-
Cigarette smoking and risk of glioma: A prospective
cohort study.
Silvera
SA, Miller
AB, Rohan
TE.
Department of Epidemiology and Population Health, Albert Einstein College of
Medicine, Bronx, NY, USA.
The etiology of glioma, the most commonly diagnosed malignant brain tumor
among adults in the United States, is poorly understood. N-nitroso compounds
are known carcinogens, which are found in cigarette smoke and can induce
gliomas in rats. On this basis, it has been hypothesized that cigarette
smoking may be associated with an increased risk of glioma. We investigated
the association between cigarette smoking and glioma risk in the National
Breast Screening Study, which included 89,835 Canadian women aged 40-59
years at recruitment between 1980 and 1985. Linkages to national cancer and
mortality databases yielded data on cancer incidence and deaths from all
causes, respectively, with follow-up ending between 1998 and 2000. Cox
proportional hazard models were used to estimate hazard ratios (HRs) and 95%
confidence intervals (CIs) for the association between cigarette smoking and
risk of glioma. During a mean of 16.4 years of follow-up, we observed 120
incident glioma cases. Among ever smokers, women who reported having quit
smoking had a 51% increase in risk of glioma compared with never smokers (HR
= 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an
increase in risk. When the association with former smokers was further
examined by years since quitting, women who had quit smoking >10 years
before baseline were at a decreased risk of glioma compared with women who
had quit within the 10 years prior to baseline (HR = 0.55, 95% CI =
0.29-1.07), indicating that the association between former smokers and
glioma may be driven by women, who recently quit smoking. Compared with
nonsmokers, duration of cigarette smoking, number of cigarettes smoked per
day and pack-years of smoking were associated with increased glioma risk,
although the increases in risk were relatively modest. The present study
provides some support for a positive association between cigarette smoking
and risk of glioma. (c) 2005 Wiley-Liss, Inc.
PMID: 16217772 [PubMed - in process]
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Hormonal and reproductive factors and risk of glioma: A
prospective cohort study.
Silvera
SA, Miller
AB, Rohan
TE.
Department of Epidemiology and Population Health, Albert Einstein College of
Medicine, NY, USA.
The etiology of glioma, the most commonly diagnosed malignant brain tumor
among adults in the United States, is poorly understood. Given the lower
incidence rate of glioma in women than in men, it has been hypothesized that
reproductive and hormonal factors may be involved in the etiology of glioma.
We conducted a secondary analysis of data from the National Breast Screening
Study, which included 89,835 Canadian women, aged 40-59 years at recruitment
between 1980 and 1985. Linkages to national cancer and mortality databases
yielded data on cancer incidence and deaths from all causes, respectively,
with follow-up ending between 1998 and 2000. Cox proportional hazards models
were used to estimate hazard ratios and 95% confidence intervals (CI) for
the association between hormonal and reproductive factors and risk of glioma.
During a mean of 16.4 years of follow-up, we observed 120 incident glioma
cases. Compared with women with a relatively early age at menarche (</=12
years), women who were 13-14 years of age at menarche had a 64% increased
risk of glioma (95% CI = 1.01-2.65), and women who were older than 14 years
of age at menarche had a 66% increased risk of glioma (95% CI = 0.86-3.20,
p(trend) = 0.06). Age at first live birth, parity, menopausal status, use of
oral contraceptive and use of hormone replacement therapy were not
associated with altered glioma risk in our study population. Additional
prospective studies are needed to confirm our findings. (c) 2005 Wiley-Liss,
Inc.
PMID: 16152609 [PubMed - in process]
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-
Effect of Ukrain on matrix metalloproteinase-2 and
Secreted Protein Acidic and Rich in Cysteine (SPARC) expression in human
glioblastoma cells.
Gagliano
N, Moscheni
C, Torri
C, Magnani
I, Bertelli
AA, Nowicky
W, Gioia
M.
Departments of aHuman Morphology-LITA Segrate bBiology and Genetics,
University of Milan, Milan, Italy cUkrainian Anti-Cancer Institute, Vienna,
Austria.
