Biomedical subjects

H M Reyes

Publications and source records attributed to H M Reyes.

At least 19 recordsLinked to original sources

PubMed2001

Use of porcine acellular dermal matrix as a dermal substitute in rats.

OBJECTIVE: To examine porcine acellular dermal matrix (ADM) as a xenogenic dermal substitute in a rat model. SUMMARY BACKGROUND DATA: Acellular dermal matrix has been used in the treatment of full-thickness skin injuries as an allogenic dermal substitute providing a stable wound base in human and animal studies. METHODS: Xenogenic and allogenic ADMs were produced by treating porcine or rat skin with Dispase and Triton X-100. Full-thickness skin defects (225 mm2) were created on the dorsum of rats (n = 29), porcine or rat ADMs were implanted in them, and these were overlain with ultrathin split-thickness skin grafts (STSGs). In two adjacent wounds, 0.005- or 0.017-inch-thick autografts were implanted. In other experiments, the antimicrobial agent used during ADM processing (azide or a mixture of antibiotics) and the orientation of the implanted ADM (papillary or reticular side of ADM facing the STSG) were studied. Grafts were evaluated grossly and histologically for 30 days after surgery. RESULTS: Significant wound contraction was seen at 14, 20, and 30 days after surgery in wounds receiving xenogenic ADM, allogenic ADM, and thin STSGs. Contraction of wounds containing xenogenic ADM was significantly greater than that of wounds containing allogenic ADM at 30 days after surgery. Graft take was poor in wounds containing xenogenic ADM and moderately good in those containing allogenic ADM. Wound healing was not significantly affected by the antimicrobial agent used during ADM preparation or by the ADM orientation. CONCLUSION: Dispase-Triton-treated allogenic ADM was useful as a dermal substitute in full-thickness skin defects, but healing with xenogenic ADM was poor.

Animals↗

PubMed1998

Cryptococcal rib osteomyelitis in a pediatric patient.

A case of cryptococcal rib osteomyelitis in a pediatric patient is described. Isolated cryptococcal osteomyelitis in pediatric patients is a rare entity, and only 10 cases have been reported in the literature. The radiological findings are reviewed to include chest films, nuclear bone scan, and computed tomographic imaging scan. Because of its rarity, the management of isolated cryptococcal osteomyelitis is controversial. Although antifungal antibiotics and surgery are the two therapeutic options, the treatment of cryptococcal osteomyelitis has not been standardized yet. This patient was treated successfully with limited resection of the involved rib and antifungal chemotherapy. This article describes the second case in the literature of cryptococcal rib osteomyelitis in a pediatric patient, reviews the literature of similar cases, and evaluates the current role of surgery in its treatment.

Adolescent↗

PubMed1998

Characterization of acellular dermal matrices (ADMs) prepared by two different methods.

The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness skin injuries as a dermal substitute depends on its low antigenicity, capacity for rapid vascularization, and stability as a dermal template. These properties will be determined largely by the final composition of the ADM. We have treated human skin with either Dispase followed by Triton X-100 detergent or NaCl followed by SDS detergent, cryosectioned the resulting ADMs, and then characterized them immunohistochemically. Staining for cell-associated antigens (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid), elastin, and collagen type VII was dramatically reduced or absent from ADMs prepared by both methods. However, significant amounts of elastin, keratan sulfate, laminin, and collagen types III and IV were still observed in both ADMs. Both methods of ADM preparation resulted in extensive extraction of both cellular and extracellular components of the skin but retention of the basic dermal architecture. In general, ADM prepared by the NaCl-SDS method retained larger amounts of each antigen than did that prepared by the Dispase-Triton method. This was most evident for laminin and type VII collagen but larger amounts of type IV collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl-SDS ADM.

Cytoskeletal Proteins↗

PubMed1996

Protein kinase C activity is altered in HL60 cells exposed to 60 Hz AC electric fields.

