PubMed Health⌕ Search

Biomedical subjects

David W Andrews

Publications and source records attributed to David W Andrews.

At least 19 recordsLinked to original sources
PubMed2007

The C-terminus of cytochrome b5 confers endoplasmic reticulum specificity by preventing spontaneous insertion into membranes.

The molecular mechanisms that determine the correct subcellular localization of proteins targeted to membranes by tail-anchor sequences are poorly defined. Previously, we showed that two isoforms of the tung oil tree [Vernicia (Aleurites) fordii] tail-anchored Cb5 (cytochrome b5) target specifically to ER (endoplasmic reticulum) membranes both in vivo and in vitro [Hwang, Pelitire, Henderson, Andrews, Dyer and Mullen (2004) Plant Cell 16, 3002-3019]. In the present study, we examine the targeting of various tung Cb5 fusion proteins and truncation mutants to purified intracellular membranes in vitro in order to assess the importance of the charged CTS (C-terminal sequence) in targeting to specific membranes. Removal of the CTS from tung Cb5 proteins resulted in efficient binding to both ER and mitochondria. Results from organelle competition, liposome-binding and membrane proteolysis experiments demonstrated that removal of the CTS results in spontaneous insertion of tung Cb5 proteins into lipid bilayers. Our results indicate that the CTSs from plant Cb5 proteins provide ER specificity by preventing spontaneous insertion into incorrect subcellular membranes.

Amino Acid Sequence↗
PubMed2006

tBid elicits a conformational alteration in membrane-bound Bcl-2 such that it inhibits Bax pore formation.

During initiation of apoptosis, Bcl-2 family proteins regulate the permeability of mitochondrial outer membrane. BH3-only protein, tBid, activates pro-apoptotic Bax to release cytochrome c from mitochondria. tBid also activates anti-apoptotic Bcl-2 in the mitochondrial outer membrane, changing it from a single-spanning to a multispanning conformation that binds the active Bax and inhibits cytochrome c release. However, it is not known whether other mitochondrial proteins are required to elicit the tBid-induced Bcl-2 conformational alteration. To define the minimal components that are required for the functionally important Bcl-2 conformational alteration, we reconstituted the reaction using purified proteins and liposomes. We found that purified tBid was sufficient to induce a conformational alteration in the liposome-tethered, but not cytosolic Bcl-2, resulting in a multispanning form that is similar to the one found in the mitochondrial outer membrane of drug-treated cells. Mutations that abolished tBid/Bcl-2 interaction also abolished the conformational alteration, demonstrating that a direct tBid/Bcl-2 interaction at the membrane is both required and sufficient to elicit the conformational alteration. Furthermore, active Bax also elicited the Bcl-2 conformational alteration. Bcl-2 mutants that displayed increased or decreased activity in the conformational alteration assay showed corresponding activities in inhibiting pore formation by Bax in vitro and in preventing apoptosis in vivo. Thus, there is a strong correlation between the direct interaction of membrane-bound Bcl-2 and tBid with activation of Bcl-2 in vitro and in vivo.

Animals↗
PubMed2006

The structure of Escherichia coli signal recognition particle revealed by scanning transmission electron microscopy.

Structural studies on various domains of the ribonucleoprotein signal recognition particle (SRP) have not converged on a single complete structure of bacterial SRP consistent with the biochemistry of the particle. We obtained a three-dimensional structure for Escherichia coli SRP by cryoscanning transmission electron microscopy and mapped the internal RNA by electron spectroscopic imaging. Crystallographic data were fit into the SRP reconstruction, and although the resulting model differed from previous models, they could be rationalized by movement through an interdomain linker of Ffh, the protein component of SRP. Fluorescence resonance energy transfer experiments determined interdomain distances that were consistent with our model of SRP. Docking our model onto the bacterial ribosome suggests a mechanism for signal recognition involving interdomain movement of Ffh into and out of the nascent chain exit site and suggests how SRP could interact and/or compete with the ribosome-bound chaperone, trigger factor, for a nascent chain during translation.

Escherichia coli↗
PubMed2006

Bcl-XL is qualitatively different from and ten times more effective than Bcl-2 when expressed in a breast cancer cell line.