Glioblastoma is a highly malignant brain tumor with a highly invasive
phenotype and hence an unfavorable prognosis even in response to
multidisciplinary treatment strategies. Ukrain, a semi-synthetic
thiophosphoric acid derivative of the purified alkaloid chelidonine, has
been used in the therapy of several solid tumors, but little is known about
its effect on glioblastoma and, in general, about the molecular mechanisms
responsible for its effects. We used RT-PCR, Western blot and SDS-zymography
to investigate the effects of three doses of Ukrain (0.1, 1 and 10 mumol/l)
on the expression of genes and proteins involved in the extracellular matrix
remodeling associated with tumor invasion in human cultured glioblastoma
cells treated for 24, 48 and 72 h. We analyzed the expression of matrix
metalloproteinase-2 and -9, the main mediators of glioblastoma invasiveness,
and secreted protein acidic and rich in cysteine (SPARC), involved in the
regulation of cell-matrix interactions. There was a significant,
dose-related decrease of glioblastoma cell proliferation and a tendency to
downregulation of SPARC at the protein level 72 h after 10 mumol/l Ukrain,
suggesting the drug may be a useful therapeutic tool for brain tumors.
PMID: 16428937 [PubMed - in process]
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Atopic dermatitis and cancer risk.
Wang
H, Diepgen
TL.
Department of Clinical Social Medicine, Occupational and Environmental
Dermatology, University of Heidelberg, Thibaut Str. 3, 69115 Heidelberg,
Germany.
Summary Background Epidemiological studies have provided growing evidence of
a link between atopy and cancer risk. Objectives To review the evidence from
case-control studies and cohort studies on a possible association between
atopic dermatitis (AD) and cancer risk, with particular attention to the
case definition of AD. Methods Studies with quantitative data on the
association between AD (eczematous disease) and cancer risk were obtained
from MEDLINE in combination with a review of cited references. Results In 23
publications, AD was implicated in the risk of haematological [childhood
leukaemia (n = 3), adult leukaemia (n = 3), non-Hodgkin lymphoma (NHL; n =
4) and different haematological cancers (n = 1)], pancreatic (n = 5), skin
(n = 2) and brain malignancies (n = 5). The overall picture of the results
of these studies shows that a history of AD may be associated with a
decreased risk of pancreatic cancer, brain tumour and childhood leukaemia,
although in most instances the findings were not statistically significant.
No consistent associations were observed for skin cancer or NHL. The
definition of AD had varying quality, and was imprecise in the majority of
publications. Conclusions The findings of the epidemiological studies tend
to support a lower risk of cancer among persons with a history of AD.
Although a more careful definition of AD is needed, these epidemiological
studies could provide an estimate of the background cancer risk in patients
with AD when the long-term effects of treatments for AD are assessed.
PMID: 16433786 [PubMed - in process]
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Radiation to shrink brain tumor improves cognitive
function.
[No authors listed]
Publication Types:
PMID: 16456912 [PubMed - indexed for MEDLINE]
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Proton magnetic resonance spectroscopic imaging to
differentiate between nonneoplastic lesions and brain tumors in children.
Hourani
R, Horska
A, Albayram
S, Brant
LJ, Melhem
E, Cohen
KJ, Burger
PC, Weingart
JD, Carson
B, Wharam
MD, Barker
PB.
Russell H. Morgan Department of Radiology and Radiological Science, Johns
Hopkins University, Baltimore, Maryland, USA.
PURPOSE: To investigate whether in vivo proton magnetic resonance
spectroscopic imaging (MRSI) can differentiate between 1) tumors and
nonneoplastic brain lesions, and 2) high- and low-grade tumors in children.