We examined the effects of electric fields (EFs) on the activity and subcellular distribution of protein kinase C (PKC) of living HL60 cells. Sixty Hertz AC sinusoidal EFs (1.5-1,000 mV/cm p-p) were applied for 1 h to cells (10(7)/ml) in Teflon chambers at 37 degrees C in the presence or absence of 2 microM phorbol 12-myristate 13-acetate (PMA). PMA stimulation alone evoked intracellular translocation of PKC from the cytosolic to particulate fractions. In cells that were exposed to EFs (100-1,000 mV/cm) without PMA, a loss of PKC activity from the cytosol, but no concomitant rise in particulate PKC activity, was observed. In the presence of PMA, EFs (33-330 mV/cm) also accentuated the expected loss of PKC activity from the cytosol and augmented the rise in PKC activity in the particulate fraction. These data show that EFs alone or combined with PMA promote down-regulation of cytosolic PKC activity similar to that evoked by mitogens and tumor promoters but that it does not elicit the concomitant rise in particulate activity seen with those agents.

Carcinogens↗

PubMed1996

The outcome for children with blunt trauma is best at a pediatric trauma center.

PURPOSE: The mortality rate for pediatric trauma patients cared for in adult trauma centers has been shown, by means of TRISS methodology, not to differ significantly from that of the Major Trauma Outcome Study (MTOS). The question remains, however, whether the outcome of injured children is better in a designated pediatric trauma center (DPTC). The authors' hypothesis is that outcome is better at a DPTC. METHODS: The records of 1,797 children (0 to 15 years of age) admitted to a DPTC between 1987 and 1993 were reviewed. TRISS methodology was used to calculate probability of survival for outcome comparison with the MTOS. The data also was compared with outcome in relation to the admitting Glasgow Coma Score (GCS) reported in the National Pediatric Trauma Registry (NPTR). RESULTS: The outcome of all children at this DPTC had a Z score of +1.4199 (P > .1). The Z score of children admitted because of penetrating trauma (PT, n = 460) did not differ significantly from that of the MTOS. However, the children admitted because of blunt trauma (BT, n = 1,337) had a Z score of +3.3501 (M score = .90), which is significantly better than that of the MTOS (P < .001). The BT population with an ISS of > or = 9 (n = 149) had a Z score of +2.8686 (P < .005) (M = .95). By GCS comparison, the BT group had a outcome similar to that reported in the NPTR. Head injury was the cause of death for 26 (84%) of the 31 PT deaths and 20 (83%) of the 24 BT deaths (three of the remaining four had associated severe head injury). Only 1 of 24 (4%) BT liver injuries and 5 (21%) of 24 BT splenic injuries required surgical intervention. This low incidence of liver and splenic surgical invention is similar to that reported by other DPTCs, but for children treated at adult centers the rates are 37% to 58% and 43% to 53% for liver & splenic surgical intervention, respectively. CONCLUSION: Children with BT have a significantly better outcome at a DPTC; the outcome for children with PT does not differ. Successful nonoperative treatment of blunt abdominal injuries is more likely to occur at a DPTC than at adult trauma centers "with pediatric committment." Thus, children with blunt injuries should be taken to a DPTC, when available.

Adolescent↗

PubMed1995

Demographics of civilian cranial gunshot wounds: devastation related to escalating semiautomatic usage.

The demographics and outcome of patients with gunshot wounds to the head over the past 10 years at Chicago's Cook County Hospital was examined. The study group consisted of 476 consecutive patients admitted to this urban level I trauma center with a diagnosis of penetrating craniocerebral missile injury. All patients followed a protocol that included aggressive surgical management when indicated. The Glasgow Outcome Score was used to assess outcome. There is an alarming rise in firearm violence in general and craniocerebral injury in particular. Some patients with severe neurologic deficits and massive cerebral damage can benefit from aggressive treatment and make a good recovery. A large proportion of this violence is most likely attributable to gang activity. Factors correlating with poor outcome included hypotension, apnea, bihemispheric injuries, or ventricular penetration. Although aggressive surgical and medical management improves the outcome of these patients, much more stringent preventative measures are required to control this violent epidemic.

Adolescent↗

PubMed1995

The new epidemic in children: penetrating injuries.

