摘要:

A variety of studies strongly hint that cell membranes can be important targets for new and existing anti-tumor drugs. Traditionally, the search for new anti-cancer agents has focused on compounds designed to act on the biosynthesis, stabillity or function of DNA; it may be timely, however, to broaden our search horizon and consider targets outside of the nucleus. Thus, the cell membrane as well as membraneous organelles may well play a key role in the future of anti-tumor drug development.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Bone metastases in breast cancer are common and frequently lead to serious skeletal related morbid complications. Metastases develop in areas of metabolically active trabecular bone. It is presumed that breast cancer cells undergo the same stepwise process for metastases development as demonstrated in other tumor types. The specific factor or factors responsible for the osteotropism of breast cancer have not been identified. The morbid events associated with skeletal metastases, such as pathologic fracture, and spinal cord compression, may be assessed objectively by a variety of techniques including skeletal radiography, radionuclide scanning, computed tomographic scanning and magnetic resonance imaging. Biochemical parameters or markers of skeletal metastases are not sensitive enough to detect clinically occult disease. Therapeutic Interventions for bone metastases include local and systemic therapies. Surgery and radiation therapy are most frequently used for relief of pain or impending fracture, or when bone fracture or neurologic compromise has already developed. Systemic treatment of bone metastases appears to be as effective as systemic treatment of other metastatic sites. Both hormone and chemotherapy may provide significant palliation. Clinical research suggests that the adjunctive use of bisphosphonates may significantly reduce the incidence of skeletal-related morbid events associated with osteolytic bone disease. Future research efforts directed at determining the osteotrophic factors responsible for bone metastases in breast cancer, the pathophysiology of the bone remodeling process in metastatic disease and the prophylactic use of bisphosphonates may lead to significant clinical benefit for those in whom bone metastases from breast cancer develop.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2i.v. over 30 min, followed in 1 h by 5-fluorouracil (5-FU), 375 mg/m2i.v. bolus on days 1–5, and carboplatin (CBDCA), 50–100 mg/m2i.v. bolus on days 2–4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2on days 2–4, resulted In grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2(seven patients) and 50 mg/m2(15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found. However, no statistically significant correlation was found between platinum-DNA adduct formation and disease response, survival or toxicity in this study. The results presented here suggest that the combination of 5-FU, L and CBDCA is tolerable at a CBDCA dose of 50 mg/m2days 2–4; however, higher doses of CBDCA are poorly tolerated due to hematologic toxicity. At the CBDCA dose level of 50 mg/m2on days 2–4, no significant disease responses were observed. We conclude that higher doses of CBDCA are highly toxic and limited our ability to deliver adequate doses of L-modulated 5-FU.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosphamide, adriamycin and fluorouracil (CAF); or CMF and CAF. Partial response occurred in five patients (15±12%), stable disease occurred in 15 patients (45 ± 17%) and progressive disease occurred in 13 patients (40 ± 17%). The median duration of response was 5 months. The median actuarial survival was 11 months. Toxicity was mild, even in patients who had previously received anthracyclines; generally it was mainly hematological. We thus recommend mitoxantrone-containing regimens as salvage chemotherapy in advanced breast cancer.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Between January 1986 and September 1989, 28 patients over the age of 14 years were treated with a combination of mitoxantrone, cytosine-arabinoside (Ara-C) and 6-thioguanine (MAT) at the Kuwait Cancer Control Centre (KCCC). All patients were newly diagnosed cases of acute non-lymphoblastic leukemia (ANLL). Fifty-eight courses of treatment were given as induction and consolidation therapy. The main toxicity was bone marrow suppression. Other toxicities were mainly nausea and vomiting, hepatotoxicity, renal dysfunction and alopecia. In most patients these were mild and tolerable. Complete remission (CR) was achieved in 18 out of 28 (64%) patients. In six patients it was achieved after one course, in 11 patients after two courses and in one patient after three courses. The median survival was 16 months and for those who achieved CR it was 33 months. The actuarial 3 year survival following CR was 43% and the relapsefree survival was 24%. There was little difference in the CR rate for patients below 40 years compared with older patients. However, there was a remarkable difference in survival, with none of the older patients surviving more than 2 years and an actuarial 3 year survival for younger patients of 49%. The study confirms the efficacy of the mitoxantrone-containing combination as a first-line therapy for ANLL.