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Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho‐educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. A pre‐post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow‐up surveys, before and after the intervention. Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P< 0.001). Anxiety and concerns were significantly lower after receiving the talking book (P= 0.015 and P= 0.004, respectively). Nearly half of participants (s= 17, 48%) reported using the book during appointments. Most reported finding it easier to communicate (n= 31, 89%) and to ask more questions (n= 21, 62%). The talking book shows promise in improving knowledge, reducing anxiety and enhancing communication. Strategies to support the implementation of the talking book are required. Further studies to translate the book into different languages are also planned. We pilot tested a low literacy, psycho‐educational talking book (written booklet, with accompanying audio‐recording) to examine: (i) the effect of the tool on knowledge, anxiety, concerns and communication; and (ii) acceptability. The talking book shows promise in improving knowledge, reducing anxiety, and enhancing communication.

Background: Microtubules are cellular organelles with functions that include control of cell division by mitosis, cell morphology, and transport of material within the cell. The anticancer drug paclitaxel (Taxol) promotes accelerated assembly of excessively stable microtubules. Consequently, treated cells tend to become arrested in mitosis. The drug also induces apoptotic cell death in vitro and in vivo. Prior to this study, the relative contributions of mitotic arrest and apoptosis to the in vivo antitumor effect and the relationship between the two factors had not been established; moreover, it is not known whether paclitaxel-induced mitotic arrest inevitably results in cell death. Purpose: Our aim was to quantify the mitotic arrest and apoptosis induced by paclitaxel in 16 murine tumors in vivo and to correlate these two factors with the drug's antitumor effect. Methods: Inbred C3Hf/Kam mice were implanted with one of the following 16 syngeneic tumors: seven adenocarcinomas (MCa-4, MCa-29, MCa-35, MCa-K, OCa-I, ACa-SG, and HCa-I), two squamous cell carcinomas (SCC-IV and SCC-VII), six sarcomas (FSa, FSa-II, Sa-IIa, Sa-NH, NFSa, and Sa-4020), and one lymphoma (Ly-TH). The tumor growth delay induced by paclitaxel (40 mg/kg body weight given intravenously) was measured in 163 control and 163 treated mice, and its significance was assessed by Student's t test. In a separate group of 439 mice, the percentage of cells in mitosis or apoptosis was scored micromorphometrically at various times after paclitaxel administration. The significance of correlations between paclitaxel-induced tumor growth delay and paclitaxel-induced levels of mitosis or apoptosis was determined by simple correlation and Spearman's rank correlation. P values reported represent two-sided tests of statistical significance. Results: Statistically significant tumor growth delays were found in response to paclitaxel treatment of mice for three of four murine mammary carcinomas (all P[< or =].010), an ovarian carcinoma (P = .00003), a salivary gland adenocarcinoma (P = .0002), a lymphoma (P = .0002), and two of six sarcomas (both P[< or =].034), but not for either of two squamous cell carcinomas or for the hepatocellular carcinoma. Paclitaxel-induced mitotic arrest was apparent in all tumor types, but to various degrees, and was not significantly correlated with growth delay ([R.sup.2] = .16; P = .124). In contrast, apoptotic cell death in response to paclitaxel was not ubiquitous, but it was strongly correlated with growth delay ([R.sup.2] = .59; P = .001). The pretreatment level of apoptosis was correlated with both paclitaxel-induced apoptosis ([R.sup.2] = .71; P = .00004) and tumor growth delay ([R.sup.2] = .55; P = .001). Conclusion: The antitumor effect of paclitaxel was correlated with paclitaxel-induced apoptosis and base-line apoptosis, but not with mitotic arrest. Implications: Apoptosis is an important mechanism of cell death in response to paclitaxel treatment of in vivo murine tumors. An underlying tumor type-specific propensity for apoptosis is implied by the correlation between pretreatment and paclitaxel-induced apoptosis. Both the extent of pretreatment apoptosis and the paclitaxel-induced percentage of apoptosis may be useful predictors of response to the drug. [J Natl Cancer Inst 1996;88: 1308-14]

Our previous studies of tonsillar cancers from New South Wales, Australia, and Jilin Province in the north-east of China, provided evidence that the proportion of these cancers attributable to human papillomavirus (HPV) varies geographically. This study provides the first data on HPV in tonsillar cancers from Hong Kong.

