Biomedical subjects

Attila Nagy

Publications and source records attributed to Attila Nagy.

At least 37 records · Page 2Linked to original sources

PubMed2005

Receptors for luteinizing hormone releasing hormone (LHRH) expressed in human non-Hodgkin's lymphomas can be targeted for therapy with the cytotoxic LHRH analogue AN-207.

We determined by immunohistochemistry the presence of LHRH receptors in surgical specimens of human non-Hodgkin's lymphomas (NHL) and investigated the expression of LHRH receptors in two human NHL cell lines, RL and HT by RT-PCR, Western blot and radioligand binding studies. In in vivo experiments with nude mice bearing tumours of these NHL cell lines, the efficacy of cytotoxic LHRH analogue AN-207 and its cytotoxic radical AN-201 was examined. LHRH receptors were detected in 94.1% of the human NHL specimens and in both NHL cell lines. AN-207 significantly (P < 0.01) inhibited the growth of RL and HT tumours, while the non-targeted AN-201 had no effects. Blockade of the LHRH receptors with an excess of LHRH agonist Decapeptyl suppressed the antitumour effects of AN-207. Our findings indicate that LHRH receptors expressed in a high percentage of human NHL specimens can be used for effective targeted therapy with the cytotoxic LHRH analogue AN-207.

Animals↗

PubMed2005

Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207.

OBJECTIVE: To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. DESIGN: Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays. SETTING: Experimental laboratory research. ANIMAL(S): Female athymic nude mice (Ncr, nu/nu). INTERVENTION(S): Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2-pyrrolinodoxorubicin) on a control vehicle solution. MAIN OUTCOME MEASURE(S): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count, and LHRH receptor expression. RESULT(S): AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore, mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors. CONCLUSION(S): Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.

Animals↗

PubMed2005

Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238.

BACKGROUND/AIMS: The efficacy of a targeted cytotoxic hybrid somatostatin analogue AN-238 and of its superactive radical 2-pyrrolinodoxorubicin (AN-201) to induce apoptosis of HepG2 and Hep3B human hepatoma cell lines were studied. AN-238 was designed to selectively target tumor cells expressing somatostatin receptor subtypes (sst(s)). Its effects on HepG2 or Hep3B cells displaying or lacking tumor suppressor p53, respectively, were compared. Normal rat isolated hepatocytes were also tested. METHODS: sst(s) were characterized by binding assays and RT-PCR. Cytotoxicity was quantified by flow cytometry. DNA fragmentation was studied by gel electrophoresis, PARP cleavage by Western blot and ROS formation using fluorescent probes. RESULTS: Specific binding of iodinated RC-160 to HepG2 and Hep3B cells, and its displacement by AN-238 was characterized. mRNA for hsst(2A) was found in both cell lines. Flow cytometry showed a stronger effect of AN-238 than AN-201 to induce sub-G1 phase. DNA fragmentation, nuclear bodies, and PARP cleavage were observed. In addition, AN-238 increased formation of ROS more potently than AN-201. However, no inductions of DNA fragmentation by AN-201 or AN-238 were observed on rat hepatocytes. CONCLUSIONS: Our results indicate that, in liver cancer, the cytotoxic somatostatin analogue AN-238 is a powerful agent that can induce apoptosis, through sst(s) and independently of p53.

Apoptosis↗

PubMed2005

Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog.

OBJECTIVES: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. METHODS: Nude mice with xenografts of Panc-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. RESULTS: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. CONCLUSIONS: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.

Animals↗

PubMed2005

Multisensory responses and receptive field properties of neurons in the substantia nigra and in the caudate nucleus.

The basal ganglia are widely regarded as structures involved in sensorimotor co-ordination, but little is known about the sensory background of their function. We publish here descriptions of the excitatory sensory responses and receptive field properties of the visual, auditory, somatosensory and multisensory caudate nucleus and substantia nigra pars reticulata neurons. Altogether 111 caudate nucleus and 124 substantia nigra sensory neurons were recorded in halothane-anaesthetized, immobilized, artificially ventilated cats. The sensory properties of the caudate and nigral neurons were found to be quite similar. A majority of the units were unimodal while a significant proportion of them were multisensory. The visual and the somatosensory modalities predominated for both nuclei. The sensory receptive fields were extremely large. The visual and auditory receptive fields covered the whole physically approachable sensory field and the somatosensory receptive fields covered the whole body surface of the animal. The receptive field properties of the multisensory caudate and nigral units were similar to those of the unimodal neurons. We observed no signs of retinotopical or somatotopical organization within the basal ganglia. The particular sensory receptive field properties, together with the significant number of multisensory neurons in the basal ganglia, suggest the existence of a multisensory pathway of presumably tectal origin involving the caudate nucleus and the substantia nigra that may serve for the sensory feedback of motor actions co-ordinated by the basal ganglia.