OBJECTIVE: It is our hypothesis that there has been a dramatic increase in penetrating injuries in children. The purpose of this study is to verify this "new" epidemic in children and to note some of its characteristics. METHODS: We performed a 7-year retrospective review of the trauma registry at our urban pediatric (< 16 years of age) trauma center (UPTC). RESULTS: The percentage of admissions due to penetrating injuries at our UPTC has gradually risen over the past 7 years primarily due to gunshot wounds. In 1992 and 1993, compared to 1987 and 1988, the incidence of penetrating injuries has increased from 20 to 36% in all children and from 45 to 66% in the 12-to-15-year-old age group. CONCLUSION: Injuries due to penetrating trauma have, indeed, increased to epidemic proportions.

Adolescent↗

PubMed1994

Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy.

We have recently demonstrated that a single local injection of the avian pathogen Newcastle disease virus (NDV; strain 73-T) causes complete regression of human neuroblastoma xenografts in athymic mice (R. M. Lorence, K. W. Reichard, B. B. Katubig, H. M. Reyes, A. Phuangsab, B. R. Mitchell, C. J. Cascino, R. J. Walter, and M. E. Peeples. J. Natl. Cancer Inst., 86: 1228-1233, 1994). In this report, we tried to determine if this in vivo antineoplastic effect of NDV extends to human sarcomas. Athymic mice with s.c. HT1080 fibrosarcoma xenografts (7-14 mm) were randomly divided into two groups and treated i.t. with a single injection of either 10(7) plaque-forming units of NDV or phosphate-buffered saline. Complete tumor regression occurred in 8 of 10 mice treated with NDV while unabated tumor growth occurred in all 9 mice treated with phosphate-buffered saline (P < 0.001). To determine if complete tumor regression was long lasting, the 8 mice were monitored for 1 year, during which time no tumor recurred. To test the antitumor effects of NDV on tumors derived from a fresh human sarcoma, a similar experiment was performed in athymic mice using TH15145 synovial sarcoma xenografts at their first and second passages. Of 9 mice with TH15145 xenografts, a single i.t. injection of NDV (10(7) plaque-forming units) caused complete regression of 3 tumors and > 80% regression in 3 more tumors. In contrast, tumors in all 5 mice treated with phosphate-buffered saline exhibited unabated growth (P < 0.03 for > 80% tumor regression). Since HT1080 fibrosarcoma cells express the N-ras oncogene, we explored the effects that transfection of this oncogene has on the sensitivity to NDV. Cultured human fibroblasts that were made tumorigenic following N-ras-transfection were found to be 1000-fold more sensitive to NDV than normal fibroblasts in a cytotoxicity assay. Oncogene expression by the HT1080 fibrosarcoma may therefore contribute to the long-lasting complete regression of this sarcoma following a single local injection of NDV.

Animals↗

PubMed1994

Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy.

BACKGROUND: Neuroblastoma is the most common pediatric extra-cranial solid cancer. Using conventional therapies, children older than 1 year of age with advanced neuroblastoma have a poor prognosis. The development of new approaches for treating such children with neuroblastoma continues to be one of the most important goals today in pediatric oncology. Despite numerous anecdotal reports of human tumor regression during viral infections, the use of viruses to directly lyse neuroblastoma cells has never been reported as a potential therapy. Newcastle disease virus (NDV) has been shown to replicate in and kill cultured human and rat neuroblastoma cells but not normal human fibroblasts. PURPOSE: Our purpose was to determine if this selective killing of human neuroblastoma (IMR-32) cells is maintained during the in vivo treatment of established tumors. METHODS: Two experiments were performed using NDV strain 73-T. Athymic mice with subcutaneous IMR-32 human neuroblastoma xenografts (6-12 mm) were treated intralesionally with live NDV, UV-inactivated NDV, or phosphate-buffered saline (PBS). To study virus replication in situ, mice were given intratumoral or intramuscular injections of NDV. These mice were then killed at various times, and the amount of infectious virus present in tumor or muscle was determined. RESULTS: After one injection of live NDV, 17 of 18 tumors regressed completely, whereas rapid tumor growth occurred in all 18 mice treated with PBS and in all nine mice treated with UV-inactivated NDV (P < .0001). The one tumor that showed only a partial response to a single injection regressed completely after a second NDV treatment. Six months following virus-induced regression, only one tumor had recurred. No significant acute or chronic side effects of live NDV were noted in athymic mice given doses up to 500 times that used in this study. Virus levels increased more than 80-fold between 5 and 24 hours in virus-injected tumors (P < .04), while no infectious virus was produced in NDV-injected muscle tissue. CONCLUSIONS: NDV 73-T appears to replicate selectively in human IMR-32 neuroblastoma xenografts, leading directly to a potent antitumor effect as demonstrated by long-lasting, complete tumor regression occurring after a single local injection of virus. IMPLICATION: These experiments may provide an important step in the development of new therapeutic approaches to challenging cancers such as neuroblastoma.

