Graduate Student Literature Review: Labeling challenges of plant-based dairy-like products for consumers and dairy manufacturers.

The global market for plant-based products is increasing at a faster rate than the market for traditional dairy products. Current regulations provide standards for those traditional dairy products but lack the same regulations for similar plant-based products. Resulting from this difference in regulation is consumer confusion over the differences between the 2 types of products. The purpose of this review paper was to understand how the differences between traditional dairy and plant-based dairy-like products could affect litigation by consumer and dairy manufacturers against potential misleading labeling. A review of the available literature found 4 relevant articles for analysis. Consumers and manufacturers can pursue claims against potentially misleading product labeling but must provide sufficient evidence to prove deception or injury. Past litigation against plant-based products for being misleading has ruled in favor of the plant-based defendants. These rulings were based on the notion that reasonable consumers would not be misled. Consumer and manufacturing advocates for dairy products should focus more resources on the education of consumers rather than litigation if the goal is to promote dairy products. Long-term regulatory changes could be made through the Defending Against Imitations and Replacements of Yogurt, Milk, and Cheese to Promote Regular Intake of Dairy Everyday Act, which is currently under legislative review.

Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors.

OBJECTIVE: This study was performed to evaluate the association between the type of neurosurgeon (general or pediatric) and either the extent of tumor removal or the frequency of complications in children undergoing malignant brain tumor resections. METHODS: Data were analyzed from three recent Children's Cancer Group studies: two on medulloblastomas/primitive neuroectodermal tumors and one on malignant gliomas. Neurosurgeons were classified as general neurosurgeons, as designated pediatric neurosurgeons in their institutions, or as members of the American Society of Pediatric Neurosurgeons (ASPN), which requires pediatric neurosurgical experience and practice standards. RESULTS: Data forms from 732 children were analyzed; 485 were from children with medulloblastomas/primitive neuroectodermal tumors, and 247 were from children with malignant gliomas. Operations were performed by 269 neurosurgeons, including 213 general neurosurgeons, 29 designated pediatric neurosurgeons, and 27 ASPN members. The mean number of operations per surgeon was 1.8, 4.9, and 7.6 for general neurosurgeons, designated pediatric neurosurgeons, and ASPN members, respectively. There was a significant relationship between the extent of tumor resection or the amount of residual tumor and the type of neurosurgeon. Designated pediatric neurosurgeons and ASPN members were more likely to remove more than 90% of the tumor and to leave less than 1.5 cc of residual tumor than were general neurosurgeons (P<0.05). In these studies, the probability of extensive tumor removal correlated with the number of operations the neurosurgeon performed (P<0.01). Neurological complications occurred in the following proportion of cases: general neurosurgeons, 23%; designated pediatric neurosurgeons, 32%; and ASPN members, 18%. CONCLUSION: Pediatric neurosurgeons are more likely than general neurosurgeons to extensively remove malignant pediatric brain tumors. In these tumors, extent of removal has been demonstrated to influence survival.

Immunotherapy of malignant brain tumors in children and adults: from theoretical principles to clinical application.

In the span of just 10 years, our understanding of the cancer-immune system relationship has increased exponentially, and yet we are only beginning to understand the intricacies of cytokine and immune cell interactions. This paper reviews the interactions of the immune system with brain tumors. In principle, the immune system is uniquely qualified to be an instrument for cancer therapy. An immune response directed against cells bearing tumor antigens could provide a specific and effective mechanism for killing residual tumor. While the theoretical background for immunotherapy as a treatment for brain tumors is elegant and persuasive, a substantial clinical breakthrough has yet to be made. This paper reviews the major forms of both animal and human data on types of immunotherapy, such as passive serological immunotherapy, active, and adoptive immunotherapy. Next a review of existing data on effects of cytokines, immune regulation, and tumor cytotoxicity is detailed. The review concludes with the clinical trials using interferons and other methodologies. The trials presented here demonstrate the challenging work being done to take basic science into the clinical realm. As this work continues, our ability to design effective immune therapies will mature and yield increased therapeutic success.

Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study.

PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) +/- SE at 7 years were 55%+/-5% and 54%+/-5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63%+/-5% versus 45%+/-5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32%+/-10% v 58%+/-4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (MO v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70%+/-5%, 57%+/-10%, and 40%+/-8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus > or = 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78%+/-6% v 54%+/-11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, > or = 3 years with < or = 1.5 cm2 residual tumor, had a 78%+/-6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group.

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children's Cancer Group.

OBJECT: Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading. optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64 +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (< or = 1.5 cm2 compared with > 1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.

The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population.

PURPOSE: To analyze patterns of failure in patients (pts) with high-risk posterior fossa primitive neuroectodermal tumors (PF-PNETs) treated with combined modality therapy on a large, randomized multiinstitutional study. METHODS AND MATERIALS: One hundred eighty-eight prospectively staged pts with PF-PNET confirmed by central pathology review, with high-risk features, were treated on Children's Cancer Group Study 921 (CCG-921), comparing two chemoradiotherapy regimens. Patterns of initial sites of failure were analyzed, specifically evaluating the impact of Chang M-stage. RESULTS: Progression-free survival (PFS) correlated with the presence or absence of metastatic disease (p < 0.001), with 5-year PFS of 68 +/- 5.8% for M0 vs. 43 +/- 6.8% for M+ pts. The cumulative incidence functions (CIF) of recurrence were different (p = 0.005) and at 5 years were 29 +/- 4.7% for M0 pts and 48 +/- 5.5% for M+ pts. Involvement of the PF at time of initial failure as measured by CIF correlated with M-stage (p = 0.047) and occurred in 18 +/- 3.9% of M0 pts and 8 +/- 2.9% of M+ pts overall; PF as the only site of relapse also correlated with M-stage (p = 0.019) and was seen in 6 +/- 2.5 and 0% of M0 and M+ pts, respectively, at 5 years. Relapse in the spine and/or cerebrospinal fluid (CSF) at initial recurrence was correlated with M-stage (p < 0.002), with 5-year cumulative incidences of 14 +/- 3.7%, 26 +/- 8.2%, 40 +/- 15%, and 40 +/- 7.7% for M0, M1, M2, and M3 pts, respectively. Isolated spine/CSF recurrence correlated with M-stage (p = 0.034) and occurred in 2 +/- 1.5% of M0 and 9 +/- 3.2% of M+ pts by 5 years. The median time to relapse for pts who failed was 1.2 years (range 0.2-5.3). Ninety percent of all relapses occurred by 3 years. CONCLUSIONS: Original sites of disease are at the highest risk for relapse, but the entire neuraxis remains at significant risk, despite combined-modality treatment. M-Stage was prognostic for spine/CSF relapse as well as PFS and may be an important tool in guiding therapy. A more aggressive approach to local control in the neuraxis is warranted, especially in M+ patients.

Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group.

We reviewed the data of children with high-stage primitive neuroectodermal tumors (medulloblastomas) who were treated on Children's Cancer Group-921 protocol to evaluate the correlation between tumor resection and prognosis. Patients enrolled in the study had either tumors that were operatively categorized to be Chang tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis. Resections were analyzed in two ways, as follows: 1) by the extent of resection (percent of the tumor that was removed), as estimated by the treating neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was left), as estimated from postoperative scans. Two hundred and three children were enrolled in the study with institutional diagnoses of primitive neuroectodermal tumors-medulloblastomas; diagnoses were confirmed by central neuropathological review in 188 patients. Progression-free survival (PFS) at 5 years was 54% (standard error, 5%). As in previous Children's Cancer Group studies, age and M stage correlated with survival; PFS was significantly lower in children 1.5 to 3.0 years old at diagnosis and in those with any evidence of tumor dissemination (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of residual tumor correlated with PFS. However, adjusting for other factors, extent of residual tumor was important; PFS was 20% (standard error, 14%) better at 5 years in children with no dissemination (M Stage 0) who had < 1.5 cm2 of residual tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual tumor (P = 0.033). On the basis of our observations, we conclude that extent of tumor resection, as estimated by the neurosurgeon, does not correlate with outcome but that extent of residual tumor does correlate with prognosis in certain children (those who are > 3 years old, with no tumor dissemination). In contrast to age and M stage, the major factors associated with outcome, residual tumor is an important variable in outcome, one that neurosurgeons can control.

Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial.

PURPOSE: To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors (S-PNETs). PATIENTS AND METHODS: After surgery and staging, 55 patients aged 1.5 to 19.3 years with S-PNETs were randomized to receive craniospinal radiotherapy (RT) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea (CCNU), vincristine (VCR), and prednisone (standard treatment) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1. RESULTS: Three-year Kaplan-Meier estimates (estimate +/- SE) of survival and progression-free survival (PFS) rates for patients with confirmed diagnoses of S-PNET were 57% +/- 8% and 45% +/- 8%, respectively; survival and PFS rates for children with PNETs located in the pineal region were 73% +/- 12% and 61% +/- 13%, respectively, and were significantly different from the other S-PNETs (P < .03). The 8-in-1 arm had greater toxicity than the standard-treatment arm. Distributions of PFS between the two treatment groups were not significantly different (P > .5). Other univariate prognostic factors that influenced PFS included metastasis (M) stage (P < .03: M0 50% +/- 9% v M1-4 0%) and age (P < .02: 1.5 to 2 years 25% +/- 13% v > or = 3 years 53% +/- 9%). CONCLUSION: In this first randomized treatment trial for S-PNETs in children, no significant differences were detected between the two treatment groups. M0 and pineal site of involvement were independent predictors of a better outcome. However, survival was better than previously reported.

Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group.

PURPOSE: To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy. PATIENTS AND METHODS: Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen. RESULTS: Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease. CONCLUSION: (1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.

Prognostic factors in children with supratentorial (nonpineal) primitive neuroectodermal tumors. A neurosurgical perspective from the Children's Cancer Group.

Supratentorial primitive neuroectodermal tumors (S-PNETs), which have also been called cerebral neuroblastomas, have been considered to be the hemispheric equivalent of posterior fossa medulloblastomas. Twenty-seven children with S-PNETs (excluding pineoblastomas) which were confirmed by central pathology review were treated on the CCG-921 protocol from 1986 to 1992. After operation, all patients were staged with CSF cytology and spinal myelography or magnetic resonance scans and were treated with craniospinal irradiation and chemotherapy. Data from these 27 patients have been reviewed to evaluate neurosurgical treatment, survival, and prognostic variables that correlate with survival. Overall survival at 5 years was 34% (SE 20%) and progression-free survival (PFS) was 31% (SE 18%), which is lower than the survival of patients with posterior fossa PNETs (medulloblastomas). PFS was significantly worse in children 1.5-3 years of age at diagnosis and in those with evidence of tumor dissemination at the time of diagnosis. Large preoperative tumors were more likely to be associated with greater than 1.5 cm2 residual tumor postoperatively. Neurosurgeons estimated that less than 1.5 cm2 of residual tumor was present in 52% of the cases; postoperative scans confirmed that in 58%. For children with less than 1.5 cm2 residual tumor, postoperative survival at 4.0 years was 40% (SE 22%); for those with greater than 1.5 cm2 residual tumor, survival was 13% (SE 8%). The difference did not reach statistical significance, due to small numbers in this series, though a trend did exist (p = 0.19). Large series will be required to clarify the effects of extent of resection on survival.

Trisomy 11 and other nonrandom trisomies in congenital fibrosarcoma.

