Biomedical subjects

W K Yung

Publications and source records attributed to W K Yung.

At least 19 recordsLinked to original sources

PubMed2001

Transfer of E2F-1 to human glioma cells results in transcriptional up-regulation of Bcl-2.

Strong evidence exists to support the tenet that activation of E2F transcription factors, via alterations in the p16-cyclin D-Rb pathway, is a key event in the malignant progression of most human malignant gliomas. The oncogenic ability of E2F has been related to the E2F-mediated up-regulation of several proteins that positively regulate cell proliferation. However, E2F may indirectly enhance proliferation by activating antiapoptotic molecules. In this work, we sought to ascertain whether E2F-1-mediated events involve the up-regulation of the antiapoptotic molecule Bcl-2. Western blot analyses showed up-regulation of Bcl-2 but not of Bcl-x(L) by 24 h after the transfer of E2F-1. Northern blot studies showed that transfer of E2F-1 also up-regulated Bcl-2 RNA. In support of these findings and the concept that E2F-1 has a direct effect in the induction of Bcl-2, we found a putative E2F binding site within the Bcl-2 sequence. Subsequent gel-mobility shift and supershift experiments involving the CTCCGCGC site in the bcl-2 promoter showed that E2F-1 bound Bcl-2. Transactivation experiments consistently showed that ectopic E2F-1 activated responsive elements located in the -1448/-1441 region in the P1 promoter region of the bcl-2 gene. As expected, other members of the E2F family of transcription factors such as E2F-2 and E2F-4 also transactivated the bcl-2 promoter. Our results demonstrate that E2F-1 modulates the expression of the antiapoptotic molecule Bcl-2 and suggest that up-regulation of Bcl-2 may favor the oncogenic role of E2F-1 and other members of the E2F family of transcription factors.

Binding Sites↗

PubMed2001

Inhibition of breast cancer growth in vivo by antiangiogenesis gene therapy with adenovirus-mediated antisense-VEGF.

Increased expression of VEGF in several types of tumours has been shown to correlate with poor prognosis. We used a replication-deficient adenoviral vector containing antisense VEGF cDNA (Ad5CMV-alphaVEGF) to down-regulate VEGF expression and increase the efficiency of delivery of the antisense sequence in the human breast cancer cell line MDA231-MB. Transfection of these cells with Ad5CMV-alphaVEGF in vitro reduced secreted levels of VEGF protein without affecting cell growth. Moreover, injection of the Ad5CMV-alphaVEGF vector into intramammary xenografts of these cells established in nude mice inhibited tumour growth and reduced the amount of VEGF protein and the density of microvessels in those tumours relative to tumours treated with the control vector Ad5(dl312). Our results showed that antisense VEGF(165)cDNA was efficiently delivered in vivo via an adenoviral vector and that this treatment significantly inhibited the growth of established experimental breast tumours. The Ad5CMV-alphaVEGF vector may be useful in targeting the tumour vasculature in the treatment of breast cancer.

Adenoviridae↗

PubMed2001

Tumor suppressor MMAC/PTEN inhibits cytokine-induced NFkappaB activation without interfering with the IkappaB degradation pathway.

The phosphoinositide 3-kinase (PI 3-kinase) pathway has been implicated in the activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB). To investigate the role of this pathway in NFkappaB activation, we employed mutated in multiple advanced cancers/phosphatase and tensin homologue (MMAC/PTEN), a natural antagonist of PI 3-kinase activity. Our results show that cytokine-induced DNA binding and transcriptional activities of NFkappaB were both inhibited in a glioma cell line that was stably transfected with MMAC/PTEN. The ability of interleukin-1 (IL-1) to induce inhibitor (IkappaB) degradation or nuclear translocation of NFkappaB was, however, unaffected by MMAC/PTEN expression, suggesting that PI 3-kinase utilizes another equally important mechanism to control NFkappaB activation. It is conceivable that NFkappaB is directly phosphorylated through such a mechanism because treatment with protein phosphatase 2A significantly reduced its DNA binding activity. Moreover, IL-1-induced phosphorylation of p50 NFkappaB was potently inhibited in MMAC/PTEN-expressing cells. Whereas the mediators of NFkappaB phosphorylation remain to be identified, IL-1 was found to induce physical interactions between the PI 3-kinase target Akt kinase and the IkappaB.IkappaB kinase complex. Physical interactions between these proteins were antagonized by MMAC/PTEN consistent with their potential involvement in NFkappaB activation. Taken together, our observations suggest that PI 3-kinase regulates NFkappaB activation through a novel phosphorylation-dependent mechanism.

