Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. 28 patients [14 males and 14 females] aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks [mean +/- SD=15.22 +/- 7.8].64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. [Over all response to therapy was 85.7%]. The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved

Production, quality control and biological evaluation of [153]Sm-EDTMP in wild-type rodents

Nowadays various bone pain palliative therapeutic agents have been developed for bone metastases. Among those, [153]Sm-ethylenediamine tetramethylene phosphonic acid [[153]Sm-EDTMP] is the major therapeutic agent which is widely used in the world. In this study, production, quality control and biodistribution studies of this therapeutic radiopharmaceutical have been presented and followed by imaging studies in a wild-type rabbit for the first time in order to make preparations for this agent to be officially approved in the country. [153]Sm-EDTMP was produced using [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized EDTMP in 4h at 100°C. The analytical data for the structure determination and purity of the ligand was obtained and shown to be identical to an authentic sample from a European vendor. The Radiochemical purity of [153]Sm-EDTMP was checked by RTLC and ITLC. The biodistribution of [153]Sm-EDTMP in wild-type rodents was checked and SPECT imaging as well as following sacrificing the animal. The radiolabeled Sm complex was prepared in high radiochemical purity [>99%, RTLC] followed by initial biodistribution data with the significant bone accumulation [>70%] of the tracer in 48h which is comparable with the reported methods. The produced [153]Sm-EDTMP properties suggest good potential for efficient use of this radiopharmaceutical for bone pain palliation and as substitute for other agents, such as [89]SrCl[2] and [32]P, currently used in the country

Effectiveness of radiation synovectomy with samarium-153 particulate hydroxyapatite in rheumatoid arthritis patients with knee synovitis: a controlled randomized double-blind trial

OBJECTIVES: The aim of the present study was to investigate the effectiveness of Samarium153-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid arthritis patients (60 knees) with chronic knee synovitis participated in a controlled double-blinded trial. Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group) or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium153-particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0) and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness, flexion, extension, knee circumference, Likert scale of improvement, percentage of improvement, SF-36 generic quality of life questionnaire, Stanford Health Assessment Questionnaire (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral corticosteroids, events and adverse effects, calls to the physician, and hospital visits. RESULTS: The sample was homogeneous at baseline, and there were no withdrawals. Improvement was observed in both groups in relation to T0, but no statistically significant differences between groups were observed regarding all variables at the time points studied. The Sm/TH group exhibited more adverse effects at T1 (p<0.05), but these were mild and transitory. No severe adverse effects were reported during follow-up. CONCLUSION: Intra-articular injection of Samarium153-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up.

Systemic Radionuclide Therapy of Painful Prostate Cancer Bone Metastases With Samarium-153-edtmp

Most patients with prostate cancer (PC) will develop painful bone metastases, which alters their quality of life. Objective: This study aimed to evaluate the efficacy and toxic hematological profile of samarium for the treatment of PC metastases’ bone pain. Methods: Twenty-nine PC patients (median age: 69 years, range: 46-84; Gleason score equal to or higher than 7 in 66.7% and under 7 in 33.3% of patients presenting multiple painful bone metastases were treated with intravenous injection of 153Sm-EDTMP. Response to treatment was defined as either a reduction of at least 25% in patient’s pain score, using a 0 to 10 scale (score 0: no pain, score 10: maximum pain), or in daily analgesic dosage. Complete blood counts were performed before 153Sm–EDTMP administration and 4 and 8 weeks after treatment with the purpose of evaluating hematological side effects of the agent. Results: Twenty-five patients (86.2%) responded to treatment (median time: 1.5 month, range: 1.0 to 2.0 months). A reduction equal to or higher than 25% in post-treatment values compared to baseline values was seen in hemoglobin (Hb) of 3 (12.0%) patients, in leukocytes (Lo) of 16 (64.0%) patients, and in platelets (Pl) of 19 (76.0%) patients. Hb under 10g/dl, Lo under 2.0x103/ul, and Pl under than 50.0x103/ul were seen in 7 (28.0%), 3 (12.0%) and 2 (8.0%) out of 25 patients analyzed after 153Sm–EDTMP, respectively. No infectious or bleeding episodes were seen in any patient during the study. Conclusion: 153Sm-EDTMP is effective for acute control of PC patients’ bone pain. However, additional studies with bone marrow assessment before and after 153Sm–EDTMP are necessary to clarify the origin of cytopenias found in our cases.

