No description available.

Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT), which provides transient symptomatic relief and limited survival advantage. Successful implementation of radiosensitization strategies in DMG remains elusive. In this project, we identify Napabucasin, an NAD(P)H Quinone Dehydrogenase 1 (NQO1)-bioactivatable reactive oxygen species (ROS) inducer, as a potent radiosensitizer in DMG both in vitro and in vivo. We show Napabucasin-mediated ROS production and cytotoxicity are dependent on NQO1, and establish the novel safety, feasibility, and survival benefit of convection-enhanced drug delivery (CED) of Napabucasin to circumvent the blood-brain barrier (BBB) concurrent with RT in an orthotopic DMG mouse model. Using this multi-modality strategy, we identify a promising treatment paradigm in DMG that may also be utilized to develop novel therapeutic treatments for other brain tumors.

Family process stressors, family system resources, parental coping patterns, and parental adaptation were assessed for 58 mothers who had a child with cancer who was being seen at selected pediatric hematology-oncology centers in two Southeastern states. The respondents completed a self-report questionnaire containing the Coping and Health Inventory for Parents, five subscales from the Family Environment Scale, and items asking demographic questions. The dependent measure was the Parental Adaptation Assessment, a modified version of the Spinetta Family Adjustment Scale, developed for this study to measure parents’ perception of their adaptation to the experience of caring for a child with cancer. The criteria for subject inclusion in the study were: (a) two parents living in the home; and, (b) the child’s cancer diagnosis was to have occurred not less than 3 months and not more than 4 years prior to data collection. The Double ABCX Model of Family Adaptation was used as the basis for variable selection. Frequency distributions, correlations between the 11 independent variables and mother’s adaptation, and a stepwise regression analysis were used to analyze the data. Two family process stressors (conflict and control) and two family system resources (cohesion and expressiveness) were significantly (p < .05) correlated with mother’s adaptation. The regression analyses showed that two variables (cohesion and mother’s age) explained 34% of the variance in mother’s adaptation. Results show family cohesion and mother’s age to be the only significant predictors of her perceived adaptation. Family process stressors and parental coping patterns failed to account for any significant variance in mother’s adaptation. Implications for family stress theory, psychosocial oncology research, and family therapy practice are discussed. Recommendations for further research are suggested. / Ph. D.

No description available.

In this study the researcher explored and described the utilization of Gestalt play therapy concepts and techniques in order to strengthen the sense of self of the pediatric hematology/oncology patient. Literature studies were compiled to examine the concepts of the pediatric hematology/oncology patient, sense of self and Gestalt play therapy. These literature studies provided the theoretical frame in which the study was executed. During the empirical study qualitative data was gathered by means of unstructured interviews within an instrumental case study. Eight therapy sessions were conducted with the participant in order to explore how Gestalt play therapy concepts and techniques could be utilized to strengthen the sense of self of the pediatric hematology/oncology patient. Following the analysis of the data the researcher was able to describe how the Gestalt play therapy concepts and techniques were utilized to strengthen the sense of self of the pediatric hematology/oncology patient. / Social Work / M. Diac. (Play Therapy)

The purpose of this retrospective study was to investigate some psychosocial factors that may be related to the development of childhood cancer. The questions that guided the study were: When compared to families of healthy children (1) Do the family structure, dynamics and atmosphere present any commonalities among children with cancer? (2) Are there any personality characteristics common to children with cancer? (3) Have children with cancer experienced more of stressful events during the year that preceded diagnosis? (4) Have children with cancer experienced a major loss? Twelve children between the ages of 2 to 13 who were diagnosed with a form of cancer were compared to twelve healthy but accidently injured children of the same age, and sex and socioeconomic background hospitalized at the 2nd Pediatric Department of The University of Athens. A semistructured interview was used to gather information from their mothers within the month that followed the child's diagnosis or accident. Chi-square and T-test analyses were used at the .05 level of significance to determine differences between groups on each of the variables. Findings revealed that, compared to healthy children, children with cancer tended to belong to "broken home" families in which most had experienced (a) the loss or absence of a significant person (particularly the father) early in their life or (b) an unhappy marriage between their parents, frequently resulting from an "arranged" marriage. Within their family children occupied a special status and were raised as "only" or "first-borns." A major upcoming event was anticipated in most of their families within the same month that the diagnosis was pronounced; this event was aborted as a result of the child's diagnosis. Limitations of the study, discussion of the methodology and recommendations for further research are presented.