Acoustic Stimulation↗

PubMed2005

Targeted cytotoxic bombesin analog AN-215 effectively inhibits experimental human breast cancers with a low induction of multi-drug resistance proteins.

The cytotoxic analog of bombesin (BN)/gastrin releasing peptide (GRP) AN-215 consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin analog carrier, displays a high affinity to BN/GRP receptors and can be targeted to tumors that express these receptors. We evaluated the antitumor effect and the toxicity of AN-215 in 5 human breast cancer cell lines xenografted into nude mice. In addition, we measured the mRNA expression of multi drug resistance protein 1 (MDR-1), multi drug resistance related protein 1 (MRP-1) and breast cancer resistance protein (BCRP) by real-time PCR analysis after treatment with AN-215. All five cell lines expressed BN/GRP receptors, and AN-215 significantly (P < 0.05) inhibited tumor growth in all models, while its cytotoxic radical AN-201 had no significant effect in four models. In MX-1 tumors, AN-201 had a significantly weaker antitumor effect than AN-215. The effect of AN-215 was nullified by a blockade of BN/GRP receptors with a bombesin antagonist. Low or no induction of MDR-1, MRP-1 and BCRP occurred after treatment with AN-215. In conclusion, targeted chemotherapy with the cytotoxic BN/GRP analog AN-215 strongly inhibits breast cancers that express BN/GRP receptors and might provide a new treatment modality for mammary carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Inhibition of experimental U-118MG glioblastoma by targeted cytotoxic analogs of bombesin and somatostatin is associated with a suppression of angiogenic and antiapoptotic mechanisms.

Human gliomas express receptors for bombesin and somatostatin that can be used for targeted chemotherapy. In the present study, the efficacy and the mechanism of action of cytotoxic bombesin analog AN-215, and cytotoxic somatostatin analog AN-238 were investigated in U-118MG human glioblastomas xenografted into nude mice. The expression of vascular endothelial growth factor (VEGF) and the apoptotic markers Bcl-2 and Bax was analyzed by Western blotting. The toxicity was evaluated by measuring leukocyte levels and body weights. Treatment with AN-215 or AN-238 reduced tumor growth by approximately 50%, and diminished the levels of VEGF by 45 and 75%, respectively. The relative ratio of Bcl-2 to Bax proteins was decreased by approximately 90%, indicating a net apoptotic gain and efficacy of treatment. Specific receptors for bombesin and somatostatin were found in U-118MG tumors. Our results suggest that targeted cytotoxic analogs, AN-215 and AN-238, could be useful for the treatment of human glioblastomas.

Animals↗

PubMed2005

[Benign cystic mesothelioma, a rare tumor of the peritoneum].

We report the case of a 28-year-old woman, who presented with acute abdominal and pelvic pain, the appearance of appendicitis. Because of her symptoms urgent operation was performed. Appendicetomy was performed, during the operation multiple cystic lesions were discovered on the right ovary and the peritoneal surface of the mesentery. Laparatomy was performed with removal of the visible cystic lesions, which contained mucous fluid. Final histology revealed benign cystic mesothelioma, which is a rare lesion of the peritoneum, occurring mainly in women in reproductive age. The etiology of cystic mesothelioma is still unclear. The short-term prognosis is favourable, but high recurrence rate. Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long term outcome. We hope that surgical eradication was effective to prevent recurrence. One year after the operation the patient is complaint and symptom free.

Abdomen, Acute↗

PubMed2004

The structure of the complex of calmodulin with KAR-2: a novel mode of binding explains the unique pharmacology of the drug.

