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PubMed2000

The Synthesis of a Novel Strained Diyneparacyclophane and Its Dimer by Metal-Mediated Coupling.

Relieve strain with a twist! Synthesis of the paracyclophane 1 and its dimer 2 employed a sequence of metal-mediated couplings. The X-ray analysis of 2 revealed a helical twist inherent in this structure, which created extended arms, that trapped a molecule of solvent. A carboxylic acid derivative of 1 was also prepared, and its structure indicated the diyne rod moiety of 1 is distorted more than in analogous compounds.

Journal Article↗
PubMed2000

A proteomic analysis of secreted proteins from xylan-induced Bacillus sp. strain K-1.

The expression level of extracellular proteins in an alkaliphilic bacterium, Bacillus sp. strain K-1, grown in a xylan-containing medium, is significantly increased when compared with that grown in the nonxylan culture medium. A proteomic approach has been efficiently applied to separate and characterize these differentially expressed secretory proteins. Eight prominent protein spots were identified and subjected to N-terminal amino acid sequencing. The results show that three spots share considerable similarity with the xylanolytic enzymes and that two spots share considerable similarity with the GltC regulatory protein and 3-dehydroquinate dehydratase, respectively. In addition, the three other proteins show little similarity with the known proteins in the database. In conclusion, our results demonstrate that the proteomic approach is a highly efficient method to rapidly study the differential expression of the secreted proteins by Bacillus sp. strain K-1 grown under xylan-induced condition.

Bacillus↗
PubMed2000

Childhood-onset schizophrenia/autistic disorder and t(1;7) reciprocal translocation: identification of a BAC contig spanning the translocation breakpoint at 7q21.

Childhood-onset schizophrenia (COS) is defined by the development of first psychotic symptoms by age 12. While recruiting patients with COS refractory to conventional treatments for a trial of atypical antipsychotic drugs, we discovered a unique case who has a familial t(1;7)(p22;q21) reciprocal translocation and onset of psychosis at age 9. The patient also has symptoms of autistic disorder, which are usually transient before the first psychotic episode among 40-50% of the childhood schizophrenics but has persisted in him even after the remission of psychosis. Cosegregating with the translocation, among the carriers in the family available for the study, are other significant psychopathologies, including alcohol/drug abuse, severe impulsivity, and paranoid personality and language delay. This case may provide a model for understanding the genetic basis of schizophrenia or autism. Here we report the progress toward characterization of genomic organization across the translocation breakpoint at 7q21. The polymorphic markers, D7S630/D7S492 and D7S2410/D7S646, immediately flanking the breakpoint, may be useful for further confirming the genetic linkage for schizophrenia or autism in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:749-753, 2000. Published 2000 Wiley-Liss, Inc.

Autistic Disorder↗
PubMed1978

Mitomycin-C and megestrol acetate in treatment of breast cancer refractory to hormonal and combination chemotherapy.

Fifty patients with breast cancer refractory to endocrine manipulation and/or combination chemotherapy were treated with mitomycin-C 20 mg/m2 I.V. every 4-6 weeks and megestrol acetate 160 mg daily. Of 48 evaluable patients, 4% achieved complete remission (CR), 23% had partial remission (PR). Median duration of response for CR and PR was 7 months. Non-responders had a median survival of 2 months. The difference in survival of responders (both CR and PR) and non-responders was statistically significant at p less than 0.01 level. Attenuated doses of mitomycin-C were administered at increasing intervals due to cumulative myelosuppressive toxicity.

Adult↗
PubMed1978

The value of adriamycin in the treatment of diffuse malignant pleural mesothelioma.

Thirty-six patients with diffuse malignant pleural mesothelioma were seen over a period of 15 years. The median age was 60 years (range, 21 to 75 years), and the male to female ratio was 2.3 to 1. The most common symptoms were chest pain and shortness of breath and all patients presented with pleural effusion on chest x-ray. The diagnosis was established by tissue biopsy in all cases. The median survival time for all patients was 12.5 months. Twenty-one patients were treated with an adriamycin-containing regimen and in this group, the median survival time from histological diagnosis was 14 months. In contrast, the median survival time for the 15 patients, who did not receive adriamycin, was 6 months (p = 0.009). The median survival time from the initiation of chemotherapy was 9 months for the adriamycin group and 2 months for patients treated with other type of chemotherapy (p = 0.001). Adriamycin appears to be of benefit in the treatment of diffuse malignant pleural mesothelioma.

