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PubMed1986

[Combination of selective intra-arterial infusion of an anticancer agent via the vascular access port with RF local hyperthermia].

It is desirable for multidisciplinary cancer treatments to be concentrated as selectively as possible onto the cancer-bearing organs in order to augment the anticancer effects and minimize the untoward effects. Combined treatments of selective intraarterial infusion of anticancer agents via an implanted Vascular Access Port with local hyperthermia using 13.56 MHz RF have been performed in 12 patients with extensive cancers. In 9 out of these 12 cases (75%), more than 50% reduction in tumor size has been obtained. Tumor-diminishing effect was more remarkable in patients who underwent bolus infusion of anticancer agents such as 1 mg/kg of mitomycin C under charcoal hemoperfusion for rapid removal of anticancer agents from the blood stream.

Aged↗

PubMed1987

Efficacy of anticancer agents in vitro and in vivo using cultured human endometrial carcinoma cells--study of therapeutic index.

Employing the new cell line, NUE-1, which was derived from cells of ascites in a woman with endometrial carcinoma, the sensitivity test for anticancer agents was carried out in culture and xenografts in nude mice. Anticancer activity in vitro was evaluated by counting surviving cells, and the therapeutic index was expressed by LD50 for mice/MLD90 in vitro. NUE-1 cells were inoculated subcutaneously in BALB/c nude mice, and then tumors serially transplanted were used as materials. Anticancer agents (ADM, CDDP, CHA3, CQ, MMC) at 1/3 LD50 dosage for mice were administered intraperitoneally on a schedule of 3 doses for every 4 days. The results were as follows: The therapeutic index of ADM was highest at five to nineteen times the others In vivo, ADM demonstrated + activity, whereas others had no significant effect There was a close correlation between the therapeutic index and in vivo anticancer effect using nude mice.

Animals↗

PubMed1987

[Anticancer drug induced sister chromatid exchange and correlation to cell survival in human brain tumor cells].

Sister chromatid exchanges (SCEs) induced by four anticancer drugs, 3-(4-amino-2-methyl-5-pyrimidyl) methyl-1-(2-chloroethyl)-1-nitrosourea (ACNU), 1-3-bis (2-chloroethyl)-1-nitrosourea (BCNU), nitrogen mustard (HN2), cis-diamminedichloroplatinum (II) (cis-Pt) were examined on five cell lines derived from human malignant glioma biopsy specimens, and compared to results obtained with colony-forming efficiency (CFE) assay. Treatment of the five cell lines with these four drugs produced concentration-dependent increases in SCEs. Treatment with ACNU induced the most SCEs in SF-126 cells decreasing in SF-268 cells followed by SF-210 cells, SF-295 cells, and the least SCEs in SF-188 cells. The results of the SCE assay with BCNU in these cell lines were similar with ones with ACNU. In contrast to results obtained with nitrosoureas, the most SCEs were induced in SF-188 cells and the least were induced in SF-126 cells by the treatment of HN2. The frequency of SCEs induced with cis-Pt was almost similar in the five cell lines. The number of SCEs induced by the treatment of ACNU, BCNU, HN2 and cis-Pt in five cells lines showed a good correlation with cytotoxicity measured by CFE assays, and induction of SCEs occurred at much lower concentrations of these anticancer drugs than those required to induced cell kill. These results suggest that measurement of induced SCEs in human brain tumor cells treated with some anticancer drugs provide a more sensitive indicator of drug action than CFE assay and that SCE assays may be a useful method of the in vitro sensitivity test to some anticancer drugs.

Antineoplastic Agents↗

PubMed1987

Clinical studies on a new screening assay for anticancer agents using nude mice and isotopic evaluation.