Radiolesão vascular como efeito deletério da braquiterapia intra-arterial com dose elevada de Samário-153 em coelhos hipercolesterolêmicos / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits

OBJETIVO: Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com Samário-153 (153 Sm) em coelhos hipercolesterolêmicos, com doses elevadas. MÉTODOS: Foram analisados 43 coelhos hipercolesterolêmicos, brancos, da raça New Zealand, e o total de 86 artérias ilíacas submetidas a lesão por balão de angioplastia. Divididos em três grupos: dois (GI) irradiados com as doses de 15Gy (n=14) e 60Gy (n=36) e um grupo controle (n=36). Foram realizadas avaliação histológica morfométrica e análise histológica qualitativa para análise tecidual. RESULTADOS: Foram observadas uma redução significativa da neoproliferação intimal (NPI) no GI 15 Gy (p<0,0001), uma redução da área de camada média (ACM) (p<0,0001) e por cento estenose (p<0,0001) comparada com os demais grupos. O GI 60 Gy teve o maior índice de PNI, aumento da ACM, AV e porcentagem de estenose. No GI 60 Gy, observou-se maior número de células xantomatosas (GI 60Gy:86,11 por cento e GI 15Gy:14,29 por cento, p<0,0001), tecido amorfo hialino (GI 60Gy:58,33 por cento e GI 15 Gy:0 por cento, p=0,0001) e proliferação vascular (GI60 Gy:30,56 por cento e GI15 Gy:0 por cento, p=0,0221). Outras análises teciduais não apresentaram diferença estatística entre os grupos. CONCLUSÃO: A dose elevada de 60Gy ocasionou intensa proliferação celular considerada radiolesão vascular, ao contrário da dose de 15Gy que apresentou excelente inibição da neo-proliferação intimal.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11 percent and 15-Gy IG: 14.29 percent, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33 percent and 15-Gy IG:0 percent, p=0.0001) and vascular proliferation (60-Gy IG:30.56 percent and 15-Gy IG:0 percent, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

Remarkable rate acceleration of SmI3-mediated iodination of acetates of Baylis-Hillman adducts in ionic liquid: facile synthesis of (Z)-allyl iodides / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Stereoselective transformation of Baylis-Hillman acetates 1 into corresponding (Z)-allyl iodides 2 has been achieved by treatment of 1 with samarium triiodide in THF. Remarkable rate acceleration of samarium triiodide-mediated iodination of 1 was found when ionic liquid 1-n-butyl-3-methyl-imidazolium tetrafluroborate ([bmim]BF(4)) was used as reaction media in stead of THF. This novel approach proceeds readily at 50 degrees C within a few minutes to afford (Z)-allyl iodides 2 in excellent yields. A mechanism involving stereoselective iodination of the acetates of Baylis-Hillman adducts by samarium triiodide is described, in which a six-membered ring transition state played a key role in the stereoselective formation of 2.

Study on the reactions of azo compounds with acyl halides mediated by Sm/TiCl4 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Amides can be obtained in good to excellent yield by Sm/TiCl(4) mediated reductive cleavage of N=N bond in azo compounds and successive acylation in one pot. It offers an alternative method for the synthesis of amides from very simple starting materials directly.

Synthesis, structure characterization and anti-tumor activity of lanthanide complex Ln (Phen)2 (5-Fu)3 (NO3) (NO3 )2 / 药学学报

<p><b>AIM</b>To study the biochemistry of lanthanides, the cooperative action of inorganic and organic anti-tumor drugs.</p><p><b>METHODS</b>A series of rare earth complexes were synthesized with Ln(NO3) 6H2O, Phen and 5-Fu. Their anti-tumor activity was measured by the improved MTT, SRB methods.</p><p><b>RESULTS</b>The formula of complex Ln[(Phen)2(5-Fu)3(NO3)](NO3)2(Ln = Y, La, Ce, Sm, Gd, Dy, Er; Phen = 1, 10-phenanthroline; 5-Fu = fluorouracil) was characterized by elemental analyses, molar conductivity, IR, TGA, and 13C NMR spectra. The preliminary biological activity studies indicated that Lanthanide complex has strong anti-tumor activity in vitro.</p><p><b>CONCLUSION</b>The complex might have anti-tumor cooperation action.</p>

Alterações histopatológicas associadas à braquiterapia intra-arterial com o samário-153 / Histophatologics changes associated to intraarterial brachytherapy with samarium-153

A lesão da parede arterial provocada por balão de angioplastia ou implante de próteses endovasculares em modelos experimentais e humanos pode provocar a reestenose do vaso, principalmente por migração e proliferação de células musculares lisas e síntese de matriz extracelular. Vários estudos demonstraram que a braquiterapia intra-arterial atua nestes fatores e, conseqüentemente, no tratamento da reestenose coronariana. Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com samário-153 (153Sm), utilizando uma dose considerada ideal e outra elevada em coelhos hipercolesterolêmicos. Foram analisados 43 coelhos hipercolesterolêmicos e um total de 86 artérias ilíacas submetidas à lesão por balão de angioplastia, divididos em três grupos, sendo irradiados com as doses de 15Gy (n = 14) e 60Gy (n = 36) e controle (n = 36). Foram realizadas análise morfométrica (área neo-intimal, área da camada média, área do vaso) e análise histológica qualitativa para avaliação tecidual. O colesterol médio foi de 1.362 ± 497mg/dl nos três grupos. O achado mais relevante foi uma significativa inibição da hiperplasia neo-intimal no grupo irradiado com a dose de 15Gy, maior do que o controle e com a dose de 60Gy. Na dose de 60 Gy, além de ineficaz para inibir a proliferação neo-intimal, teve características tissulares e estruturais sugestivas de radiolesão, como presença de células xantomatosas, tecidos hialino e amorfo, proliferação vascular. Estas células, bem como o aumento das dimensões morfométricas do vaso, foram proporcionais aos graus de lesão nas lâminas elásticas interna e externa, sendo observados principalmente com a dose de 60Gy. Os segmentos médios das artérias ilíacas, representando o local de maior contato com o balão, tiveram maiores alterações morfométricas e celulares em relação aos segmentos referenciais (proximal e distal) nos três grupos. Em conclusão, o grupo de artérias submetidas à irradiação de 15Gy foi eficaz para a inibição da proliferação neo-intimal. O grupo irradiado com a maior dose de 60Gy foi ineficaz para inibir a hiperplasia neo-intimal e apresentou características morfométricas e teciduais compatíveis com a radiolesão vascular.

comparative study of samarium-153-ethylenediaminetertramethylene phosphoric acid with pamidronate disodium in the treatment of patients with painful metastatic bone cancer

To assess the therapeutic efficacy and toxicity of samarium-153-ethylenediaminetetramethylene phosphonic acid [153Sm-EDTMP] and pamidronate disodium in patients with painful metastatic bone cancer. Subjects and Eighteen patients with histopathologically confirmed malignancy and multifocal bone metastases were randomized into two equal groups of 9 patients each. Group A was treated with 153Sm-EDTMP, while group B was treated with pamidronate disodium. The pain score for each patient was recorded before and after therapy using visual analogue scales that graded both the intensity and frequency of the bone pain. Therapeutic response was classified as inefficient, mild, effective and excellent. Pain score in each group prior to therapy was more than 6. In group A, 2 [22.2%] and 7 [77.8%] cases showed mild and effective response, respectively. The therapeutic efficacy of 153Sm-EDTMP was adjudged to be 77.8%. Transient myelosuppression was generally mild and reversible with white blood cells and platelets recovering after 6 weeks. In group B, palliative response in 4 cases [44.4%] was inefficient, in 1 case [11.1%] mild, in 3 cases [33.3%] effective and in 1 case [11.1%] excellent, with a therapeutic efficacy of 44.4% for pamidronate disodium. No hematological toxicity was noted. The data showed that the therapeutic efficacy of 153Sm-EDTPM was higher than that of pamidronate disodium [for pain relief maintained more than 3 weeks] and its incidence of blood toxicity was also higher than that of pamidronate disodium

Efeitos da braquiterapia intra-arterial com samário-153 sobre a neoproliferação intimal / Effects of intra-arterial brachytherapy with Samarium- 153 over intimal neoproliferation

Estudos experimentais e em humanos o balão de angioplastia pode levar à estenose pela migração e proliferação das células musculares lisas e a síntese de matriz extracelular. Estudos têm mostrado a ação da braquiterapia contra esses mecanismos. Nós desenhamos este estudo para avaliar a inibição do tecido de proliferação pelo Samário-153(153Sm). Quarenta e três coelhos hipercolesterolêmicos foram submetidos à lesão de ambas artérias ilíacas e separados em três grupos: com a dose de 15 Gy (n=14), com 60 Gy (n=36) e controle (n=36). A análise histológica morfométrica mostrou significante redução da neo-íntima com 15 Gy, quando comparado com os outros grupos. A dose de 60 Gy teve modificações estruturais e tissulares sugestivas de radiolesão.As previous demonstrated by experimental and human models, balloon dilation during angioplasty could lead to injury and stenosis due to smooth muscle cell migration and proliferation as well as extracellular matrix synthesis. Brachytherapy has been usefull against these factors. We pourposed was this study to evaluate neointimal tissue proliferation inhibition by Samarium-153 (153 Sm). Forty-three hypercholesterolemic rabbits underwent balloon injury in their both iliac arteries. They were separated into three groups: throught 15 Gy irradiation doses (n=14), 60 Gy (n=36) and control group (n= 36). Histopathologic and morphometric analysis showed a significant neointimal reduction with 15 Gy, comparing to others groups to control and 60 Gy dosis. The 60 y doses determined structure and tissue changes as the ones of radiation lesion...

Cáncer de mama y 153 Samario EDTMP / Breast cancer and Samarium 153 EDTMP

Objetivo: evaluar la toxicidad y eficacia terapéutica del Sm153 EDTMP en pacientes con cáncer de mama avanzado y dolor producido por metástasis óseas con reacción osteoblástica y su repercusión centellográfica y de laboratorio. Materiales y métodos: 54 pacientes (edad promedio: 62) con metástasis óseas y dolor con Samario en dosis de 0,5; 1 y 1,5 mCi/kg; 5 pacientes fueron retratadas. Se realizó control clínico y laboratorio al inicio, semanalmente durante el primer mes y luego mensualmente. Se correlacionaron centellografías óseas pre y post tratamiento. De las 54 pacientes, 21 (primer grupo) recibieron 0,5 mCi/kg; 29 (segundo grupo) 1 mCi/kg y 4 pacientes (tercer grupo) 1,5 mCi/kg. Resultados: la respuesta positiva al tratamiento se valoró mediante la atenuación o desaparición del dolor y la disminución del uso de analgésicos. El primer grupo tuvo una respuesta positiva del 76 por ciento, el segundo de 83 por ciento y el tercero de 75 por ciento. La duración de la respuesta varió entre 3 y 9 meses. La toxicidad más frecuente fue trombocitopenia y luego leucopenia, ambas fueron reversibles y presentaban relación directa a la dosis administrada. La correlación centellográfica muestra una disminución de la intensidad de fijación en las pacientes retratadas. Conclusiones: el uso de radiofármacos con afinidad ósea como el Sm resulta ser una alternativa, dada su eficacia y accesibilidad de costos. En nuestro grupo de pacientes tratadas con una dosis de 1 mCi/kg se alcanzó una respuesta del 83 por ciento sin mayor aaumento de la toxicidad, la cual fue reversible