MATERIALS AND METHODS: Thirty-two children (20 males and 12 females, mean
age = 10 +/- 5 years) with primary brain lesions were evaluated
retrospectively. Nineteen patients had a neuropathologically confirmed brain
tumor, and 13 patients had a benign lesion. Multislice proton MRSI was
performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho),
NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the
contralateral hemisphere. Normalized lesion peak areas (Cho(norm), Cr(norm),
and NAA(norm)) expressed relative to the contralateral hemisphere were also
calculated. Discriminant function analysis was used for statistical
evaluation. RESULTS: Considering all possible combinations of metabolite
ratios, the best discriminant function to differentiate between
nonneoplastic lesions and brain tumors was found to include only the ratio
of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases
correctly classified). The best discriminant function to differentiate
between high- and low-grade tumors included the ratios of NAA/Cr and
Cho(norm) (Wilks' lambda, P = 0.001; 89.5% of original grouped cases
correctly classified). Cr levels in low-grade tumors were slightly lower
than or comparable to control regions and ranged from 53% to 165% of the
control values in high-grade tumors. CONCLUSION: Proton MRSI may have a
promising role in differentiating pediatric brain lesions, and an important
diagnostic value, particularly for inoperable or inaccessible lesions. J.
Magn. Reson. Imaging 2006. Published 2005 Wiley-Liss, Inc.
PMID: 16374884 [PubMed - in process]
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Cellular Phones, Cordless Phones, and the Risks of Glioma
and Meningioma (Interphone Study Group, Germany).
Schuz
J, Bohler
E, Berg
G, Schlehofer
B, Hettinger
I, Schlaefer
K, Wahrendorf
J, Kunna-Grass
K, Blettner
M.
Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes
Gutenberg-University of Mainz, Mainz, Germany; Institute of Cancer
Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
The widespread use of cellular telephones has generated concern about
possible adverse health effects, particularly brain tumors. In this
population-based case-control study carried out in three regions of Germany,
all incident cases of glioma and meningioma among patients aged 30-69 years
were ascertained during 2000-2003. Controls matched on age, gender, and
region were randomly drawn from population registries. In total, 366 glioma
cases, 381 meningioma cases, and 1,494 controls were interviewed. Overall
use of a cellular phone was not associated with brain tumor risk; the
respective odds ratios were 0.98 (95% confidence interval (CI): 0.74, 1.29)
for glioma and 0.84 (95% CI: 0.62, 1.13) for meningioma. Among persons who
had used cellular phones for 10 or more years, increased risk was found for
glioma (odds ratio = 2.20, 95% CI: 0.94, 5.11) but not for meningioma (odds
ratio = 1.09, 95% CI: 0.35, 3.37). No excess of temporal glioma (p = 0.41)
or meningioma (p = 0.43) was observed in cellular phone users as compared
with nonusers. Cordless phone use was not related to either glioma risk or
meningioma risk. In conclusion, no overall increased risk of glioma or
meningioma was observed among these cellular phone users; however, for
long-term cellular phone users, results need to be confirmed before firm
conclusions can be drawn.
PMID: 16443797 [PubMed - as supplied by publisher]
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Anticancer effects of fenretinide in human
medulloblastoma.
Damodar
Reddy C, Guttapalli
A, Adamson
PC, Vemuri
MC, O'rourke
D, Sutton
LN, Phillips
PC.
Division of Neuro-Oncology, The Children's Hospital of Philadelphia,
Philadelphia, PA 19104, USA; Division of Neurosurgery, The Children's
Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of
Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) a synthetic retinoid is
in clinical trials for the treatment of several malignancies. However, its
biological effects and therapeutic value in childhood brain tumor
medulloblastoma (MB) has not been investigated. In this study, we report for
the first time that fenretinide (2.5-10muM) induces apoptotic cell death in
human MB cells. We observed significant inhibition of cell survival in four
MB cell lines (D425MED, D458MED, D283MED and D341MED) as determined by MTT
assays. These results were further supported by inhibition of
anchorage-independent colony formation in soft agar. Fenretinide-induced
decrease in cell viability was in part due to activation of caspase-3
dependent cell death, which was further supported by the cleavage of
poly(ADP-ribose) polymerase-1 (PARP-1), a caspase-3 substrate. Cell death
was partially prevented by the antioxidant, l-ascorbic acid suggesting that
free radical intermediates might be involved in fenretinide effects. These
results suggest that pharmacologically achievable concentrations of
fenretinide are effective in killing MB cells and thus show its therapeutic
potential to treat human MB.