Animals↗

PubMed1994

Endoscopically defined treatment strategies in patients with locally advanced esophageal cancer.

Sixty-five consecutive, locally advanced esophageal cancer patients were treated by the West Side Medical Center Esophageal Service at the Cook County and University of Illinois hospitals. Each patient was prospectively evaluated with multiple endoscopies including esophagogastroduodenoscopy, bronchoscopy, nasopharyngoscopy, and laryngoscopy. Twenty-four patients (37%) had endoscopic findings that significantly altered therapeutic regimens. Patients identified as having an obvious or impending esophageal fistula or poor performance status were treated in a palliative fashion. Forty (61.5%) patients were considered candidates for treatment with multimodal therapy which included radiation, chemotherapy, and surgery. There was a response rate of 82.5% and a 1-year disease-free survival of 88.9% which was statistically significant when compared to the other patient treatment groups. These data illustrate the necessity of multiple endoscopic evaluation of locally advanced esophageal cancer patients for stratification into appropriate treatment groups. Aggressive treatment afforded selected patients excellent relief of presenting symptomatology, as well as an improved, more acceptable, disease-free survival.

Adenocarcinoma↗

PubMed1994

Spatial association of HIV-1 tat protein and the nucleolar transport protein B23 in stably transfected Jurkat T-cells.

The human immunodeficiency virus (HIV-1) encodes a transactivator protein, the product of the tat gene (tat), which is essential for virus replication. In this study, immunogold electron microscopy was used in a stably transfected Jurkat T-cell line that constitutively expresses HIV-1 tat protein to determine the subcellular and intranuclear distribution of tat protein. Two nucleocytoplasmic shuttle proteins C23/nucleolin and B23 and a third nucleolar antigen that was detected by monoclonal antibody MAb 1277 were also examined. In addition, spatial association of C23 and B23 with tat protein at several subcellular locations was examined in dual-labeling experiments. The results showed that tat protein was found in both the cytoplasm and nucleus but was especially prominent within the dense fibrillar and granular components of the nucleolus. There was little labeling of tat protein in the fibrillar centers where MAb 1277 antigen was localized at a comparatively high level. The subcellular and intranucleolar distribution of tat protein was virtually identical to the pattern seen with C23 and B23. Although the intranuclear distributions of C23, B23 and tat protein were very similar, C23 and tat protein were seldom spatially associated. In contrast, B23 and tat protein were frequently spatially associated in the nucleolus and in several other subcellular locations including the cytoplasm, nucleoplasm, at the nuclear envelope and plasma membrane. While a physical association was not directly demonstrated in this study, the spatial association between B23 and tat protein strongly suggest that such an association may exist.

Animals↗

PubMed1994

Arteriography in the evaluation of penetrating pediatric extremity injuries.