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Is it Justified to treat a small, localized and relatively indolent malignancy by systemic combined chemotherapy? Five patients with locally advanced skin tumors were treated by salvage cisplatin and adriamycin for three to five courses. Three achieved complete response, one achieved partial response and one succumbed to an unrelated cause. The rapid Induction of response, high response rate, unmaintained complete remissions of long duration and relatively low rate of toxicity may justify the use of this combination for the treatment of small skin tumors when other treatment options are of no avail.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Recent interest in site-selective cAMP analogs has focused on the role of 8-chloro-adenosine (8-Cl- adenosine) In the inhibition of tumor cell growth by 8-chloro-cAMP (8-Cl-cAMP) (Van Lookeren Campagne,et al. Cancer Res1991; 51: 1600–5). We have evaluated 8-Cl-cAMP and 8-Cl-adenosine for their growth inhibitory activity against two human colon adenocarcinoma cell lines, HCT116 and FET. Because these cell lines have been adapted to grow in chemically defined medium we were able to evaluate the effect of serum on 8-Cl-cAMP's growth inhibitory activity. In addition, cells grown in serum-free medium were tested for their sensitivity to 8-Cl-cAMP, serum-activated 8-Cl-cAMP and 8-Cl-adenosine. IC50values, determined by measuring cell growth using a MTT colorimetric assay, showed that ‘serum activation’ of 8-Cl-cAMP was required to achieve inhibition of HCT116 (IC50= 1.3 ± 0.1 (μM) and FET (IC50= 2.0 ± 0.1 μM) cell growth. IC50values were not reached at the highest concentrations tested (IC50> 500 μM) in the absence of serum, permitting us to conclude that 8-Cl-cAMP does not have growth Inhibitory activity between 1.0 and 500 μM doses. HCT116 and FET cells grown in media containing serum and in the presence of 8-Cl-adenosine had IC50values of 0.6 ± 0.1 and 0.9 ± 0.2 μM, respectively. HCT116 and FET cells grown in chemically defined medium containing 8-Cl-adenosine exhibited IC50values of 1.0 ± 0.1 and 3.1 μM, respectively. Reversed-phase HPLC analysis showed an 11.4 ± 0.7% conversion of 8-Cl-cAMP to 8-Cl-adenosine in 1 h at 37°C In the presence of 10% fetal bovine serum (FBS). Analysis of the continued conversion of 8-Cl-cAMP after 72 h in media containing 10% FBS revealed that 69.5 ± 0.7% of the 8-Cl-cAMP was converted to 8-Cl-adenosine. These results strongly support the conclusion that enzymatic conversion of 8-Cl-cAMP to 8-Cl-adenosine occurs in the presence of serum and that 8-Cl-adenosine is the active inhibitory compound.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We have reported that fucoxanthin, a natural carotenoid, inhibited the growth of human neuroblastoma GOTO cells. In the present study, we show that a metabolite of fucoxanthin, halocynthiaxanthin, which is isolated from sea squirtHalocynthia roretzi, has a more potent inhibitory effect. Halocynthiaxanthin (5 μg/ml) caused complete suppression of GOTO cell proliferation, whereas fucoxanthin reduced the growth rate by only 88.8% compared with the control, at day 2 after the drug treatment. Furthermore, halocynthiaxanthin also inhibited the growth of other human malignant tumor cells. Thus halocynthiaxanthin seems to be a promising anti-neoplastic agent.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The influence of suramin on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and poly(adenosine diphosphate ribose)polymerase (PADPR) as well as on primary cultures of rat and chick embryo cells was examined by using some short-term tests. AT and DNase I were inhibited by suramin in a dose-dependent manner (DE50= 65 and 100 μg/ml, respectively). PADPR activity was increased over a concentration range of 40–320 μg/ml. At concentrations above 40 μg/ml suramin decreased scheduled and unscheduled DNA synthesis. At doses of below 20 fig/ml the substance slightly stimulated unscheduled DNA synthesis in embryonic cells. Suramin enhanced nucleoid sedimentation and diminished the viscosity of alkaline cell lysates. From the present results it is concluded that suramin, at clinically relevant concentrations, is able to interact with enzyme systems which are critical to important nuclear functions and to interfere-in a cell specific manner—with histones and/or matrix proteins, resulting in greater chromatin compactness.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Mistletoe lectin (ML) I increases the production of cytokines by mononuclear cells and has been proposed as a useful biological response modifier in the treatment of cancer. Two other lectins, ML II and ML III, have been identified in mistletoe. We report that the N-terminal sequences of the three A chains of ML I, ML II and ML III are identical, and have interesting homology with the N-terminal sequences of the A chain of ricin-like toxins and of single-chain ribosome-inhibiting proteins. In addition, the three mistletoe lectins inhibit the growth of the human tumor cell line Molt 4, ML III being the most potent, followed by ML II and ML I. This inhibition is suppressed by addition of rabbit anti-ML I antibodies to the cultured cells. The data obtained suggest that the three lectins have amino acid sequences which show extensive homology and exert very similar biological effects. They may be derived from the same precursor.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID