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S Shusterman

Publications and source records attributed to S Shusterman.

At least 19 recordsLinked to original sources
PubMed2001

The angiogenesis inhibitor tnp-470 effectively inhibits human neuroblastoma xenograft growth, especially in the setting of subclinical disease.

Tumor vascularity is highly correlated with disease outcome in neuroblastoma. Thus, novel therapeutics that target the vascular endothelium are candidates for incorporation into clinical trials. We therefore examined the effect of TNP-470 on human neuroblastoma growth in mouse models reflecting both clinically evident and minimal disease. Mice were inoculated s.c. or by tail vein injection with 10(7) human neuroblastoma-derived CHP-134 cells and treated with TNP-470 (100 mg/kg/dose s.c. three times a week or by continuous infusion) or saline. Treatment was given as a single agent in established xenografts, 10 days after 450 mg/kg of cyclophosphamide, or 12 h after tumor inoculation. Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone both s.c. and by continuous infusion with a treatment to control ratio (T:C) at day 16 of 0.3 (P < 0.001) and a T:C at day 30 of 0.4 (P = 0.029) for each dosing method, respectively. TNP-470 also significantly inhibited tumor growth when administered following cyclophosphamide (T:C at day 30 = 0.2, P < 0.001) and inhibited disease establishment when given shortly after xenograft inoculation (T:C at day 30 = 0.1, P < 0.001) or tail vein injection. TNP-470 was shown to directly inhibit angiogenesis by Matrigel assay (P =.010) and to increase the apoptotic index in treated tumors. These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth rate and tumorigenicity. We speculate that TNP-470 may be a useful adjuvant therapy for high-risk neuroblastoma patients, particularly when used in settings of minimal disease status.

Angiogenesis Inhibitors↗
PubMed2001

Angiogenesis inhibitor TNP-470 during bone marrow transplant: safety in a preclinical model.

High-dose therapy with stem cell rescue is a treatment option for patients with advanced solid tumors. Although this approach has promise for some pediatric cancers, especially neuroblastoma, it is limited by the risk of relapse posttransplant as well as concern about possible reinfused tumor cells in autologous stem cell products. Antiangiogenic agents given during and after recovery from high-dose therapy with stem cell rescue may decrease the risk of relapse. TNP-470 is an antiangiogenic agent now in clinical trials. Although it inhibits the growth of bone marrow (BM) colony-forming cells in vitro, no significant hematological toxicity has been seen in Phase I trials. To assess the feasibility of using antiangiogenic agents during the period of posttransplant hematopoietic engraftment, we have developed a model of stem cell transplant in mice. Mice were lethally irradiated and then rescued with stem cells containing a transgene expressed in the hematopoietic lineage. Mice were then treated with TNP-470 or placebo, and assessed for survival, successful engraftment, and kinetics of engraftment. Both treated and control mice demonstrated reliable multilineage engraftment as well as normal lymphoid maturation with no excess mortality in the treated group. WBCs were lower but still within the normal range at d+28 in mice treated with bolus TNP-470, but not in those treated with continuous infusion TNP-470, compared with controls. These data indicate that inhibitors of angiogenesis do not adversely impact engraftment after stem cell transplantation.

Angiogenesis Inhibitors↗
PubMed2000

Localization of a hereditary neuroblastoma predisposition gene to 16p12-p13.

BACKGROUND: Hereditary predisposition to develop neuroblastoma segregates as an autosomal dominant Mendelian trait. PROCEDURE: We have performed linkage analysis on 10 families with neuroblastoma to localize a hereditary neuroblastoma predisposition gene (HNB1). RESULTS: A single genomic interval at chromosome bands 16p12-p13 was consistent with linkage (lod = 3.46), and identification of informative recombinants defined a 25.9-cM critical region between D16S748 and D16S3068. Loss of heterozygosity was identified in 5/12 familial (42%) and 55/259 nonfamilial (21%) neuroblastomas at multiple 16p polymorphic loci. A 12.8-cM smallest region of overlap of deletions was identified within the interval defined by linkage analysis (tel-D16S764-D16S412-cen). CONCLUSIONS: Taken together, these data suggest that HNB1 is located at 16p12-p13 and that inactivation of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.

