Biomedical subjects

K Y Chen

Publications and source records attributed to K Y Chen.

At least 73 records · Page 4Linked to original sources

PubMed1997

Marked elevation of hypusine formation activity on eukaryotic initiation factor 5A in v-HA-RAS transformed mouse NIH3T3 cells.

Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor is ubiquitously present in eukaryotic cells and archebacteria. In this reaction, deoxyhypusine synthase catalyzes the conversion of one unique lysine residue on eIF-5A to deoxyhypusine using spermidine as the substrate. Hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Hypusine formation activity can be measured by an in vitro labeling technique in polyamine-depleted cells. In addition, an in vitro cross-labeling assay can be employed to measure simultaneously the relative deoxyhypusine synthase activity and protein substrate amount. Using these approaches, together with Western blot analysis, we showed that hypusine formation activity is serum-responsive and significantly elevated in Ras oncogene transfected NIH3T3 cells as compared to NIH3T3 cells. The large difference, >30-fold, in hypusine formation activity between these two cells is mainly due to difference in the amount of newly synthesized eIF-5A precursor rather than deoxyhypusine synthase. The deoxyhypusine synthase activity is about three-fold higher in Ras-3T3 cells than in 3T3 cells, and remains constant throughout serum stimulation in both cells. Despite the significant difference in eIF-5A protein amounts, the eIF-5A mRNA levels in 3T3 cells and in Ras-3T3 cells are almost identical. Furthermore, unlike serum-dependent increase in eIF-5A precursor protein, the eIF-5A mRNA in both cells is constitutively expressed after serum stimulation, suggesting that eIF-5A gene is regulated at posttranscriptional/translational level during serum stimulation and cell transformation.

3T3 Cells↗

PubMed1997

Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts.

Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (elF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on elF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27-32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of alpha-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (elF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15-23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46-54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and elF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the elF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of elF-5A precursor protein may be regulated at either translational or post-translational level.

Antineoplastic Agents↗

PubMed1997

Antisense oligonucleotides to corticotropin-releasing factor impair memory retention and increase exploration in rats.

Corticotropin-releasing factor is known as a stress peptide which stimulates adrenocorticotropin and corticosterone release. It also has a direct central effect to produce various behavioural activations in rats. In the present study, we have designed and studied the effects of an antisense oligonucleotide directed against the corticotropin-releasing factor gene in rats. Local injection of this antisense oligonucleotide into the hippocampus (1 nmol, five injections) significantly impaired the retention performance of an inhibitory avoidance task in rats. In another experiment, the same injection (1 nmol, four injections) also markedly increased rearing response and total distance travelled by rats in a novel activity chamber. Meanwhile, it markedly decreased grooming behaviour in rats. When directly injected into the hypothalamus in another group of animals (1 nmol, four injections), this antisense oligonucleotide significantly decreased the plasma adrenocorticotropin level. The effectiveness of these antisense oligonucleotide treatments was verified by a significant reduction in the level of corticotropin-releasing factor messenger RNA in specific brain regions as determined by quantitative reverse transcription polymerase chain reaction analysis. These results strengthen the importance of corticotropin-releasing factor in modulating memory processing and exploratory behaviour in rats. This work also provides an important tool for studying other physiological functions that corticotropin-releasing factor may mediate or modulate in mammals.

Adrenocorticotropic Hormone↗

PubMed1997

Mandibular odontogenic fibrosarcoma. Case report.

A rare case of mandibular odontogenic fibroma is presented which transformed to a stage 1A odontogenic fibrosarcoma with a local recurrence after surgical resection and unusually delayed pulmonary metastases eight years later. Prolonged follow-up of these patients after complete surgical resection, including regular chest X-rays, is recommended.

Adult↗

PubMed1997

Improving energy expenditure estimation by using a triaxial accelerometer.