3'-(beta-Chloroethyl)-2',4'-dioxo-3,5'-spiro-oxazolidino-4-deacetoxyvinblastine (KAR-2) is a potent anti-microtubular agent that arrests mitosis in cancer cells without significant toxic side effects. In this study we demonstrate that in addition to targeting microtubules, KAR-2 also binds calmodulin, thereby countering the antagonistic effects of trifluoperazine. To determine the basis of both properties of KAR-2, the three-dimensional structure of its complex with Ca(2+)-calmodulin has been characterized both in solution using NMR and when crystallized using x-ray diffraction. Heterocorrelation ((1)H-(15)N heteronuclear single quantum coherence) spectra of (15)N-labeled calmodulin indicate a global conformation change (closure) of the protein upon its binding to KAR-2. The crystal structure at 2.12-A resolution reveals a more complete picture; KAR-2 binds to a novel structure created by amino acid residues of both the N- and C-terminal domains of calmodulin. Although first detected by x-ray diffraction of the crystallized ternary complex, this conformational change is consistent with its solution structure as characterized by NMR spectroscopy. It is noteworthy that a similar tertiary complex forms when calmodulin binds KAR-2 as when it binds trifluoperazine, even though the two ligands contact (for the most part) different amino acid residues. These observations explain the specificity of KAR-2 as an anti-microtubular agent; the drug interacts with a novel drug binding domain on calmodulin. Consequently, KAR-2 does not prevent calmodulin from binding most of its physiological targets.

Animals↗

PubMed2004

Reversible mechanical unzipping of amyloid beta-fibrils.

Amyloid fibrils are self-associating filamentous structures, the deposition of which is considered to be one of the most important factors in the pathogenesis of Alzheimer's disease and various other disorders. Here we used single molecule manipulation methods to explore the mechanics and structural dynamics of amyloid fibrils. In mechanically manipulated amyloid fibrils, formed from either amyloid beta (Abeta) peptides 1-40 or 25-35, beta-sheets behave as elastic structures that can be "unzipped" from the fibril with constant forces. The unzipping forces were different for Abeta1-40 and Abeta25-35. Unzipping was fully reversible across a wide range of stretch rates provided that coupling, via the beta-sheet, between bound and dissociated states was maintained. The rapid, cooperative zipping together of beta-sheets could be an important mechanism behind the self-assembly of amyloid fibrils. The repetitive force patterns contribute to a mechanical fingerprint that could be utilized in the characterization of different amyloid fibrils.

Adsorption↗

PubMed2004

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones: results of a retrospective, single center study between 1996-2002.

AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing preoperative ERCP (< or =90 d before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st of January 1996 to the 31st of December 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (> or =8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCP. RESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients). Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g. skill of the endoscopist, other diagnostic tools).

Bile Ducts↗

PubMed2004

Differential actin binding along the PEVK domain of skeletal muscle titin.

Parts of the PEVK (Pro-Glu-Val-Lys) domain of the skeletal muscle isoform of the giant intrasarcomeric protein titin have been shown to bind F-actin. However, the mechanisms and physiological function of this are poorly understood. To test for actin binding along PEVK, we expressed contiguous N-terminal (PEVKI), middle (PEVKII), and C-terminal (PEVKIII) PEVK segments of the human soleus muscle isoform. We found a differential actin binding along PEVK in solid-state binding, cross-linking and in vitro motility assays. The order of apparent affinity is PEVKII>PEVKI>PEVKIII. To explore which sequence motifs convey the actin-binding property, we cloned and expressed PEVK fragments with different motif structure: PPAK, polyE-rich and pure polyE fragments. The polyE-containing fragments had a stronger apparent actin binding, suggesting that a local preponderance of polyE motifs conveys an enhanced local actin-binding property to PEVK. The actin binding of PEVK may serve as a viscous bumper mechanism that limits the velocity of unloaded muscle shortening towards short sarcomere lengths. Variations in the motif structure of PEVK might be a method of regulating the magnitude of the viscous drag.

Actin Cytoskeleton↗

PubMed2004

[Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy. Results of a 7-year, retrospective, single center study].

UNLABELLED: The optimal treatment for bile duct stones (in terms of accuracy, complications and cost) is unclear. The aim of our study was to determine the predictive factors for preoperative ERCP. PATIENTS AND METHODS: Patients who underwent preoperative ERCP (= 90 days before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st January 1996 to the 31st December 2002. The indication for ERCP was elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (> or = 8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and combination of factors were compared to the results of the ERCP. RESULTS: 206 preoperative ERCP-s were performed during the observed period, 200 were successful (97.1%). Bile duct stone was detected in 81 patients (39.3%), it was successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones: the positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSIONS: The practical conclusion of this study is that preoperative ERCP is highly recommended in patients with three or more positive factors. In contrast, ERCP is not indicated in patients with zero or one factor. Preoperative ERCP should be offered to patients with two positive factors, however the practice should be based also on the local conditions (e.g. skill of the endoscopist, other diagnostic tools).

