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PubMed1989

Potentiation of some anticancer agents by dipyridamole against drug-sensitive and drug-resistant cancer cell lines.

In this study, we have used two different vincristine (VCR)-resistant variants, VJ-300 and HC-7-5/VCR. VJ-300 was isolated from a human cancer KB cell line and HC-7-5/VCR from a human cancer HC-7-5 cell line. VJ-300 and HC-7-5/VCR are both multidrug-resistant (MDR) variants, showing resistance to multiple anticancer drugs such as VCR, adriamycin, actinomycin D and daunomycin. Dipyridamole, a specific inhibitor of nucleoside transport, potentiated these anticancer drugs about 2- to 10-fold against KB and VJ-300. Dipyridamole almost completely reversed drug resistance to actinomycin D in VJ-300 cells with about a 70-fold higher resistance to actinomycin D. Dipyridamole inhibited the efflux of actinomycin D and VCR from VJ-300 cells. Dipyridamole enhanced the uptake of VCR but not that of actinomycin D in VJ-300 and KB. Dipyridamole at 10-100 microM inhibited photoaffinity labeling with [3H]azidopine of the cell-surface protein P-glycoprotein in VJ-300 cells. Dipyridamole potentiated 5-fluorouracil and hexylcarbamoyl-5-fluorouracil in cultured KB and VJ-300, but it annihilated the cytotoxic action of 5-fluorouridine. Potentiation of 5-fluorouracil by dipyridamole against HC-7-5 and HC-7-5/VCR was also observed, but appeared to be less than in VJ-300 and KB cells. Dipyridamole almost completely inhibited the cellular accumulation of 5-fluorouridine, but not that of 5-fluorouracil. Thus, dipyridamole appeared to potentiate anticancer agents through pleiotropic action sites, one of which is inhibition of enhanced efflux of MDR cell lines and the other of which is inhibition of nucleoside transport. Dipyridamole might be a useful and potent agent to potentiate anticancer agents and reverse drug-resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions.

1. Little information is available about the pharmacokinetic interactions of anticancer drugs in man. However, clinically significant drug interactions do occur in cancer chemotherapy, and it is likely that important interactions have not been recognized. 2. Specific cytochrome P450 (CYP) enzymes have been recently shown to be involved in the metabolism of several essential anticancer agents. In particular, enzymes of the CYP3A subfamily play a role in the metabolism of many anticancer drugs, including epipodophyllotoxins, ifosphamide, tamoxifen, taxol and vinca alkaloids. CYP3A4 has been shown to catalyse the activation of the prodrug ifosphamide, raising the possibility that ifosphamide could be activated in tumour tissues containing this enzyme. 3. As examples of recently found, clinically significant interactions, cyclosporin considerably increases plasma doxorubicin and etoposide concentrations. Although cyclosporin and calcium channel blockers may influence the pharmacokinetics of certain anticancer agents by inhibiting their CYP3A mediated metabolism, it is more likely that these P-glycoprotein inhibitors inhibit P-glycoprotein mediated drug elimination. 4. Appropriate caution should be exercised when combining P-glycoprotein inhibitors and potential CYP3A inhibitors with cancer chemotherapy.

Antineoplastic Agents↗

PubMed1992

Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity.

The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.

Antibiotics, Antineoplastic↗

PubMed1992

L-histidinol in experimental cancer chemotherapy: improving the selectivity and efficacy of anticancer drugs, eliminating metastatic disease and reversing the multidrug-resistant phenotype.

Human cancer chemotherapy is limited by two major problems: the failure of commonly used anticancer drugs to act against tumor cells in a specific manner and the ability of malignant cells to resist killing by antineoplastic agents. Experimentally, both of these problems can be solved by using L-histidinol in combination with conventional anticancer drugs. A structural analogue of the essential amino acid L-histidine and an inhibitor of protein biosynthesis. L-histidinol improves the selectivity and the efficacy of a variety of cancer drugs in several transplantable murine tumors. Furthermore, L-histidinol circumvents the drug-resistant traits of a variety of cancer cells, including those showing multidrug resistance. This review will summarize these properties of L-histidinol, present new evidence on its ability to increase the vulnerability of both drug-sensitive and drug-resistant human leukemia cells to various anticancer drugs, and show that, in addition to inhibiting protein synthesis, L-histidinol acts as an intracellular histamine antagonist. The establishment of a connection between the latter mechanism and the capacity to modulate anticancer drug action has resulted in a clinical trial in the treatment of human cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo.

