Ga-67 visualization of the coexistence of two mucosa-associated lymphoid tissue (MALT) lymphomas in the thyroid and stomach.
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Adult↗
Biomedical subjects
D Yoshida
Publications and source records attributed to D Yoshida.
Relationship between ATP synthesis and 201Tl uptake in transformed and non-transformed cell lines.
201Tl tumour imaging is an established procedure, but little is known about its biological significance in transformed and non-transformed cells. In investigating the relationship between 201Tl uptake and intracellular ATP, we wished to determine whether the observed difference in delayed uptake is attributable to re-uptake via Na-K ATPase by using transformed (HeLa) and non-transformed (human fibroblast: hFB) cell lines. In each cell line, ATP was measured using the Luciferin-Luciferase method (LLM). The change in 201Tl uptake was assessed under conditions of mitochondrial suppression. Additionally, we assessed whether glycolysis is involved in 201Tl uptake under conditions of mitochondrial suppression and anaerobic incubation. Re-uptake via Na-K ATPase (HeLa vs hFB: 37.3 vs 24.2%) showed a clear difference in delayed uptake between HeLa and hFB. With HeLa, 201Tl uptake decreased biphasically with a reduction in ATP levels, whereas with hFB a linear correlation was evident. Despite the suppression of mitochondrial potential, a 5% glucose loading accelerated glycolysis with HeLa, and increased ATP (10.0 +/- 4.0%) and 201Tl uptake (16.2 +/- 3.0%). Conversely, neither ATP nor 201Tl uptake increased with hFB. Our results provide evidence that 201Tl uptake in transformed cells is related to enhanced glycolysis as well as mitochondrial ATP synthesis.
2,4-Dinitrophenol↗
Malignant fibrous histiocytoma in the parietal bone.
Malignant fibrous histiocytomas (MFHs) are mesenchymal tumors, usually arising in soft tissue of the extremities and are remarkably resistant to radiation and chemotherapy. A 45-year-old female presented with a rare case of MFH originating in the cranial bone manifesting as a lump in the left parietal region with no neurological abnormality. Neuroimaging revealed the presence of an osteolytic tumor in the left parietal bone invading into muscle and subdural region, penetrating through the dura. Selective external carotid angiography disclosed a marked tumor stain. Examination of the whole body excluded neoplastic disease elsewhere. The patient was treated by surgical excision, radiation, and two courses of multi-drug chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisolone. Since there is no established treatment against this malignancy, a longer follow-up is necessary to determine whether cure has been achieved.
Combined Modality Therapy↗
Subcellular distribution of thallium: morphological and quantitative study in rat myocardium.
UNLABELLED: The purpose of this study is to determine the subcellular distribution of thallium (SDTl) by electron microscopy and a newly designed fixation method that makes insoluble grains of Tl visible. METHODS: To obtain the high dose necessary for electron microscopic visualization, we employed TlCl instead of 201TlCl. EM was performed in fixed rat myocardium resected at 20 min (early phase) and 3 hr (delay phase) after intravenous injection of TlCl. To fix Tl in the cell, we used orthovanadate in our fixative. Atomic absorption spectroscopy (AAS) of Tl and quantification of subcellular distribution of 201Tl (SD201Tl) were studied to prove the propriety of our fixation. RESULTS: AAS detected Tl in the Tl-loaded specimen but not in the control, indicating that Tl was the origin of the grains observed in the former. In the early phase, numerous grains were observed in mitochondria, sarcoplasmic reticulum (SR), myofibrils, and nuclei, but no such grains were visible in controls. In the delay phase, grains were retained in mitochondria, SR and nuclei, but not in myofibrils. Electron microscopic SDTl(%) correlated with SD201Tl(%) calculated from isolated fractions. CONCLUSION: In both the early and delay phases, mitochondria are the major site of Tl and 201Tl uptake.
Animals↗
Estramustine in malignant glioma.
Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas.
Animals↗
Targeting microtubule-associated proteins in glioblastoma: a new strategy for selective therapy.
