Biomedical subjects

T Tsuruo

Publications and source records attributed to T Tsuruo.

At least 109 records · Page 6Linked to original sources

PubMed1998

Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins.

Animal in vivo studies and human epidemiological observations indicated potent anticancer effects for tea. Here we demonstrate that epigallocatechin gallate (EGCG), a major tea catechin, strongly and directly inhibits telomerase, an enzyme essential for unlocking the proliferative capacity of cancer cells by maintaining the tips of their chromosomes. Telomerase inhibition was elaborated in a cell-free system (cell extract) as well as in living cells. In addition, the continued growth of two representative human cancer cell lines, U937 monoblastoid leukemia cells and HT29 colon adenocarcinoma cells, in the presence of nontoxic concentrations of EGCG showed life span limitations accompanied with telomere shortening, chromosomal abnormalities, and expression of the senescence-associated beta-galactosidase. It is suggested that telomerase inhibition could be one of the major mechanisms underlying the anticancer effects of tea.

Adenocarcinoma↗

PubMed1998

Functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of monoblastoid leukemia cells.

A large family of protein tyrosine phosphatases (PTPs) bidirectionally regulate intracellular signaling pathways by reversing agonistic or antagonistic phosphorylation events derived from the action of protein tyrosine kinases. Receptor-like PTP PTP-U2 is expressed during phorbol ester-induced differentiation of monoblastoid leukemia U937 cells. We found that the shorter isoform, PTP-U2S, was expressed at an earlier phase in the course of differentiation and the longer isoform, PTP-U2L, was induced at a later phase. In the presence of 12-O-tetradecanoylphorbol-13-acetate, ectopic expression of PTP-U2L in U937 cells enhanced several characteristics of terminally differentiated cells. Most striking was that PTP-U2L enhanced apoptosis of the differentiated cells, which was only partially inhibited by caspase inhibitor Z-Asp-CH2-DCB. The catalytically inactive mutant PTP-U2L(C --> S) still retained the ability to enhance the differentiation but retained the ability to enhance the following apoptosis of the cells to a lesser extent. These data indicate a functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of U937 cells. Since terminally differentiated blood cells often undergo apoptosis, the data also suggest that PTP-U2L might be involved in physiological turnover of hematopoietic cells in vivo.

Apoptosis↗

PubMed1998

Modulation of multidrug resistance by taxuspine C and other taxoids from Japanese yew.

Taxuspine C (1), a new taxoid from the Japanese yew Taxus cuspidata, increasing the cellular accumulation of vincristine (VCR) in multidrug-resistant tumor cells as potent as verapamil enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When taxuspine C (1) was given i.p. daily at 200 mg/kg with 0.2 mg/kg VCR for 5 days, a treated/control (T/C) value of 138% was obtained. The other new taxoids, taxezopidines G (8) and H (9), from the yew also increased the VCR accumulation as potent as verapamil. These results suggest that some taxoids may be useful for overcoming multidrug resistance in tumor cells.

Animals↗

PubMed1998

Efficient protection of cells from the genotoxicity of nitrosoureas by the retrovirus-mediated transfer of human O6-methylguanine-DNA methyltransferase using bicistronic vectors with human multidrug resistance gene 1.

