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Biomedical subjects

Z Fan

Publications and source records attributed to Z Fan.

At least 19 recordsLinked to original sources
PubMed2004

Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney.

Both mammals and birds can concentrate urine hyperosmotic to plasma via a countercurrent multiplier mechanism, although evolutionary lines leading to mammals and birds diverged at an early stage of tetrapod evolution. We reported earlier (Nishimura H, Koseki C, and Patel TB. Am J Physiol Regul Integr Comp Physiol 271: R1535-R1543, 1996) that arginine vasotocin (AVT; avian antidiuretic hormone) increases diffusional water permeability in the isolated, perfused medullary collecting duct (CD) of the quail kidney. In the present study, we have identified an aquaporin (AQP) 2 homolog water channel in the medullary cones of Japanese quail, Coturnix coturnix (qAQP2), by RT-PCR-based cloning techniques. A full-length cDNA contains an 822-bp open reading frame that encodes a 274-amino acid sequence with 75.5% identity to rat AQP2. The qAQP2 has six transmembrane domains, two asparagine-proline-alanine (NPA) sequences, and putative N-glycosylation (asparagine-124) and phosphorylation sites (serine-257) for cAMP-dependent protein kinase. qAQP2 is expressed in the membrane of Xenopus laevis oocytes and significantly increased its osmotic water permeability (P(f)), inhibitable (P < 0.01) by mercury chloride. qAQP2 mRNA (RT-PCR) was detected in the kidney; medullary mRNA levels were higher than cortical levels. qAQP2 protein that binds to rabbit anti-rat AQP2 antibody is present in the apical/subapical regions of both cortical and medullary CDs from normally hydrated quail, and the intensity of staining increased only in the medullary CDs after water deprivation or AVT treatment. The relative density of the approximately 29-kDa protein band detected by immunoblot from the medullary cones was modestly higher in water-deprived/AVT-treated quail. The results suggest that 1) medullary CDs of quail kidneys express a mercury-sensitive functioning qAQP2 water channel, and 2) qAQP2 is at least partly regulated by an AVT-dependent mechanism. This is the first clear identification of AQP2 homolog in nonmammalian vertebrates.

Algorithms↗
PubMed2004

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Base Sequence↗
PubMed2003

Atomic force microscopy and nanoindentation characterization of human lamellar bone prepared by microtome sectioning and mechanical polishing technique.

Surface topography, microstructure, and micromechanical properties of human lamellar bone were characterized by atomic force microscopy and nanoindentation. The lamellar bone surfaces were prepared by two different methods: microtome sectioning and mechanical polishing. The lamellar bone surfaces prepared by mechanical polishing revealed that thin lamellae formed depressions approximately 200 nm deep, whereas the surfaces prepared by microtome sectioning were flat. Atomic force microscopy surface topographic images at higher magnification showed differences between thick and thin lamellae in polished samples, but these differences were less pronounced in microtomed samples. Roughness measurements confirmed that there was a significant difference between thick (21.0 nm) and thin lamellae (8.3 nm) in polished samples (p < 0.001). The difference in surface roughness between thick (13.9 nm) and thin lamellae (12.7 nm) in microtomed sample was statistically insignificant (p = 0.74). Higher elastic modulus values were observed for thick lamella in microtomed samples compared with that of thin lamellae, whereas measured elastic modulus differences between thick and thin lamellae in polished samples were found to be statistically insignificant.

Biomechanical Phenomena↗
PubMed2003

Congenital lack of COX-2 affects mechanical and geometric properties of bone in mice.

We compared the mechanical properties of bones from mice lacking either a functional cycloxygenase-1 (C57BL6/DBA COX-1-/-; n = 9) or COX-2 (C57BL6/DBA COX-2-/-; n = 9) gene and wild type mice (C57BL6/DBA; n = 10). Twenty-eight right femora from 3-month-old male mice were used to determine bulk structural and material properties of bone by three-point bending. Bone matrix properties were also measured by nanoindentation to access the changes in bulk mechanical properties due to changes in bone matrix or bone geometry. The bulk material properties (elastic modulus, P < 0.05; ultimate stress, P < 0.01) of COX-2-/- bones were lower than those of wild-type mice whereas the bulk structural properties (stiffness, P > 0.2; breaking force, P > 0.1) were similar to those of the wild-type mice. COX-2-/- mice had a longer moment of inertia but their cortical bones were thinner and contained many more intra-cortical pores compared with the bones of the other two groups. Finally, the bone matrix properties of COX-1-/- mice, COX-2-/- mice and their heterozygous littermates were similar to those of C57BL6/DBA wild-type mice.