Cytokines↗

PubMed2001

Future directions for temozolomide therapy.

Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.

Antineoplastic Agents, Alkylating↗

PubMed2001

Delivery of cell cycle genes to block astrocytoma growth.

Current therapies for glioblastoma multiforme are ineffective. Therefore, novel therapies that target specific differences between normal and malignant cells are urgently needed. Abnormalities of cell-cycle related genes are a common feature of cancer in general and astrocytic tumors in particular. The role of these proteins is to help to regulate cell proliferation, differentiation and apoptosis. Restoring wild-type activity of critical regulators of the cell cycle to astrocytic tumors generally results in modification of the growth properties, and often the viability, of the cancer cells. Transfer of p53 induces growth arrest and, more importantly, apoptosis. Restoration of the Rb pathway results in either reversible growth arrest or senescence. Expression of E2F-1 induces transient increase of proliferation followed by massive apoptosis. Overexpression of MMAC/PTEN arrests cell cycle progression in G1 and promotes anoikis. Current knowledge of the functions of these cell-cycle controllers can be used to design small peptides and drugs to induce cell-cycle related anti-cancer effect. Inactivation of the p53 and Rb pathways in cancer cells is also being used to engineer mutant viruses that are able to replicate exclusively in cancer cells.

Animals↗

PubMed2001

Introduction of mutant p53 into a wild-type p53-expressing glioma cell line confers sensitivity to Ad-p53-induced apoptosis.

Transient expression of the tumor suppressor gene p53 via adenoviral-mediated gene transfer induces apoptosis in glioma cells expressing mutant p53, while causing cell cycle arrest in cells with wild-type p53. To determine whether a change in p53 status of a wild-type p53-expressing cell line such as U-87 MG would alter its apoptotic resistant phenotype in response to Ad-p53 infection, we generated cell lines U-87-175.4 and U-87-175.13 via retroviral-mediated gene transfer of the p53 (175H) mutant into the U-87 MG parental line. Control cell lines U-87-Lux.6 and U-87-Lux.8 were also generated and express the reporter gene luciferase. Both U-87-175.4 and U-87-175.13, but not control cell lines, exhibited morphology characteristic of apoptosis after Ad-p53 infection. Furthermore, expression of other p53 mutants (248W, 273H) in U-87 MG also sensitized cells to Ad-p53-induced apoptosis. Apoptosis was confirmed by TUNEL and cell cycle analysis. Several p53 response genes were examined in cells infected with Ad-p53, and among these, BCL2, p21WAF1/CIP1, CPP32/caspase 3, and PARP showed differences in expression between U87-175 and U87-Lux cell lines. Taken together, our data demonstrate that the introduction of p53 mutants in U-87 MG promotes an apoptotic response in association with adenoviral-mediated wild-type p53 gene transfer. These results underscore the importance of glioma p53 genotype for predicting tumor response to p53-based gene therapy.

Adenoviridae↗

PubMed2001

Survival and recurrence factors in adult medulloblastoma: the M.D. Anderson Cancer Center experience from 1978 to 1998.