Retrovirus-mediated transfer of O6-methylguanine-DNA methyltransferase (MGMT; E.C. 2.1.1.63) and a human multidrug-resistance gene (MDR1) confers resistance to nitrosoureas and natural product antitumor agents, respectively. In a previous study, we constructed two bicistronic retroviral vectors, Ha-MDR-IRES-MGMT and Ha-MGMT-IRES-MDR, that allow co-expression of the MGMT gene and the MDR1 gene to protect cells from the toxicity of combination chemotherapy. Each cell transduced with Ha-MDR-IRES-MGMT or Ha-MGMT-IRES-MDR showed high-level resistance to vincristine and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosou rea (ACNU), indicating that the two drug-resistance genes can be functionally co-expressed from these vectors. In the present study, we examined whether the expression of MGMT from these MDR1-MGMT bicistronic retroviral vectors could protect cells from the genotoxicity of nitrosoureas. Three independent Ha-MDR-IRES-MGMT-transduced clones and three independent Ha-MGMT-IRES-MDR-transduced clones of HeLa MR cells showed 12-23-fold and 27-30-fold higher MGMT activity than the parental cells. These clones are more resistant to ACNU mutagenicity measured by the frequency of the emergence of 6-thioguanine-resistant colonies after ACNU treatment over the frequency seen in the parental cells. The ACNU-induced sister chromatid exchange (SCE) was markedly suppressed in these clones. Murine bone marrow cells were transduced with either Ha-MDR-IRES-MGMT or Ha-MGMT-IRES-MDR. Non-selected populations of the transduced cells showed only marginal increases in drug resistance and MGMT activity. Remarkable increase in drug resistance and MGMT activity were observed after a short exposure of the transduced cells to vincristine. The Ha-MDR-IRES-MGMT-transduced, vincristine-selected bone marrow cells showed 27-fold resistance to vincristine, 7-fold resistance to ACNU, and 10-fold higher MGMT activity than the non-transduced, non-selected cells. The Ha-MGMT-IRES-MDR-transduced, vincristine-selected cells showed 8-fold resistance to vincristine, 16-fold resistance to ACNU and 19-fold higher MGMT activity than the non-transduced, non-selected cells. The rates of ACNU-induced SCE in the vincristine-selected cells were as follows: non-transduced cells (non-selected) and HaMDR-transduced cells>Ha-MDR-IRES-MGMT-transduced cells>Ha-MGMT-IRES-MDR-transduced cells. Again, the only marginal levels of increases in the rates of ACNU-induced SCE were observed in non-selected population of the transduced cells. These results indicate that the MDR1-MGMT bicistronic retrovirus vectors would be useful to protect normal hematopoietic cells from nitrosourea-induced mutagenesis, and drug-selectable bicistronic constructs would have great advantage over non-selectable vectors.

Animals↗

PubMed1998

Involvement of Bcl-2 cleavage in the acceleration of VP-16-induced U937 cell apoptosis.

Apoptosis is cellular suicide functionally opposite of mitosis. It plays an important role in tissue growth control and removal of damaged and premalignant cells. The decrease in death suppressor Bcl-2 protein level was implicated in the many types of apoptotic cell death. Because Bcl-2 protein was recently found to be cleaved during apoptosis induced by Fas ligation, IL-3 withdrawal, and alphavirus infection, we assessed whether Bcl-2 protein was also cleaved during the anticancer drug (VP-16)-induced apoptotic cell death in U937 cells. We found that Bcl-2 protein was cleaved in vivo and in vitro after the treatment of VP-16. We also found that caspase-3/CPP32, which was activated after VP-16 treatment, was responsible for the direct cleavage of Bcl-2 protein. The overexpression of the cleaved Bcl-2 fragment increased the sensitivity to VP-16 and promoted apoptotic cell death. Therefore, caspase-3/CPP32 accelerates VP-16-induced U937 cell apoptosis by cleaving death suppressor Bcl-2 protein to produce a death promoter Bcl-2 fragment.

Animals↗

PubMed1998

Requirement of expression of P-glycoprotein on human natural killer leukemia cells for cell-mediated cytotoxicity.

The requirement of P-glycoprotein, a product of the multidrug resistance (MDR)1 gene, for natural killer (NK) cell-mediated cytotoxicity was examined by using a human NK-like cell line, YTN, which is cytotoxic toward JY cells. YTN cells express P-glycoprotein, a judged by flow cytometry and polymerase chain reaction of reverse-transcribed mRNA. YTN cell-mediated cytotoxicity was inhibited by MDR-reversing reagents as well as the F(ab')2 fragment of a monoclonal antibody against P-glycoprotein. Furthermore, antisense oligonucleotides for MDR1 mRNA inhibited expression of P-glycoprotein as well as YTN cell-mediated cytotoxicity. Thus, this study provides firm evidence that P-glycoprotein plays an essential role in cell-mediated cytotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides.