BACKGROUND: This report presents a summary of preclinical data concerning the use of estramustine, an antimicrotubule agent against human glioblastoma cells. The strategy for the investigation of estramustine is predicated on the unique affinity of this agent for microtubule-associated proteins (MAPs). METHODS: A series of laboratory investigations were used to demonstrate antiproliferative effects (MTT assay, colony forming assay, thymidine incorporation), cell cycle synchronization (flow cytometry), intracellular localization of binding sites (immunocytochemistry, electron microscopy), and activity in subcutaneous xenografts of human glioblastoma. RESULTS: Estramustine has potent in vitro activity against human glioblastoma cells and can enhance the cytotoxic effects of ionizing radiation. Estramustine-binding protein was abundantly expressed in glioblastoma cells and may contribute to the selective effects of estramustine on neoplastic cells. This agent has activity against subcutaneous xenografts of human glioblastoma. Synthesized novel estrogen carbamates also can inhibit proliferation of glioblastoma cells. CONCLUSIONS: Cytoskeletal elements (MAPs) of glioblastoma cells may provide a useful target for therapy with agents like estramustine because of the potent antimitotic effects of this agent and its affinity to a protein that is expressed in glioma cells. These observations have stimulated a search for other estrone carbamates with antimitotic activity that exceeds more conventional antimicrotubule agents.
Animals↗
A prospective evaluation of the safety and efficacy of methohexital in the emergency department.
A prospective observational study in an inner-city teaching hospital was conducted to evaluate the safety and efficacy of intravenous methohexital (MTX) in the emergency department (ED). Pulse oximetry, vital signs and Glasgow Coma Scale (GCS) scores were recorded serially for 30 minutes after the administration of MTX to 76 adult patients. Likert scales of 1 to 5 were used to record the physician's assessment of the adequacy of sedation and the patient's assessments of recall and pain of the procedure. Patients received an average of 88 +/- 21 mg of MTX for a variety of indications (orthopedic procedures, 78%; sedation for other procedures, 14%; intubation, 5%; and psychiatric interview, 3%). No patient had clinically significant changes in heart rate or blood pressure. Eight (10.5%) had apnea, although only one patient had oxygen saturations of less than 90%. Each episode was brief and easily managed with bag-valve-mask ventilation. Risk factors for apnea included a history of alcoholism (P = .0003) and recent recreational narcotic use (P = .0139). Patients were maximally sedated in an average of 37 +/- 42 seconds. In the subset of initially alert patients, GCS scores decreased from 15 at baseline to 5.9 +/- 4.5. The physician's assessment of the adequacy of sedation was excellent (4.7 +/- 0.7). Patients reported little recall (1.3 +/- 0.9) or pain (1.3 +/- 0.8). It was concluded that MTX caused clinically insignificant changes in hemodynamics or oxygenation, although respiratory depression did occur; significant respiratory depression was brief and easily managed. MTX provided rapid and excellent levels of sedation with little or no patient recall or pain.
Adult↗
In vitro inhibition of cell proliferation, viability, and invasiveness in U87MG human glioblastoma cells by estramustine phosphate.
OBJECTIVE: Several determinants of cell motility are highly dependent on the cytoskeleton, in particular, microtubules. To our knowledge, there have been no previous reports regarding the anti-invasive ability by an antimicro-tubule agent, estramustine phosphate (EMP), on glioblastoma cell lines. We investigated the modulated cell proliferation and invasiveness by EMP in vitro. METHODS: We determined the relative survival rate by cell proliferation assay and the percent survival fraction by monotetrazolium assay. Furthermore, an invasion index was used to quantify the migrating and invasive potential of the human glioblastoma cell line, U87MG, in Boiden's chamber with reconstituted basement membrane (Matrigel; Collaborative Research, Lexington, MA). RESULTS: We found that 0.5 mumol/L EMP had no effect in any of the assays. Concentrations of 1, 5, and 10 mumol/L demonstrated a concentration- and time-dependent depression in all of the assays. A range of drug concentration of EMP, 1 to 10 mumol/L, in which cell invasiveness was successfully inhibited, was comparable with antiproliferative capacity. CONCLUSION: The data add to the findings that EMP not only offers selective antiproliferative activity against glioblastoma but also reduces invasiveness, consistent with its main mechanism of action. Such findings form the basis for the development of agents that use non-DNA targets for the treatment of glioblastomas and may improve control over tumor proliferation and invasion.
Antineoplastic Agents, Alkylating↗
Spontaneous intraventricular hemorrhage caused by lateral ventricular meningioma--case report.
A 39-year-old female presented with acute intraventricular hemorrhage manifesting as sudden onset of headache associated with gradually progressing somnolence and left oculomotor nerve paresis. Intraventricular hemorrhage occurred from a meningioma of the lateral ventricle. Computed tomography and magnetic resonance (MR) imaging revealed intraventricular hemorrhage and a mass in the right trigone. The tumor was totally removed. Her postoperative course was uneventful except for left homonymous hemianopia. The histological diagnosis was fibroblastic meningioma. The MR imaging was highly suggestive of hemorrhage from the tumor periphery.