Child↗
PubMed2000

Inhibition of tumor growth in a human neuroblastoma xenograft model with TNP-470.

UNLABELLED: Background and Procedure High-risk neuroblastoma disease features are correlated with tumor vascularity, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We therefore examined the efficacy of TNP-470 (TAP Pharmaceuticals, Deerfield, IL) in human neuroblastoma xenograft models. RESULTS: Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone with a treatment to control ratio (T/C) at day 21 = 0.4 (P <.001). TNP-470 also significantly inhibited tumorigenicity when administered shortly after xenograft inoculation (T/C at day 30 = 0.1, P <.001) and when administered following cyclophosphamide (T/C at day 35 = 0.1, P <.001). CONCLUSIONS: These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth both alone and when given with conventional chemotherapy, suggesting that it may be a useful adjunctive therapy for high-risk neuroblastoma patients.

Angiogenesis Inhibitors↗
PubMed2000

Long term survivors of childhood leukemia.

Changes in therapy, primarily intensification, for childhood leukemias have significantly improved cure rates during the past 30 years. The increasing number of survivors has led to a heightened appreciation of the late complications of treatment caused by both radiation and chemotherapy. Important late effects include decreased growth, poor school performance, altered cardiac function, infertility, and second malignant neoplasms. The long term outcome of children and adolescents suffering from the most recently recognized acute complication of treatment, avascular necrosis of weight-bearing bones, is still not known. These, and all patients treated on clinical trials, should be followed throughout their lives. Many of the complications of treatment are often not realized until years after the completion of therapy; some have been found to be related to dose intensity, emphasizing the importance of clinical trials that examine reduction of therapy for diseases with excellent cure rates. A successful example of this strategy is the elimination or reduction of radiation dose for the prevention of central nervous system acute lymphocytic leukemia. This has resulted in fewer long term central nervous system complications without a decrease in survival rates. As knowledge of late effects increases, design of future trials will need to focus on striking a balance between cure and long term toxicity.

Adolescent↗
PubMed1998

Morphometric analysis of the primary and permanent dentitions in hemifacial microsomia: a controlled study.

Hemifacial microsomia (HFM), a developmental abnormality involving the first and second branchial arches, is one of the most common craniofacial abnormalities. Although the general presentations of hemifacial microsomia--such as unilateral microtia, macrostomia, and hypoplasia of the mandibular ramus and condyle--are wellknown, the effects on the teeth are not well-documented. This study examined the primary and permanent tooth dimensions of dental casts of 50 hemifacial microsomia patients compared with those of 50 normal control patients matched for sex and dental status. The results showed that the mesiodistal dimensions of the mandibular second primary molar and the mandibular permanent first molar teeth on the affected side in hemifacial microsomia were significantly smaller compared with those of control teeth (p < 0.001). Furthermore, in the maxillary and mandibular first permanent molars and the maxillary and mandibular first and second primary molars, the teeth in the apparently "normal" side of hemifacial microsomia were also significantly reduced in the mesiodistal dimensions. Comparison of overall dimensions revealed that all primary and permanent molars in hemifacial microsomia were significantly smaller in the mesiodistal dimensions compared with control teeth. A general gradient effect was observed, with the most posterior tooth in each arch being the most severely affected and no effect being seen in the canines and the incisors. These findings suggest that the dental lamina in hemifacial microsomia is affected, and support the hypothesis that its pathogenesis involves an abnormality of the neural crest. Furthermore, these results also support the concept that hemifacial microsomia is a bilateral rather than a unilateral condition.

Branchial Region↗
PubMed1998

Microbiological findings in prepubertal periodontitis. A case report.

Generalized pre-pubertal periodontitis (GPP) is a rare entity that usually affects children with severe systemic diseases. We report the case of a 7-year-old male patient diagnosed with GPP, with no apparent systemic condition, who lost all his primary teeth to periodontal disease. Before extractions, while he was still in mixed dentition the subgingival plaque was collected and analyzed using DNA probes to 40 different microorganisms. Putative periodontopathogens such as Prevotella intermedia, Selenomonas noxia, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans could be identified throughout the mouth. More intriguing was the colonization of the sulcus of some secondary teeth by potentially harmful microorganisms found in pockets of diseased adjacent primary teeth.