Adult↗
PubMed1979

Combined chemoimmunotherapy for advanced breast cancer: a comparison of BCG and levamisole.

One hundred and fourteen evaluable patients with metastatic breast cancer were treated with a program consisting of 5-FU, Adriamycin, cyclophosphamide (FAC) and nonspecific immunotherapy with Levamisole. The results of this treatment program were compared to those observed with FAC and Bacillus Calmette Guerin (BCG) and FAC chemotherapy alone, both groups treated prior to the study reported in this paper. The overall response rates and complete response rates for all three treatment regimens were identical. The duration of remission, survival of all patients and survival of responders was similar for both chemoimmunotherapy regimens, being superior to the FAC chemotherapy alone group. Immunotherapy with Levamisole was well tolerated and side-effects were experienced by less than one-fourth of the patients. Overall, Levamisole was better tolerated than BCG and was easier to administer than the latter drug. These results suggest than nonspecific immunotherapy with Levamisole might prolong remission and survival of patients with metastatic breast cancer. Since the results achieved with BCG and Levamisole appear similar, the therapeutic ratio favors the use of Levamisole.

Antineoplastic Agents↗
PubMed1979

Bone marrow metastases without cortical bone involvement in breast cancer patients.

Bone marrow involvement by breast carcinoma in the absence of demonstrable bone lesions is unusual. We report six patients with medullary tumor without demonstration of cortical bone abnormality on scan or radiographs. This represents 2.8% of 213 patients with breast cancer in which bone marrow examination was performed and 6.2% of those in which marrow involvement was demonstrated.

Adenocarcinoma↗
PubMed1979

Combination chemotherapy with vincristine and methotrexate for advanced refractory breast cancer.

Eighteen patients with advanced breast cancer refractory to combination chemotherapy with 5-FU, Adriamycin, Cytoxan (FAC) were treated with methotrexate 30 to 40 mg/m2 iv and vincristing 1.5 mg/m2 iv at weekly intervals. Of 17 evaluable patients, 4 (23%) achieved a partial remission with a median duration of remission of 6 months and a median survival of 10 months. In another seven of seventeen patients (41%) the disease remained stable. Toxicity was minimal.

Adult↗
PubMed1979

Male breast cancer: a natural history study.

Eighty-seven cases of male breast cancer seen over a 30-year period were reviewed. The overall observed and corrected five-year survival rates of 42% and 53% correspond well with the results in other series. Factors predicting disease-free interval and survival included size of primary lesion, ipsilateral axillary status, and presence of ulceration, which appear to be similar to those observed for female breast cancer. Eighteen patients (21%) had a second primary tumor (seven with cutaneous malignancies) and were of an older age group with a higher incidence of positive family history of breast cancer as well as other tumors. The overall prognosis of breast cancer in males does not appear to be less favorable than that in females.

Adult↗
PubMed1979

The natural history of breast cancer patients with brain metastases.

One hundred one breast cancer patients with brain metastases (BM) were reviewed. The median survival from BM was 4.0 months. Seventy percent were receiving chemotherapy at the diagnosis of BM and 43% were showing a clinical response. Prolonged survival was seen in patients who underwent surgical resection, those with the brain as site of first metastasis, and those with a long free interval who survived the initial 5 months after BM. Long-term survivors (greater than 18 months from BM) demonstrated indolent disease by all parameters measured.

Adult↗
PubMed1981

Management of breast cancer patients failing adjuvant chemotherapy with adriamycin-containing regimens.