Opportunistic infection is always a potentially life threatening complication in pediatric oncology patients and hematopoietic stem cell transplant recipients. With the advances in various disease treatment protocols, the overall and event-free survivals of this high risk population improve significantly. In this thesis, the author reported a number of original studies to discuss different strategies in prevention of this serious complication. Firstly, the author demonstrates that pediatric oncology patients are still vulnerable to various vaccine-preventable infectious diseases up to 18 months after stopping chemotherapy. For those vaccine-preventable infectious diseases, pediatric oncology patients can mount a significant and persistent immune response to common inactivated vaccine (namely diphtheria-tetanus-pertussis vaccine). For non-vaccine preventable infectious diseases, regular monitoring of plasma viral load and strategic use of antiviral agents as pre-emptive or prophylactic agent is an effective approach to prevent infection. In hematopoietic stem cell transplant setting, adoptive transfer of acquired immunity from donor to recipient and incorporation of this parameter in donor selection process can be considered. The findings of the studies can be applied to clinical setting. The future direction of our studies includes the immune responses of other common vaccines namely pneumococcal vaccine and pandemic influenza vaccine in high risk population. The role of transfer of donor's varicella zoster immunity in prevention of herpes zoster infection in transplant recipient can be further explored. With the advances in supportive care of our vulnerable patients, the survival rate is expected to be further improved in the future. / by Frankie Wai Tsoi, Cheng. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 193-208). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

Abstract not available

The development of resistance to chemotherapeutic drugs is the main obstacle to the successful treatment of many cancers, including childhood neuroblastoma, the most common solid tumour of infants. One factor that may play a role in determining response of neuroblastoma tumours to therapeutic agents is the p53 tumour suppressor gene. A number of previous studies have suggested that this tumour suppressor protein is inactive in neuroblastoma due to its cytoplasmic sequestration. This thesis therefore has examined the functionality of p53 and its role in determining drug response of neuroblastoma cells. An initial study was undertaken that characterised an unusually broad multidrug resistance (MDR) phenotype of a neuroblastoma cell line (IMR/KAT100). The results demonstrated that the MDR phenotype of the IMR/KAT100 cells was associated with the acquisition of mutant p53. To explore the role of p53 in drug resistance further, p53-deficient variants in cell lines with wild-type p53 were generated by transduction of p53-suppressive constructs encoding either shRNA or a dominant-negative p53 mutant. Analysis of these cells indicated that: (i) in contrast to previous reports, wild-type p53 was fully functional in all neuroblastoma lines tested, as evidenced by its activation and nuclear translocation in response to DNA damage, transactivation of target genes and control of cell cycle checkpoints; (ii) inactivation of p53 in neuroblastoma cells resulted in establishment of an MDR phenotype; (iii) knockdown of mutant p53 did not revert the drug resistance phenotype, suggesting it is determined by loss of wild-type function rather than gain of mutant function; (iv) p53-dependent cell senescence, the primary response of S-type neuroblastoma cells to DNA damage, is replaced, after p53 inactivation, by mitotic catastrophe and subsequent apoptosis. In contrast to neuroblastoma, p53 suppression had no effect or increased drug susceptibility in several other tumour cell types, indicating the importance of tissue context for p53- mediated modulation of tumour cell sensitivity to treatment. Taken together, these data provide strong evidence for p53 having a role in mediating drug resistance in neuroblastoma and suggest that p53 status may be an important prognostic marker of treatment response in this disease.

The development of resistance to chemotherapeutic drugs is the main obstacle to the successful treatment of many cancers, including childhood neuroblastoma, the most common solid tumour of infants. One factor that may play a role in determining response of neuroblastoma tumours to therapeutic agents is the p53 tumour suppressor gene. A number of previous studies have suggested that this tumour suppressor protein is inactive in neuroblastoma due to its cytoplasmic sequestration. This thesis therefore has examined the functionality of p53 and its role in determining drug response of neuroblastoma cells. An initial study was undertaken that characterised an unusually broad multidrug resistance (MDR) phenotype of a neuroblastoma cell line (IMR/KAT100). The results demonstrated that the MDR phenotype of the IMR/KAT100 cells was associated with the acquisition of mutant p53. To explore the role of p53 in drug resistance further, p53-deficient variants in cell lines with wild-type p53 were generated by transduction of p53-suppressive constructs encoding either shRNA or a dominant-negative p53 mutant. Analysis of these cells indicated that: (i) in contrast to previous reports, wild-type p53 was fully functional in all neuroblastoma lines tested, as evidenced by its activation and nuclear translocation in response to DNA damage, transactivation of target genes and control of cell cycle checkpoints; (ii) inactivation of p53 in neuroblastoma cells resulted in establishment of an MDR phenotype; (iii) knockdown of mutant p53 did not revert the drug resistance phenotype, suggesting it is determined by loss of wild-type function rather than gain of mutant function; (iv) p53-dependent cell senescence, the primary response of S-type neuroblastoma cells to DNA damage, is replaced, after p53 inactivation, by mitotic catastrophe and subsequent apoptosis. In contrast to neuroblastoma, p53 suppression had no effect or increased drug susceptibility in several other tumour cell types, indicating the importance of tissue context for p53- mediated modulation of tumour cell sensitivity to treatment. Taken together, these data provide strong evidence for p53 having a role in mediating drug resistance in neuroblastoma and suggest that p53 status may be an important prognostic marker of treatment response in this disease.