In our study of 125 subjects (53 men and 72 women) for two 24-h periods, we validated energy expenditure (EE), estimated by a triaxial accelerometer (Tritrac-R3D), by using a whole-room indirect calorimeter under close-to-normal living conditions. The estimated EE was correlated with the measured total EE for the 2 days (r = 0. 925 and r = 0.855; P < 0.001) and in minute-by-minute EE (P < 0.01). Resting EE formulated by the Tritrac was found to be similar to the measured values [standard errors of estimation (SEE) = 0.112 W/kg; P = 0.822]. The Tritrac significantly underestimated total EE, EE for physical activities, EE of sedentary and light-intensity activities, and EE for exercise such as stepping (all P < 0.001). We developed a linear and a nonlinear model to predict EE by using the acceleration components from the Tritrac. Predicted EE was significantly improved with both models in estimating total EE, total EE for physical activities, EE in low-intensity activities, minute-by-minute averaged relative difference, and minute-by-minute SEE (all P < 0. 05). Furthermore, with our generalized models and by using subjects' physical characteristics and body acceleration, EE can be estimated with higher accuracy (averaged SEE = 0.418 W/kg) than with the Tritrac model.

Acceleration↗

PubMed1997

Serum responses to the combination of Epstein-Barr virus antigens from both latent and acute phases in nasopharyngeal carcinoma: complementary test of EBNA-1 with EA-D.

Elevated serum IgA to antigens of EBV is associated with nasopharyngeal carcinoma (NPC). We have tested 620 NPC sera by ELISA for the presence of antibodies to EBV-encoded DNA binding protein, EBV-specific DNA polymerase, early antigen-diffused (EA-D), EBV nuclear antigen 1 (EBNA-1), EBV-specific thymidine kinase, and BamHI Z fragment EBV replication antigen. Sensitivity of these proteins was in the range of 51.5-79.5% for IgA and 69.4-82.8% for IgG. The complementary use of EBNA-1 with EA-D, however, could increase the sensitivity significantly to 98.1%. Western blot analysis further showed that the combination of EBNA-1 and EA-D is most useful for the detection of NPC. This is the first report of using double biomarkers including EBV gene products from both latent and active infections. The results of this study suggest that EBV in NPC may not be latent alone and that the method may be valuable for the early detection, early treatment, and better survival rate of patients with NPC. Because the application of recombinant EBV protein in ELISA is cost-effective and feasible for mass screening, the method may be of worth for further clinical investigation.

Adult↗

PubMed1997

Detection of Epstein-Barr virus in primary cutaneous amyloidosis.

To determine the association of Epstein-Barr virus (EBV) with primary cutaneous amyloidosis (PCA), a retrospective study was conducted on skin tissue from 27 Chinese patients with lichen amyloidosus and macular amyloidosis. In situ hybridization with oligonucleotide probes was used to detect the expression of EBV-encoded RNAs (EBERs). Eleven of 27 cases (40.7%) were found to contain the EBV genome. No EBV genome was detected in the skin of the control groups, including three cases of secondary cutaneous amyloidosis, two cases of primary systemic amyloidosis, and four cases of lichen simplex chronicus. Our study showed no correlation between the presence of EBV in PCA patients and the patients' age, sex, clinical type or severity of the skin lesions. Although our results suggest that EBV may be associated with some cases of PCA, the true aetiological role of EBV in PCA remains unknown.

Adult↗

PubMed1997

Expression of DNA topoisomerase II alpha and multidrug resistance p-glycoprotein in acute leukemia.

BACKGROUND: Drug resistance is a major cause of treatment failure in acute leukemia. Overexpression of multidrug resistance gene and decreased activity of topoisomerase II alpha are suggested as two important mechanisms for this resistance. METHODS: We used immunohistochemical method to determine the expressions of both topoisomerase II alpha (topo II alpha) and p-glycoprotein (gp-170) in bone marrow biopsy specimens from 68 cases of acute leukemia. Patients were divided into four groups: (1) leukemia cells with high score for topo II alpha and negative for gp-170; (2) leukemia cells with high score for topo II alpha and positive for gp-170; (3) leukemia cells with low score for topo II alpha and negative for gp-170; and (4) leukemia cells with low score for topo II alpha and positive for gp-170. The clinical responses were then followed as routine, and the clinical correlation was evaluated by analysis of variance and Pearson Chi-Square test. RESULTS: The measure of the single parameter (either topo II alpha or gp-170 alone) did not show a significant difference in the overall survival. However, the complete response rate was much higher in the first group patients whose bone marrow reading score was high in topo II alpha and negative for gp-170 expression. Survival duration increased with the increase in the complete response rate. CONCLUSIONS: Combined parameters of topo II alpha and gp-170 are more useful than any individual parameter for the prognosis of acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72-74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/m2, 2 h infusion at day 1, followed by 5-FU 400 mg/m2/day, continously infused for 4 days was given concurrently during the first and fifth weeks of radiotherapy. RESULTS: The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1-4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up time of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far. CONCLUSIONS: Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradiation adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.