Tratamiento paliativo del dolor óseo con samario-153-EDTMP en pacientes con cáncer / Palliative treatmen for bone pain with samarium-153-EDTMP in patients with cancer

El dolor óseo es una causa común de consulta médica y de predominio en la práctica oncológica. Los síntomas asociados con metástasis son comunes y contribuyen a una reducción importante en la calidad de vida de la población afectada. Recientemente se cuenta con un recurso terapéutico que consiste en la administración sistemática de radiofármacos que se concentran selectivamente en hueso. En un año atendimos nueve pacientes, ocho con cáncer de próstata y uno con cáncer de mama, con rango de edad de 46 a 80 años que cumplieron con los requisitos para recibir el tratamiento, consistente en la aplicación endovenosa de 0.75 milicuries de samario-153 por kilogramo de peso. A las 24 horas se realizó rastreo óseo para corroborar la concentración del radiofármaco en las lesiones blásticas. También se solicitó registro diario del dolor utilizando una escala de cero a 10, así como biometría hemática completa y determinación de antígeno prostático específico a las seis semanas. Los nueve pacientes tratados presentaron disminución del dolor, la cual se cuantificó en 80 por ciento con una duración media de tres meses y sin terapia con analgésicos. Consideramos que el samario-153 es una excelente alternativa para el tratamiento paliativo del dolor óseo, especialmente en aquellos pacientes en quienes han fallado otros esquemas terapéuticos

Uso de radioisótopos en metástasis óseas dolorosas: samario 153 EDTMP / Use of radioisotopes in painful bone metastasis: samarium 153 EDTMP

Los pacientes con dolor debido a metástasis óseas deben ser tratados por un equipo multidisciplinario. Los mecanismos de producción del dolor son poco conocidos y su fisiopatología es compleja, su evolución es progresiva y su manejo difícil. Entre las alternativas terapéuticas del dolor está el uso de isótopos radioactivos, que irradian al órgano blanco mediante emisión de partículas beta. Entre estos isótopos se encuentra el Samario153-EDTMP que está diponible en nuestro país y que tiene una bio distribución favorable y características fisioquímicas y de toxicidad aceptables para ser utilizado en metástasis principalmente osteoblásticas con alivio progresivo del dolor desde las primeras 48 horas y con una duración entre 4 a 35 semanas

Emprego do samário 153-EDTMP no tratamento do adenocarcinoma de próstata avançado. Resultados preliminares / The use of samarium 153-EDTMP for treatment of advanced prostatic adenocarcinoma

Introduçäo: Os autores analisam os efeitos do emprego endovenoso do Samário 153-EDTMP no tratamento de 35 pacientes portadores de adenocarcinoma de próstata refratário à hormonioterapia com metástases ósseas dolorosas. Material e métodos: Entre novembro de 1995 e março de 1998, 35 pacientes com metástase óssea de adenocarcinoma de próstata näo responsivo ao tratamento hormonal foram submetidos à aplicaçäo endovenosa do Samário 153-EDTMP (1,0 a 1,5 mCi/Kg de peso), com finalidade antiálgica. Sessenta porcento dos pacientes tinham pelo menos 20 metástases ósseas, 30 porcento usaram morfina e 68,5 porcento já haviam sido irradiados. Foram avaliadas a resposta à dor, a mielotoxicidade e os níveis de PSA após a aplicaçäo. Resultados: Verificou-se resposta completa à dor em 8 (24,2 porcento) e resposta parcial em 14 pacientes (42,4 porcento) dentre 33 pacientes avaliáveis, totalizando-se 66,6 porcento de resposta global à dor. O tempo de duraçäo de resposta variou de 30 a 60 dias nos casos de resposta completa e entre 20 a 90 dias nos casos de resposta parcial. A ocorrência de toxicidade medular ocorreu em 17 de 23 casos avaliáveis sendo predominantemente através de leucopenia e plaquetopenia sempre de regressäo espontânea, sendo que em nenhum caso a toxicidade foi letal. A queda parcial de PSA após a aplicaçäo ocorreu em 3 e a progressäo em 19 de 22 casos avaliáveis. O seguimento dos pacientes variou entre 7 e 903 dias (média 190 dias), com sobrevida global de 51,1 porcento aos 6 meses e de 20,9 porcento ao final de um ano. A sobrevida mediana foi de 6,2 meses. Conclusöes: Os resultados sugerem que o Samário é uma alternativa segura no tratamento paliativo do câncer de próstata hormônio refratário