To overcome the problem of multidrug resistance, we investigated the effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein (P-gp) was decreased from 100% to 26% by 20 micromol/L MDR1-AS in the K562/ADM cells, and from 48.1% to 10.2% by 2.5 micromol/L MDR1-AS in the AML blast cells. Western blot analysis also showed a decrease in the amount of P-gp in the MDR1-AS-treated K562/ADM cells. This effect was specific to MDR1-AS, and not observed with sense or random control oligonucleotides. The expression of mdr1 mRNA in K562/ADM and AML blast cells treated with MDR1-AS was decreased compared with the random control. Intracellular rhodamine retention and [3H]daunorubicin also increased after antisense treatment. Chemosensitivity to daunorubicin increased in MDR1-AS-treated blast cells up to 5.9-fold in the K562/ADM cells and 3.0- to 6.4-fold in the AML blast cells. The expression of mdr1 mRNA derived from colony cells decreased in the MDR1-AS-treated groups. No inhibitory effect of the oligonucleotides on normal bone marrow progenitors was observed. These findings suggest that MDR1-AS is useful to overcome multidrug resistance in the treatment of leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

2-Deoxyglucose inhibits chemotherapeutic drug-induced apoptosis in human monocytic leukemia U937 cells with inhibition of c-Jun N-terminal kinase 1/stress-activated protein kinase activation.

Human monocytic leukemia U937 cells undergo apoptosis when treated with antitumor drugs, such as etoposide, camptothecin and mitomycin C. The molecular mechanism of the drug-induced apoptosis is not well understood. In this study, we found that 2-deoxyglucose (2DG), an analog of D-glucose and an inducer of glucose-regulated stress, inhibited anticancer drug-induced but not tumor necrosis factor-alpha-induced apoptosis of U937 cells. 2DG did not reduce initial cellular damage caused by etoposide, an inhibitor of topoisomerase II, suggesting that 2DG affected subsequent cellular responses involved in apoptosis. 2DG inhibited the etoposide-induced activation of c-Jun N-terminal kinase 1/stress-activated protein kinase (JNK1/SAPK) and the subsequent activation of CPP32, both of which are positive regulators for etoposide-induced apoptosis of U937 cells. Our results indicate that 2DG inhibits apoptosis by blocking the signals from cellular DNA damage for JNK1/SAPK activation.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolytic bone metastasis.

The interactions of the cells in the bone microenvironment play important roles in bone remodeling. Osteoblasts are involved in the bone remodeling through the production of soluble factors that regulate proliferation and differentiation of osteoclasts and through cell-cell interactions. Histological studies have suggested that endothelial cells are also associated with some osteolytic bone diseases. However, it is still unclear how endothelial cells contribute to bone resorption. We established bone-derived endothelial cells (BDECs) to study their roles in bone remodeling. The established BDECs promoted bone resorption in a murine neonatal calvaria organ culture system by secreting a soluble bone resorption-inducing factor(s) when stimulated by several inflammatory cytokines. This bone resorption-inducing factor was identified as interleukin-11 (IL-11). IL-11 is known to enhance bone resorption by promoting osteoclastogenesis and by suppressing the activity of osteoblasts. The production of IL-11 in BDECs was also promoted by conditioned medium of human melanoma A375M cells. Because A375M cells formed osteolytic bone metastasis in vivo, BDECs might be involved in pathological osteolysis by producing IL-11. These results suggest that endothelial cells in bone play important roles in the promotion of bone resorption by secreting IL-11 in physiological and pathological conditions.

Animals↗

PubMed1998

A novel anti-platelet monoclonal antibody induces mouse platelet aggregation through an Fc receptor-independent mechanism.

Platelets are nonproliferative and terminally differentiated cells. Platelets offer an attractive model system to study the various biochemical events leading to structural and functional alterations in activated cells. When platelets are exposed to stimuli, they are activated, undergo a dramatic shape change, adhere to each other, and aggregate. Several monoclonal antibodies (mAbs) that recognize CD9, GPIIb/IIIa (alpha IIb beta 3 intergrins), or GPIV are known to stimulate human platelet aggregation. However, no mAbs able to induce aggregation of mouse platelets have been reported. We have established an anti-mouse platelet mAb (AIP21) that can promote mouse platelet aggregation by itself. Because mouse platelets did not express the Fc receptor (FcR, CD32) on their surfaces and because AIP21 is an IgM subclass, AIP21 might promote platelet aggregation through an FcR-independent mechanism. We could not identify the antigen recognized by AIP21, but flow cytometric analysis revealed that it was not identical to CD9, GPIV, or integrins (i.e., alpha IIb, alpha v, alpha 5, alpha 6, beta 1, and beta 3 integrins). During the aggregation of mouse platelets mediated by AIP21, several 50-68-kDa proteins are rapidly phosphorylated at tyrosine residues. This phosphorylation by AIP21 was dose-dependent and did not require plasma components. We identified the 52-kDa phosphorylated protein as Shc. These results indicate that AIP21 could be useful for investigating the mechanisms of mouse platelet aggregation.