Sixty-two patients with breast cancer treated with Adriamycin-containing adjuvant chemotherapy developed recurrent disease. Four patients refused to take any form of systemic therapy at the time of relapse. Fifty-eight patients were managed with various treatment modalities, and of these 33 (57%) achieved on objective remission, 11 (19%) had stable disease and 14 patients (24%) did not respond to any form of therapy. Twenty-four patients received more than one treatment modality. Thirty-eight patients were treated with chemotherapy and 35 received endocrine therapy. Eight of 20 patients (40%) achieved objective remission upon retreatment with higher dose of 5-fluorouracil, Adriamycin, and cyclophosphamide at time of relapse, and seven of 18 patients (38%) treated with other chemotherapeutic agents showed objective remission. Fourteen of 35 patients (40%) achieved objective remission with hormonal therapies. The median survival from first relapse was 15 months for all patients, and was 25.7 months for responding patients. Survival was significantly longer in asymptomatic patients compared with those who were symptomatic from recurrent disease.

Adult↗
PubMed1981

A phase II evaluation of methyl CCNU and actinomycin D in the treatment of advanced sarcomas in adults.

Twenty-nine patients with metastatic sarcoma were treated with a combination of methyl CCNU and actinomycin D. Patients with adequate bone marrow reserve received methyl CCNU 100 mg/m2 orally on day 1 and actinomycin D 0.3 mg/m2/day intravenously for five days. Both drugs were repeated every four weeks. Patients with inadequate bone marrow reserve received methyl CCNU 75 mg/m2 and actinomycin D 0.2 mg/m2/day for five days. All patients had received prior chemotherapy and had progressive disease at the start of the study. There was one complete response in a patient with peritoneal mesothelioma which lasted 18 months and the patient is still alive at 38+ months. Ten patients had stable disease including three patients who had responses between 25% to 50%. No responses were seen in 18 patients. The median time to progression for patients with stable disease was five months and for those with progressive disease was two months (P = 0.001). The median survival for patients with stable disease was 20 months compared with three months for patients with progressive disease (P = 0.001). The combination was generally very well tolerated and myelosuppression was insignificant. However, with the dosages and schedule used in this study, the combination of methyl CCNU and actinomycin D does not appear to have significant activity in advanced soft tissue sarcomas. Further studies with this combination are indicated in patients with mesothelioma.

Adult↗
PubMed1982

Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer.

Patients with metastatic breast cancer previously treated with non-Adriamycin containing chemotherapy were treated with Adriamycin at a dose of 60 mg/m2 administered as a continuous infusion through a central venous catheter. The duration of Adriamycin infusion was escalated by 100% increments from 24-96 hours, but the majority of patients were maintained on 96-hour infusions. Thirteen of 27 patients achieved objective response (1 CR, 12 PR), six improved, and eight failed to respond to Adriamycin. Administration of Adriamycin by infusion led to a decrease in the severity of nausea and vomiting, but had no effect on myelosuppression and alopecia secondary to Adriamycin. The cardiac toxicity of Adriamycin was reduced in patients who received maintenance therapy with 96-hour infusions of Adriamycin.

Adult↗
PubMed1982

Peptichemio versus melphalan (L-PAM) in advanced breast cancer.

Peptichemio is a polypeptide complex of L-phenylalanine mustard. Because of structural similarities between melphalan (L-PAM) and Peptichemio a prospective randomized study was done to compare the therapeutic efficacy of these two agents. After failing various combinations of doxorubicin, cyclophosphamide, fluorouracil, methotrexate, and vincristine patients with advanced breast cancer were randomized to receive either Peptichemio or L-PAM. Peptichemio was administered at 75-100 mg/m2 and L-PAM at 30-40 mg/m2 IV q 3-4 week interval. Of 56 evaluable patients, 28 received peptichemio and 28 received L-PAM. There were no objective responses in the L-PAM group, and disease stabilized in four patients (14%). The median duration of stable disease was three months (range, 3-4 months). In the peptichemio group seven patients (25%) achieved a partial remission, one patient (3%) achieved less than partial remission and three patients (11%) had stable disease. The median duration of response was six months (range, 5-7+ months) for responding patients and three months (range, 2-5 months) for stable disease. The major toxicity of both drugs was myelosuppression which was cumulative. In conclusion, peptichemio is an active agent in advanced breast cancer, but L-PAM is ineffective in previously treated patients with metastatic breast cancer.