Medulloblastoma is a rare adult primary brain tumor for which limited retrospective studies are available to elucidate natural history or to guide therapy. A retrospective chart and imaging review of adult patients (aged >18 years) with medulloblastoma was performed to identify survival and prognostic factors. Fifty-seven patients were evaluated at the University of Texas M.D. Anderson Cancer Center from 1978-1998. Statistical analysis of prognostic factors and overall survival was performed for a subgroup of 28 patients who were followed exclusively at our institution from the time of diagnosis until death or last follow-up. These 28 patients had an overall survival of 91% at 3 years and 84% at 5 years, whereas median survival was not reached after a median follow-up of 168 weeks (range, 9-602 weeks). Progression-free survival for all patients was 68% at 3 years and 62% at 5 years, and was not statistically different between poor- and standard-risk patients. Univariate analysis of clinical features, such as age, sex, extent of local disease, extent of resection, and use of adjuvant chemotherapy, did not identify any prognostic variables for survival among the 28 patients. Patterns of recurrence revealed that the posterior fossa was the most common site (56%), followed by bone marrow (25%). Adult medulloblastoma appears to have a favorable prognosis after treatment with maximally surgically feasible resection followed by craniospinal irradiation. Optimal treatment remains to be clarified, as both standard-risk and poor-risk patients have prolonged disease-free survival. The marked difference between survival and progression-free survival suggests that salvage therapy, usually with combination chemotherapy in this cohort of patients, is of benefit. More formal analysis of the survival benefit was not possible, however, because of the small number of patients treated at recurrence with any one therapeutic regimen.

Adult↗

PubMed2001

Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer.

We report a case in which brain metastases originating from breast cancer responded to treatment with oral capecitabine. The metastases had progressed and Karnofsky performance status deteriorated despite whole brain irradiation, hormonal treatment, and systemic chemotherapy that included 5-fluorouracil (5-FU). In contrast, 2 months of treatment with oral capecitabine produced a partial response, documented by lesion size on magnetic resonance imaging and an improvement in performance status; both measures continued to improve during 11 months of capecitabine treatment.

Adult↗

PubMed2001

Co-expression of E2F-2 enhances the p53 anti-cancer effect in human glioma cells.

Gliomas are highly resistant to conventional treatment. Improved knowledge of the molecular defects of glioma cells offers new avenues for the development of gene therapy strategies. Transfer of the p53 gene has proven effective in suppressing proliferation in human glioma cell lines. However, several human glioma cell lines are resistant to p53-induced cell death. The E2F family of transcription factors are pivotal for the regulation of cell-cycle and cell-death related genes in gliomas. In the present study, we sought a more effective strategy for glioma treatment by examining the therapeutic potential of the simultaneous transfer of p53 and E2F-2 to gliomas. Trypan blue cell viability assays and flow cytometric cell-cycle analysis demonstrated that the transfer of both p53 and E2F-2 induced cell death in D-54 MG, a p53-resistant glioma cell line. In addition, transfer of E2F-2 did not interfere with the apoptotic properties of exogenous wild-type p53 in U-251 MG cells. Finally, the expression of E2F-2 in D-54 MG cells suppressed the expression of the apoptotic molecule mdm-2 induced by exogenous p53 in these cells. These results show that co-expression of E2F-2 and p53 enhances the anti-cancer effect of p53 in gliomas.

Actins↗

PubMed2001

Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines.

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an invasive human lung cancer cell line that produces high levels of uPAR, resulted in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the multiplicity of infection from 25 to 200 caused a corresponding decrease in the level of uPAR protein within 5 days of treatment, as shown by Western blot analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR-infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70% decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the levels in cells of mock and vector controls. The Matrigel invasion assay showed the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased by 70% relative to mock- and vector-infected controls. Infection of tumor cells with Ad-uPAR before implantation significantly reduced the incidence of lung metastasis by 85% as compared with the control virus-infected cells injected into nude mice through the tail vein. Our collective results show that the uPAR system is a potential target of treatment for lung cancers.

Adenoviridae↗

PubMed2001

Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells.