We previously reported the development of epidermal growth factor receptor (EGFR)-targeted immunoliposomes that bind and internalize in tumor cells which overexpress EGFR and/or mutant EGFR variant III (EGFRvIII), enabling intracellular delivery of potent anticancer agents in vitro. We now describe in vivo proof-of-concept for this approach for the delivery of multiple anticancer drugs in EGFR-overexpressing tumor models. Anti-EGFR immunoliposomes were constructed modularly with Fab' fragments of cetuximab (IMC-C225), covalently linked to liposomes containing probes and/or anticancer drugs. Pharmacokinetic and biodistribution studies confirmed long circulation times (t(1/2) = 21 hours) and efficient accumulation in tumors (up to 15% ID/g) irrespective of the presence of the targeting ligand. Although total accumulations of anti-EGFR immunoliposomes and nontargeted liposomes in EGFR-overexpressing tumors were comparable, only immunoliposomes internalized extensively within tumor cells (92% of analyzed cells versus <5% for nontargeted liposomes), indicating different mechanisms of delivery at the cellular level. In vivo therapy studies in a series of xenograft models featuring overexpression of EGFR and/or EGFRvIII showed the superiority of immunoliposomal delivery of encapsulated drugs, which included doxorubicin, epirubicin, and vinorelbine. For each of these drugs, anti-EGFR immunoliposome delivery showed significant antitumor effects and was significantly superior to all other treatments, including the corresponding free or liposomal drug (P < 0.001-0.003). We conclude that anti-EGFR immunoliposomes provide efficient and targeted drug delivery of anticancer compounds and may represent a useful new treatment approach for tumors that overexpress the EGFR.

Animals↗

PubMed2006

Galectin-3 regulates mitochondrial stability and antiapoptotic function in response to anticancer drug in prostate cancer.

Prostate cancer is one of the malignant tumors which exhibit resistance to anticancer drugs, at least in part due to enhanced antiapoptotic mechanisms. Therefore, the understanding of such mechanisms should improve the design of chemotherapy against prostate cancer. Galectin-3 (Gal-3), a multifunctional oncogenic protein involved in the regulation of tumor proliferation, angiogenesis, and apoptosis has shown antiapoptotic effects in certain cell types. Here, we show that the expression of exogenous Gal-3 in human prostate cancer LNCaP cells, which do not express Gal-3 constitutively, inhibits anticancer drug-induced apoptosis by stabilizing the mitochondria. Thus, Gal-3-negative cells showed 66.31% apoptosis after treatment with 50 micromol/L cis-diammine-dichloroplatinum for 48 hours, whereas two clones of Gal-3-expressing cells show only 2.92% and 1.42% apoptotic cells. Similarly, Gal-3-negative cells showed 43.8% apoptosis after treatment with 300 micromol/L etoposide for 48 hours, whereas only 15.38% and 14.51% of Gal-3-expressing LNCaP cells were apoptotic. The expression of Gal-3 stimulated the phosphorylation of Ser(112) of Bcl-2-associated death (Bad) protein and down-regulated Bad expression after treatment with cis-diammine-dichloroplatinum. Gal-3 also inhibited mitochondrial depolarization and damage after translocation from the nuclei to the cytoplasm, resulting in inhibition of cytochrome c release and caspase-3 activation. These findings indicate that Gal-3 inhibits anticancer drug-induced apoptosis through regulation of Bad protein and suppression of the mitochondrial apoptosis pathway. Therefore, targeting Gal-3 could improve the efficacy of anticancer drug chemotherapy in prostate cancer.

Apoptosis↗

PubMed2006

Inhibition of p53 response in tumor stroma improves efficacy of anticancer treatment by increasing antiangiogenic effects of chemotherapy and radiotherapy in mice.