Adult↗

PubMed1996

Effects of inhibitors of deoxyhypusine synthase on the differentiation of mouse neuroblastoma and erythroleukemia cells.

Deoxyhpusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Polyamines (putrescine, spermidine, and spermine) have been implicated in tumor growth and differentiation. Because deoxyhypusine/hypusine formation is one of the most specific polyamine-dependent biochemical events, we decided to use N1-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor for deoxyhypusine synthase, to assess the role of hypusine formation on tumor growth and differentiation. GC7 suppressed the growth of N2a mouse neuroblastoma cells and DS19 murine erythroleukemia cells at micromolar concentrations. However, within a narrow concentration range, GC7 could promote the differentiation of mouse neuroblastoma cells in the presence of suboptimal amount of dibutyryl cAMP. In contrast, GC7 blocked the differentiation of DS19 cells induced with hexamethylene bisacetamide. Polyamine depletion by difluoromethyl ornithine (DFMO) has previously been shown to promote differentiation of neuroblastoma cells but inhibits erythrodifferentiation. Since our studies demonstrated that GC7 mimics the action of DFMO on tumor differentiation, it is likely that the effect of DFMO on tumor differentiation is mediated by hypusine formation and that GC7 represents a more specific inhibitor that can alter the differentiation program in certain tumor cells.

Animals↗

PubMed1996

Molecular cloning and functional expression of human deoxyhypusine synthase cDNA based on expressed sequence tag information.

Deoxyhypusine synthase is an NAD(+)-dependent enzyme that catalyses the formation of a deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor by transferring an aminobutyl moiety from spermidine to the epsilon-amino group of a unique lysine residue. We have recently cloned and characterized the Neurospora crassa deoxyhypusine synthase cDNA using a reverse genetics approach. A GenBank search showed that a stretch of the deduced amino acid sequence (96 amino acids) of Neurospora deoxyhypusine synthase matches a short human expressed sequence tag (EST), Z25337, with greater than 70% amino acid identity. Gene-specific primers based on this EST were used together with universal primers to obtain 1219 bp and 1078 bp cDNAs from a human cDNA library. The 1219 bp and 1078 bp sequences, each containing an open reading frame, encode polypeptides of respectively 368 and 321 amino acids. The short sequence is identical to the long one except that it is missing a stretch of 47 amino acids spanning residues 261-307. The 368-amino-acid sequence of human deoxyhypusine synthase shares a high degree of identity ( > 50%) and similarity ( > 60%) with that of the Neurospora and yeast deoxyhypusine synthases. After cloning into an expression vector, the 368-amino-acid recombinant protein exhibits high deoxyhypusine synthase activity. In contrast, the 321-amino-acid recombinant protein shows no detectable activity.

Amino Acid Sequence↗

PubMed1996

Regulation of dihydrofolate reductase gene expression and E2F components in human diploid fibroblasts during growth and senescence.