A new screening assay for anticancer agents was established using an in vivo nude mouse model. Assessment of the chemosensitivity of individual human tumors was determined by [3H]thymidine incorporation by the treated tumors. Three hundred and thirty tumors derived from cancer patients were transplanted into nude mice s.c. and treated with anticancer agents. Mitomycin C, 5-fluorouracil, cyclophosphamide, and doxorubicin were used in the present studies. In 270 of 330 cancers, chemosensitivity was evaluated by this method (evaluable rate, 81.8%). The rate of positive sensitivity against all tumors was 21.9% in mitomycin C, 12.2% in 5-fluorouracil, 27.4% in cyclophosphamide, and 23.6% in doxorubicin, respectively. The tumor sensitivity to anticancer agents varied according to the type of cancer. Retrospective and prospective clinical studies were performed to determine the usefulness of the nude mouse-isotope assay for the prediction of tumor sensitivity. The 24-month survival rates of 24 gastric cancer patients treated with tumor-sensitive agents was significantly higher than that of 28 patients treated with tumor-resistant agents. The end results after chemotherapy in far-advanced and inoperable terminal cases of gastrointestinal cancers was also investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with tumor-sensitive agents was longer than that of eight patients treated with tumor-resistant agents. From prospective correlative studies carried out on 25 patients, this assay correlated with clinical responses (overall agreement, 76.0%; P less than 0.05) with specific agreements of sensitivity and resistance of 37.5 and 94.1%, respectively. From these results, it seems reasonable to conclude that nude mouse-isotope assay is a screening assay to identify appropriate agents for the treatment of patients with cancer. However, there is still a need to develop a better protocol in this assay, especially for antimetabolites, and to continue research in order to find more sufficient assays to predict clinical sensitivity to anticancer agents.

Animals↗

PubMed1986

[Sensitivity testing of anticancer drugs using the human tumor clonogenic assay].

The response to cancer chemotherapy varies from patient to patient with the same histologic type of tumor. However, anticancer drugs are considerably toxic to the patient, and it is therefore very important to have an accurate knowledge of the sensitivity of anticancer drugs against an individual patient's tumor in establishing successful chemotherapy. We have investigated the sensitivity testing of anticancer drugs using the human tumor clonogenic assay since 1980. Specimens were obtained by aspiration of ascites, pleural effusions and bone marrow and by biopsy of primary and metastatic tumors. Drugs tested in the present study were adriamycin, aclarubicin, THP-adriamycin, mitoxantrone, 40497s (an active compound derived from ifosfamide), mitomycin C, cisplatinum and methotrexate. One hundred and fifty-two specimens were obtained from cancer patients and tested for their drug sensitivity using the assay. Of the 152 specimens, 63 (41%) formed more than 30 colonies in control plates and could be used to evaluate drug sensitivity. Of these, 45 instances were evaluable for examination in an in vitro-in vivo association, and 42 (93%) showed a correlation between in vitro sensitivity and clinical response. In summary, the results indicated that the human tumor clonogenic assay was an excellent technique for testing the in vitro sensitivity of anticancer drugs. However, technical developments yielding higher colony efficiency would be required to facilitate practical use of the assay.

Antineoplastic Agents↗

PubMed1984

[Changes of anticancer activity and pulmonary toxicity of bleomycins in differences of administration schedules and routes in mice].

Anticancer activity and pulmonary toxicity of bleomycin and peplomycin in mice were found to be dependent on administration schedules and routes. That is, at the same total dose of 50 mg/kg, the anticancer activity against Lewis lung carcinoma was most strongly exhibited by continuous infusion of peplomycin for 7 days among all schedules tested and decreased in the order of the continuous infusion greater than 4 times injections per day for 10 days greater than daily injection for 10 days greater than daily injection for 2 days. In contrast, the pulmonary toxicity occurred lowest in the continuous infusion and strongest in daily injection for 10 days among the schedules. With respect to administration routes, the anticancer activity and the pulmonary toxicity of them were strongly exhibited in the order of i.v. much greater than i.m. greater than s.c. greater than i.p., except that no route dependency was observed in the continuous infusion. The pulmonary toxicity of peplomycin was lower than that of bleomycin in every administration schedules and routes. From these results, the continuous infusion was concluded to be the best schedule to increase the anticancer activity and to reduce the pulmonary toxicity.

Animals↗

PubMed1982

Identification of metabolism pathways of anticancer drugs by high-pressure liquid chromatography in combination with field desorption mass spectrometry.

