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Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
OBJECTIVE
Glioblastoma
is a primary glial neoplasm with a median survival of approximately 1 year. There are anecdotal reports that postoperative infection may confer a survival advantage in patients with
glioblastoma
. However, only a few case reports in the literature, along with 2 retrospective cohort studies, show some potential link between infection and prolonged survival in patients with
glioblastoma
. The objective of this study was to evaluate the effect of postoperative infection in patients with
glioblastoma
using a large national database. METHODS The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was searched to identify patients 66 years of age and older with
glioblastoma
, with and without infection, from 1997 to 2010. The primary outcome was survival after diagnosis. The statistical analysis was performed with a graphical representation using Kaplan-Meier curves, univariate analysis with the log-rank test, and multivariate analysis with proportional hazards modeling. RESULTS A total of 3784 patients with
glioblastoma
were identified from the database, and from these, 369 (9.8%) had postoperative infection within 1 month of surgery. In patients with
glioblastoma
who had an infection within 1 month of surgery, there was no significant difference in survival (median 5 months) compared with patients with no infection (median 6 months; p = 0.17). The study also showed that older age, increased Gagne comorbidity score, and having diabetes may be negatively associated with survival. CONCLUSIONS
Infection
after craniotomy within 1 month was not associated with a survival benefit in patients with
glioblastoma
.
...
PMID:The effect of postoperative infection on survival in patients with glioblastoma. 2793 60
T-type Ca
2+
channels (TTCC) have been identified as key regulators of cancer cell cycle and survival.
In vivo
studies in
glioblastoma
(
GBM
) murine xenografts have shown that drugs able to block TTCC
in vitro
(such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacologic blockers have limited selectivity for TTCC and are unable to distinguish between TTCC isoforms. Here we analyzed the expression of TTCC transcripts in human
GBM
cells and show a prevalence of Cacna1g/Ca
v
3.1 mRNAs.
Infection
of
GBM
cells with lentiviral particles carrying short hairpin RNA against Ca
v
3.1 resulted in
GBM
cell death by apoptosis. We generated a murine
GBM
xenograft via subcutaneous injection of U87-MG
GBM
cells and found that tumor size was reduced when Ca
v
3.1 expression was silenced. Furthermore, we developed an
in vitro
model of temozolomide-resistant
GBM
that showed increased expression of Ca
v
3.1 accompanied by the activation of macroautophagy. We confirmed a positive correlation between Ca
v
3.1 and autophagic markers in both
GBM
cultures and biopsies. Of note, Ca
v
3.1 knockdown resulted in transcriptional downregulation of p62/SQSTM1 and deficient autophagy. Together, these data identify Ca
v
3.1 channels as potential targets for slowing
GBM
progression and recurrence based on their role in regulating autophagy. SIGNIFICANCE: These findings identify Ca
v
3.1 calcium channels as a molecular target to regulate autophagy and prevent progression and chemotherapeutic resistance in
glioblastoma
.
...
PMID:T-Type Ca
v
3.1 Channels Mediate Progression and Chemotherapeutic Resistance in Glioblastoma. 3075 43
Oncolytic viruses induce local tumor destruction and inflammation. Whether virotherapy can also overcome immunosuppression in noninfected tumor areas is under debate. To address this question, we have explored immunologic effects of oncolytic herpes simplex viruses (oHSVs) in a genetically engineered mouse model of isocitrate dehydrogenase (IDH) wild-type
glioblastoma
, the most common and most malignant primary brain tumor in adults. Our model recapitulates the genomics, the diffuse infiltrative growth pattern, and the extensive macrophage-dominant immunosuppression of human
glioblastoma
.
Infection
with an oHSV that was armed with a UL16-binding protein 3 (ULBP3) expression cassette inhibited distant tumor growth in the absence of viral spreading (abscopal effect) and yielded accumulation of activated macrophages and T cells. There was also abscopal synergism of oHSVULBP3 with anti-programmed cell death 1 (anti-PD-1) against distant, uninfected tumor areas; albeit consistent with clinical trials in patients with
glioblastoma
, monotherapy with anti-PD-1 was ineffective in our model. Arming oHSV with ULBP3 led to upregulation of antigen processing and presentation gene sets in myeloid cells. The cognate ULBP3 receptor NKG2D, however, is not present on myeloid cells, suggesting a noncanonical mechanism of action of ULBP3. Overall, the myeloid-dominant, anti-PD-1-sensitive abscopal effect of oHSVULBP3 warrants further investigation in patients with IDH wild-type
glioblastoma
.
...
PMID:Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma. 3129 99
Glioblastoma
(
GBM
) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in
GBM
is
CDKN2A
gene loss, located close to the cluster of
type I IFN
genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of
GBM
. We have analyzed the
CDKN2A-IFN I
gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic effect in six
GBM
CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of
GBM
patients have some
IFN
deletion. Moreover,
GBM
susceptibility to NDV is dependent on the loss of the
type I IFN
.
Infection
of
GBM
with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.
...
PMID:Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion. 3251 84
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