The routine use of arteriography for evaluating penetrating extremity injuries is undergoing reevaluation in the adult literature. Its role in children is less clear. Eighty-seven children treated for penetrating extremity trauma over a 5-year period were studied retrospectively to define the usefulness of arteriography. The ages ranged from 2 to 16 years. Twenty-four arteriograms were performed. Twelve were for patients who exhibited physical signs of vascular injury (diminished pulse, distal ischemia, expanding hematoma, or bruits/thrills over the wound). The other 12 were performed on asymptomatic children with wounds in proximity to major vessels. Two other patients with ongoing hemorrhage were taken directly to the operating room. Of the 12 arteriograms performed for abnormal physical signs, eight (67%) showed vascular injuries. None of the studies performed for proximity alone had abnormal results (P < .01). Ten of 10 patients with vascular injuries had abnormal physical findings, whereas only four of 77 patients without vascular injuries had abnormal findings (sensitivity 100%, specificity 95%). Eighty-five percent of patients have had follow-up in the pediatric surgery clinic, and no missed injuries or complications have been discovered. Timely diagnosis and repair is the cornerstone for successful management of vascular injuries. While the arteriogram is an important adjunct in patients who have abnormal physical findings, proximity to major vessels alone fails to identify patients at risk for significant injuries. Angiography may not be warranted in patients whose physical examination results are normal. Noninvasive modalities such as B-mode ultrasound and Doppler may have future application in the evaluation of these cases.

Adolescent↗

PubMed1994

Surgical and genetic aspects of persistent müllerian duct syndrome.

Persistent müllerian duct syndrome (PMDS) is characterized by the presence of a uterus, cervix, and fallopian tubes in an otherwise normally differentiated 46.XY male. During embryogenesis, regression of müllerian structures in normal males is mediated by antimüllerian hormone (AMH), also called müllerian inhibiting substance (MIS), produced by fetal Sertoli's cells. PMDS has been attributed to deficient AMH activity or to abnormalities in the AMH receptor. The authors report on two patients with PMDS in whom the abnormalities were discovered during surgery for inguinal hernia and cryptorchidism. During the initial operations in each case, testicular biopsies were obtained, and the gonads and müllerian elements were replaced in the pelvis. A second operative procedure, performed several months later, included proximal salpingectomies with dissection of the vasa deferentia on pedicles of myometrium. This permitted excision of the vestigial uterine corpus, leaving a tiny remnant of cervix with the vasa deferentia. The testes were further mobilized so that bilateral orchidopexies could be completed. In the first case, a molecular abnormality was present at position 377 of the first exon of the AMH gene. Thymine replaced cytosine, which altered a CGG arginine codon to a TGG tryptophan codon, rendering the AMH molecule unstable. The molecular abnormality in the first case differs from the first abnormality in AMH reported by Knebelmann et al, thus indicating heterogeneity in this condition. The molecular basis for deficient AMH activity in the second patient has not yet been defined. No molecular abnormalities were found in the exons of this patient's AMH gene.

Anti-Mullerian Hormone↗

PubMed1994

Vascular trauma and reconstructive approaches.

Vascular trauma is becoming more common in children. Iatrogenic injuries are beginning to yield to accidental and intentional trauma as the leading cause. In addition to technical considerations, difficulties in the management of these injuries include the high incidence of spasm and the effects of diminished blood flow on limb growth. The literature regarding pediatric vascular injuries is reviewed. Evaluation and management of these injuries is then discussed, with emphasis on the special problems encountered in children as well as on some areas of controversy. Prevention is still the best treatment for iatrogenic as well as traumatic vascular injuries in children.

Adolescent↗

PubMed1993

Traumatic death in urban children, revisited.

OBJECTIVE: Trauma is the leading cause of death in children older than 1 year in the United States. We performed an analysis of the causes of death due to trauma in children in a large urban community to suggest means of prevention in such communities. We also examined data obtained before and after the designation of pediatric trauma centers to determine whether this has made a difference. DATA SOURCES: Records of the Medical Examiner, Cook County, Illinois, from 1983 through 1988. STUDY SELECTION: The admitting log was reviewed for all children before their 16th birthday. During the 6-year study period, 3121 autopsies were performed on children, 36.1% of whom died due to traumatic injuries. We reviewed the records of those children who died secondary to these injuries. DATA EXTRACTION: Record review on pediatric trauma deaths as to cause of death, time of death, age, sex, and any other pertinent information. RESULTS: Of all trauma deaths, fire was the most common cause of death, followed by motor vehicle-related injuries, homicides, drownings, and falls. These findings differ from national statistics. Improvement in outcome was seen following the designation of general trauma centers, with further improvement seen following the designation of specific pediatric trauma centers. CONCLUSIONS: Identification of causes of pediatric trauma death enables us to suggest methods of prevention. The centralized care of seriously injured children through the establishment of trauma centers and, specifically, pediatric trauma centers might help to prevent these deaths. Further study of pediatric trauma deaths, including hospital and ambulance records, is needed to improve medical care.