PMID: 16399227 [PubMed - as supplied by publisher]
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Evaluation of health status and health-related quality of
life in a cohort of Italian children following treatment for a primary brain
tumor.
Cardarelli
C, Cereda
C, Masiero
L, Viscardi
E, Faggin
R, Laverda
A, Bisogno
G, Perilongo
G.
Department of Pediatrics, Division of Hematology-Oncology, Pediatric Neuro-Oncology
Program, University of Padua, Padua, Italy.
BACKGROUND: This study is a pilot experience aiming to investigate the
compliance of an institutional cohort of Italian children treated for a
malignant disease and their families in completing the health utilities
index2, (HUI2) and the effectiveness of this measured in terms of their
health status (HS) and health-related quality of life (HRQL). It
specifically, it aimed to compare the HS and the HRQL, as expressed by the
HUI2 global utility score, in cohorts of patients who had brain tumors,
extra-cerebral solid tumors, or leukemia/lymphoma. PROCEDURE: Fifty
survivors of brain tumors, between 8 and 30 years at the time of the
assessment ("self") and/or their parents ("proxy"),
attending the Pediatric Oncology Out Patient clinic of Padua, Italy,
completed the HUI2 questionnaire. Eighty-nine children with acute
leukemia/lymphoma and 74 with extra-cerebral solid tumors and/or their
parents were also assessed. RESULTS: The mean "self" and
"proxy" HUI2 global utility scores in the brain tumor patients
were 0.87 and 0.84, respectively, while in the cohorts of children with
other solid tumors and leukemia/lymphoma, there were 0.94, 0.91, 0.96, and
0.92, respectively. The differences between the HUI2 global utility scores
in the "self" and "proxy" assessment within each cohort
of children were not statistically significant. In decreasing order of
frequency, the attributes affected most commonly were: "emotion,"
"pain," "sensation," and "cognition" both by
"self" and "proxy" assessment. CONCLUSIONS: In this
Italian population of childhood cancer survivors the HUI2 questionnaire
proved to be a user-friendly tool, which provided information regarding HS
and HRQL. A larger cohort of cancer children is needed to confirm the
efficacy of the HUI2 questionnaire in distinguishing groups of children on
this basis by disease category. Pediatric Blood Cancer (c) 2006 Wiley-Liss,
Inc.
PMID: 16421901 [PubMed - as supplied by publisher]
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Ginseng saponin metabolite suppresses phorbol
ester-induced matrix metalloproteinase-9 expression through inhibition of
activator protein-1 and mitogen-activated protein kinase signaling pathways
in human astroglioma cells.
Jung
SH, Woo
MS, Kim
SY, Kim
WK, Hyun
JW, Kim
EJ, Kim
DH, Kim
HS.
Department of Neuroscience, Ewha Institute of Neuroscience, College of
Medicine, Ewha Woman's University, Seoul, South Korea.
Aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in
the process of invasion and angiogenesis of malignant tumors as well as in
inflammatory diseases of the CNS. Therefore, the development of compounds
that can inhibit or suppress MMP-9 is required to treat brain tumors. We
investigated the effects of a ginseng saponin metabolite, compound K
(20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol), on MMP-9 expression in
human astroglioma cells. Compound K significantly inhibited the secretion
and protein expression of MMP-9 induced by PMA. The inhibitory effect of
compound K on MMP-9 expression correlated with decreased MMP-9 mRNA levels
and suppression of MMP-9 promoter activity. The compound K-mediated
inhibition of MMP-9 gene expression appears to occur via AP-1 because its
DNA-binding and transcriptional activities were suppressed by the agent.
Furthermore, compound K significantly repressed the PMA-mediated activation
of p38 MAPK, ERK and JNK, which are upstream modulators of AP-1. Finally,
compound K inhibited the in vitro invasiveness of glioma cells. Therefore,
inhibition of MMP-9 expression by compound K might have therapeutic
potential for controlling the growth and invasiveness of brain tumors.
Copyright 2005 Wiley-Liss, Inc.
PMID: 16049964 [PubMed - indexed for MEDLINE]
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Barriers to carrier mediated drug and gene delivery to
brain tumors.