Animals↗
PubMed2003

Roles of the PI-3K and MEK pathways in Ras-mediated chemoresistance in breast cancer cells.

Activated Ras utilises several downstream pathways, including the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway and the phosphoinositide 3-kinase (PI-3k)/Akt pathway, to promote cell proliferation and to inhibit apoptosis. To investigate which pathway plays a major role in Ras-induced drug resistance to chemotherapeutic agents in breast cancer cells, we transfected MCF7 breast cancer cells with a constitutively active H-RasG12V and examined the toxicities of three commonly used breast cancer chemotherapeutic agents, paclitaxel, doxorubicin, and 5-fluorouracil in these cells under the conditions that PI-3K or MEK were selectively inhibited by their respective specific inhibitors or dominant negative expression vectors. We found that Ras-mediated drug resistance is well correlated with resistance to apoptosis induced by anticancer agents in MCF7 breast cancer cells. Although inhibition of MEK/MAPK or PI-3K/Akt can each enhance the cytotoxicity of paclitaxel, doxorubicin, or 5-fluorouracil, inhibition of the PI-3K/Akt pathway seems to have a greater effect than inhibition of the MEK/MAPK pathway in reversing Ras-mediated drug resistance. Our results indicate that the PI-3K pathway may play a more important role in receptor tyrosine kinase-mediated resistance to chemotherapy and suggest that PI-3K/Akt might be a critical target molecule for anticancer intervention in breast cancer.

Antineoplastic Agents↗
PubMed2003

Molecular characterization of a distinct potyvirus from whitegrass in China.

Apotyvirus isolated from perennial whitegrass ( Pennisetum centrasiaticum Tzvel.) in North China was characterized at the molecular level. The 3' terminal nucleotide (nt) sequence of 1669 nt of the viral RNA genome has been determined, which covered the coding region of the C-terminal part of the large nuclear inclusion protein (NIb, RNA polymerase), capsid protein (CP) gene and the 3' nontranslated region (NTR). The CP gene consisted of 909 nt (including the stop codon) encoding 302 amino acid residues, and the 3' NTR was 241 nt in length excluding the polyadenylated tract. Sequence comparison of the amino acids of CPs showed that this virus was most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus with percent identities of 77% to 78% while that of the 3' NTRs suggested that it was most closely related to Zea mosaic virus with identity of 72%. This virus isolate was to some extent closely related to other members of the Sugarcane mosaic virus subgroup of potyviruses for the CP amino acid sequences. Phylogenetic analyses of the sequences indicated that this virus isolate represented a distinct potyvirus, and the name Pennisetum mosaic virus (PenMV) is proposed.

Capsid Proteins↗
PubMed2002

Anisotropic properties of human tibial cortical bone as measured by nanoindentation.

The purpose of this study was to investigate the effects of elastic anisotropy on nanoindentation measurements in human tibial cortical bone. Nanoindentation was conducted in 12 different directions in three principal planes for both osteonic and interstitial lamellae. The experimental indentation modulus was found to vary with indentation direction and showed obvious anisotropy (one-way analysis of variance test, P < 0.0001). Because experimental indentation modulus in a specific direction is determined by all of the elastic constants of cortical bone, a complex theoretical model is required to analyze the experimental results. A recently developed analysis of indentation for the properties of anisotropic materials was used to quantitatively predict indentation modulus by using the stiffness matrix of human tibial cortical bone, which was obtained from previous ultrasound studies. After allowing for the effects of specimen preparation (dehydrated specimens in nanoindentation tests vs. moist specimens in ultrasound tests) and the structural properties of bone (different microcomponents with different mechanical properties), there were no statistically significant differences between the corrected experimental indentation modulus (Mexp) values and corresponding predicted indentation modulus (Mpre) values (two-tailed unpaired t-test, P > 0.5). The variation of Mpre values was found to exhibit the same trends as the corrected Mexp data. These results show that the effects of anisotropy on nanoindentation measurements can be quantitatively evaluated.