BACKGROUND: Bcl-2 and Bcl-XL are anti-apoptotic paralogues that inhibit apoptosis elicited by a wide variety of stimuli, and play critical roles in cancer development and resistance to treatment. Many clinical studies have indicated that expression of these anti-apoptotic proteins in tumours is associated with poor prognosis. It has therefore been assumed that in cells the essential difference between Bcl-2 and Bcl-XL involves regulation of expression and that they are otherwise functionally similar. To examine this issue, we have compared the function of the proteins and of mutants of Bcl-2 and Bcl-XL specifically targeted to different subcellular sites. METHODS: We generated clones of the human breast cancer line MCF-7 stably expressing known amounts of Bcl-2, or Bcl-XL as determined by quantitative immunoblotting. Clones expressing equivalent amounts of wild-type and mutants of Bcl-2 and Bcl-XL with subcellular localization restricted to the cytoplasm, endoplasmic reticulum or outer mitochondrial membrane were studied in both MCF-7 and Rat-1 fibroblasts. In MCF-7 cells we measured the functional activities of these proteins in preventing apoptosis induced by four different agents (doxorubicin, ceramide, thapsigargin, TNF-alpha). Etoposide and low serum were used to compare the effect of Bcl-2, Bcl-XL and mutants located at the endoplasmic reticulum on induction of apoptosis in fibroblasts. RESULTS: We noted both qualitative and quantitative differences in the functional activity of these two anti-apoptotic proteins in cells: Bcl-2 localized to the endoplasmic reticulum inhibits apoptosis induced by ceramide and thapsigargin but not by doxorubicin or TNFalpha, while Bcl-XL at the endoplasmic reticulum is active against all four drugs. In fibroblasts Bcl-2 localized to the ER did not prevent cell death due to etoposide whereas Bcl-XL in the same location did. Finally in MCF-7 cells, Bcl-XL is approximately ten times more active than Bcl-2 in repressing apoptosis induced by doxorubicin. This difference can be manifest as a large difference in clonal survival. CONCLUSION: When examined in the same cellular context, Bcl-2 and Bcl-XL differ substantially in the potency with which they inhibit apoptosis, mediated in part by differences in the inhibition of specific subcellular pathways.

Animals↗
PubMed2006

Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase 1.

The involvement and potential interdependence of inositol trisphosphate (IP3) receptors and Bcl-2 in the regulation of Ca2+ signaling is not clear. Here, we have explored the mechanism(s) of how Bcl-2 suppresses the IP3-sensitive Ca2+ release in MCF-7 cells focusing on the possible role of protein phosphatase 1 (PP1). We found that through influences on protein-protein interaction, Bcl-2 may alter the balance between the effects of phosphatase (PP1) and kinase (PKA) on the IP3 R1 signaling complex. Using various experimental approaches including phosphatase inhibition and RNAi, we show that Bcl-2 by competing with IP3R1 for the binding of PP1 can reduce the IP3-mediated calcium signal and protect cells from mitochondrial dysfunction and cell death.

Adenosine Triphosphate↗
PubMed2006

Bcl-2 changes conformation to inhibit Bax oligomerization.

Bcl-2 inhibits apoptosis by regulating the release of cytochrome c and other proteins from mitochondria. Oligomerization of Bax promotes cell death by permeabilizing the outer mitochondrial membrane. In transfected cells and isolated mitochondria, Bcl-2, but not the inactive point mutants Bcl-2-G145A and Bcl-2-V159D, undergoes a conformation change in the mitochondrial membrane in response to apoptotic agonists such as tBid and Bax. A mutant Bcl-2 with two cysteines introduced at positions predicted to result in a disulfide bond that would inhibit the mobility of alpha5-alpha6 helices (Bcl-2-S105C/E152C) was only active in a reducing environment. Thus, Bcl-2 must change the conformation to inhibit tBid-induced oligomerization of integral membrane Bax monomers and small oligomers. The conformationally changed Bcl-2 sequesters the integral membrane form of Bax. If Bax is in excess, apoptosis resumes as Bcl-2 is consumed by the conformational change and in complexes with Bax. Thus, Bcl-2 functions as an inhibitor of mitochondrial permeabilization by changing conformation in the mitochondrial membrane to bind membrane-inserted Bax monomers and prevent productive oligomerization of Bax.

Animals↗
PubMed2006

Auto-activation of the apoptosis protein Bax increases mitochondrial membrane permeability and is inhibited by Bcl-2.

Interactions among Bcl-2 family proteins mediated by Bcl-2 homology (BH) regions transform apoptosis signals into actions. The interactions between BH3 region-only proteins and multi-BH region proteins such as Bax and Bcl-2 have been proposed to be the dominant interactions required for initiating apoptosis. Experimental evidence also suggests that both homo- and hetero-interactions are mediated primarily by the BH3 regions in all Bcl-2 family proteins and contribute to commitment to or inhibition of apoptosis. We found that a peptide containing the BH3 helix of Bax was not sufficient to activate recombinant Bax to permeabilize mitochondria. However, an extended peptide containing the BH3 helix and additional downstream sequences activated Bax to permeabilize mitochondria and liposomes. Bcl-2 inhibited the membrane-permeabilizing activity of peptide-activated Bax. This activity of Bcl-2 was inhibited by the extended but not the BH3-only peptide despite both peptides binding to Bcl-2 with similar affinity. Further, membrane-bound Bax activation intermediates directly activated soluble Bax further permeabilizing the membrane. Bcl-2 inhibited Bax auto-activation. We therefore propose that Bax auto-activation amplifies the initial death signal produced by BH3-only proteins and that Bcl-2 functions as an inhibitor of Bax auto-activation.

Animals↗
PubMed2006

A review of 3 current radiosurgery systems.

BACKGROUND: Stereotactic radiosurgery and fractionated stereotactic radiotherapy have become widespread techniques applied to the treatment of a variety of intracranial lesions. Rapid evolution of new technologies has now enabled clinicians to treat tumors outside the cranium and down the spinal axis. This review compares 3 commercially available systems in widespread use throughout the world. METHODS: Literature review and interviews with practitioners in the United States were performed to establish data for a comparative analysis of the Gamma Knife (Elekta, Sweden), Novalis (BrainLabs, Germany), and CyberKnife systems (Accuray, Sunnyvale, CA). Cost analyses were deliberately excluded because of the need for detailed cost-benefit analysis beyond the scope of the review. RESULTS: An unbiased comparative analysis was not possible because of the lack of objective data from a standard metric for these systems. Despite this shortcoming, disparate features of each system were compared and contrasted. CONCLUSION: A careful assessment of each system, including its operational features, capabilities, and yearly capacity must be weighed against the composition of the radiosurgery team, the case mix of the practice, and the objectives of the clinical unit to yield the best fit.

Brain Diseases↗
PubMed2005

Glycerol rhizotomy versus gamma knife radiosurgery for the treatment of trigeminal neuralgia: an analysis of patients treated at one institution.