Inactivation of p53 function, which frequently occurs in tumors, can significantly modulate tumor cell sensitivity to radiation and chemotherapeutic drugs. However, in addition to acting on malignant cells, anticancer agents act on the cells of tumor stroma, causing activation of a p53 response. The effect of this response on treatment outcome has been the subject of the present study. Tumors with p53-deficient stroma were generated using mouse tumorigenic packaging cells that produce a p53 inhibitory retrovirus, encoding a dominant-negative p53 mutant. Tumors maintaining wild-type p53 in their stroma were formed by cells of similar origin but deficient in retroviral production due to the deletion of the packaging signal in the retroviral vector. Comparison of these tumor models, differing only in p53 status of their stromas, showed that tumors with p53-deficient stroma were significantly more sensitive to experimental chemotherapy and radiotherapy. A similar effect was achieved when anticancer treatment was combined with pharmacologic suppression of p53 by the cyclic form of pifithrin alpha, a small-molecule inhibitor of p53. Potentiation of the anticancer effect of chemotherapy and radiotherapy by p53 suppression in the tumor stroma is likely to be due to the increased sensitivity of p53-deficient endothelium to genotoxic stress as shown both in cell culture and in experimental tumors. Thus, reversible pharmacologic suppression of p53 may be a viable approach to improving anticancer treatment via an enhanced antiangiogenic effect of chemotherapy and radiotherapy.

Angiogenesis Inhibitors↗

PubMed1979

Inhibition of nitroso chemical carcinogen activation of rat hepatic guanylate cyclase by anticancer agents.

Recent studies have demonstrated that nitroso chemical carcinogens activate guanylate cyclase (EC 4.6.1.2) which catalyzes the production of guanosine 3',5'-monophosphate. This nucleotide is thought to be involved in normal and abnormal cell growth. We examined the effect of 3 major classes of anticancer chemotherapeutic agents, the antimetabolites (methotrexate and 6-mercaptopurine), antitumor antibiotics (adriamycin and actinomycin D), and alkylating agents (cytoxan, uracil mustard, isophosphamide, chlornaphazine, and 1-propranol-3,3'-iminodimethane sulfonate) on the activation of guanylate cyclase by nitroso chemical carcinogens. The anticancer chemotherapeutic agents noncompetitively blocked the activation of rat hepatic guanylate cyclase by N'-nitro-N-nitroso-N-propylguanidine (NNPG) and hydrazine. Adriamycin, methotrexate, and uracil mustard were the most effective inhibitors completely abolishing the effect of 1 mM NNPG on guanylate cyclase activity. The remainder of the anticancer chemotherapeutic agents abolished the NNPG activation of guanylate cyclase 40--70%. Since a previously described guanylate cyclase inhibitor has been shown to terminate the growth of an undifferentiated prostatic cancer in tissue culture the present data may indicate that one of the mechanisms by which anticancer chemotherapeutic agents exert their effects is by inhibition of tumor guanylate cyclase activity.

Alkylating Agents↗

PubMed2005

Functional and structural characteristics of anticancer peptide Pep27 analogues.

BACKGROUND: A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. RESULTS: Pep27anal2 characterized substituting (2R-->W), (4E-->W), (11S-->W) and (13Q-->W) in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 - 30 microM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601). Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk) nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable alpha-helical conformations in solutions. CONCLUSION: The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

Journal Article↗

PubMed2002

[A checking system for injectable anticancer drugs using each patient's own data and its evaluation].