Anisotropy↗
PubMed2001

A comparison between microsatellite analysis and cytology of urine for the detection of bladder cancer.

We have studied, in a blinded fashion, cytology and microsatellite analysis on urine sediments of 143 Chinese with or without bladder lesions. Microsatellite analysis succeeded in all 143 individuals, while cytology could not be performed on 42 subjects due to insufficient urine samples. Both microsatellite analysis and routine urine cytology succeeded in 81 bladder cancer patients. Seventy-three patients (90%) were identified by microsatellite analysis, while only 41 patients (51%) were identified by cytology. However, four patients were identified by routine cytology but not by microsatellite analysis. Our results proved that microsatellite analysis is more sensitive than routine cytology but the two methods are complementary to each other.

Adult↗
PubMed2001

C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to radiation. Blockade of EGFR with C225 anti-EGFR antibody was previously shown to synergistically enhance radiation-induced tumor growth delay. The purpose of this study was to assess whether C225 can increase tumor cure by radiation. METHODS AND MATERIALS: Nude mice bearing 8-mm-diameter A431 tumor xenografts in the hind leg were treated with C225 antibody, graded single doses of local tumor irradiation, or both. C225 was given i.p. at a dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 plus 6 days after irradiation. Tumor cure was the treatment endpoint assessed by the TCD(50) assay 120 days after treatment. The onset of recurrences of tumors not cured was also determined. RESULTS: C225 antibody increased the antitumor effects of radiation by reducing TCD(50) values and delaying tumor recurrences. Tumor radiocurability was enhanced by a factor of 1.18 by a single dose and by a factor of 1.92 by three doses of C225. Likewise, the appearance of tumor recurrences was delayed by a factor of 1.37 by a single dose and by a factor of 2.13 by three doses of C225. CONCLUSION: The data presented here demonstrate that C225 can increase tumor radiocurability and delay the appearance of recurrences of tumors not cured by radiation treatment.

Animals↗
PubMed2001

Protection against chemotherapy-induced cytotoxicity by cyclin-dependent kinase inhibitors (CKI) in CKI-responsive cells compared with CKI-unresponsive cells.

Inactivation of the retinoblastoma (Rb) protein caused by gene mutation, association with oncoproteins from small DNA viruses, mutational inactivation of p16(Ink4a), or overexpression of cyclin D is a common feature of many human cancer cells and is causally associated with the aberrant proliferation control of cancer cells; whereas normal cells maintain an integrated cell cycle machinery and are subject to cell cycle checkpoint control by cyclin-dependent kinase (CDK) inhibitors (CKIs). To determine whether this difference can be translated into a therapeutic advantage to protect normal cells from adverse cytotoxicity caused by chemotherapy, we established cell model systems for ecdysone-inducible expression of p16(Ink4a), p21(Waf1), and p27(Kip1) in one CKI-responsive cell line (A431 human vulvar epidermoid carcinoma cells with functional Rb) and one CKI-unresponsive cell line (SiHa human cervical cancer cells with nonfunctional Rb). Expression of p16(Ink4a), p21(Waf1), or p27(Kip1) in both SiHa and A431 cells strongly inhibited CDK2 activity, indicating functional expression of the CDK inhibitors in both cell lines. However, only in A431 cells did expression of p16(Ink4a), p21(Waf1), or p27(Kip1) cause Rb dephosphorylation, arrest cell cycle traversal, and potently inhibit cell proliferation. Induction of p16(Ink4a), p21(Waf1), or p27(Kip1) in SiHa cells failed to cause Rb dephosphorylation or to arrest cell cycle traversal, and such induction only minimally inhibited cell proliferation. We then compared the chemosensitivity of clones derived from these two cell lines when the CKIs were and were not induced. Induction of p16(Ink4a), p21(Waf1), or p27(Kip1) conferred strong resistance to paclitaxel- or cisplatin-mediated cytotoxicity on the CKI-responsive A431 cells but not on the CKI-unresponsive SiHa cells. Our results support a novel chemotherapy strategy for treating patients with Rb pathway-impaired cancers by concurrent administration of chemotherapy with CKIs as chemoprotective agents for normal cells.