The separation and structure elucidation of the metabolites of many anticancer drugs by combined gas chromatography-mass spectrometry using conventional ionization techniques is not possible because of their high polarity and involatility. For the direct analysis of anticancer drug metabolites without their derivatization and extraction from biological fluids, high-pressure liquid chromatography (HPLC) in combination with field desorption (FD) mass spectrometry have developed as powerful methods. Specific techniques and preconditions for the HPLC separation of metabolites suitable for their subsequent analysis by FD mass spectrometry have been worked out. Most important for the isolation by reversed-phase HPLC is the selection of suitable volatile aqueous eluents and the purification of metabolites by removal of excess alkali metal ions from the biological sample. Essential advances for FD mass spectrometric analyses with high sensitivity are the development of adjustable insertion probes permitting optimal alignment of the field ion emitter, precise control of the emitter temperature and spectra accumulation techniques which provide enhanced reproducibility of FD spectra. In metabolism studies of the clinical anticancer drugs, methotrexate (MTX), cyclophosphamide (CP) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), the combined application of HPLC and FD mass spectrometry enabled the identification and quantitation of involatile and labile metabolites that were previously resistant to structural analysis. The toxicologically important metabolites of MTX, 7-hydroxy-MTX and MTX-oligoglutamyl conjugates were identified by their FD mass spectra in serum, urine and erythrocytes of patients receiving high-dose MTX. 4-Hydroxy-CP, the unstable key metabolite for the antitumor selectivity of CP, has been directly characterized by FD mass spectrometry, and its presence as a urinary product in man was first demonstrated by FD mass spectral analysis of its 4-benzylthio derivative. The particular advantage of the FD technique for the analysis of highly polar, polyfunctional metabolite conjugates was demonstrated by the structural identification of phosphoramide mustard-nucleoside adducts, and of several metabolites in the glutathione conjugation pathway of m-AMSA, from rat bile. In addition to HPLC, FD mass spectrometry has been successfully applied to the quantitation of MTX, CP and their metabolites in serum and urine and, because of its outstanding specificity, may prove useful in selected pharmacokinetic studies of anticancer drugs.

Aminoacridines↗

PubMed1982

[History and significance of sensitivity test of anticancer drugs].

Many anticancer drugs are now available for clinical use. Unfortunately, most are extremely toxic to normal tissue. Use of one or more toxic drugs inactive against the given patient's own cancer may not only deny the patients the benefit of active therapy but may actually make the patient's cancer grow faster. The need for adjuvant chemotherapy can scarcely be doubted. However, distant metastases may be present at the time of primary surgery in many cases. Some form of generalized therapy like drug therapy or immunotherapy must therefore be used to supplement our local form of treatment such as surgery and radiation therapy for cancer. Already the dangers of cancer chemotherapy are reported as adverse effect, not only in the case of advanced cancer patients, but, that of post operative adjuvant chemotherapy. Therefore, predictive assays analogous to antibiotic sensitivity tests are needed to rule out inactive drugs and select active drugs with least toxicity. The treatment of patients with cancer according to the result of tests of sensitivity of cancer cells to anticancer drugs has been introduced many years ago. The examination of the sensitivity is carried out on explanted tumor cells by two different methodical approaches-observation of the cytotoxic effect of the preparation tested to the growth of the tissue culture of the tumor examined, and a short-term examination with the indication of the effect of anticancer drugs according to the decreased utilization or incorporation of the precussors of the synthesis of proteins, RNA and DNA labeled with radioisotopes, or according to the release of enzymes from tumor cells damaged by an efficient anticancer drug. However, clinicians know that there are many disagreements between the sensitivity test and clinical results. Each sensitivity test has its limitation and problems for resolution. Research toward the goal of the sensitivity test is to divise more appropriate method which is simple prompt and precise for drug selection.

Animals↗

PubMed1995

Viability of wild type p53-containing and p53-deficient tumor cells following anticancer treatment: the use of human papillomavirus E6 to target p53.