A checking system was developed for risk management of injectable anticancer drug use. Because the dosage and administration of injectable anticancer drugs vary with each patient, checking the prescription and aseptic i.v. admixing can be markedly complicated and time-consuming for pharmacists. The system we investigated in this study provided real-time checking of dosage, drip infusion rate, dosing periods, and dosing-free periods. The prescription parameters for this check included height, weight, body surface area, the medical history of each patient, the patient's ICD10 code' and disease indication from the package insert. Moreover, when preparing for aseptic i.v. admixing, the liquid volume after the anticancer drug has been mixed with other injectable drugs is calculated automatically. The time limits for stability after mixing and clinical laboratory test results are listed on the Work Sheet. As a result, 24 medication errors were prevented in the first 6 months of use of this system. These consisted of over- and under-doses, excessive dosing periods, insufficient dosing-free periods' etc. The time required for preparation of aseptic i.v. admixing decreased by 73% after introducing this system. Because clinical laboratory test results were referenced beforehand, patients to whom the drug should not be administered were recognized in advance. Thus 13 such cases were identified before i.v. admixing. Therefore this system may be useful in terms of rational anticancer drug use and risk management.

Antineoplastic Agents↗

PubMed2005

[Development of an individualized therapy for establishing the optimal dosage by the pharmacokinetics profiles of anticancer agents].

Therapeutic drug monitoring (TDM) is widely applied to a variety of medications, including antibiotics, immunosuppressants, and antidepressants, but the clinical utility of TDM for anticancer agents is currently limited by several factors. The primary reason is the poorly-defined concentration-effect relationships for most anticancer drugs. TDM has the potential to improve the clinical use of anticancer agents. This paper reviews the relations between the pharmacokinetics of a new anticancer agent, amrubicin, and the clinical response and toxic side effects in patients. The plasma concentration of amrubicin peaked immediately after a bolus intravenous injection of the drug and declined in a biexponential manner thereafter, whereas that of C-13 hydroxy metabolite amrubicinol also peaked just after amrubicin injection but decreased more gradually compared with that of amrubicin. The apparent total clearance of amrubicin showed a large interindividual variability, despite adjustment of dosage for body surface area. Leukocytopenia of grades 3 or 4 occurred in most patients, and thrombocytopenia and anemia of grades 3 or 4 were also common. Since the area-under the curves of amrubicin and amrubicinol seemed to be associated with the severity of hematological toxicities, it is thought that the plasma concentration of amrubicin and amrubicinol may provide useful information for establishing the optimal dosage of amrubicin in each patient.

Aged↗

PubMed1997

[Development of new anticancer drugs--the historical background and current status in Japan].

Historically the development of new anticancer drugs in Japan was initiated in 1950s by M. Ishidate et al. for alkylating agents and by H. Umezawa, T. Hata et al. for antitumor antibiotics. In current cancer chemotherapy, appreciable clinical responses have been reported against some types of hematological and childhood malignancies and solid cancers such as chorionic, ovarian, testicular cancers. However, solid cancers such as many GI-tract, lung, breast and other cancers are still drug-refractory. Since many of these cancers have been discovered at their advanced forms, the drug treatment has been a very important modality. From these reasons, efforts have been placed on the search of new anticancer drugs. Recently, new anticancer drugs relating to taxanes, camptothecins, platinum compounds have exhibited excellent clinical activities against some solid cancers. From these experiences, searches of novel anticancer drugs including those against molecular targets have been continued. The author is greatly indebted to the late Professor Morizo Ishidate for the initiation of his career in cancer research.

Antineoplastic Agents↗

PubMed1991

Toxicity of anticancer agents, growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice.

An investigation of the usefulness of a segregating stock of nude mice [AF nude mice (AF-nu)] for screening anticancer agents was undertaken. The toxicity of anticancer agents, takes and growth rates of human tumour xenografts and chemosensitivities of xenografts in AF-nu were studied and compared with those in BALB/cA nude mice (BALB/cA-nu). The results showed differences in the pattern of mortalities of AF-nu and BALB/cA-nu administered a range of anticancer agents. Body weight changes in the two nude mouse strains differed in the case of 5-fluorouracil, but not for nimustine, adriamycin and vincristine. All tumours transplanted in AF-nu grew as in BALB/cA-nu. Growth rates of 2 xenografts (gastric cancer and glioblastoma) were not significantly different between the 2 nude mouse strains, but those of 2 lung tumour xenografts were significantly greater in AF-nu than those in BALB/cA-nu. There were no significant differences in chemosensitivities of human tumours in AF-nu and BALB/cA-nu (consistency rate as evaluated by our criteria was 88%). From these results, it is suggested that AF-nu are more suitable for anticancer agent screening and experimental chemotherapy of human tumour xenografts than BALB/cA-nu because of lower costs and high reproductive rate. Although they are genetically heterogeneous, sets of experimental animals sharing the same gene pool can be produced routinely.