Animals↗

PubMed1998

Genetically recessive mutant of human monocytic leukemia U937 resistant to tumor necrosis factor-alpha-induced apoptosis.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces apoptosis in various cell systems by binding to the TNF receptor (TNFR). To study TNF-alpha-induced apoptosis, we isolated and characterized a novel TNF-alpha-resistant variant, U937/TNF clone UA, from human monocytic leukemia U937 cells. The UA cells resist apoptosis induced by TNF-alpha and anti-Fas antibody but not by anticancer drugs, such as VP-16 and Ara-C. Somatic cell hybridization between U937 and UA showed that apoptosis resistance to TNF-alpha in UA was genetically recessive. The hybridization analysis also showed that UA and another recessive mutant clone, UC, belong to different complementation groups in TNF-alpha-induced apoptosis signaling. In UA cells, TNF-alpha-induced disruption of mitochondrial membrane potential and CPP32 activation were abrogated. Expression of TNFR, Fas, and Bcl-2 family proteins was not changed in UA cells. These results suggest that the apoptosis resistant UA cells could have a functional defect in apoptosis signaling from the TNFR to mitochondria and interleukin-1beta converting enzyme (ICE) family protease activation. UA cells could be used to study signaling linkage between cell death-inducing receptor and mitochondria.

Apoptosis↗

PubMed1998

Suppression of interleukin-11-mediated bone resorption by cyclooxygenases inhibitors.

We previously found that human melanoma (A375M) and human breast cancer (MDA-MB-231) cells formed osteolytic bone metastasis in vivo. These cancer cells produced interleukin-11 (IL-11) by themselves and stimulated its production from osteoblasts. Interleukin-11 could increase the number of osteoclasts and raise the calcium concentration in the medium of neonatal murine calvaria organ culture, indicating bone resorption in vitro. Therefore, IL-11 could play an important role in the promotion of osteolysis at the site of bone metastasis. In the present study, we used the calvaria culture system to try to clarify the mechanisms of IL-11-mediated bone resorption. The murine calvaria expressed both the specificity-determining alpha subunit and the signal-transducing beta subunit (gp130) of the IL-11 receptor. When IL-11 was added to the calvaria culture, the concentrations of prostaglandin E2 (PGE2) was elevated. Pretreatment of calvaria with cyclooxygenases inhibitors (e.g., indomethacin, NS-398, and dexamethasone) suppressed the production of PGE2 and the bone resorption induced by IL-11. Addition of exogenous PGE2 overcame the inhibitory effect of cyclooxygenases inhibitors and promoted bone resorption. These results indicate that IL-11 promotes bone resorption through a PGE2 synthesis-dependent mechanism and that cyclooxygenases inhibitors could be interesting drugs to suppress IL-11-mediated osteolytic bone metastasis of cancer cells.

Animals↗

PubMed1998

Down-regulation of epidermal growth factor receptor-signaling pathway by binding of GRP78/BiP to the receptor under glucose-starved stress conditions.

GRP78/BiP, a molecular chaperone in the endoplasmic reticulum, is induced under such adverse conditions for cell survival as glucose starvation. Induction of GRP78 has been shown to coincide with G1 cell cycle arrest, which is an important cellular defense system. In this study, we investigated involvement of GRP78 in the mechanism of growth arrest by using human epidermoid carcinoma A431 cells. Under a chemical stress condition with 2-deoxyglucose, GRP78 was induced 3-4-fold. In the stressed cells, an underglycosylated form of epidermal growth factor receptor (EGFR) was produced and the mature form was decreased. We found that the molecular chaperone GRP78 in the endoplasmic reticulum formed a stable complex with the underglycosylated EGFR but did not with the mature form. This complex formation occurred specifically under the stress conditions, and the complex was dissociated upon removal of the stress. Treatment of the GRP78-underglycosylated EGFR complex with ATP resulted in a release of the underglycosylated EGFR from GRP78, indicating that the complex could be formed through the chaperone function of GRP78. In accordance with the complex formation with endoplasmic reticulum-resident GRP78, the underglycosylated EGFR could not be translocated to the cell surface. As a result, EGF could not induce expression of cyclin D3, a G1 cyclin, in the stressed cells, whereas it did in non-stressed cells. These results indicated that, in the stressed cells, GRP78 participated in down-regulation of EGF-signaling pathway by forming a stable complex with EGFR and inhibiting EGFR translocation to the cell surface.