Continuous xenografts from 10 children with acute lymphoblastic leukemia (ALL) were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Relative to primary engrafted cells, negligible changes in growth rates and immunophenotype were observed at second and third passage. Analysis of clonal antigen receptor gene rearrangements in 2 xenografts from patients at diagnosis showed that the pattern of clonal variation observed following tertiary transplantation in mice exactly reflected that in bone marrow samples at the time of clinical relapse. Patients experienced diverse treatment outcomes, including 5 who died of disease (median, 13 months; range, 11-76 months, from date of diagnosis), and 5 who remain alive (median, 103 months; range, 56-131 months, following diagnosis). When stratified according to patient outcome, the in vivo sensitivity of xenografts to vincristine and dexamethasone, but not methotrexate, differed significantly (P = .028, P = .029, and P = .56, respectively). The in vitro sensitivity of xenografts to dexamethasone, but not vincristine, correlated significantly with in vivo responses and patient outcome. This study shows, for the first time, that the biologic and genetic characteristics, and patterns of chemosensitivity, of childhood ALL xenografts accurately reflect the clinical disease. As such, they provide powerful experimental models to prioritize new therapeutic strategies for future clinical trials.

Acute lymphoblastic leukemia cells from 19 children, including 7 who remain in first complete remission (CR1), were engrafted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-level infiltration of bone marrow, spleen, and liver was observed, with variable infiltration of other organs. The immunophenotypes of xenografts were essentially unaltered compared with the original patient sample. In addition, sequencing of the entire p53 coding region revealed no mutations in 14 of 14 xenografts (10 from patients at diagnosis and 4 at relapse). Cells harvested from the spleens of engrafted mice readily transferred the leukemia to secondary and tertiary recipients. To correlate biologic characteristics of xenografts with clinical and prognostic features of the patients, the rates at which individual leukemia samples engrafted in NOD/SCID mice were analyzed. Differences in biologic correlates were encountered depending on stage of disease: a direct correlation was observed between the rate of engraftment and length of CR1 for samples harvested at relapse (r = 0.96; P = .002), but not diagnosis (r = 0.38; P = .40). In contrast, the in vivo responses of 6 xenografts to vincristine showed a direct correlation (r = 0.96; P = .002) between the length of CR1 and the rate at which the leukemia cell population recovered following vincristine treatment, regardless of whether the xenografts were derived from patients at diagnosis or relapse. This study supports previous findings that the NOD/SCID model of childhood ALL provides an accurate representation of the human disease and indicates that it may be of value to predict relapse and design alternative treatment strategies in a patient-specific manner.

Cytokine-mediated expansion has been proposed and successfully used to facilitate engraftment post transplantation. This study examined whether cryopreservation following expansion has a detrimental effect on the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34+ cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL), and megakaryocyte growth and development factor (MGDF). Expanded CD34+ cells were transplanted into NOD-SCID mice either fresh or following cryopreservation and thawing. After thawing, recovery of nucleated cells was 94%, of CD34 cells was 63%, and of day-14 progenitors was 17%. The loss of day-14 progenitor cells among the thawed expanded cells did not influence the kinetics of human engraftment in the mouse. Bone marrow (BM) of mice transplanted with thawed expanded CD34+ cells (14 ± 3.9%) showed significantly higher levels of human engraftment than mice transplanted with fresh expanded CD34+ cells (1.5 ± 0.5%, p = 0.0064). Thawed expanded CD34+ cells had significantly higher SCID Engrafting Potential (SEP) than freshly expanded CD34+ cells (p < 0.001). Results suggest that prior cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.