Animals↗

PubMed2003

The effects of anticancer chemotherapeutic drugs on cognitive function and other neuropsychiatric dimensions in breast cancer patients.

This preliminary study aimed to apply a novel computerized measure derived from the content analysis of 5-min speech samples from patients with breast cancer to measure cognitive impairment and other neuropsychiatric dimensions during the course of anticancer chemotherapeutic treatment. Since such patients are often administered other pharmacological agents to alleviate their symptoms in addition to anticancer chemotherapeutic agents, another aim was to try to distinguish the mental effects of the anticancer drugs from the effects of any other drugs administered. Before and during the course of their anticancer chemotherapy, 12 breast cancer patients gave 5-min verbal samples, elicited by purposely ambiguous instructions, to talk about any personal life experiences. The recorded verbal samples were scored by a computer program (PCAD 2000) to measure the magnitude of cognitive impairment and other relevant neuropsychiatric dimensions. All of the pharmacological agents administered to the patients were recorded. The computer program automatically compared the scores derived from each verbal sample to already established norms to determine whether each score was within normal limits or one to three standard deviations from the norms. Significantly elevated Cognitive Impairment Scale scores were found in the verbal samples of 9 of the 12 patients. All patients had instances of elevated Health/Sickness Content Analysis Scale scores as well as frequent significantly elevated scores in shame anxiety and in death anxiety. In the Quality of Life Content Scale, the scores were uniformly low, ranging from +1.64 to -9.11. Further studies are being carried out to determine which patients are especially susceptible to cognitive impairment under these treatment conditions.

Antineoplastic Agents↗

PubMed2002

Metvan: a novel oxovanadium(IV) complex with broad spectrum anticancer activity.

Among the 25 bis(cyclopentadienyl)vanadium(IV) and 14 oxovanadium(IV) compounds synthesised and evaluated for anticancer activity, bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (metvan) was identified as the most promising multitargeted anticancer vanadium complex with apoptosis-inducing activity. At nanomolar and low micromolar concentrations, metvan induces apoptosis in human leukaemia cells, multiple myeloma cells and solid tumour cells derived from breast cancer, glioblastoma, ovarian, prostate and testicular cancer patients. It is highly effective against cisplatin-resistant ovarian cancer and testicular cancer cell lines. Metvan is much more effective than the standard chemotherapeutic agents dexamethasone and vincristine in inducing apoptosis in primary leukaemia cells from patients with acute lymphoblastic leukaemia, acute myeloid leukaemia or chronic acute myeloid leukaemia. Metvan-induced apoptosis is associated with a loss of mitochondrial transmembrane potential, the generation of reactive oxygen species and depletion of glutathione. Treatment of leukaemia cells from acute lymphoblastic leukaemia, acute myeloid leukaemia and chronic acute myeloid leukaemia patients with metvan inhibits the constitutive expression as well as the gelatinolytic activities of matrix metalloproteinase-9 and -2. Treatment of human malignant glioblastoma and breast cancer cells with metvan at concentrations > 1 microM is associated with a nearly complete loss of the adhesive, migratory and invasive properties of the treated cancer cell populations. Metvan shows favourable pharmacokinetics in mice and does not cause acute or subacute toxicity at the dose levels tested (12.5 - 50 mg/kg). Therapeutic plasma concentrations > or = 5 microM, which are highly cytotoxic against human cancer cells, can be rapidly achieved and maintained in mice for at least 24 h after intraperitoneal bolus injection of a single 10 mg/kg non-toxic dose of metvan. Metvan exhibits significant antitumour activity, delays tumour progression and prolongs survival time in severe combined immunodeficient mouse xenograft models of human malignant glioblastoma and breast cancer. The broad spectrum anticancer activity of metvan together with favourable pharmacodynamic features and lack of toxicity warrants further development of this oxovanadium compound as a new anticancer agent. Metvan could represent the first vanadium complex as an alternative to platinum-based chemotherapy.