Adult↗
PubMed1983

Multimodal treatment of locoregionally advanced breast cancer.

Fifty-two patients with locally advanced primary breast cancer (T3, T4/N2, N3) without distant metastases were treated with three cycles of combination chemotherapy consisting of 5-FU, Adriamycin and cyclophosphamide (FAC) and immunotherapy with Bacillus Calmette-Guerin (BCG) followed by local therapy (simple mastectomy and/or radiotherapy to breast/chest wall and regional lymphatics) and adjuvant chemotherapy to complete two years of treatment. Forty-nine of 52 (94%) patients were rendered free of clinically detectable disease. The median disease-free interval was 24 months. At a median follow-up time of 60 months, 40% of patients remained free of disease, off all therapy. Those patients who completed two years of therapy and started adjuvant chemotherapy promptly after local treatment had a 48% disease-free survival at five years. Local recurrences were observed in 21% of patients. Distant metastases developed in 40% of patients. Despite good tolerance, treatment compliance was poor. The complete remission rate with this multimodal approach is high and long-term disease-free survival is achieved in a considerable number of patients.

Adult↗
PubMed1983

Phase II evaluation of vinblastine, methotrexate, and calcium leukovorin rescue in patients with refractory metastatic breast cancer.

Seventy-five evaluable patients with metastatic breast cancer refractory to frontline chemotherapy were treated with vinblastine 1.5 mg/m2 by continuous intravenous infusion for five days, intravenous infusion of methotrexate 200 mg/m2, and appropriate calcium leukovorin rescue. Thirty-eight patients were treated with vinblastine followed by methotrexate and calcium leukovorin, while 37 patients were treated with these same drugs in reverse sequence. In 17 patients (23%) an objective remission was achieved, while 39 remained stable for a period in excess of eight weeks. The median duration of remission was two months, and the median duration of survival was six months. The two regimens were well balanced for commonly used pretreatment prognostic factors. There was no difference in response rate and duration of response between the two treatment regimens. In patients with no prior exposure to methotrexate, the remission rate was 37% (11 of 30) compared with 13% (6 of 45). The treatment was well tolerated, and the dose-limiting toxicity was myelosuppression. This combination of drugs is effective in patients who have not been exposed to either drug, while it is only marginally effective in patients previously treated with methotrexate or vinblastine.

Adult↗
PubMed1983

Benign versus malignant hepatic lesions. A diagnostic dilemma with breast cancer patients.

The diagnosis of hepatic metastases heralds a grave prognosis in breast cancer patients. The authors describe seven patients with breast cancer who were found to have hepatic defects that were suspected to present metastatic disease on initial screening and investigations. However, these patients were subsequently shown to have benign hepatic lesions after careful history-taking and supplementary diagnostic techniques, in most cases with the aid of hepatic angiographic examinations. The authors believe that thorough investigation is indicated to elucidate the nature of hepatic defects, especially in cancer patients with no other site of metastatic involvement.

Adult↗
PubMed1984

Carminomycin. A new anthracycline analog in the treatment of advanced breast cancer.

Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks. Of 21 evaluable patients, 1 patient achieved complete remission, 5 patients achieved partial responses, and 11 remained stable. Cases of acute drug toxicity included myelosuppression, phlebitis, and gastrointestinal symptoms; there were four cases of mild alopecia, which consisted of thinning of the scalp hair. There were three cases of biopsy-proven cardiomyopathy, contrary to previous reports from the United Soviet Socialist Republic, which indicated that this drug was relatively free of cardiotoxicity. The median duration of remission for responders was 23 weeks. It is believed that Carminomycin has significant activity against metastatic breast cancer and, because its side effects, especially nausea, vomiting, and alopecia, were considerably milder than those experienced with Adriamycin, further investigation of this drug is warranted.

Adult↗