Huynh
GH, Deen
DF, Szoka
FC Jr.
Joint Graduate Group in Bioengineering, University of California at San
Francisco and Berkeley, San Francisco, CA 94143-0446, United States.
Brain tumor patients face a poor prognosis despite significant advances in
tumor imaging, neurosurgery and radiation therapy. Potent chemotherapeutic
drugs fail when used to treat brain tumors because biochemical and
physiological barriers limit drug delivery into the brain. In the past
decade a number of strategies have been introduced to increase drug delivery
into the brain parenchyma. In particular, direct drug administration into
the brain tumor has shown promising results in both animal models and
clinical trials. This technique is well suited for the delivery of liposome
and polymer drug carriers, which have the potential to provide a sustained
level of drug and to reach cellular targets with improved specificity. We
will discuss the current approaches that have been used to increase drug
delivery into the brain parenchyma in the context of fluid and solute
transport into, through and from the brain, with a focus on liposome and
polymer drug carriers.
PMID: 16318895 [PubMed - in process]
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Clinical trials of gene therapy, virotherapy, and
immunotherapy for malignant gliomas.
Barzon
L, Zanusso
M, Colombo
F, Palu
G.
1Department of Histology, Microbiology and Medical Biotechnologies,
University of Padova, Padova, Italy.
Despite advances in surgical and adjuvant therapy, the prognosis for
malignant gliomas remains dismal. This gloomy scenario has been recently
brightened by the increasing understanding of the genetic and biological
mechanisms at the basis of brain tumor development. These findings are being
translated into innovative therapeutic approaches, including gene therapy,
virotherapy, and vaccination, some of which have already been experimented
in clinical trials. The advantages and disadvantages of all these different
therapeutic modalities for malignant gliomas will be critically discussed,
providing perspective for future investigations.Cancer Gene Therapy advance
online publication, 6 January 2006; doi:10.1038/sj.cgt.7700930.
PMID: 16410822 [PubMed - as supplied by publisher]
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PTEN negatively regulates neural stem cell self-renewal
by modulating G0-G1 cell cycle entry.
Groszer
M, Erickson
R, Scripture-Adams
DD, Dougherty
JD, Le
Belle J, Zack
JA, Geschwind
DH, Liu
X, Kornblum
HI, Wu
H.
Departments of Molecular and Medical Pharmacology, Pathology and Laboratory
Medicine, Microbiology, Immunology, and Molecular Genetics, and Pediatrics,
and Department of Neurology and The Neuropsychiatric Institute, David Geffen
School of Medicine, University of California, Los Angeles, CA 90095.
Previous studies have demonstrated that a small subpopulation of brain tumor
cells share key characteristics with neural stem/progenitor cells in terms
of phenotype and behavior. These findings suggest that brain tumors might
contain "cancer stem cells" that are critical for tumor growth.
However, the molecular pathways governing such stem cell-like behavior
remain largely elusive. Our previous study suggests that the phosphatase and
tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, one
of the most frequently mutated genes in glioblastomas, restricts neural
stem/progenitor cell proliferation in vivo. In the present study, we sought
to determine the role of PTEN in long-term maintenance of stem cell-like
properties, cell cycle entry and progression, and growth factor dependence
and gene expression. Our results demonstrate an enhanced self-renewal
capacity and G(0)-G(1) cell cycle entry and decreased growth factor
dependency of Pten null neural/stem progenitor cells. Therefore, loss of
PTEN leads to cell physiological changes, which collectively are sufficient
to increase the pool of self-renewing neural stem cells and promote their
escape from the homeostatic mechanisms of proliferation control.
PMID: 16373498 [PubMed - as supplied by publisher]
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Patient satisfaction with awake craniotomy for tumor
surgery: a comparison of remifentanil and fentanyl in conjunction with
propofol.
Manninen
PH, Balki
M, Lukitto
K, Bernstein
M.