One of the mechanisms in which anticancer therapies function is to induce cell death by apoptosis. In this regard, the biological activity of p53 may be critical since the presence of p53 appears to play a role in apoptosis following genotoxic stress. In experimental systems using in vitro transformed primary cells, there is a direct correlation between the presence of p53 and apoptosis. For example, E1A/ras-transformed primary mouse fibroblasts are less viable and undergo apoptosis following genotoxic stress if these cells contain a wild type p53. In comparison, similarly transformed cells which are p53-deficient are more viable and will not undergo apoptosis under these conditions. Although these are important observations, it remains to be established whether there exists a similar relationship between the presence of wild type p53 and loss of cell viability following therapy in human tumour cells. One way to address this question is to target wild type p53 in human tumour cells using human papillomavirus E6 which mediates the degradation of wild type p53 through the ubiquitin pathway. In this manner, E6 engineered p53-deficient and parental p53-containing human tumour cells provides an appropriate experimental system in which to determine whether wild type p53 in tumour cells has influence on cell viability following genotoxic anticancer treatments. In the present study, the wild type p53 protein in human fibrosarcoma HT1080 cells were targeted with HPV-18 E6 and the viability of these cells in response to treatment with adriamycin, u.v.-irradiation and gamma-irradiation was examined. Data is presented which shows that p53-containing and p53-deficient cells were equally sensitive to these treatments. These data argue that the wild type p53 in these tumour cells does not cause these cells to be less viable when treated with anticancer agents or u.v.-irradiation. Therefore, the status of p53 alone in tumour cells may not be an indicator of response to anticancer treatments.

Cell Death↗

PubMed1995

Metallothionein null cells have increased sensitivity to anticancer drugs.

Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anticancer agents, and reactive oxygen species. We have examined the effect of the loss of MT expression on the cytotoxicity of anticancer agents and mutagens using embryonic fibroblast cells from transgenic mice with targeted disruptions of MT I and II genes (MT -/-). MT -/- cells expressed no detectable MT. Compared to wild type cells, MT -/- cells showed enhanced sensitivity to a 2-h exposure to cisplatin, melphalan, bleomycin, cytarabine, or N-methyl-N'-nitro-N-nitrosoguanidine but were equally sensitive to doxorubicin and neocarzinostatin. Basal expression of the DNA damage-response genes, gadd 45 and gadd 153, were elevated in MT -/- cells compared to MT +/+ cells. Anticancer drug treatment, however, did not produce a greater increase in gadd 45 or gadd 153 expression in MT null cells compared to MT +/+ cells. These results support the hypothesis that endogenous MT levels affect the sensitivity of mammalian cells to mutagens and clinically important anticancer drugs.

Animals↗

PubMedDate not supplied

Sequence-dependent modulation of anticancer drug activities by 7-ethyl-10-hydroxycamptothecin in an HST-1 human squamous carcinoma cell line.

BACKGROUND: We studied the modulatory effects of 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, on the antitumor activities of clinically important anticancer drugs including cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C (MMC), etoposide (VP-16), and adriamycin (ADR). MATERIALS AND METHODS: The HST-1 human carcinoma cells were treated with graded concentrations of these anticancer drugs either alone or in combination with IC50 concentration of SN-38, administered in several different treatment schedules, and antitumor activity was evaluated by the growth inhibition assay. RESULTS: SN-38 potentiated the antitumor activity of CDDP in all schedules with a maximal effect observed with a simultaneous administration, while SN-38 enhanced the cytotoxicity of MMC, 5-FU, or VP-16 only in certain schedules. By contrast, SN-38 attenuated the anticancer effect of ADR in all schedules. CONCLUSIONS: These results demonstrate that SN-38 may have the advantage of augmenting the anticancer activity in combination with CDDP, MMC, 5-FU, and VP-16, depending on the schedule of administration, and should thus be incorporated into the design of a clinical trial for obtaining maximal therapeutic synergy.

Antineoplastic Agents, Phytogenic↗

PubMed1994

[Anticancer effect of balloon laserthermia on human cholangiocellular carcinoma].