Adult↗

PubMed2004

Same fold with different mobility: backbone dynamics of small protease inhibitors from the desert locust, Schistocerca gregaria.

SGCI (Schistocerca gregaria chymotrypsin inhibitor) and SGTI (Sch. gregaria trypsin inhibitor) are small, 35-residue serine protease inhibitors with intriguing taxon specificity: SGTI is specific for arthropod proteases while SGCI is an excellent inhibitor on both mammalian and arthropodal enzymes. Here we report the cloning, expression, and (15)N backbone dynamics investigations of these peptides. Successful expression could be achieved by a "dimeric" construct similar to the natural precursor of the inhibitors. An engineered methionine residue between the two modules served as a unique cyanogen bromide cleavage site to cleave the precursor and physically separate SGCI and SGTI. The overall correlation time of the precursor (5.29 ns) as well as the resulted SGCI (3.14 ns) and SGTI (2.96 ns) are as expected for proteins of this size. General order parameters (S(2)) for the inhibitors are lower than those characteristic of well-folded proteins. Values in the binding loop region are even lower. Interestingly, the distribution of residues for which a chemical exchange (R(ex)) term should be considered is strikingly different in SGCI and SGTI. Together with H-D exchange studies, this indicates that the internal dynamics of the two closely related molecules differ. We suggest that the dynamic properties of these inhibitors is one of the factors that determine their specificity.

Amino Acid Sequence↗

PubMed2004

Induction of apoptosis by AN-152, a cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), in LHRH-R positive human breast cancer cells is independent of multidrug resistance-1 (MDR-1) system.

OBJECTIVE: More than 50% of human breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can be used for targeted chemotherapy with agents like AN-152, in which doxorubicin is linked to analog [D-Lys6]LHRH. We compared the effects of AN-152 and doxorubicin in human breast cancer cells. METHODS: MCF-7, T47D, HCC-70 and ZR-75-1 cells were analysed for expression of LHRH-R using RT-PCR, immunostaining and flow cytometry. Apoptosis and expression of MDR-1 gene product Pgp were measured by flow cytometry. Cleavage of doxorubicin from AN-152 by serum carboxylesterase (CE) was inhibited by DFP. RESULTS: In MCF-7, T47D and HCC-70 cells we found cell surface expression of LHRH-R. In ZR-75-1 cells only sparse surface expression was found. In HCC-70 cells, induction of apoptosis by AN-152 was stronger than by doxorubicin in medium containing fetal calf serum (FCS). Pretreatment with DFP increased AN-152-induced apoptosis in LHRH-R positive MCF-7 and HCC-70 cells and reduced apoptosis in ZR-75-1 cells. In serum-free medium apoptosis induced by AN-152 was stronger than that induced by doxorubicin in HCC-70, T47D and MCF-7 cells, but weaker in ZR-75-1 cells. In medium containing FCS, both AN-152 and doxorubicin induced surface expression of MDR-1 gene product Pgp, but the effect of AN-152 was weaker. Pgp-expression induced by AN-152 was inhibited by pretreatment with DFP. AN-152 did not induce Pgp-expression in serum-free medium. CONCLUSION: The cytotoxic LHRH analog AN-152 induces apoptosis independent of MDR-1 in LHRH-R positive breast cancer cells. The efficacy and/or specificity of AN-152 is improved by suppression or absence of CE activity.

Antibiotics, Antineoplastic↗

PubMed2004

Internalization of cytotoxic analog AN-152 of luteinizing hormone-releasing hormone induces apoptosis in human endometrial and ovarian cancer cell lines independent of multidrug resistance-1 (MDR-1) system.