The diffuse and extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modifications of the proteolysis of extracellular matrix components. A key molecule in regulating plasminogen-mediated extracellular proteolysis is the urokinase-type plasminogen activator (uPA). To investigate the role of uPA in the invasive process of brain tumors, we stably transfected a human glioblastoma cell line SNB19 with a vector capable of expressing an antisense transcript complementary to the 1020 bases at the 3' end of the uPA cDNA. Parental, vector-, and antisense construct-stably transfected cell lines were analyzed for uPA mRNA transcript by Northern blot analysis, for uPA enzyme activity by zymography, and for uPA protein levels by Western blotting. The levels of uPA mRNA, protein, and enzyme activities were significantly lower in antisense clones than in parental and vector controls. Radioreceptor binding studies demonstrated that uPA receptor levels remained the same in parental, vector-, and antisense-transfected cells. The antisense-transfected cells showed a markedly lower level of invasion in the Matrigel invasion assays, and their spheroids failed to invade the fetal rat brain aggregates in the coculture system. Green fluorescent protein (GFP) expressing parental and antisense transfectants was generated for detection in mouse brain tissue without any posttreatment. Intracerebral injection of antisense stable transfectants significantly reduced tumor formation compared with that in controls. Our results suggested that down-regulation of uPA expression may be a feasible approach to reducing the malignancy and invasiveness of glial tumors.

Animals↗

PubMed2000

A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo.

Effective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues. In this study, we constructed a tumor-selective adenovirus, Delta24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses verified that this deletion rendered Delta24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the Delta24 adenovirus could replicate in and lyse cancer cells with great efficiency. Lysis of most human glioma cells was observed within 10 - 14 days after infection with Delta24 at 10 PFU/cell. In vivo, a single dose of the Delta24 virus induced a 66.3% inhibition (P<0.005) and multiple injections, an 83.8% inhibition (P<0.01) of tumor growth in nude mice. However, normal fibroblasts or cancer cells with restored Rb activity were resistant to the Delta24 adenovirus. These results suggest that the E1A-mutant Delta24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway.

Adenoviridae↗

PubMed2000

A reliability test of standard-based quantitative PCR: exogenous vs endogenous standards.

The quantitative measurement of gene expression requires consistent and reliable standards. At least two categories of standards, endogenous and exogenous, are currently used for quantitative PCR. The reliability of these two methods, however, has not been carefully compared. We hypothesized that a reliable quantitative PCR assay would be able to detect known dilutions of a given single-stranded (ss-) cDNA. By measuring VEGF ss-cDNA copy numbers or signal ratios of GAPDH/VEGF in 10x and 100x diluted samples of two original ss-cDNA preparations, an exogenous recombinant DNA standard (a VEGF-mimic plasmid) and an endogenously expressed GAPDH standard were tested for their ability to detect dilution factors. Using the recombinant DNA standard, the dilution factor was detected as 10.3 and 135.0 in 10x and 100x diluted samples of the original CaSki cell ss-cDNA, respectively. The detected dilution factors were 12.3 and 226.2, respectively, in 10x and 100x diluted ss-cDNA from U-251 MG cells. On the other hand, with the endogenous GAPDH standard, the dilution factors were detected as 2.7 and 8.0 in the same 10x and 100x dilutions of the original U-251 MG cell ss-cDNA. Using the same endogenous GAPDH standard, the detected dilution factors were both 4.8 in 10x and 100x dilutions of the original CaSki cell ss-cDNA. It was also found that the number of endogenous copies of GAPDH mRNA was about 1000 times higher than VEGF. The high internal lockup ratio of GAPDH vs VEGF copy numbers and the requirement for additional primer pairs make the use of an abundant endogenous standard an unreliable choice in quantitative or semi-quantitative PCR. In contrast, exogenous standard-based quantitative PCR was shown to be an accurate and reliable method for the quantitation of gene expression.

Central Nervous System Neoplasms↗

PubMed2000

Health-related quality of life in patients with anaplastic astrocytoma during treatment with temozolomide.

One of the objectives of this phase II study was to determine whether temozolomide (TMZ) improved the health-related quality of life (HRQL) of patients with recurrent anaplastic astrocytoma (AA). HRQL was assessed at baseline (pretreatment) and every 4 weeks at each treatment cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) (version 2.0) and the Brain Cancer Module (BCM20). Changes from baseline in the scores of seven preselected HRQL domains (role and social functioning, global QL, visual disorder, motor dysfunction, communication deficit and drowsiness) were determined at 6 months as well as prior to, and at the time of, disease progression. The significance of the changes was assessed by calculating statistical significance, effect sizes and the proportions of patients with improvement in their HRQL scores (changes of >/=10 points). After 6 months of treatment, patients who were free of progression of disease reported either an improvement or maintenance of all the preselected HRQL domains scores. Patients with disease progression by 6 months usually experienced improvement in HRQL before progression, but there was a sharp decline in most of the preselected domains at progression. We conclude that treatment of recurrent AA with temozolomide is associated with significant HRQL benefits.