Department of Anesthesia, Toronto Western Hospital, Toronto, University
Health Network, University of Toronto, Toronto, Ontario, Canada.
pirjo.manninen@uhn.on.ca
In this study we compared the effectiveness of the use of remifentanil to
fentanyl in conjunction with propofol in providing conscious sedation for
awake craniotomy for tumor surgery and to assess patient satisfaction with
both techniques. The ability to maintain appropriate levels of sedation,
adequate analgesia, and hemodynamic stability was assessed in 50 patients
randomized to receive either fentanyl or remifentanil. All complications
were documented. Patients were interviewed at 1 h, 4 h, and 24 h after
surgery to note their recall of procedure and pain and their overall
satisfaction. There were no differences in sedation and pain scores or in
hemodynamic and respiratory variables between the two groups. The incidence
of intraoperative complications was not different (fentanyl, 14;
remifentanil, 16). Respiratory complications occurred in 9 (18%) patients (fentanyl
6, remifentanil 3). The recall and satisfaction scores were not different;
93% of all patients were completely satisfied at all interview times. The
use of remifentanil infusion in conjunction with propofol is a good
alternative to fentanyl and propofol for conscious sedation for the awake
craniotomy and these techniques are both well accepted by the patient.
Publication Types:
PMID: 16368836 [PubMed - indexed for MEDLINE]
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Phase II study of temozolomide plus pegylated liposomal
doxorubicin in the treatment of brain metastases from solid tumours.
Caraglia
M, Addeo
R, Costanzo
R, Montella
L, Faiola
V, Marra
M, Abbruzzese
A, Palmieri
G, Budillon
A, Grillone
F, Venuta
S, Tagliaferri
P, Del
Prete S.
Oncology Department, S.Giovanni di Dio Hospital, ASL Napoli 3 Via Giovanni
XXIII, 80028 Frattaminore, Naples, Italy. michele.caraglia@fondazionepascale.it
OBJECTIVE: A combination regimen of temozolomide (TMZ) and pegylated
liposomal doxorubicin has been evaluated in the treatment of brain
metastases from solid tumours. STUDY DESIGN: Nineteen consecutive patients
(pts) have been enrolled in a prospective phase II trial and treated with
TMZ 200 mg/m2 (days 1-5) and pegylated liposomal doxorubicin 35 mg/m2 (day
1) every 28 days. The study was prospectively projected according to the
Simon's two-stage optimal design. RESULTS: Major toxicities have been grade
III neutropenia and thrombocytopenia in one patient (pt) and grade III
erythrodisesthesia in two pts. Three pts achieved a complete response (CR)
and four a partial response (PR), for an overall response rate of 36.8% (95%
CI: 19.1-59.2), which exceeded the target activity in the study design. A
significant improvement in quality of life was demonstrated by FACT-G
analysis. The median Progression Free Survival (PFS) was 5.5 (95% CI:
2.7-8.2) months while the median Overall Survival (OS) was 10.0 months (95%
CI: 6.3-13.7). CONCLUSIONS: The TMZ/pegylated liposomal doxorubicin regimen
was well tolerated with an encouraging activity in brain metastases from
solid tumours.
Publication Types:
PMID: 16010592 [PubMed - indexed for MEDLINE]
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Brain tumors provide new clues to the source of cancer
stem cells: does oncology recapitulate ontogeny?
Gilbertson
RJ.
Departments of Developmental Neurobiology and Hematology/Oncology, St. Jude
Children's Research Hospital, Memphis Tennesee, USA.
Recent studies of leukemia and solid tumors have provided compelling
evidence for the existence of cancer stem cells, but the origin of these
cells remains a matter of considerable debate. By comparing the gene
expression profiles of ependymomas with those of cells in the normal
developing nervous system, we were able to pinpoint radial glia as candidate
stem cells of this brain tumor. These data suggest strongly that ependymomas
arise directly from transformed radial glia and they provide a novel method
that could be used to map the cell of origin of other types of cancer.
PMID: 16357533 [PubMed - in process]
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School experiences after treatment for a brain tumour.
Upton
P, Eiser
C.
CR-UK Child and Family Research Unit, University of Sheffield, Sheffield,
UK.