The induction of dihydrofolate reductase (DHFR), a key enzyme in DNA biosynthesis that is induced just before the onset of S phase, is markedly attenuated in senescent human fibroblasts (Pang and Chen, 1994, J. Cell. Physiol., 160:531-538). Footprinting analysis of the 365 bp promoter region of the human DHFR gene (-381 to -17) indicated that nuclear proteins bind to a cluster of cis-elements, including two overlapping E2F binding sequences, two Sp1 sites, and one Yi sequence. Gel mobility shift assays were performed to assess the role of each cis-element in the regulation of DHFR gene expression. We found that 1) Sp1 binding activity was constitutively expressed throughout the cell cycle in early passage and senescent cells; 2) Yi binding activity was undetectable in both early passage and senescent cells; and 3) E2F binding activity was serum-inducible, senescence-dependent, and prominent in presenescent cells but strikingly diminished in senescent cells. Northern blot analysis of the expression of E2F and DP family members showed that the E2F-1, E2F-4, and E2F-5 mRNA was growth- and senescence-dependent, whereas E2F-3, DP-1, and DP-2 expression was constitutive and senescence-independent. In contrast, E2F-2 mRNA was not detectable in IMR-90 or WI-38 human fibroblasts. Western blot analysis showed that among the E2F-associated proteins, the expression of E2F-1, cyclin A, and cyclin B but not p107 was cell cycle- and senescence-dependent. A nuclear extract mixing experiment suggested that an inhibitory factor may further reduce E2F binding activity in senescent cells.

Base Sequence↗

PubMed1996

Determination of the appropriate fraction number and size of the HDR brachytherapy for cervical cancer.

Based on the linear-quadratic model, we have made two isoeffect tables for transforming the traditional low dose rate (LDR) point A doses at 20, 30, 40, 50, 60, and 70 Gy to those of the high dose rate (HDR) dose per fraction. HDR fractions ranged from 1 to 12, with corresponding sizes for each fraction. We also propose the therapeutic gain ratio (TGR) method for determining the appropriate fraction number of HDR brachytherapy in cervical cancer. TGR is defined as addition of the calculated biological therapeutic difference with the supposed physical therapeutic difference of HDR brachytherapy. Through the TGR method, we predicted that after 2 to 3, 2 to 4, and 4 to 7 fractions of HDR treatments, the tumor control rate and complication rate would be equivalent to those of LDR point A doses of 30, 40, and 70 Gy, respectively. The TGR is affected by many factors, such as the equivalent total dose of LDR, dose rate of LDR, HDR fraction number, T1/2, and differences between LDR and HDR in the dose in critical organs. The TGR method might explain why a low fraction number of HDR can be used in clinical practice. We may use this principle to replace the traditional trial-and-error method for transcribing the relationship between LDR and HDR treatments.

Brachytherapy↗

PubMed1996

Fluorine-18 fluoromisonidazole tumour to muscle retention ratio for the detection of hypoxia in nasopharyngeal carcinoma.

In vivo demonstration of hypoxia is of significance for tumour patient management. Fluorine-18 fluoromisonidazole ([18F]FMISO) is a proven hypoxic imaging agent. We developed an [18F]FMISO tumour to muscle retention ratio (TMRR) for the detection of tumour hypoxia in nasopharyngeal carcinoma (NPC). Data were acquired by positron emission tomography (PET) of the nasopharynx and neck after intravenous injection of 370 MBq of [18F]FMISO. Two imaging protocols were adopted: a long protocol for comprehensive dynamic information and a short protocol for a simple, clinically convenient imaging procedure. Tomograms were reconstructed and evaluated visually. ROI analysis on the basis of time-activity curve evaluation was performed to calculate the TMRR of NPC or cervical nodal metastases (CNMs) in relation to the suboccipital muscles at 2 h. The calculation of the TMRR was exactly the same for both the long and the short protocol as two 30-min composite frames had been created immediately after intravenous injection and 2 h after injection of [18F]FMISO in the long protocol. The normal tissue to muscle retention ratio (NTMRR) was derived similarly from the normal nasopharynx. The data of 12 controls and 24 patients with NPC were analysed. The long protocol was used in 15 patients, and the short protocol in nine. In controls, the mean NTMRR+/-1 SD was 0.96+/-0.14. The mean TMRRs for NPC and CNMs were 2.56+/-1.50 and 1.35+/-0.51, respectively; these values were significantly higher than the mean NTMRR for normal controls (P<0.005 in each case). At the retention threshold value of 1.24, tumour hypoxia occurred in 100% of the primary lesions of NPC and 58% of CNMs. The TMRR for undifferentiated carcinoma was significantly lower than that for non-keratinized carcinoma (P<0.05). The [18F]FMISO TMRR is a simple and clinically useful index for detecting tumour hypoxia in NPC.