Chromosome studies in a 7-week-old female infant with an intraabdominal malignant fibrosarcoma showed a hyperdiploid karyotype of 50,XX, +der(6)del(6)(p23)add(6)(q11), +8, +10, +11,add(12)(p13). Trisomy 11 appears to be a nonrandom primary cytogenetic abnormality in the congenital or infantile form of this mesenchymal tumor and is also a nonrandom gain in congenital mesoblastic nephroma. A possible developmental link between these two mesenchymal tumors, mediated by a gene or genes on chromosome 11 is postulated.

Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group.

PURPOSE: Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis. PATIENTS AND METHODS: Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases. RESULTS: On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy. CONCLUSION: While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence.

Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system.

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs.

Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group.

Cytogenetic analyses of pretreatment bone marrows were performed at local institutions as part of Childrens Cancer Group (CCG) protocol CCG-107 for infants less than 1 year of age with previously untreated acute lymphoblastic leukemia (ALL). Cytogenetic analyses from 39 patients (17 males and 22 females) were accepted after review. Several unique cytogenetic features were observed. Twelve patients (31%) had a t(4;11)(q21;q23) and had a significantly shorter event-free survival (EFS) than did the other patients with adequate cytogenetic analyses (P = .009). Five additional patients had an 11q23 breakpoint, not associated with 4q21. When EFS for these 5 patients was compared with that of the t(4;11) patients, even with these small numbers there was a strong, although not significant, suggestion that the t(4;11) patients have a reduced EFS (P = .09), indicating that the specific translocation, t(4;11)(q21;q23), and not an 11q23 breakpoint per se, may be associated with the poor prognosis of these infants. Structural abnormalities were present in 27 of 28 patients with abnormal karyotypes. A new recurring abnormality, t(5;15)(p15:1;q11) or t(5;15)(p15.3;q13), was identified in 3 patients (Arthur et al, Blood 70:274a, 1987 [abstr, suppl 1]). Two females had structural abnormalities involving Xp11, a breakpoint rarely seen in ALL. Fourteen (36%) patients had a single structural abnormality, and 13 (33%) had complex karyotypes. No patients had hyperdiploidy with more than 50 chromosomes. Only normal chromosomes were observed in 11 patients (28%), and their outcome did not differ from patients with abnormal karyotypes. These cytogenetic abnormalities found in the leukemic cells of infants are clearly different from those in older children and adults, and may explain, in part, the unique biologic characteristics of infant ALL.

Choroid plexus tumors in childhood. Response to chemotherapy, and immunophenotypic profile using a panel of monoclonal antibodies.

Clinical and immunophenotypic (IP) data are presented on three children with choroid plexus (CP) tumors. Two children ages 0.2 and 2 years old with histologically proven malignant tumors had subtotal tumor resections and were treated with ten monthly cycles of eight-drugs-in-1-day chemotherapy without radiation therapy (XRT). Both are free of tumor 4 and 7 years later. The literature on survival of children with CP carcinomas after chemotherapy and XRT is reviewed. Monoclonal antibodies to 17 neuroectodermal, neuronal, glial, and leukocytic markers on frozen sections were used to IP the two malignant tumors and a CP papilloma. All tumors expressed two neuroectodermal markers (PI-153/3 and UJ 223.8), cytokeratin 19, and a neural and leukocyte marker (Thy-1). Two of three expressed neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP) and one expressed NF-M and common leukocyte antigen. None had strong expression for the panneuroectodermal antigen UJ13/A. There was variable expression of the other markers. The most common IP profile for CP tumors (cytokeratin 18+, PI-153/3+, Thy-1+, UJ 223.8+, and GFAP+ and UJ13A-, UJ 127.11-, and NF-L-) is discussed in the context of the current knowledge of the ontogenetic origin of the CP. It was concluded that chemotherapy for malignant CP tumors can be associated with long-term survival in young children and that the unique IP profile of CP tumors with coexpression of three intermediate filaments suggests new and provocative evidence of their cellular complexity and heterogeneity.