Persistence in gestural communication predicts sociality in wild chimpanzees.

A key challenge for primates is coordinating behaviour with conspecifics in large, complex social groups. Gestures play a key role in this process and chimpanzees show considerable flexibility communicating through single gestures, sequences of gestures interspersed with periods of response waiting (persistence), and rapid sequences where gestures are made in quick succession, too rapid for the response waiting to have occurred. The previous studies examined behavioural reactions to single gestures and sequences, but whether this complexity is associated with more complex sociality at the level of the dyad partner and the group as a whole is not well understood. We used social network analysis to examine how the production of single gestures and sequences of gestures was related to the duration of time spent in proximity and individual differences in proximity in wild East African chimpanzees (Pan troglodytes schweinfurthii). Pairs of chimpanzees that spent a longer duration of time in proximity had higher rates of persistence sequences, but not a higher rate of single gestures or rapid sequences. The duration of time spent in proximity was also related to the rate of responding to gestures, and response to gesture by activity change. These results suggest that communicative persistence and the type of response to gestures may play an important role in regulating social interactions in primate societies.

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Pulmonary Relapse of Osteosarcoma Following Presentation With a Pneumomediastinum and Localized Disease at Diagnosis.

Pneumothorax is a well-described complication of osteosarcoma. Conversely, the presence of a pneumomediastinum to our knowledge has been reported just once in a patient with osteosarcoma, and never without detectable lung metastasis. We report the case of an 18-year-old male with a localized, distal femur osteosarcoma who was found to have an asymptomatic pneumomediastinum and pneumatocele at diagnosis, and then 16 months later experienced a pulmonary relapse. Our case suggests that these findings may represent the presence of occult metastatic disease and cautions providers to treat appropriately and provide surveillance with a high index of suspicion for pulmonary recurrence.

The repertoire and intentionality of gestural communication in wild chimpanzees.

A growing body of evidence suggests that human language may have emerged primarily in the gestural rather than vocal domain, and that studying gestural communication in great apes is crucial to understanding language evolution. Although manual and bodily gestures are considered distinct at a neural level, there has been very limited consideration of potential differences at a behavioural level. In this study, we conducted naturalistic observations of adult wild East African chimpanzees (Pan troglodytes schweinfurthii) in order to establish a repertoire of gestures, and examine intentionality of gesture production, use and comprehension, comparing across manual and bodily gestures. At the population level, 120 distinct gesture types were identified, consisting of 65 manual gestures and 55 bodily gestures. Both bodily and manual gestures were used intentionally and effectively to attain specific goals, by signallers who were sensitive to recipient attention. However, manual gestures differed from bodily gestures in terms of communicative persistence, indicating a qualitatively different form of behavioural flexibility in achieving goals. Both repertoire size and frequency of manual gesturing were more affiliative than bodily gestures, while bodily gestures were more antagonistic. These results indicate that manual gestures may have played a significant role in the emergence of increased flexibility in great ape communication and social bonding.

Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas.

BACKGROUND: Patients with relapsed pediatric sarcomas have a poor outcome and are in need of novel effective therapies. METHODS: We retrospectively reviewed the records of patients at Children's Healthcare of Atlanta who were treated with gemcitabine (675 mg/m(2)) intravenously (IV) on Day 1 and Day 8, and docetaxel (75 mg/m(2)) IV on Day 8, repeated every 3 weeks. RESULTS: Nineteen patients with a median age of 11 years were treated from 2006-2010 and received 123 total courses. Two patients (11%), both with rhabdomyosarcoma, demonstrated objectives responses [one complete response (CR) and one partial response (PR)]. Seven other patients (39%) had stable disease (SD). The 1-year progression-free survival (PFS) of the entire cohort was 24% ± 10% with a median time to progression of 2 months (range: 0.5-14 months). The 1-year overall survival (OS) was 43% ± 11%. Grade 3 or 4 toxicities occurred in 14 patients (74%) and 52 courses (42%), and were most commonly hematologic (neutropenia = 37, anemia = 17, and thrombocytopenia = 23 courses). CONCLUSIONS: The dismal outcomes for patients with relapsed and refractory sarcomas and the lack of effective sarcoma salvage regimens highlight the need for new approaches. This report of the therapeutic activity of gemcitabine and docetaxel (GEMDOX) in rhabdomyosarcoma and other pediatric reports describing activity in osteosarcoma and Ewing sarcoma suggest that this combination should be considered for formal evaluation in a pediatric specific clinical trial. At a minimum, it appears to offer a reasonable, tolerable, palliative option.

Intentional gesturing increases social complexity by allowing recipient's understanding of intentions when it is inhibited by stress.

Examining the links between intentional communication and social relationships provides insights into the cognitive skills needed to manage a differentiated set of social bonds. Great apes gesture intentionally, but how this intentionality relates to sociality is still unclear. Stress in the form of dominant audience members inhibits understanding of intentions, downgrading cognition to understanding of behaviour, but intentional communication may enable social bonding in stressful conditions. We examined the associations between gestural communication, sociality, stress and the outcome of interactions in wild chimpanzees. Social network size was positively associated with intentional but not non-intentional communication. When a dominant bystander was present with whom the recipient was weakly bonded, and gesturing was non-intentional, recipients produced avoidance response toward signallers to whom they were weakly bonded, indicating understanding of behaviour. Signallers used intentional gestures more frequently to recipients who were stressed, and intentional gestures evoked approach behaviour by the recipients, indicating understanding of intentionality. These results suggest that the presence of dominant bystanders is stressful, inhibiting understanding of intentionality. However, intentional gestures facilitate social bonding by allowing understanding of intentions. The cognitive skills underpinning intentional gestures may therefore play a key role in enabling primates to meet the demands of sociality. This article is part of the theme issue 'Cognition, communication and social bonds in primates'.

How to Maintain a Healthy Gut Microbiome in Children with Cancer? Gut Microbiome Association with Diet in Children with Solid Tumors Postchemotherapy.

Malnutrition is a common complication in children with cancer. Cancer treatment and malnutrition can disrupt gut microbiome diversity and composition. The gut microbiome is of broad interest to better understand the mechanisms of malnutrition in cancer therapy. This study aimed to compare the gut microbiome between children with solid tumors postchemotherapy and healthy controls, and investigated the association of the putative microbiome differences with diet. Study participants were 27 children (7-18 years) with solid tumors within the first year after the completion of chemotherapy and 22 healthy controls. The study groups did not have a statistically significant difference in age, race, sex, and body mass index. At study intake, the participants completed the Block Kids Food Screener for dietary intakes in the past week. Fecal specimens were collected and analyzed for the gut microbiome. The cancer and control groups differed in gut microbial ß-diversity and abundance analyses. The macronutrient intakes such as carbohydrates, fiber, beta-carotene, and vitamin B6 were positively associated with α-diversity. Children with adequate vitamin B6 had a higher Chao1 diversity index than children with inadequate or excessive intake (p = 0.0004). Children with excessive selenium intake had a trend for higher Pielou's_e index than children with inadequate intake (p = 0.091). Maintaining a healthy gut microbiome is critical among children with cancer. This study provides new insights on the linkages between dietary intakes and the gut microbiome in children with solid tumors postchemotherapy. These findings, if replicated in future independent studies, may help anticipate malnutrition and plan for personalized nutrition approaches during chemotherapy in pediatric cancers.

The use of zoledronic acid in pediatric cancer patients.

BACKGROUND: The third generation bisphosphonate zoledronic acid has demonstrated efficacy in reducing skeletal-related events in adult patients with multiple cancer types that have skeletal disease. The use of zoledronic acid in pediatric oncology patients with bone metastases for the purpose of reducing pain, improving bone strength and altering the progression of metastatic disease has not been thoroughly evaluated. PROCEDURE: From October 2005 to December 2008, 19 patients at the Aflac Cancer Center received one or more doses of zoledronic acid as part of their therapy. A retrospective review of these patients was performed and information was collected including indication for treatment, toxicities, and outcomes. RESULTS: Most patients (n = 15) received zoledronic acid following relapse of their malignancy with metastatic disease present in one or more bony sites. Hypocalcemia and hypophosphatemia were frequent, but did not result in clinical symptoms. More significant toxicities associated with zoledronic acid, including clinically apparent renal insufficiency and osteonecrosis of the jaw, were not seen. Overall, zoledronic acid was well tolerated in this population. CONCLUSIONS: The benefits of zoledronic acid seen in randomized trials of adults with bone metastases have sparked interest in its use for children with metastatic cancer. The administration of zoledronic acid in pediatric oncology appears safe, and may result in improved bone strength and pain control. Further evaluation is warranted to prospectively evaluate its efficacy and long-term safety in pediatric patients with cancer and skeletal metastases.

Intracavitary cisplatin therapy for pediatric malignancies.

BACKGROUND: Local control is essential for the successful treatment of pediatric solid tumors. Complete excision is often not possible and local control therapies are limited. Intracavitary cisplatin (IC-CDDP) may be utilized to supplement local control. The aim of the study was to determine the toxicity and efficacy of locally instilled intracavitary cisplatin in patients with recurrent tumors in closed body cavities. PROCEDURE: From 2001 to 2009, 12 patients (1-20 years) with recurrent or unresectable malignant tumors were treated with IC-CDDP. Nine had pulmonary lesions. Three patients had abdominal tumors. CDDP (200 mg/m(2)) was instilled by chest tube or Tenckhoff catheter. Patients were shifted every 15-30 min to allow distribution. After 4 hr, residual was drained by gravity. In 10/13 courses, sodium thiosulfate (STS) was administered to prevent nephrotoxicity. Three other patients received amifostine. RESULTS: Malignant pleural effusions resolved in 5/7 patients. This response was temporary in three patients. No patients had ascites prior to treatment. Three patients are alive and disease-free, 18 months, 4 years, and 6 years from treatment. They also had surgery and chemotherapy. Transient renal toxicity was noted in most patients. One patient, treated with amifostine, had persistent renal dysfunction. CONCLUSIONS: IC-CDDP was effective in treating malignant pleural effusions and may be a palliative option for refractory disease. Long-term survival was achieved in two patients, treated at first diagnosis. The benefit of IC-CDDP in these patients is difficult to assess. Renal dysfunction is usually mild, and typically resolves, but warrants preventive measures with IC-CDDP therapy.

Perinatal Nicotine Reduces Chemosensitivity of Medullary 5-HT Neurons after Maturation in Culture.

Perinatal exposure to nicotine produces ventilatory and chemoreflex deficits in neonatal mammals. Medullary 5-HT neurons are putative central chemoreceptors that innervate respiratory nuclei and promote ventilation, receive cholinergic input and express nicotinic acetylcholine receptors (nAChRs). Perforated patch clamp recordings were made from cultured 5-HT neurons dissociated from the medullary raphé of 0-3 day old mice expressing enhanced yellow fluorescent protein driven by the enhancer region for PET1 (ePet-EYFP). The effect of exposure to low (6 mg kg-1day-1) or high (60 mg kg-1day-1) doses of nicotine in utero (prenatal), in culture (postnatal), or both and the effect of acute nicotine exposure (10 µM), were examined on baseline firing rate (FR at 5% CO2, pH = 7.4) and the change in FR with acidosis (9% CO2, pH 7.2) in young (12-21 days in vitro, DIV) and older (≥22 DIV) acidosis stimulated 5-HT neurons. Nicotine exposed neurons exhibited ∼67% of the response to acidosis recorded in neurons given vehicle (p = 0.005), with older neurons exposed to high dose prenatal and postnatal nicotine, exhibiting only 28% of that recorded in the vehicle neurons (p < 0.01). In neurons exposed to low or high dose prenatal and postnatal nicotine, acute nicotine exposure led to a smaller increase in FR (∼+51% vs +168%, p = 0.026) and response to acidosis (+6% vs +67%, p = 0.014) compared to vehicle. These data show that exposure to nicotine during development reduces chemosensitivity of 5-HT neurons as they mature, an effect that may be related to the abnormal chemoreflexes reported in rodents exposed to nicotine in utero, and may cause a greater risk for sudden infant death syndrome (SIDS).

Visual attention, indicative gestures, and calls accompanying gestural communication are associated with sociality in wild chimpanzees (Pan troglodytes schweinfurthii).

The challenges of life in complex social groups may select for complex communication to regulate interactions among conspecifics. Whereas the association between social living and vocalizations has been explored in nonhuman primates, great apes also have a rich repertoire of gestures, and how the complexity of gestural communication relates to sociality is still unclear. We used social network analysis to examine the relationship between the duration of time pairs of chimpanzees spent in proximity (within 10 m) and the rates of gestural communication accompanied by visual attention of the signaler, one-to-one calls, indicative gestures (collectively self-relevance cues), and synchronized pant-hoot calls. Pairs of chimpanzees that spent a longer duration of time in proximity had a higher rate of visual gestures accompanied by these behaviors. Further, individual chimpanzees that had a greater number of proximity bonds had a larger social network maintained through gestures accompanied by synchronized pant-hoot calls. In contrast, gestures unaccompanied by these behaviors were not positively associated with either proximity bonds in pairs of chimpanzees or individual differences in sociality. These results suggest that self-relevance cues and synchronized pant-hoot calls accompanying gestures may increase the efficiency of gestural communication in social bonding and that multimodal communication may have played a key role in language evolution. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Complex Sociality of Wild Chimpanzees Can Emerge from Laterality of Manual Gestures.

Humans are strongly lateralized for manual gestures at both individual and population levels. In contrast, the laterality bias in primates is less strong, leading some to suggest that lateralization evolved after the Pan and Homo lineages diverged. However, laterality in humans is also context-dependent, suggesting that observed differences in lateralization between primates and humans may be related to external factors such as the complexity of the social environment. Here we address this question in wild chimpanzees and examine the extent to which the laterality of manual gestures is associated with social complexity. Right-handed gestures were more strongly associated with goal-directed communication such as repair through elaboration in response to communication failure than left-handed gestures. Right-handed gestures occurred in evolutionarily urgent contexts such as in interactions with central individuals in the network, including grooming reciprocity and mating, whereas left-handed gestures occurred in less-urgent contexts, such as travel and play. Right-handed gestures occurred in smaller parties and in the absence of social competition relative to left-handed gestures. Right-handed gestures increased the rate of activities indicating high physiological arousal in the recipient, whereas left-handed gestures reduced it. This shows that right- and left-handed gestures differ in cognitive and social complexity, with right-handed gestures facilitating more complex interactions in simpler social settings, whereas left-handed gestures facilitate more rewarding interactions in complex social settings. Differences in laterality between other primates and humans are likely to be driven by differences in the complexity of both the cognitive skills underpinning social interactions and the social environment.

Convergence and divergence in gesture repertoires as an adaptive mechanism for social bonding in primates.

A key challenge for primates living in large, stable social groups is managing social relationships. Chimpanzee gestures may act as a time-efficient social bonding mechanism, and the presence (homogeneity) and absence (heterogeneity) of overlap in repertoires in particular may play an important role in social bonding. However, how homogeneity and heterogeneity in the gestural repertoire of primates relate to social interaction is poorly understood. We used social network analysis and generalized linear mixed modelling to examine this question in wild chimpanzees. The repertoire size of both homogeneous and heterogeneous visual, tactile and auditory gestures was associated with the duration of time spent in social bonding behaviour, centrality in the social bonding network and demography. The audience size of partners who displayed similar or different characteristics to the signaller (e.g. same or opposite age or sex category) also influenced the use of homogeneous and heterogeneous gestures. Homogeneous and heterogeneous gestures were differentially associated with the presence of emotional reactions in response to the gesture and the presence of a change in the recipient's behaviour. Homogeneity and heterogeneity of gestural communication play a key role in maintaining a differentiated set of strong and weak social relationships in complex, multilevel societies.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement.

PURPOSE: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. METHODS AND MATERIALS: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. RESULTS: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse-free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse-free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. CONCLUSIONS: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

Wild chimpanzees modify modality of gestures according to the strength of social bonds and personal network size.

Primates form strong and enduring social bonds with others and these bonds have important fitness consequences. However, how different types of communication are associated with different types of social bonds is poorly understood. Wild chimpanzees have a large repertoire of gestures, from visual gestures to tactile and auditory gestures. We used social network analysis to examine the association between proximity bonds (time spent in close proximity) and rates of gestural communication in pairs of chimpanzees when the intended recipient was within 10 m of the signaller. Pairs of chimpanzees with strong proximity bonds had higher rates of visual gestures, but lower rates of auditory long-range and tactile gestures. However, individual chimpanzees that had a larger number of proximity bonds had higher rates of auditory and tactile gestures and lower rates of visual gestures. These results suggest that visual gestures may be an efficient way to communicate with a small number of regular interaction partners, but that tactile and auditory gestures may be more effective at communicating with larger numbers of weaker bonds. Increasing flexibility of communication may have played an important role in managing differentiated social relationships in groups of increasing size and complexity in both primate and human evolution.

Gestural Communication and Mating Tactics in Wild Chimpanzees.

The extent to which primates can flexibly adjust the production of gestural communication according to the presence and visual attention of the audience provides key insights into the social cognition underpinning gestural communication, such as an understanding of third party relationships. Gestures given in a mating context provide an ideal area for examining this flexibility, as frequently the interests of a male signaller, a female recipient and a rival male bystander conflict. Dominant chimpanzee males seek to monopolize matings, but subordinate males may use gestural communication flexibly to achieve matings despite their low rank. Here we show that the production of mating gestures in wild male East African chimpanzees (Pan troglodytes schweunfurthii) was influenced by a conflict of interest with females, which in turn was influenced by the presence and visual attention of rival males. When the conflict of interest was low (the rival male was present and looking away), chimpanzees used visual/ tactile gestures over auditory gestures. However, when the conflict of interest was high (the rival male was absent, or was present and looking at the signaller) chimpanzees used auditory gestures over visual/ tactile gestures. Further, the production of mating gestures was more common when the number of oestrous and non-oestrus females in the party increased, when the female was visually perceptive and when there was no wind. Females played an active role in mating behaviour, approaching for copulations more often when the number of oestrus females in the party increased and when the rival male was absent, or was present and looking away. Examining how social and ecological factors affect mating tactics in primates may thus contribute to understanding the previously unexplained reproductive success of subordinate male chimpanzees.

Chimpanzees modify intentional gestures to coordinate a search for hidden food.

Humans routinely communicate to coordinate their activities, persisting and elaborating signals to pursue goals that cannot be accomplished individually. Communicative persistence is associated with complex cognitive skills such as intentionality, because interactants modify their communication in response to another's understanding of their meaning. Here we show that two language-trained chimpanzees effectively use intentional gestures to coordinate with an experimentally naive human to retrieve hidden food, providing some of the most compelling evidence to date for the role of communicative flexibility in successful coordination in nonhumans. Both chimpanzees (named Panzee and Sherman) increase the rate of non-indicative gestures when the experimenter approaches the location of the hidden food. Panzee also elaborates her gestures in relation to the experimenter's pointing, which enables her to find food more effectively than Sherman. Communicative persistence facilitates effective communication during behavioural coordination and is likely to have been important in shaping language evolution.

Intracranial metastatic neuroblastoma treated with gamma knife stereotactic radiosurgery: report of two novel cases.

Intracranial metastasis of neuroblastoma (IMN) is associated with poor survival. No curative therapy for the treatment of IMN currently exists. Unfractionated radiotherapy may be beneficial in the treatment of IMN given the known radiosensitivity of neuroblastoma as well as its proclivity to metastasize as discrete lesions. We present two patients with IMN treated with Gamma Knife stereotactic radiosurgery (SRS). Single-fraction radiotherapy yielded temporary reduction of tumor burden and stability of disease in both patients. SRS may be a useful palliative tool in the treatment of IMN and expands the overall treatment options for this disease.

Intensity-modulated radiotherapy with use of cone-down boost for pediatric head-and-neck rhabdomyosarcoma.

PURPOSE: To report our initial experience using intensity-modulated radiotherapy (IMRT) with a cone-down boost for pediatric head-and-neck rhabdomyosarcoma (RMS). METHODS AND MATERIALS: A review of institutional treatment records identified children treated with IMRT for head-and-neck RMS between January 2000 and February 2007. All patients had undergone chemotherapy according to cooperative group RMS protocols. The initial planning target volume (PTV) covered the prechemotherapy tumor extent with variable margins, generally 1-2 cm. The boost PTV covered the postchemotherapy tumor volume, usually with a margin of 0.5-1 cm. RESULTS: A total of 20 patients were treated with IMRT for head-and-neck RMS. Of these 20 patients, 4 had Group II, 15 Group III, and 1 Group IV disease. The site was parameningeal in 12, nonparameningeal in 6, and orbit primary in 2. Of the 20 patients, 14 were treated with a cone-down boost after a median dose of 36 Gy (range, 30-45.6). The mean initial PTV was 213.5 cm(3), and the mean boost PTV was 76.9 cm(3). Patients received a median total dose of 50.4 Gy. The median follow-up time was 29 months. The 3-year Kaplan-Meier local control rate was 100%, although 1 patient developed an in-field recurrence 50 months after IMRT. The 3-year event-free survival rate, overall survival rate, and risk of central nervous system failure was 74%, 76%, and 7%, respectively. CONCLUSIONS: Our preliminary follow-up of pediatric head-and-neck RMS patients treated with IMRT revealed excellent local control. The initial targeting of the prechemotherapy tumor volume with 1-2-cm margin to 30.6 or 36 Gy followed by a cone-down boost to the postchemotherapy tumor volume with a 0.5-1-cm margin allowed for significant sparing of normal tissues and provided good local control.

Expression of inhibitor-of-apoptosis protein (IAP) livin by neuroblastoma cells: correlation with prognostic factors and outcome.

Livin is a recently identified member of the Inhibitor-of-Apoptosis protein (IAP) family of antiapoptosis proteins, and expression has been reported in melanoma and some types of carcinoma. We evaluated livin expression in paraffin-embedded tumor tissue from 68 patients with neuroblastoma (NB) and 7 NB cell lines by immunoperoxidase using an anti-livin monoclonal antibody. Eighteen (26.5%) of the 68 NB tumor tissues showed high livin expression, 36 (53%) showed low-intermediate expression, and 14 (20.5%) were negative. Similarly, 4 NB cell lines showed high livin expression, and 3 showed intermediate expression. In primary NB tissue, livin was observed mainly in tumor neuropil, an extension of tumor cell cytoplasm, and the cytoplasm itself. By reverse transcriptase-polymerase chain reaction, livin expression was confirmed in all 7 NB lines and in frozen tissue from 1 of 3 primary tumors examined to date, in agreement with immunohistochemical data; both livin alpha and beta isoforms were detected. In the NB cases, we further analyzed the correlation between livin expression and clinical and biological features with established prognostic significance (i.e., age at diagnosis, stage, histology, and MYCN oncogene status), and patients' outcome. Livin expression alone did not appear to have an effect on survival; however, patients with high livin expression and amplified MYCN had significantly decreased survival compared with patients lacking both markers or with either of these markers alone. These results suggest that (a) livin is expressed in primary and cultured neuroblastoma cells and (b) high livin expression may identify a subset of neuroblastoma patients with a particularly poor prognosis among those with MYCN amplified tumors.