Adult↗
Copper chelation inhibits tumor angiogenesis in the experimental 9L gliosarcoma model.
To investigate the effects of copper (Cu)-depletion diet and D-penicillamine treatment (CDPT) on both tumor growth and angiogenesis, we studied Fischer-344 rats in which 9L gliosarcoma cells had been subcutaneously implanted. We focused primarily on the alteration of Cu contents and the vascular density. Compared with the normal diet group, the CDPT group showed a significant reduction of tumor weight and a decrease in Cu concentration. Furthermore, the CDPT group demonstrated smaller blood vessels with significantly lower vascular density. This decrease of tumor growth was achieved by angiosuppression. Our study indicated that CDPT selectively caused Cu chelation from the tumor tissue; the normal brain tissue did not show lower Cu concentration after the treatment. The prevention of tumor angiogenesis by this method may be very useful in cancer therapy and may help elucidate the microenvironmental mechanisms for cancer cells.
Animals↗
Suppression of tumor growth in experimental 9L gliosarcoma model by copper depletion.
The effect of copper (Cu) depletion on the growth of tumors was investigated in a rat brain tumor model. 9L gliosarcoma cells were injected subcutaneously in 5-week-old male Fischer-344 rats. The control group (n = 18) received a normal diet throughout the experiment and the depletion group (n = 18) received a Cu-deficient diet starting 3 weeks prior to tumor implantation, and 2 mg of D-penicillamine orally, once daily, on the 3 days before and after implantation. Six animals from each group were killed at 1, 2, and 3 weeks following the implantation to measure the tumor weights and determine the tissue Cu concentration by atomic absorption spectrophotometry. The tumor weights increased much more rapidly in the control than in the depletion group. The Cu concentrations in tumor tissue of the depletion group were significantly lower than in the control group. There was no statistical significance in Cu concentration in the brain tissues of the control and depletion groups. Our study indicated that a Cu-deficient diet and D-penicillamine treatment can inhibit subcutaneous glioma growth in this rat model.
Animals↗
Dual-isotope SPECT of skull-base invasion of head and neck tumors.
UNLABELLED: Skull-base invasions of head and neck tumors were examined by simultaneous bone and tumor dual-isotope SPECT (S-SPECT) with 99mTc-hydroxy-methylene-diphosphonate (99mTc-HMDP) and 201Tl-chloride. The effectiveness and reliability of tumor diagnosis by this method was the primary interest in this study. METHODS: Before S-SPECT imaging, a phantom experiment using dried skull-bone specimens was performed to establish anatomical details of the skull base with the SPECT camera. Radionuclide crosstalk, window widths and control patients were also examined prior to S-SPECT imaging. Twenty patients with suspected tumor invasion of the skull base underwent S-SPECT. RESULTS: Preliminary experiments revealed that crosstalk effects could be disregarded with adequate window width and routine administrative doses of the radionuclides. S-SPECT detected bone destruction and the extent of tumor invasion for all 12 patients in whom skull-base involvement was diagnosed by CT or MRI. For the three patients in whom CT or MRI revealed no tumor invasion, the S-SPECT images did not show any abnormal accumulation in similar regions. In the remaining five patients without CT and MRI confirmation of skull-base invasion, the S-SPECT findings showed skull-base abnormalities in three. Tumor invasion was confirmed surgically or by clinical follow-up. The remaining two patients had negative S-SPECT images. CONCLUSION: S-SPECT is an effective and reliable diagnostic technique for detecting tumor invasion in the complex bony regions of the skull base.
Adult↗
Estramustine sensitizes human glioblastoma cells to irradiation.
Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G2-M consistent with its known effects on the mitotic spindle and potentially could be used as a radiation enhancer. We determined the effects of estramustine on the cell cycle of glioblastoma cells by flow cytometry. These findings were compared with clonogenic survival in cells pretreated with varying concentrations of estramustine prior to irradiation. These experiments indicated that 24 h treatment with 1 microM estramustine had no effect on the percentage of G2-M cells and did not enhance the cytotoxic effects of radiation while 10 microM estramustine increased the G2-M fraction by 100% associated with a potentiation factor as high as 8.5 and a relative radiation sensitivity at 70% cytotoxicity of 5.2 compared with 15.4 for control cells. Estramustine can be administered p.o. on a daily schedule with minimal systemic toxicity. These data suggest that estramustine may be an effective radiation enhancer for glioblastoma.
Brain Neoplasms↗
Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes.
Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine accumulates in glioma cells, resulting in a concentration-dependent inhibition of proliferation. We have shown that estramustine treatment results in a rapid inhibition of deoxyribonucleic acid synthesis (within 4 h) in human glioblastoma cells associated with an alteration of cell size and shape, consistent with its known antimicrotubule activity. To extend these findings, we performed an immunohistochemical analysis of microtubules with a monoclonal antibody to beta-tubulin, using a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to measure the antimitotic effects of estramustine on both human glioblastoma and astrocyte cultures. Within 4 hours, estramustine (10 mumol/L) caused a dramatic alteration in the tubulin staining in glioma cells, characterized by a disorganization in microtubules. Cell shape and microtubule staining in astrocytes were relatively preserved. Estramustine had a concentration-dependent cytotoxic effect in tumor cultures, whereas it had no effect on astrocyte viability at any concentration. Differences in the antimitotic effects do not appear to be related to variations in proliferation rates among these different types of cells. These data suggest that although estramustine is a potent inhibitor of proliferation in glioblastoma cells, it has modest antiproliferative effects on astrocytes and its selective activity is closely correlated with its antimicrotubule properties.
Astrocytes↗
[Evaluation of arterial infusion chemotherapy for advanced gallbladder cancer using implantable port].
Seven patients with advanced gallbladder cancer were treated by arterial infusion chemotherapy. Five patients had unresectable tumor, and two had liver metastases after resection of primary tumor. The response rate was 42.9% (3 PR), and the 1-year survival rate was 35.7%. No severe side effect was found. We conclude that arterial infusion chemotherapy is effective for advanced gallbladder cancer, and that a more effective regimen and adjuvant therapy should be established.
Aged↗
Suppression of 9L gliosarcoma growth by copper depletion with copper-deficient diet and D-penicillamine.
Trace element such as Cu and Zn have important chemical and biological properties. Recently, tissue Cu and Zn concentrations have been correlated with prognosis in selected malignancies. In addition, depletion of trace metals has suppressive effects on tumor growth in experimental rat models. We measured tissue levels of Cu and Zn and investigated the inhibitory effects on tumor growth in a rat brain tumor model by the Cu-depletion. 9L gliosarcoma cells were injected subcutaneously in 24 anesthetized 5 week old male Fischer-344 rats. Control animals (n = 12) were given a normal diet throughout the experiment and hypocupremic rats (n = 12) were given a Cu-deficient diet beginning 3 weeks before and after tumor implantation, and administered 2 mg of D-Penicillamine peri os., once daily, 3 days before and after implantation. At the time of sacrifice, samples were taken to measure tumor weights. To determine tissue Cu and Zn levels, atomic absorption spectrophotometry was used. Cu, Zn and Cu/Zn ratio were significantly higher in control tumors than brain tissues. Cu levels and Cu/Zn ratio were significantly lower in hypocupremic tumors than those in control tumors. Zn levels in hypocupremic tumors were significantly higher than control tumors. Our study indicated that Cu depletion by a Cu-deficient and D-Penicillamine reduced Cu concentration and Cu/Zn ratio in a tumor model with reduction of tumor weight. A metabolic approach that restricts Cu to alter the microenvironment within the cell must become a new horizon of cancer therapy.
Animals↗
Quantitative analysis of copper, zinc and copper/zinc ratio in selected human brain tumors.
Serum copper and zinc concentrations and copper/zinc ratios have been shown to be increased in several types of human malignancies, including human brain tumors. In this study, copper and zinc levels and copper/zinc ratios were determined by atomic absorption analysis in tissue and serum from 29 primary and metastatic brain tumor patients. Metastatic carcinomas and malignant gliomas revealed significantly higher tissue copper concentrations than control tissues and meningiomas. Malignant gliomas demonstrated significantly higher tissue copper/zinc ratios. Both serum copper and copper/zinc ratio were significantly higher in the metastatic carcinoma group than control; however, serum copper levels in malignant glioma patients were not significantly different from control tissues. There were no differences both in the serum and the tissue concentrations of these trace elements in meningiomas and controls. These data suggested that copper, an important angiogenic factors, is accumulated within the malignant tissues of metastatic carcinoma and malignant glioma, but not meningiomas. These findings may have implications regarding angiogenesis in these tumors.
Brain Neoplasms↗
Intracranial fibromyxoma in a four-year-old child.
A case of an intracerebral fibromyxoma in a 4-year-old female with a developing left hemiplegia is described. Primary intracranial benign fibrous tumors are rare. A review of the relevant patients in the literature revealed 12 other cases. The management of this patient and an analysis of reported cases are presented.
Brain Neoplasms↗