Cell Cycle Proteins↗
PubMed2001

Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks.

The cytotoxic T lymphocyte protease granzyme A (GzmA) initiates a novel caspase-independent cell death pathway characterized by single-stranded DNA nicking. The previously identified GzmA substrate SET is in a multimeric 270-420-kDa endoplasmic reticulum-associated complex that also contains the tumor suppressor protein pp32. GzmA cleaved the nucleosome assembly protein SET after Lys(176) and disrupted its nucleosome assembly activity. The purified SET complex required only GzmA to reconstitute single-stranded DNA nicking in isolated nuclei. DNA nicking occurred independently of caspase activation. The SET complex contains a 25-kDa Mg(2+)-dependent nuclease that degrades calf thymus DNA and plasmid DNA. Thus, GzmA activates a DNase (GzmA-activated DNase) within the SET complex to produce a novel form of DNA damage during cytotoxic T lymphocyte-mediated death.

Amino Acid Sequence↗
PubMed2001

Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells.

We investigated the signalling pathways by which epidermal growth factor (EGF) modulates paclitaxel-induced apoptosis in SiHa human cervical cancer cells. SiHa cells exposed to paclitaxel underwent apoptosis, which was strongly inhibited by EGF. This inhibition of apoptosis by EGF was not altered by pharmacological blockade of phosphatidylinositol 3'-OH kinase (PI-3K) with the PI-3K specific inhibitor LY294002 or blockade of the mitogen-activated protein kinase (MAPK) kinase (MEK) with the MEK specific inhibitor PD98059, or by transfection of the cells with PI-3K or MEK dominant-negative expression vectors. EGF did not stimulate PI-3K/Akt, MEK/MAPK, or p38 MAPK activity in SiHa cells but did transiently activate the c-Jun NH2-terminal kinase (JNK). Co-exposure of SiHa cells to SB202190 at concentrations that inhibit JNK abolished the protective effect of EGF on SiHa cells against paclitaxel-induced apoptosis. Our findings indicate that the JNK signaling pathway plays an important role in EGF-mediated protection from paclitaxel-induced apoptosis in SiHa cells.

Antineoplastic Agents, Phytogenic↗
PubMed2001

The monoclonal antibody 225 activates caspase-8 and induces apoptosis through a tumor necrosis factor receptor family-independent pathway.

We previously reported that the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 induces DiFi colon cancer cells to undergo apoptosis, and this apoptosis was accompanied by activation of the two apoptosis initiation caspases, caspase-8 and caspase-9. In the current study, we found that pretreatment of DiFi cells with the caspase-8-specific inhibitor z-IETD-fmk but not pretreatment with the caspase-9-specific inhibitor z-LEHD-fmk inhibited mAb 225-induced apoptosis, indicating that caspase-8 plays an essential role in initiating mAb 225-induced apoptosis. Because caspase-8 is activated primarily by the members of the tumor necrosis factor (TNF) receptor family, such as Fas, TNF receptor-1 (TNFR1), or receptors for TNF-related apoptosis-inducing ligand (TRAIL), we investigated whether mAb 225 activated caspase-8 by regulating one or more of these known pathways. Exposure of DiFi cells to TNFalpha or TRAIL activated caspase-8 and induced apoptosis in the cells. A TNFR1-antagonistic mAb or a TRAIL decoy receptor inhibited the activation of caspase-8 and the subsequent apoptosis induced by TNFalpha or TRAIL, respectively, in the cells. However, neither the TNFR1-antagonistic mAb nor the TRAIL decoy receptor inhibited mAb 225-induced activation of caspase-8 and apoptosis in DiFi cells. DiFi cells express detectable level of Fas but are not sensitive to the treatment by the Fas-agonistic mAb CH-11. A Fas-antagonistic mAb (ZB-4) inhibited the Fas-agonistic mAb CH-11-induced caspase-8 activation and apoptosis in Jurkat T-leukemic cells (used as positive control), but had no effect on mAb 225-induced activation of caspase-8 and apoptosis in DiFi cells. Taken together, our results suggest that mAb 225 does not interact with or regulate these known death receptor pathways. An exploration is therefore warranted for a novel mechanism by which mAb 225 activates caspase-8 and triggers apoptosis in DiFi cells.