Animals↗

PubMed2000

Innovations and strategies for the development of anticancer vaccines.

In 1893, William Coley reported the spontaneous regression of a soft tissue sarcoma in several patients suffering from acute bacterial infections. Although this observation occurred over a century ago, the concept of anticancer vaccines and the immunotherapy of cancer has only recently seemed plausible. A myriad of specific and non-specific immunostimulatory approaches have been tested throughout the years with only a modicum of success. Most of these approaches were doomed from the outset since they were based on false or inadequate knowledge of tumour immunology. Recent advances in our understanding, most notably the identification of genes encoding for cancer regression antigens, currently permit investigators to pursue a more cogent strategy to develop novel and specific anticancer vaccine approaches. Several of these approaches are currently being tested in clinical trials and have already yielded exciting results. However, a number of immunologic and host obstacles to the successful application of anticancer vaccines remain. This editorial will provide an update on the clinical status of anticancer vaccines and review areas of promising research initiatives.

Adjuvants, Immunologic↗

PubMed2001

Use of bacteria as anticancer agents.

Historically, bacteria were used as oncolytic agents for malignant brain tumours. Advances in bacteriology and molecular biology have widened the scope of bacterial approaches to cancer therapy and various possibilities include the use of bacteria as sensitising agents for chemotherapy, as delivery agents for anticancer drugs, and as vectors for gene therapy. Bacterial toxins can be used for tumour destruction and cancer vaccines can be based on immunotoxins of bacterial origin. The most promising approaches are the use of genetically modified bacteria for selective destruction of tumours, and bacterial gene-directed enzyme prodrug therapy. Knowledge gained from study of bacterial genomes forms an important basis of use of bacteria as anticancer agents. TAPET (Tumour Amplified Protein Expression Therapy) uses a genetically altered strain of Salmonella as a bacterial vector, or vehicle, for preferentially delivering anticancer drugs to solid tumours. Verotoxin 1 (VT1) of Escherichia coli has been used for ex vivo purging of human bone marrow of cancer cells before autologous bone marrow transplant. E. coli genes and enzymes have become part of well-known prodrug approaches to cancer in which inert prodrugs can be converted in vivo to highly active species. IL-4 fused with Pseudomonas exotoxin has been administered directly into malignant brain tumours and binds with high affinity to IL-4 receptors, which do not exist on normal brain cells, thus destroying a major part of the tumour without harming the normal brain tissue. It is in Phase I/II clinical trials in patients with glioblastoma. No ideal anticancer agent of bacterial origin that is applicable to all types of cancers has been discovered yet. The most promising approach to malignant brain tumours appears to be the use of genetically engineered bacteria that destroy the tumour selectively while sparing the normal brain tissue.

Animals↗

PubMed1977

Enhancement of the cancer chemotherapeutic effect by anticancer agents in the form of fat emulsion.

Utilizing the lipid-adsorbing ability of lymphatic capillaries, anticancer agents were given in the form of fat emulsion in order to deliver them to regional lymph nodes. The emulsion, in which the drug solution is contained as the innermost phase, yielded high drug concentration in the lymphatic system. Intratumoral injection of emulsified anticancer agent resulted in significantly prolonged retension of the drug within the tumor tissue. Therapeutic experiments of the emulsion also disclosed remarkable tumor reduction and cure rate as compared with aqueous solution of drugs. Oral administration of emulsified 5-Fluorouracil (5-FU) was also attempted for stomach cancer. With 5-FU, the maximum concentration of drug in thoracic lymph and stomach was greater when administered as an emulsion than as an aqueous solution, and a high concentration persisted longer. As a clinical trial of the emulsion method, eight patients with inoperable malignant growth were injected locally with emulsified anticancer agents and 121 patients were given 5-FU emulsion orally. From the clinical and histological findings, it was thought that the emulsion enhanced the chemotherapeutic effect of the anticancer agent on lymph node metastasis.

Adenocarcinoma↗