The anticancer effect of the Balloon Laserthermia on human cholangiocellular carcinoma, HuCC-T1, producing the tumor marker CA19-9, was examined in order to investigate the possibility of applying the Balloon Laserthermia to patients with advanced bile duct cancer. A Simple hyperthermia (STt; t:min) or the Balloon Laserthermia (TBLTt; T:temperature, t:min) was performed on the cultured HuCC-T1 cells 96 hours after plating 1 x 10(4) cells in each well. The author observed the cells, photographed them through the microscope, and collected every supernatants for measuring CA19-9. Next, the author calculated the number of living HuCC-T1 cells 24 and 48 hours after each treatment. After lysating living HuCC-T1 cells (1 x 10(4)), CA19-9 was measured in Control, ST15, 42BLT15 and 37BLT15 groups. In in vivo experiments, the HuCC-T1 cells (1 x 10(7)) were subcutaneously inoculated into nude mice, and the mice were then treated with ST15, 42BLT15 or 42BLT30 14 days after the inoculation. Each tumor was resected and measured 7 days after the treatment, respectively, and the specimen of the tumor was microscopically examined. The anticancer effect of ST15 on HuCC-T1 cells appeared at the 48 hour point, showing a hyperthermic effect at a delayed stage. The anticancer effect of BLT appeared at the 24 hour point, showing cytocidal effect at an early stage, and this effect continued, being accompanied by hyperthermia. The 42BLT15 represented the highest anticancer effect of all experimental groups. The values of CA19-9 in the supernatants did not show a significant difference between any two groups at their respective harvest times. The values in the living HuCC-T1 cells treated with BLT significantly decreased, compared with the Control and ST15 groups. The tumor wet weight was significantly lower in 42BLT groups, compared with the Control or ST15 groups. The degeneration and/or destruction of the in vitro HuCC-T1 cells and the in vivo tissue-necrosis were very prominent in the BLT groups. The Balloon Laserthermia clearly brought about both cytocidal effect at an early stage and hyperthermic effect at a delayed stage after the treatment. The Laserthermia also presented the possibility of a qualitative degeneration of the cancer cells. The Balloon Laserthermia was considered to be useful for clinical applying.

Animals↗

PubMedDate not supplied

Clinical pharmacokinetics and pharmacodynamics of anticancer agents in pediatric patients (review).

The pharmacokinetics of several important anticancer agents used in pediatric oncology are reviewed. Many of the anticancer agents described showed age-dependent pharmacokinetics, the disposition in children being different compared to the adult pharmacokinetics. These age-dependent pharmacokinetics imply that it is inappropriate to extrapolate pharmacokinetic data from studies in adult patients. Interpatient pharmacokinetic variability in pediatric patients was large, and of a greater magnitude compared to the variability observed in adult patients. This variability in pharmacokinetics resulted in similar large variability in systemic exposure after administration of standardized doses (e.g. the maximum tolerated dose) of these anticancer agents. The variability of some of these agents is correlated with their clinical effects (either tumor response or toxicity). It is possible, using these anticancer agents, to monitor pediatric patients, identifying those patients at risk of severe toxicity (high systemic exposure) or those patients who may not benefit from treatment (Low systemic exposure). These pharmacodynamic relationships are described in this paper, since such correlations may contribute to further optimization of chemotherapy in pediatric patients.

Adolescent↗

PubMed1996

[The mechanism of apoptosis induced by anticancer agents in human leukemia cells].

Many anticancer agents induce apoptosis in human leukemia cells. Among the various leukemia cells, especially HL-60 cells and U937 cells are very sensitive to apoptosis upon anticancer agents treatment. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage in human myeloid leukemia HL-60 and U937 cells. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on anticancer agent-induced internucleosomal DNA cleavage. Our data indicate that serine and ICE-like proteases may be involved in anticancer agent-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in human myeloid leukemia HL-60 and U937 cells.

Antineoplastic Agents↗

PubMed1997

[Preoperative adjuvant chemotherapy with oral anticancer agents for stomach cancer].

We performed preoperative chemotherapy using oral anticancer agents and compared the survival rate with that of the untreated group. The statistical significance of effects in the oral anticancer agent groups was tested by multivariate analysis of the survival rate. The subjects were 488 patients who underwent resection of primary stomach cancer in the Chiba Cancer Center between 1981 and the end of 1991. Patients who were gross type 0 preoperatively, who died in the hospital or who had multiple or double cancer, were excluded. They were divided into two oral anticancer agent groups with 158 patients in the Tegafur group, 163 in the 5-FU group, and 167 patients in the untreated group. In addition to preoperative adjuvant chemotherapy, the age, gender, age, localization, gross type, depth of invasion, histological lymph node metastasis and the old histological stage were analyzed as explanatory variables. In both the Tegafur and 5-FU groups significant differences of p = 0.034 and p = 0.024 were obtained. Factors which had significant effects on survival rate were age (p < 0.0001), histological lymph node metastasis (p < 0.0001), age (p = 0.0001), depth of invasion (p = 0.002), and gross type 4 (p = 0.043). Therefore preoperative administration of oral anticancer agents appeared to have a significant effect on survival rates.