Animals↗
PubMed2001

Fibroblast growth factor and insulin-like growth factor differentially modulate the apoptosis and G1 arrest induced by anti-epidermal growth factor receptor monoclonal antibody.

DiFi human colon carcinoma cells are stimulated by the transforming growth factor-alpha (TGF-alpha)/epidermal growth factor (EGF) receptor autocrine loop. Exposure of DiFi cells to monoclonal antibody (mAb) 225, which blocks ligand-induced activation of the EGF receptor, induces G1 arrest and subsequent cell death via apoptosis. We investigated the signal pathways by which basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) modulate mAb 225-induced G1 arrest and apoptosis in DiFi cells. Both bFGF and IGF-1 activated the mitogen-activated protein kinase (MAPK) kinase (MEK) pathway in DiFi cells. Additionally, IGF-1 activated the phosphoinositide 3-kinase (PI-3K)/Akt pathway. Both bFGF and IGF-1 inhibited mAb 225-induced apoptosis; however, bFGF provided sustained protection against apoptosis, while the protection by IGF-1 was only temporary. Also, bFGF reversed the mAb 225-induced increase in the p27(Kip1) level, inhibition of cyclin-dependent kinase-2 (CDK-2) activity, dephosphorylation of the retinoblastoma (Rb) protein and the resultant G1 arrest of the cells. In contrast, IGF-1 did not reverse such effects by mAb 225. The prevention of mAb 225-induced G1 arrest and apoptosis in DiFi cells by bFGF was sensitive to the MEK/MAPK inhibitor PD98059 but not to the PI-3K inhibitor LY294002. In contrast, inhibition of apoptosis by IGF-1 in DiFi cells was sensitive only to LY294002 and not to PD98059. These results further our understanding of how mAb 225 induces apoptosis in DiFi cells.

Antibodies, Monoclonal↗
PubMed2001

Detecting bladder cancer in the Chinese by microsatellite analysis: ethnic and etiologic considerations.

BACKGROUND: Microsatellite analysis of urine sediments has shown promise as a highly sensitive and specific technique for the detection of bladder cancer. However, most studies have been conducted in Western countries with Caucasian subjects. We explored the potential of microsatellite analysis for detecting bladder cancer in Chinese people. METHODS: We performed microsatellite analysis of surgical specimens and urine sediment cells collected from Chinese patients with bladder tumors. Those microsatellite markers giving clearly readable patterns and showing susceptibility to alterations were used as a panel to detect primary tumors. A blinded study of additional patients with bladder cancer was performed to investigate the practical value of this panel for detecting bladder cancer. All statistical tests were two-sided. RESULTS: Thirty-eight bladder tumors and corresponding urine sediment specimens were initially screened for 60 microsatellite markers from 18 chromosomes. Nine markers, most of which were different from those that had been used for Western patients, with frequent alterations in the initial patients were selected for further analysis. In the subsequent blinded experiment, microsatellite alterations were observed in urine sediments from 22 (96%) of 23 patients with bladder cancer and from all three patients with inverted papilloma. None of the urine sediments from the one patient with bladder lipoma, from the one patient with neurofibroma, or from the 12 individuals without evidence of bladder tumor showed any microsatellite alterations. CONCLUSIONS: Microsatellite analysis of urine sediments could be a practical method for detecting bladder cancer in the Chinese. Our identification of different microsatellite markers highlights possible ethnic and etiologic disparities between the Chinese and Western bladder cancer patients.