OBJECTIVE: Eighty percent of human ovarian and endometrial cancers express receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can be used for targeted chemotherapy with agents such as AN-152, in which doxorubicin is linked to analog [D-Lys(6)]-LHRH. Direct receptor-mediated antiproliferative effects of AN-152 have been shown in vitro and in vivo. In LHRH-R positive cell lines, AN-152 was more effective than doxorubicin at equimolar concentrations. This study was designed to investigate the mechanism of action of AN-512 in ovarian and endometrial cancer cells in vitro. Study design Three ovarian (SKOV-3, NIH:OVCAR-3, EFO-21) and 2 endometrial carcinoma cell lines (Ishikawa, HEC-1A) were evaluated for doxorubicin- or AN-152-induced apoptosis. Internalization and cytoplasmic release of AN-152 was monitored by confocal laser scanning microscopy and inhibited by chloroquine. Cleavage of doxorubicin from AN-152 was inhibited by carboxylesterase inhibitor, diisopropyl fluorophosphate (DFP). The surface expression of multidrug resistance-1 (MDR-1) gene product P-glycoprotein (Pgp) was measured by flow cytometry. RESULTS: Induction of apoptosis by AN-152 in LHRH-R positive Ishikawa, HEC-1A, EFO-21, and NIH:OVCAR-3 cells was significantly higher than that induced by doxorubicin, whereas the percentage of apoptotic cells in LHRH-R negative SKOV-3 was higher after treatment with doxorubicin. In EFO-21 cells, apoptosis induced by AN-152 was inhibited by pretreatment with chloroquine. Pretreatment with DFP increased AN-152-induced apoptosis in LHRH-R positive cells and reduced apoptosis in LHRH-R negative SKOV-3. Both AN-152 and doxorubicin induced surface expression of MDR-1 gene product Pgp, but the effect of AN-152 was smaller than that of doxorubicin. Pgp surface expression induced by AN-152 was inhibited by pretreatment with DFP. CONCLUSION: AN-152 is internalized through the LHRH-R and induces apoptosis in LHRH-R-positive human ovarian and endometrial cancer cell lines without activating the MDR-1 efflux pump system. The efficacy and specificity of AN-152 is inversely correlated with carboxylesterase activity.

Antibiotics, Antineoplastic↗

PubMed2004

Chemotherapy targeted to cancers through tumoral hormone receptors.

Work on cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), somatostatin and bombesin, designed for targeting chemotherapy to peptide receptors on various cancers, is reviewed here as the project is at advanced stages of development and clinical trials are pending. Cytotoxic analogs of LH-RH, AN-152 and AN-207, containing doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201), respectively, target LH-RH receptors and can be used for the treatment of prostatic, breast, ovarian and endometrial cancers and melanomas. AN-201 was also incorporated into the cytotoxic analog of somatostatin, AN-238, which can be targeted to receptors for somatostatin in prostatic, renal, mammary, ovarian, gastric, colorectal and pancreatic cancers as well as glioblastomas and lung cancers, suppressing the growth of these tumors and their metastases. A cytotoxic analog of bombesin AN-215, containing 2-pyrrolino-DOX, was likewise synthesized and successfully tested in experimental models of prostate cancer, small cell lung carcinoma, gastrointestinal cancers and brain tumors expressing receptors for bombesin/gastrin-releasing peptide. This new class of targeted cytotoxic peptide analogs might provide a more effective therapy for various cancers.

Animals↗

PubMed2004

Distributed population coding of multisensory spatial information in the associative cortex.

This study describes a possible mechanism of coding of multisensory information in the anterior ectosylvian visual area of the feline cortex. Extracellular microelectrode recordings on 168 cells were carried out in the anterior ectosylvian sulcal region of halothane-anaesthetized, immobilized, artificially ventilated cats. Ninety-five neurons were found to respond to visual stimuli, 96 responded to auditory stimuli and 45 were bimodal, reacting to both visual and auditory modalities. A large proportion of the neurons exhibited significantly different responses to stimuli appearing in different regions of their huge receptive field. These neurons have the ability to provide information via their discharge rate on the site of the stimulus within their receptive field. This suggests that they may serve as panoramic localizers. The ability of the bimodal neurons to localize bimodal stimulus sources is better than any of the unimodal localizing functions. Further, the sites of maximal responsivity of the visual, auditory and bimodal neurons are distributed over the whole extent of the large receptive fields. Thus, a large population of such panoramic visual, auditory and multisensory neurons could accurately code the locations of the sensory stimuli. Our findings support the notion that there is a distributed population code of multisensory information in the feline associative cortex.

Acoustic Stimulation↗