Aggregatibacter actinomycetemcomitans↗
PubMed1997

Emergency management of oral trauma in children.

Oral trauma continues to be a common pediatric emergency, accounting for 150 emergency room dental consultations per year at Children's Hospital in Boston. Children between the ages of 18 months and 2.5 years and between 8 and 11 years are most at risk. Recent advances in the management of these dental emergencies may help children and their families avoid the psychological and financial cost of infection or loss of primary and permanent teeth. Treatment of avulsions in the young permanent dentition remains a common problem, and a universally accepted approach to its management is still evolving. The use of a doxycycline immersion prior to reimplantation by the dentist may be helpful in preventing external root resorption. As always, the best therapy against dentofacial trauma is the pediatrician's support of preventive measures.

Child↗
PubMed1994

Adaptation and verification of the relocatable Gill-Thomas-Cosman frame in stereotactic radiotherapy.

PURPOSE: Stereotactic radiotherapy (SRT) combines techniques of stereotactic radiosurgery (SRS) with radiation therapy fractionation schemes. Fractionation in SRT necessitates a relocatable immobilization system to precisely reproduce the patient's position at each treatment. The Gill-Thomas-Cosman (GTC) head frame is such an immobilization device compatible with the Brown-Roberts-Wells (BRW) stereotactic system. We describe this device, our modifications to the original design, the repeat position accuracy, and the daily verification procedure. METHODS AND MATERIALS: The original GTC frame was tested on volunteers. This testing led to an improved strapping system, the decision to construct the oral fixation appliance at our dental clinic, and the construction of a depth confirmation helmet to rapidly confirm the position of the frame on a daily basis. The GTC frame, at our institution, is not acceptable for children requiring anesthesia, and a new frame, the "Boston Childrens' Hospital" frame, was designed. This device uses the base ring of the GTC frame. Airway access is maintained through fixation on the nasal-glabellar region and the ear canal rather than the hard palate and upper gingiva. RESULTS: The modifications of the GTC frame and the verification protocol result in repeat positioning of the frame with respect to the patient anatomy, with a standard deviation of 0.4 mm for both the modified GTC frame and the Boston Childrens' Hospital frame. The relocatibility of the frames has been established in over 2,000 patient setups in over 60 patients to date. DISCUSSION: The GTC frame is a noninvasive and versatile fixation system that provides patient comfort, as well as accurate relocatibility for SRT. The frame is not appropriate for single fraction radiosurgery, as a large setup error (> 2 mm) for a single treatment cannot be excluded. The GTC frame is compatible with the BRW system, and treatment planning for SRT and SRS patients is identical. We currently treat 10-13 SRT patients per day with intracranial neoplasms on a dedicated stereotactic therapy unit. In addition, the Boston Childrens' Hospital frame allows the use of stereotactic therapy in the treatment of children under 6 years of age. This population will benefit especially from precise and highly focal cranial irradiation.

Brain Neoplasms↗
PubMedDate not supplied

Year one dental visit.

Explore the source record for details and available documents.

Child, Preschool↗
PubMedDate not supplied

The incidence of post-extraction pain and analgesic usage in children.

A parentally completed questionnaire was used to investigate the incidence of post-extraction pain in children. Significantly more patients in the study group reported pain following dental extraction than did control patients. Increasing age was significantly associated with the report of pain, but not with the use of a pain medication, even when the degree of difficulty of the extraction procedure was standardized. These findings suggest that the report of pain represents a late learned response while medication usage represents an early learned response. Those patients that reported increased severity of pain were significantly more likely to require a pain medication, but the pain medication was most effective for only mild pain. Additionally, male patients were significantly more likely to report complete effectiveness when pain medication was used. Contrary to some popularly held beliefs, the results of this study indicate that children do experience post-extraction pain and some children experience pain of sufficient intensity to require an analgesic for relief of post-extraction pain. Additionally, for a small group of patients, neither aspirin nor acetaminophen are adequate in fully relieving post-extraction discomfort. For these patients other agents may be indicated to fully relieve pain.

Adolescent↗