Transplantation of human hematopoietic stem cells is the only true test of their long-term repopulation potential. Models are readily available to evaluate murine hematopoietic stem cells, but few exist that allow reliable quantification of human stem cells. The non-obese diabetic-severe combined immunodeficient (NOD-SCID) mouse model enables quantification of human hematopoietic stem cells, but the conditions that permit human engraftment in all animals have yet to be defined. The aims of the project were, therefore, to describe the variables that allow human engraftment in the NOD-SCID mouse model and the techniques that accurately quantify this engraftment.

Abstract: This article reports data that describe perturbations in cell‐cycle dynamic kinetic parameters following in vivo treatment of a syngeneic murine mammary tumor (MCa‐4) with paclitaxel. The kinetic parameters include the duration of the S (Ts) and G2M (TG2M) phases of the cell cycle, the tumor potential doubling time (Tpot), the bromodeoxyuridine (BrdUrd) labeling index (Ll), and the fraction of proliferating cells that successfully completed mitosis following paclitaxel treatment. When tumors transplanted into the right thigh of 4‐month‐old male C3Hf/kam mice grew to 8 mm mean diameter, the mice were injected intravenously with 40 mg/kg paclitaxel. At one of a range of times thereafter (1–72 hours) animals were pulse labeled with 60 mg/kg BrdUrd. Mice were sacrificed and tumors excised either immediately or at 3 or 6 hours after BrdUrd labeling. Single‐nuclei suspensions were prepared, and the kinetic parameters evaluated using bivariate DNA versus BrdUrd flow‐cytometric methods.

Tumor necrosis and oxygen status were investigated as a function of tumor size in three syngeneic murine carcinomas, MCa-4, OCa-I, and SCC-VII, in C3Hf/Kam mice. Tumor necrosis was estimated histologically, and tumor oxygenation determined by direct polarographic histography. As tumor volume increased necrosis increased significantly in all three tumor types (p < 0.001). Similarly, as tumor volume increased from 200 to 1 400 mm3, hypoxia, defined as the percentage of measured p02 Values ±5.0 mm Hg, increased from 55.1% to 95.9%, 70.3% to 81.4%, and 56.8% to 98.5% in MCa-4, OCa-I, and SCC-VII tumors respectively (p < 0.001). Correcting p02 for necrosis reduced the tumor size dependence of measured tumor hypoxia in all three tumor types but in no case was the reduction significant. The main effect of correction was to shift the fitted curves of percent pO2 values <5.0 mm Hg down toward lower percentages for all tumors. This change was significant for MCa-4 and OCa-I tumors (p < 0.001), but not for SCC-VII (p = 0.054). Defining the influence of variables such as necrosis that affect polarographic assessment of tumor oxygenation is important to enhance the technique's reliability and prospect as an investigative and predictive tool.

Paclitaxel is a novel chemotherapeutic agent that arrests cells in the radiosensitive G2 and M phases of the cell cycle and as such may act as a specific cell cycle radiosensitizer. We recently reported that paclitaxel induces mitotic arrest in the MCA-4 murine mammary carcinoma and enhances radio-response of this tumor. However, the greatest enhancement was observed not when radiation was given at the time of peak mitotic arrest, which was 9 h after paclitaxel administration, but when it was given 24 h after paclitaxel. This implied the involvement of other mechanisms in radiosensitization; we hypothesized that tumor reoxygenation was a likely mechanism based on the observed massive loss of mitotically arrested cells at 24 h. The present study shows that paclitaxel greatly enhanced MCA-4 tumor radioresponse when radiation was given under air-breathing conditions (DMF = 1.74), but not when it was performed under hypoxic conditions. This observation supports the hypothesis of tumor reoxygenation as a mechanism of enhancement of tumor radioresponse. That reoxygenation occurred in tumors treated with paclitaxel 24 h earlier was confirmed by direct measurements of pO2 values, using the Eppendorf pO2 histograph. Median pO2 values increased from 6.2 mmHg in untreated tumors to 10.0 mmHg in tumors treated with paclitaxel. These observations emphasize the importance of timing of paclitaxel administration in relation to radiation treatment.