticancer drug, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride. By cell fusion analysis, UVS1 complemented the UV sensitivity of the mouse lymphoma cell line US31 from the eighth complementation group of UV-sensitive rodent cell lines. By enzyme-linked immunosorbent assay we found that within 3 h after UV irradiation both pyrimidine dimers and (6-4)photoproducts in UVS1 were not removed from chromosomal DNA in UVS1 at all. Twenty-four h after UV irradiation the removal rate of (6-4)photoproducts was intermediate between CHO9, the parental cell line, and 43-3B, a UV-hypersensitive Chinese hamster ovary mutant of the complementation group 1, whereas the pyrimidine dimers in UVS1 were removed less efficiently as 43-3B. Alkaline elution assay showed that the incising activity to damaged DNA after UV irradiation of UVS1 was as low as that of 43-3B. The number of 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride-induced DNA interstrand cross-links of UVS1 was almost equal to that of 43-3B and about 1.5 times more than that of CHO9, suggesting that the gene products defective in UVS1 and 43-3B are essential for the excision repair of DNA damages produced by 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride.

Animals↗
PubMed1993

Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission.

The role of total body irradiation (TBI) for allogeneic bone marrow transplantation (BMT) for acute leukemia in first complete remission was reevaluated in this study. From Japanese BMT Registry, data of 123 acute leukemia patients in first complete remission who underwent allogeneic bone marrow transplantation in 22 hospitals between 1988 and 1990 were available for the present comparative study of preparation regimens with or without total body irradiation. Two-year survivals were 77% and 51% in the TBI containing regimen group and in the non-TBI regimen group, respectively (p = 0.0010). Corresponding two-year relapse rates were 16% and 37%, respectively (p = 0.0197). Corresponding probabilities of developing interstitial pneumonitis were 21% and 24%, respectively (p = 0.8127). The analysis of causes of death indicated that non-TBI regimen increased the incidence of septicemia and lethal organ failures, such as liver, heart, lung and other multiple sites. It was emphasized that an additional role of total body irradiation was to disperse the treatment-related toxicity in allogeneic bone marrow transplantation for acute leukemia.

Acute Disease↗
PubMed1993

[Usefulness of 201T1C1-SPECT in the evaluation of radiation and chemotherapy for brain tumors].

We investigated the usefulness of Thallium-201 chloride single photon emission computed tomography (T1-SPECT) in the evaluation of radiation and chemotherapy for brain tumors. The subjects were 9 cases (10 tumors) of malignant astrocytomas. T1-SPECT was performed before and immediately after irradiation and/or intraarterial infusion of ACNU. In 5 of 10 tumors, T1-index already changed 1 or 2 months before tumor size changed on the CT. Our results suggested that T1-SPECT was useful for evaluating the viability of tumor.

Aged↗