Abstract Background Children surviving a brain tumour face major
difficulties including learning problems, lengthy school absences and
psychosocial problems, all of which can impact on school functioning. Our
aims were to provide information for parents and teachers about the skills
and resources of this group. Specifically, we aimed to: * describe the
special educational needs of these children; * document the impact of
diagnosis and treatment on school attendance; * compare parent and teacher
assessments of social, emotional and behavioural difficulties. Methods Forty
families agreed to participate (response rate = 58.82%). The children (19
males and 21 females) were aged from 6 to 16 years and had completed
treatment at least 2 years previously (range = 2 years-12 years 5 months).
Questionnaires (Strengths and Difficulties and school experience) were
completed by mothers and teachers. Results Survivors were experiencing a
wide range of physical, learning and interpersonal difficulties, according
to parent and teacher reports. Almost half the children (n = 19) had ongoing
neurological problems that were significant enough to require special help
at school. Literacy and numeracy were the most common learning difficulties.
Parents also rated brain tumour survivors as having more behavioural and
emotional problems than would be expected from population norms. For
example, survivors were rated as having more Total Difficulties (t = 6.86, P
< 0.001), Emotional Symptoms (t = 8.82, P < 0.001), Hyperactivity (t =
2.25, P = 0.03), Peer Relationship Problems (t = 7.58, P < 0.001) and
poorer Pro-social Behaviour (t = -3.34, P = 0.002) than would be expected
from population norms. These problems were also seen to be having a
significant impact on the child's functioning (t = 3.95, P < 0.001).
Teachers rated these problems as less serious than parents. Conclusion These
children experience significant problems in school some time after diagnosis
and when they are considered medically cured. Closer school-hospital liaison
is essential to maximize integration and achievement in these children.
PMID: 16398787 [PubMed - in process]
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Headache related to brain tumors.
Loghin
M, Levin
VA.
Neuro-Oncology Unit 431, UT MD Anderson Cancer Center, PO Box 301402,
Houston, TX 77230, USA.
Headache is one of the most common somatic complaints of patients seeking
medical care. Most headaches are not of serious cause and can be diagnosed
easily with a good history and physical examination. The challenges to the
physician are to determine when underlying intracranial pathology may be
causing the symptoms and signs, and to identify the few patients in whom a
tumor is the cause of the headache. The subject of headache in patients with
brain tumors has been reviewed in neurologic textbooks and in several
investigations before, as well as after, modern imaging diagnostic
techniques became available. Headache can also manifest as an acute or
chronic complication of radiation treatment and/or chemotherapy in patients
with intracranial neoplasm, but there are few data in the literature
specifically addressing this subject. This article provides an overview of
headache in patients with primary and secondary brain tumor, including
headache characteristics, the putative mechanism for these headaches, the
role of diagnostic testing, and the general principles of management.
PMID: 16343358 [PubMed]
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p53 suppresses the self-renewal of adult neural stem
cells.
Meletis
K, Wirta
V, Hede
SM, Nister
M, Lundeberg
J, Frisen
J.
Department of Cell and Molecular Biology, Medical Nobel Institute,
Karolinska Institute, SE-171 77 Stockholm, Sweden.
There is increasing evidence that tumors are heterogeneous and that a subset
of cells act as cancer stem cells. Several proto-oncogenes and tumor
suppressors control key aspects of stem cell function, suggesting that
similar mechanisms control normal and cancer stem cell properties. We show
here that the prototypical tumor suppressor p53, which plays an important
role in brain tumor initiation and growth, is expressed in the neural stem
cell lineage in the adult brain. p53 negatively regulates proliferation and
survival, and thereby self-renewal, of neural stem cells. Analysis of the
neural stem cell transcriptome identified the dysregulation of several cell
cycle regulators in the absence of p53, most notably a pronounced
downregulation of p21 expression. These data implicate p53 as a suppressor
of tissue and cancer stem cell self-renewal.
PMID: 16368933 [PubMed - in process]
-
Induction of p53-mediated apoptosis and recovery of
chemosensitivity through p53 transduction in human glioblastoma cells by
cisplatin.