Carcinoma↗

PubMed1996

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole.

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodontitis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental caries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively. 18F-fluoride ion bone scan done in three patients showed that 18F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy.

Bacteria, Anaerobic↗

PubMed1996

Superscan in patients with nasopharyngeal carcinoma.

Bone scintigraphy plays an important role in the early detection of bone metastases in patients with nasopharyngeal carcinoma and serial scans may aid the clinician to assess the therapeutic response. A superscan is a pattern described as abnormal bone scan, indicating extensive bony metastases associated with various neoplastic diseases. Bone scans from 407 patients with nasopharyngeal carcinoma were reviewed retrospectively. Only six superscans (1.5%) were found. The appearance of a superscan is frequently accompanied by an abnormal titer of serological markers IgG-VCA and IgA-VCA, liver metastases, and poor survival. Although a superscan rarely occurs in nasopharyngeal carcinoma, its appearance may represent a poor prognosis in these patients.

Adult↗

PubMed1996

Interstitial iodine 125 in advanced recurrent squamous cell carcinoma of the head and neck with follow-up evaluation of carotid artery by ultrasound.

We retrospectively reviewed our experience with 24 patients in the treatment of advanced recurrent squamous cell carcinoma of the head and neck, using salvage surgery and intraoperative iodine 125 (125I) implantation. Surgical complications and survival results were compiled and compared with those of other studies. The long-term effect of 125I on the carotid artery was evaluated by ultrasound. We had a major complication rate of 21% and an overall complication rate of 50%. Our 2-year overall and determinate survivals were 29% and 50%, respectively. Within the survival group, carotid ultrasounds were obtained to evaluate the long-term effect of 125I. All ultrasounds obtained at least 1 year from the time of treatment showed minimal or no change from the contralateral side. We conclude that intraoperative 125I and salvage surgery are an acceptable treatment for recurrent squamous cell carcinoma with minimal complication and effect on the carotid artery.

Brachytherapy↗

PubMed1996

Whole body radiation exposure with gamma unit radiosurgery.

BACKGROUND: Stereotactic radiosurgery is the use of external radiation in association with a stereotactic device to precisely locate and destroy inaccessible deep-seated lesions within the brain in a single treatment session. Very little attention has been paid to the extracranial sites of radiation exposure measurements. This study evaluates the extracranial absorbed dose due to leakage and scattered radiation of the Gamma Unit used in radiosurgery. METHODS: The absorbed doses were measured with thermoluminescent dosimetry (TLDs). Single and multiple Gamma Unit treatment with the 18mm collimator helmet was given and a Rando tissue equivalent phantom was in place to simulate a patient treatment. TLDs were placed on the phantom to measure the absorbed doses by the organs at risk. Two TLD chips were placed at each of the following organs: eye, thyroid, sternum and gonads. The irradiated TLDs were read with a Vinten TLD system 654D. The TLD factor was determined by irradiating TLDs with a cobalt-60 teletherapy unit of a known dose of radiation. RESULTS: The average maximum target absorbed dose was 30 Gy. The measured absorbed dose in selected organs from Gamma Unit radiosurgery with one or more isocenters was 21-53 cGy for the eye, 4-8 cGy for the thyroid, 3-4 cGy for the sternum and 2-3 cGy for the gonads. The dose to extracranial sites increased with the number of isocenters. The radiation dose to extracranial sites became much more substantial when multiple isocenters were used. CONCLUSIONS: The potential risk of radiation exposure is radiation induced tumors. No cases have been reported in patients treated with Gamma Unit radiosurgery. Given the benefit of Gamma Unit treatment, the clinical significance of these doses is minimal.

Brain Neoplasms↗