Administration, Oral↗

PubMedDate not supplied

Anticancer activities of 2,5,8,9-substituted 6-oxo-1,2,3,4,5,6-hexahydrophenanthridines on multi-drug-resistant phenotype cells.

Lycorine is a member of the alkaloid group from the bulb of the amaryllidaceae. This drug has been reported to have anticancer activity. Several synthetic intermediates obtained during the synthetic study of anticancer drugs based on the lycorine structure, were tested for anticancer activity using three cell lines: L1210 and HL60 cell lines which were resistant (R) or sensitive (S) to adriamycin. The two synthetic intermediates, 2-acetoxy- and 2-hydroxy-5-allyl-8,9-methylenedioxy-6-oxo-1,2,3,4,5,6-hexahydr ophenanthridine (1 and 2), both had anticancer activity in all three cell lines. However, the LD50 for the precursors was about 20 fold greater than for the native lycorine. Both 1 and 2 were cytotoxic to the adriamycin-resistant cell line, indicating that these drugs are not affected by the multidrug resistance factors. When low doses of the compounds were used, the HL60R cell line could be induced to differentiate to a cell which expressed a macrophage specific protein. These results suggest that phenanthridines 1 and 2 can be used on cells which are resistant to adriamycin, and that one mechanism of action is the induction of differentiation.

Animals↗

PubMed1997

[Analysis of induction of MDR1 gene expression by anticancer chemotherapy in bladder cancer].

Using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based quantitative analysis method, we investigated MDR1 mRNA expression levels in 58 bladder cancer specimens to determine whether MDR1 gene expression was induced or enhanced in bladder cancers during chemotherapy. In bladder cancer specimens which were obtained from patients treated with anticancer drugs, significantly higher expression levels of MDR1 mRNA were observed than in those from patients not treated with any anticancer drugs (p = 0.0134, Mann-Whitney U test). From 14 patients who had bladder cancer, clinical specimens were obtained before and after neoadjuvant intra-arterial chemotherapy. The expression levels of MDR1 mRNA were significantly higher in the post-treatment specimens than in the pre-treatment specimens (p = 0.0298, Wilcoxon signed-rank test). Of these 14 patients, 7 patients exhibited increased levels of MDR1 mRNA expression after chemotherapy. In 6 patients, there were no changes in the MDR1 mRNA expression levels before and after chemotherapy. Only one patient exhibited decreased levels of MDR1 mRNA expression after chemotherapy. No significant correlations were observed, between MDR1 mRNA expression levels and effect of the chemotherapy determined microscopically, dosage of anticancer drugs, or patient outcome. In conclusion, this study indicates that MDR1 gene expression in bladder cancers is induced and enhanced during chemotherapy. This overexpression of the MDR1 gene may contribute to resistance to anticancer drugs after repeated chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

NMR spectroscopy as a tool to investigate the structural basis of anticancer drugs.

NMR spectroscopy has been shown to be useful in determining the structures of nucleic acid fragments in solution. Over the last several years NMR spectroscopy, in conjunction with restrained molecular dynamics, has been employed to understand the 3D structures of a number of anticancer drugs and to rationalize their DNA binding behavior. In this review we address the methodologies used most frequently to determine nucleic acid structures in solution. In subsequent sections, we examine how these methods have been applied to rationalize the activities of a number of anticancer agents that target duplex DNA such as cisplatin, bleomycin and calicheamicin. Non-duplex DNA and RNA also represent interesting nucleic acid targets for anticancer drug design and applications of solution NMR spectroscopy to understanding the structures of these types of molecules (e.g. Okazaki fragments, DNA tetraplexes) are also reviewed. In the final sections, advances in NMR methodologies (e.g. linear prediction, superconducting probes) that are likely to impact the research conducted in this area are reviewed. The success of NMR spectroscopy in understanding the structural basis for clinically useful anticancer drugs bodes well for future applications of this methodology not only in rationalization of existing biological activity, but in the design of novel agents that will be useful in treating neoplastic disease.

Antineoplastic Agents↗