BACKGROUND: Medically refractory trigeminal neuralgia (TN) has been treated with a variety of minimally invasive techniques, all of which have been compared with microvascular decompression. For patients not considered good surgical candidates, percutaneous retrogasserian glycerol rhizotomy (GR) and gamma knife (GK) radiosurgery are two minimally invasive techniques in common practice worldwide and used routinely at Jefferson Hospital for Neuroscience. Using a common pain scale outcomes questionnaire, we sought to analyze efficacies and morbidities of both treatments. METHODS AND MATERIALS: Between June 1994 and December 2002, 79 patients were treated with GR and 109 patients underwent GK for the treatment of TN. GR was performed with fluoroscopic guidance as an overnight inpatient procedure. GK was performed using a single 4-mm shot positioned at the root exit zone of the trigeminal nerve. Radiation doses of 70-90 Gy prescribed to the 100% isodose line were used. Treatment outcomes including pain response, pain recurrence, treatment failure, treatment-related side effects, and overall patient satisfaction with GK and GR were compared using a common outcomes scale. Using the Barrow Neurologic Institute pain scale, patients were asked to define their level of pain both before and after treatment: I, no pain and no pain medication required; I, occasional pain not requiring medication; IIIa, no pain and pain medication used; IIIb, some pain adequately controlled with medication; IV, some pain not adequately controlled with medication; and V, severe pain with no relief with medication. We used posttreatment scores of I, II, IIIa, and IIIb to identify treatment success, whereas scores of IV and V were considered treatment failure. Results were compiled from respondents and analyzed using SAS software. Statistical comparisons used log-rank test, univariate and multivariate logistic regression, Fisher's exact test, and Wilcoxon test with significance established at p < 0.05. RESULTS: There were 63 evaluable GK patients and 36 evaluable GR patients. The median follow-up time was 34 and 29 months for the GR and GK groups, respectively. The median age was 69 and 70 years and the median number of years with TN pain was 6 and 7 years in the GR and GK groups, respectively. Thirty-one GR (86%) and 58 GK (92%) patients achieved a successful treatment outcome (p = 0.49). The median time to pain relief was < or = 24 h in the GR group and 3 weeks in the GK group (p < 0.001, ordinal logistic regression). Nineteen GR and 26 GK patients experienced pain recurrence or pain never relieved (p = 0.30). The median time to pain recurrence was 5 and 8 months in the GR and GK groups, respectively (p = 0.22). At last follow-up, however, a statistically significant greater number of GR vs. GK patients had failed treatment. Twelve or 33% of GR patients, whereas 8 or 13% of GK patients, had BNI scores of 4 or 5 (p = 0.019, Fisher's exact test). When both initial and late treatment failures were combined, the overall rate of treatment failures was 39% in the GR group and 24% in the GK group (p = 0.023, log-rank). More GR patients developed facial numbness and facial numbness morbidity than GK patients: 19 GR (54%) and 17 GK patients (30%) developed new facial numbness and 12 GR and 7 GK patients reported either somewhat or very bothersome facial numbness (p = 0.018). On multivariate analysis, only treatment with GK and severity of pain before treatment significantly predicted treatment response. GK patients were more likely to have a lower pain score at last follow-up than were GR patients (p = 0.005, OR = 4.3), and patients with pretreatment pain scores of 5 were more likely to have lower posttreatment pain scores than patients with pretreatment pain scores of 4 and lower (p = 0.003, OR = 4.0). CONCLUSION: Despite greater facial numbness morbidity and a higher failure rate, GR provided more immediate pain relief than GK. GR therefore should be considered in patients with disabling trigeminal pain requiring urgent pain relief. For all other patients, GK provides better long-term pain relief with less treatment-related morbidity, and should therefore be considered the preferred treatment for patients with medically refractory trigeminal neuralgia who are not suitable candidates for microvascular nerve decompression.

Aged↗
PubMed2005

Glioblastoma patients exhibit circulating tumor-specific CD8+ T cells.

PURPOSE: There is growing interest in developing cellular immune therapies for glioblastoma multiforme, but little is known about tumor-specific T-cell responses. A glioblastoma multiforme-specific T-cell assay was developed using monocyte-derived dendritic cells to present tumor antigens from the established glioblastoma multiforme cell line U118. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells (PBMC) and tumor cells were obtained from nine patients with newly diagnosed brain tumors: five glioblastoma multiforme, two oligodendroglioma, one ependymoma, and one astrocytoma. PBMCs were incubated overnight with autologous tumor cells or autologous dendritic cells loaded with a U118 cell lysate, and responses were detected by IFN-gamma ELISPOT and cytokine flow cytometry assays. RESULTS: PBMCs from all glioblastoma multiforme patients exhibited IFN-gamma responses to autologous tumor but not to HLA-mismatched U118 cells. Glioblastoma multiforme-specific IFN-gamma responses were primarily mediated by CD8+ T cells and represented approximately 2% of total CD8+ T cells. Additionally, all glioblastoma multiforme patients responded to autologous dendritic cells loaded with U118 lysate but not with low-grade astrocytoma cell lysates. PBMCs from four patients with other brain tumor types and one normal donor failed to respond to U118 lysate-loaded autologous dendritic cells. These data indicate that the IFN-gamma responses to U118 lysate-loaded autologous dendritic cells are glioblastoma multiforme specific. Moreover, PBMCs stimulated 1 to 2 weeks with U118 lysate-loaded dendritic cells exhibited MHC class I-restricted cytotoxicity against autologous tumor cells. CONCLUSIONS: Glioblastoma multiforme patients exhibit circulating tumor-specific CD8+ T cells that recognize shared tumor antigens from the glioblastoma multiforme cell line U118. These data show that glioblastoma multiformes are immunogenic and support the development of immunotherapy trials.

Adult↗
PubMed2005

Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis.