Carcinoma, Squamous Cell↗

PubMed1998

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(-) tumors were radioresistant, and the majority of p53(-) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(-), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(-) group (P < 0.01), and patients with radioresistant, p53(+), or p21(-) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(-), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Adult↗

PubMed1998

Circumvention of multidrug resistance by a quinoline derivative, MS-209, in multidrug-resistant human small-cell lung cancer cells and its synergistic interaction with cyclosporin A or verapamil.

PURPOSE AND METHODS: To develop a clinically useful approach to circumvent P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MDR human small-cell lung cancer (SCLC), we examined the ability of a novel quinoline compound, MS-209, to reverse MDR by inhibition of P-gp function in combination with other MDR-reversing drugs using a cytotoxicity assay. RESULTS: We established MDR human SCLC cells by culture in medium with gradually increasing concentrations of adriamycin (ADM). Compared with the parental human SCLC cells, SBC-3, the MDR variant SBC-3 cells obtained (SBC-3/ADM) were highly resistant to various chemotherapeutic agents due to P-gp expression. MS-209 reversed the resistance to ADM and vincristine (VCR) of SBC-3/ADM and H69/VP cells in a dose-dependent manner. Moreover, MS-209 in combination with cyclosporin A (CsA) or verapamil (VER) synergistically enhanced the antitumor effects of ADM and VCR on SBC-3/ADM cells. MS-209 restored ADM incorporation and this effect was enhanced by CsA and VER, suggesting that these synergistic effects were due to competitive inhibition of P-gp function. CONCLUSION: MS-209 in combination with CsA or VER might increase the efficacy of these chemotherapeutic agents against MDR human SCLC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Drug-selected complete restoration of superoxide generation in Epstein-Barr virus-transformed B cells from p47phox-deficient chronic granulomatous disease patients by using a bicistronic retrovirus vector encoding a human multi-drug resistance gene (MDR1) and the p47phox gene.

Chronic granulomatous disease (CGD) is a group of disorders characterized by the failure of phagocytes to produce superoxide. One-third of the cases of CGD in the USA and Europe results from defects in the gene encoding p47phox, a cytoplasmic component of NADPH oxidase for superoxide generation. In this study, we constructed the bicistronic retrovirus vector Ha-MDR-IRES-p47, which carries cDNAs for a human multi-drug-resistance gene (MDR1) and p47phox. The amphotropic retroviral producer cells were generated, and the supernatant of the producer cells was used to transduce Epstein-Barr virus-transformed B (EBV-B) cells, established from B cells of p47phox-deficient CGD patients, as an in vitro model of gene therapy for p47phox-deficient CGD. The transduced cells expressed both P-glycoprotein and p47phox protein, and the expression levels were increased after appropriate vincristine selection. The levels of superoxide production in the vincristine-selected cells were increased to a level similar to normal EBV-B cells. This result suggests that it is possible to achieve 100% correction of the CGD defect in p47phox-deficient EBV-B cells by using the bicistronic vector. This strategy could be employed not only in vitro, but also in vivo, in the gene therapy of a number of inherited diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants.

Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert different effects on the colon in terms of promotion or inhibition of tumor development. Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformation of colonic cells. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to compare the effects of PUFAs on the proliferation of non-malignant and malignant cells. We also determined the cellular utilization of fatty acids in media by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed at media concentrations ranging from 10 to 20 microg/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 microg/ml, which had no effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC transformants than in NIH3T3 cells (P < 0.05). There was no difference in the utilization of fatty acids between the two cell lines cultured in media supplemented with ARA. We conclude that the cellular response to exogenous long-chain PUFAs is modified during the course of malignant transformation, and that EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer.

Animals↗

PubMed1998

Monoclonal antibodies to P-glycoprotein: preparation and applications to basic and clinical research.

P-Glycoprotein, a member of the ABC transporter group, plays an important role in anticancer drug resistance. Many monoclonal antibodies to P-glycoprotein have been developed and used to study the molecular and cellular functions of P-glycoprotein. These monoclonal antibodies were used for gene cloning, purification and reconstitution of P-glycoprotein, analysis of transport functions of P-glycoprotein, immunological detection and selective killing of tumors that express P-glycoprotein for diagnostic, and therapeutic purposes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