Adult↗
PubMed2001

Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells.

BACKGROUND: HER2/neu has been implicated in the oncogenesis of human prostate cancer. Clinical studies have suggested that overexpression of HER2 may be one of the indicators of poor prognosis in prostate cancer patients. METHODS: We used Western blot analysis to examine the expression of HER2 in a panel of established human prostate cancer cell lines and used an MTT assay to evaluate the cytotoxicity on these cells of a recombinant fusion protein consisting of an HER2-specific single-chain antibody and the Pseudomonas exotoxin A, scFv(FRP5)-ETA. RESULTS: LNCaP cells express high levels of HER2 protein. Exposure of LNCaP cells to scFv(FRP5)-ETA caused remarkable cell death. In contrast, PC3M cells, which express an undetectable level of HER2 protein, were resistant to scFv(FRP5)-ETA-induced cytotoxicity. MDA PCa 2a, MDA PCa 2b, and DU145 cells express low-to-medium levels of HER2 protein and showed an HER2 level-dependent response to scFv(FRP5)-ETA-induced cytotoxicity. The scFv(FRP5)-ETA-induced cytotoxicity of LNCaP cells could be inhibited by an anti-HER2 monoclonal antibody (mAb), which downregulated the levels of HER2 protein, indicating the specificity of scFv(FRP5)-ETA in inducing cytotoxicity in LNCaP cells. Using an apoptosis ELISA, we demonstrated that scFv(FRP5)-ETA induced apoptosis in LNCaP cells. The apoptosis was inhibited by the presence of dihydrotestosterone (DHT) in culture medium. Exposure of LNCaP cells to scFv(FRP5)-ETA caused reduction in the level of the prostate-specific antigen (PSA). CONCLUSIONS: Our data suggest that scFv(FRP5)-ETA might be a useful agent for the treatment of human prostate cancer cells with high levels of HER2 expression.

ADP Ribose Transferases↗
PubMed2001

Synergistic interaction between an anti-p185HER-2 pseudomonas exotoxin fusion protein [scFv(FRP5)-ETA] and ionizing radiation for inhibiting growth of ovarian cancer cells that overexpress HER-2.

OBJECTIVES: The HER-2 proto-oncogene is overexpressed in 15-30% of ovarian cancers, providing a target for therapy in a fraction of patients. We previously described the ability of a recombinant single-chain anti-p185HER-2-Pseudomonas exotoxin A fusion protein, scFv(FRP5)-ETA, to inhibit growth of cancer cells in culture and tumor xenografts in vivo. We have also described synergistic interaction between an anti-p185HER-2-ricin A chain immunotoxin and ionizing radiation for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2. Our objective in this report was to evaluate the in vitro and in vivo effects of scFv(FRP5)-ETA against SKOv3 ovarian cancer cells that have been transfected to express >10(6) p185HER-2 receptors per cell (clone-9002-18). METHODS: Inhibition of clonogenic growth was measured in vitro by limiting dilution analysis. Inhibition of tumor growth was measured in vivo using heterografts established with the same ovarian cancer cell lines. RESULTS: Clone-9002-18 cells were substantially more sensitive than parental SKOv3 cells to the cytotoxic effects of scFv(FRP5)-ETA. Exotoxin fusion protein induced apoptosis in clone-9002-18 cells, but did not affect parental SKOv3 cells. Treatment of clone-9002-18 cells with 200- to 2000-cGy external beam irradiation in combination with scFv(FRP5)-ETA produced synergistic elimination of clonogenic tumor cells in culture. In vivo, subcutaneous or intraperitoneal growth of tumor xenografts in nu/nu mice was significantly inhibited (P = 0.004) by treatment for 10 days with scFv(FRP5)-ETA or with 131I-labeled-520C9 anti-p185HER-2 radionuclide conjugate, but additive effects were not observed with combined treatment. CONCLUSION: ScFv(FRP5)-ETA deserves further evaluation for intraperitoneal therapy of ovarian cancers that overexpress p185HER-2.

ADP Ribose Transferases↗