Bax promotes cell death by permeabilizing mitochondrial outer membranes by an unresolved mechanism. However, in cells lacking the gene c-myc, membrane permeabilization by Bax is blocked by changes in the mitochondria that prevent Bax oligomerization. Drug-treated c-myc null cells and cells expressing Myc were used to map the topology of Bax in membranes prior to and after mitochondrial permeabilization. Chemical labeling of single cysteine mutants of Bax using a membrane bilayer impermeant cysteine-specific modifying agent revealed that Bax inserted both the 'pore domain' (helices alpha5-alpha6), and the tail-anchor (helix alpha9) into membranes prior to oligomerization and membrane permeabilization. Additional topology changes for Bax were not required in Myc-expressing cells to promote oligomerization and cytochrome c release. Our results suggest that unlike most pore-forming proteins, Bax membrane permeabilization results from oligomerization of transmembrane monomers rather than concerted insertion of the pore domains of a preformed oligomer.

Apoptosis↗
PubMed2005

Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas.

OBJECTIVE: To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) after surgery in the management of residual or recurrent nonfunctioning pituitary adenomas with respect to tumor control and the development of complications. METHODS AND MATERIALS: The clinical records of patients with nonfunctioning pituitary adenomas who underwent FSRT were retrospectively analyzed. For newly diagnosed tumors, transsphenoidal surgery was performed, and, if residual tumor was identified at 3 months, FSRT was performed. If significant tumor volume persisted, transcranial surgery was performed before FSRT. We originally initiated FSRT with 2-Gy fractions to 46 Gy. We escalated the dose to 50.4 Gy thereafter. As a final modification, we dropped the daily dose to 1.8-Gy fractions delivered within 6 weeks. High-dose conformality and homogeneity was achieved with arc beam shaping and differential beam weighting. The radiographic, endocrinologic, and visual outcomes after FSRT were evaluated. RESULTS: The 68 patients included 36 males and 32 females with an age range of 15-81 years. The median follow-up was 30 months (range, 2-82 months), and the median tumor volume was 6.2 cm(3). Of the 68 patients, 20 were treated to 46 Gy and 48 to 50-52.2 Gy. Most were treated to 50.4 Gy. Eleven patients had recurrent tumors, 54 had residual tumors, and no surgery was performed in 3 patients before FSRT. We noted no radiation-induced acute or late toxicities, except for radiation-induced optic neuropathy in 2 patients. At latest follow-up, the tumor had decreased in size in 26 patients and remained stable in 41 of the 42 remaining patients. Of the 68 patients, 4 (6%) developed hypopituitarism at 6, 11, 12, and 17 months after FSRT. Reviewing available serial Humphrey visual fields, visual fields were objectively improved in 28 patients, and remained stable in 24 patients, and worsened in 2 patients. CONCLUSION: The findings of this analysis support the use of surgery followed by FSRT as a safe, effective, and integrated treatment for nonfunctioning pituitary adenomas. Additional follow-up is needed to document the long-term tumor control rates, preservation rates for vision and pituitary function, and neurocognitive outcomes.

Adenoma↗
PubMed2005

N-glycosylation at one rabies virus glycoprotein sequon influences N-glycan processing at a distant sequon on the same molecule.

Rabies glycoprotein (RGP(WT)) contains N-glycosylation sequons at Asn(37), Asn(247), and Asn(319), although Asn(37) is not efficiently glycosylated. To examine N-glycan processing at Asn(247) and Asn(319), full-length glycosylation mutants, RGP(-2-) and RGP(--3), were expressed, and Endo H sensitivity was compared. When the Asn(247) sequon is present alone in RGP(-2-), 90% of its N-glycans are high-mannose type, whereas only 35% of the N-glycans at Asn(319) in RGP(--3) are high-mannose. When both sequons are present in RGP(-23), 87% of the N-glycans are of complex type. The differing patterns of Endo H sensitivity at sequons present individually or together suggests that glycosylation of one sequon affects glycosylation at another, distant sequon. To explore this further, we constructed soluble forms of RGP: RGP(WT)T441His and RGP(--3)T441His. Tryptic glycopeptides from these purified secreted proteins were isolated by HPLC and characterized by a 3D oligosaccharide mapping technique. RGP(WT)T441His had fucosylated, bi- and triantennary complex type glycans at Asn(247) and Asn(319). However, Asn(247) had half as many neutral glycans, more monosialylated glycans, and fewer disialylated glycans when compared with Asn(319). Moreover, when comparing the N-glycans at Asn(319) on RGP(--3)T441His and RGP(WT)T441His, the former had 30% more neutral, 28% more monosialylated, and 33% fewer disialylated glycans. This suggests that the N-glycan at Asn(247) allows additional N-glycan processing to occur at Asn(319), yielding more heavily sialylated bi- and triantennary forms. The mechanism(s) by which glycosylation at one sequon influences N-glycan processing at a distant sequon on the same glycoprotein remains to be determined.