Adult↗

PubMed2000

Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades.

Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB 19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.

Brain Neoplasms↗

PubMed2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

Adult↗

PubMed2000

Inhibition of cell growth in human glioblastoma cell lines by farnesyltransferase inhibitor SCH66336.

Ras activation occurs through stimulation of an upstream growth factor receptor such as epidermal growth factor receptor (EGFR). The ultimate effect of Ras is to induce nuclear transcription via a signaling pathway sequentially involving Raf, MAP kinase kinase (MEK), and mitogen-activated protein kinase (MAPK). To transform cells, Ras oncoproteins must be posttranslationally modified with a farnesyl group in a reaction catalyzed by farnesyl protein transferase. Farnesyltransferase inhibitors, therefore, have been proposed as potent anticancer agents. This study demonstrates the growth-inhibitory effects of farnesyltransferase inhibitor SCH66336 on human glioblastoma cell lines U-251 MG, U-251/E4 MG (a stably transfected cell line with elevated EGFR expression), and U-87 MG. As determined by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) and viability assays, the concentration required to achieve 50% inhibition (IC50) ranged from 30 microM (single 24-h treatment) to 10 microM (5-day treatment). U-251/E4 MG with overexpression of EGFR were more sensitive than U-251 MG parental cells. These observations were also supported by soft agar analysis. Cells treated with SCH66336 underwent G2 arrest. Western blot analysis revealed a decrease in phospho-MAPK levels upon treatment with 10 microM SCH66336, whereas MAPK levels were unaffected by the drug. Interestingly, increased expression of EGFR was observed in U-251 MG and U-251/E4 MG but not in U-87 MG in the presence of the inhibitor. These results demonstrate that SCH66336 inhibits viability and anchorage-independent growth in a time- and dose-dependent manner in glioblastoma cell lines U-251 MG, U-251/E4 MG, and U-87 MG via a signal transduction pathway involving the down-regulation of phospho-MAPK. Overexpression of EGFR appears to alter cellular sensitivity to farnesyltransferase inhibitors. This may have a particularly important implication in glioblastoma, where over 50% of tumors have amplification and overexpression of EGFR.

Alkyl and Aryl Transferases↗

PubMed2000

Effect of disease burden on health-related quality of life in patients with malignant gliomas.

The burden imposed by disease recurrence in patients with high-grade gliomas is not well documented. We studied the frequency of self-report symptoms and the effects on health-related quality of life in patients who had recurrent glioblastoma multiforme or anaplastic astrocytoma and who had a Karnofsky performance score > or = 70. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (QLQ-C30) and the Brain Cancer Module (BCM20) before initiation of treatment for first recurrence of disease. Six symptoms (fatigue, uncertainty about the future, motor difficulties, drowsiness, communication difficulties, and headache) were reported with a frequency > 50% by both groups of patients. An additional two symptoms (visual problems and pain) were also reported with frequencies of > 50% by patients with recurrent glioblastoma multiforme. Most of the symptoms were likely due to recurrence, but previous radiation therapy and on-going corticosteroid treatment may have also been casual factors for fatigue, whereas uncertainty about the future and pain were probably nonspecific for brain cancer. Problems with motor functioning, vision, leg strength, and pain were reported more frequently by patients with recurrent glioblastoma multiforme than by those with recurrent anaplastic astrocytoma. Scores on health-related quality-of-life functioning scales were similar in the two groups. Finally, the scores for patients who had recurrent high-grade gliomas and a Karnofsky performance score > or = 70 were compared with the reported health-related quality of life scores of patients with other cancers. Their scores were similar to those of patients with metastatic cancers and worse than those of patients with localized cancers.

Adult↗