Accidents↗

PubMed1993

Modulation of the cytoskeleton and intracellular calcium in leukocytes exhibiting a cancer-associated chemotaxis defect.

Monocyte chemotaxis is severely depressed in patients with advanced tumors, but the cellular basis for this chemotactic defect is not known. Because the actomyosin cytoskeleton is thought to play a primary role in chemotaxis, we have employed flow cytometry to examine several aspects of the contractile machinery including myosin II, myosin light chain kinase (MLCK), actin, and cytoplasmic calcium in unstimulated and in formylpeptide-stimulated neutrophils and monocytes. Serum-pretreated polymorphonuclear leukocytes (PMNs) and monocytes from healthy blood donors or PMNs and monocytes isolated from tumor patients were studied. Leukocytes pretreated with serum from cancer patients exhibited decreased baseline myosin staining and a vastly different response to formylpeptide stimulation compared with leukocytes pretreated with normal human serum. In contrast, similar amounts of MLCK were observed in neutrophils and monocytes preincubated with normal or cancer serum with or without stimulation with formylpeptide. The fluorescent calcium indicator fluo-3 showed that resting and fMLP-stimulated levels of intracellular calcium were not significantly different in control and cancer serum-pretreated human leukocytes or in leukocytes isolated from tumor patients. Similarly, resting and fMLP-stimulated levels of F-actin in cancer patients' leukocytes as assessed by NBD-phallacidin staining did not differ significantly from those of normal leukocytes. Because the actomyosin cytoskeleton is intricately involved in leukocyte chemotaxis, alterations in the cytoskeleton may dramatically affect cell motility. The cytoskeletal alterations and changes in the response of leukocytes pretreated with cancer patients' serum to formylpeptide stimulation as described here may result in decreased chemotaxis by these cells.

Actins↗

PubMed1993

Retinoic acid enhances killing of neuroblastoma cells by Newcastle disease virus.

Newcastle disease virus (NDV), an avian pathogen, selectively replicates in and kills neuroblastoma (NB) cells, but not normal fibroblasts in vitro and in vivo in nude mice. NDV cytotoxicity towards NB cells is enhanced by N-myc oncogene amplification. To further define the antineoplastic effects of NDV, we examined NDV's interaction with NB cells following short-term exposure to the differentiating agent, all-trans retinoic acid (RA), and to neuraminidase. The human NB cell line IMR-32, after treatment with 50 mumol/L RA, became eight times more sensitive to NDV in a cytotoxicity assay. A time course study to determine the optimal incubation period of IMR-32 cells with RA indicated that a fourfold increase in sensitivity towards NDV killing occurred after only 8 hours of RA incubation prior to addition of virus. Maximal sensitivity was achieved at 24 hours of RA incubation and remained constant for longer incubation periods (up to 72 hours). The sensitization of IMR-32 NB cells to NDV was constant for RA doses between 3 mumol/L and 50 mumol/L. Plaque formation, which indicates replication, virus spread and cytotoxicity by a single infectious virus particle, was also enhanced by RA. This effect does not appear to require N-myc amplification in the target NB cells since RA had similar effects upon the high N-myc (IMR-32) and the low N-myc expressing cells (SK-N-SH). Enhanced sialylation has been shown by others to mediate the growth inhibitory effects of RA on a variety of tumor lines. Removal of sialic acid from the IMR-32 NB cell surface using Clostridium neuraminidase (2.7 mg/mL) inhibited 75% of NDV plaque formation. These results demonstrate that NDV killing of two NB cell lines is enhanced using clinically achievable levels of RA and that sialylation of the NB cell surface is important for virus binding and cytotoxicity.

Cytopathogenic Effect, Viral↗

PubMed1992

Newcastle disease virus selectively kills human tumor cells.

Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.

Animals↗