Animals↗
PubMed2005

Regulation of Ca2+-induced permeability transition by Bcl-2 is antagonized by Drpl and hFis1.

The regulation of mitochondrial permeability transition (MPT) is essential for cell survival. Un-controlled opening of the MPT pore is often associated with cell death. Anti-death protein Bcl-2 can block MPT as assessed by the enhanced capacity of mitochondria to accumulate and retain Ca2+. We report here that two proteins of the mitochondrial fission machinery, dynamin-related protein (Drp1) and human mitochondrial fission protein (hFis1), have an antagonistic effect on Bcl-2. Drp1, with the assistance of hFis1, sensitizes cells to MPT by reducing the mitochondrial Ca2+ retention capacity (CRC). While the reduction of CRC by Drp1/hFis1 is linked to mitochondrial fission, the antagonism between Bcl-2 and Drp1 appears to be mediated by mutually exclusive interactions of the two proteins with hFis1 . The complexity of protein-protein interactions demonstrated in the present study suggests that in addition to the previously described role of Bcl-2 in the control of apoptosis, Bcl-2 may also participate directly or indirectly in the regulation of mitochondrial fission.

Animals↗
PubMed2005

Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques.

OBJECTIVE: Patients with brain metastases were analyzed retrospectively to assess the risks and benefits of surgery with modern neurosurgical techniques, including image guidance coupled as indicated with corticography. METHODS: We retrospectively analyzed charts of patients treated surgically for brain metastases. We identified patients with single or multiple brain metastases who underwent craniotomies to reverse associated neurological symptoms or establish a diagnosis. We assessed patients according to recursive partitioning analysis (RPA) prognostic groups as well as functional grades of tumor location (eloquent versus noneloquent, Grades I-III). Perioperative complications, neurological outcomes after surgery, survival, and prognostic factors were analyzed. Statistical analysis of survival was performed with the Kaplan-Meier method. A P value of <0.05 was considered statistically significant. RESULTS: Two hundred eight patients were treated between March 1995 and December 2002. Patient age ranged from 31 to 82 years (median, 59 yr). One lesion was resected in 191 patients, and of 76 patients with multiple lesions, two or more metastases were resected in 17 patients. Tumors were located in eloquent cortex in 27 patients and near eloquent cortex in 124 patients. Four patients died within 30 days after surgery for a mortality rate of 1.9%. Neurological deterioration was noted in 13 patients (6%) after surgery for Grade I and II tumors and in 5 patients (19%) of 27 patients with Grade III tumors. Karnofsky Performance Scale scores were improved (68 patients) or unchanged (124 patients) in 192 patients and worse in 16 patients after surgery. The median survival time (MST) from the date of surgery was 8 months for all patients and 9 months for 163 patients who did not undergo prior whole-brain radiation therapy. There was no difference in survival between patients operated for single metastasis (MST, 8 mo) versus patients with two or three metastases (MST, 9 mo; P = 0.9364). By both univariate and multivariate analysis, variables significantly affecting outcome included a high Karnofsky Performance Scale score and RPA Class I assignment. By univariate analysis, significant treatment variables included postoperative radiotherapy and postoperative chemotherapy. The MSTs of RPA Class I, II, and III patients were 16.1 months, 7.2 months, and 1.4 months, respectively (P < 0.001, log-rank test). These survival data compare favorably with the stereotactic radiosurgery boost arm of the recently published Radiation Therapy Oncology Group 9508 trial. CONCLUSION: In most patients with single or multiple brain metastases, surgical resection reversed or stabilized neurological symptoms with therapeutic benefit, conveying a notable survival advantage without apparent increased risk, particularly in RPA Class I patients. In patients with Grade III single metastasis or RPA Class II multiple metastasis, surgical judgment should be exercised, and stereotactic radiosurgery boost treatment may be preferable. An algorithm for treatment of brain metastases is proposed.

Adult↗