Park
CM, Park
MJ, Kwak
HJ, Moon
SI, Yoo
DH, Lee
HC, Park
IC, Rhee
CH, Hong
SI.
Laboratory of Functional Genomics, Korea Institute of Radiological and
Medical Sciences, Seoul, Korea.
Cisplatin is a DNA-damaging chemotherapeutic drug that may have a role in
the adjuvant chemotherapy of several solid tumors, such as malignant
glioblastoma, and the status of p53 tumor suppressor protein is a critical
determinant of cisplatin chemosensitivity. In the present study, we showed
the relationship of p53 status and chemosensitivity of cisplatin between two
human malignant glioblastoma cell lines, A172 and T98G, harboring wild-type
and mutant-type p53, respectively. Cisplatin was found to be more cytotoxic
to A172 than T98G cells in a time- and concentration-dependent manner.
Cisplatin-induced cytotoxicity manifested as apoptosis, characterized by
genomic DNA fragmentation, nuclear condensation and an increase in sub-G1
population. Cisplatin induced the accumulation of p53 and p21 proteins in
A172 cells, but not in T98G cells. The introduction of the
adenovirus-mediated wild-type p53 gene into T98G cells resulted in the
decrease of viability as well as the increase in sub-G1 population with p53
accumulation, activation of caspase-3 protease and release of cytochrome c
from the mitochondria. These data strongly suggest that the expression of
p53 is essential for the cytotoxic effect of cisplatin in human malignant
glioblastoma cells, A172 and T98G, and the introduction of apoptotic signal
molecules, such as p53, will be beneficial to achieve chemosensitivity in
malignant glioma.
PMID: 16327987 [PubMed - indexed for MEDLINE]
-
Comparison of linear and volumetric criteria in assessing
tumor response in adult high-grade gliomas.
Shah
GD, Kesari
S, Xu
R, Batchelor
TT, O'Neill
AM, Hochberg
FH, Levy
B, Bradshaw
J, Wen
PY.
Brigham and Women's Hospital, Boston, MA 02115, USA.
The Response Evaluation Criteria in Solid Tumors, or RECIST criteria
(one-dimensional [1D] measurement), are widely used to measure response in
tumors, but there are few studies evaluating these criteria in brain tumors.
We compared linear and volumetric measurements in adult high-grade
supratentorial enhancing gliomas to determine the agreement between
measurements, in defining responses and in their subsequent relation to
survival. We hypothesized that the 1D RECIST criteria maybe suitable for
response assessment in adult high-grade gliomas. Tumor size on MRI scans in
104 patients with high-grade enhancing gliomas treated on clinical trial
protocols was measured by using 1D (greatest length), 2D (two-dimensional:
product of the two longest perpendicular diameters), 3D (three dimensional:
product of the longest perpendicular diameters in one plane and the longest
orthogonal diameter to that plane), enhancing volume (EV), and total volume
(TV). A total of 388 T1 postgadolinium MRI scans (104 baseline and 284
follow-up scans) were evaluated. Volumetric analysis (EV and TV) was
performed with commercially available software. Intraobserver and
interobserver correlations (rho) were high for all modalities (rho > 0.92
and rho > 0.71, respectively). Correlation was excellent (rho > 0.9)
among all modalities except for 3D (rho < 0.6). Patient response rates
ranged from 12% to 26%. Median progression-free survival (mPFS) and
six-month progression-free survival (6mPFS) were not significantly different
among the methods (range, 5.3 months to 5.9 months and 42% to 48%,
respectively). Landmark analyses of response at two months using linear
methods predicted overall survival with hazard ratios of 0.19 to 0.29 (P
< 0.005). These results suggest high concordance among 1D, 2D, TV, and EV,
but not 3D, methods in assessing enhancing tumor progression and in
estimating mPFS and 6mPFS in adult brain tumor patients. The tumor response
at two months assessed by linear methods correlated better with overall
survival. Thus, linear methods are comparable to volumetric methods, but
simpler to implement for routine clinical use and for designing clinical
trials of brain tumors.
PMID: 16443946 [PubMed - in process]-
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Volume 5, Number 6 - 6
February 2006