A STUDY ON THE PHYSICAL PROPERTIES AND BIOLOGICAL CHARACTERISTICS OF DENTAL MAGNETIC ATTACHMENTS / 대한치과보철학회지

In order to investigate various physical and biological properties of dental magnetic attachments studies on retentive characteristics, corrosion properties, cytotoxicity of different magnetic systems for dental applications were done. For the study of retentive characteristics changes of retentive force by increasing air gap, wear properties of various attachment systems and loss of magnetic force by heat treatment were measured. For the study of corrosion property of magnet covering metal electrochemical corrosion was done in artificial saliva and 0.9% NaCl solution between -1,000 mVSCE and +1,000 mVSCE. Anodic polarization curves are obtained about 6 types of samples and 2 types of solution. Corroded surfaces were examined with metallurgical microscope, scanning electron microscope and surface profilometer. For the study of cytotoxicity of magnetic attachment and its field cell growth and agar overlay test were done. The results of this study were as follows. 1.In Magnetic attachments using closed circuit retentive force at zero air gap was greater than magnets using open circuit, but decrease of retentive force by increasing air gap was also greater than open systems. 2.After 40,000 cycles of wear test all mechanical attachment resulted in varing degree of retention loss but in magnetic attachments no loss of retentive force was observed. 3.The magnetic attachment using Neodymium magnet showed early loss of retentive force about 200degrees C but attachment using Samarium magnet showed some resistance to heat treatment and complete retention loss was observed about 500degrees C. The keeper was not influenced by heat treatment in retention. 4.In electrochemical corrosion test Dyna magnetic attachment covering metal showed the highiest corrosion resistance and Shiner magnet covering metal showed the least corrosion resistance and examination of corroded surface with metallurgical microscope, scanning electron microscope and surface profilometer also showed same results with anodic polarization curves. 5.The result of cell culture tests on the magnet covered with metal showed least recognizable cytotoxicity.

Respuesta analgésica y efectos secundarios en pacientes con metástasis osteoblásticas tratados con samario-153 etilendiaminotetrametilenfosfato / Samarium 153 EDTMP in the treatment of metastatic bone pain: evaluation of analgesic response and secondary effects

Background: Samarium153 EDTMP, a beta and gamma emitter, is used in the palliative therapy of painful bone metastases. Aim: To evaluate the analgesic effects and myelotoxicity of Samarium153 EDTMP in patients with prostate, breast and renal carcinoma. Patients and methods: Twenty patients with bone metastases (11 males), aged 65 years old as a mean, received a 1 to 2 mCi/kg intravenous dose of Samarium153 EDTMP, produced in Chile. Patients were followed thereafter during 4 to 40 weeks. Pain was assessed using a visual analogue scale. Results: Pain decreased from a score of 6.4 prior to treatment, to 2.7 at the fourth week of therapy and the effect lasted a mean of 12.5 weeks. Myelotoxicity was observed in 68percent of cases (WHO stage I in 21 percent, stage II in 37 percent, stage III in 11percent and no patients in stage IV). Platelets were the most affected series and neutrophils the least affected. Cell counts returned to normal between the sixth and eighth week. Seventy nine percent of patients decreased their basal analgesic therapy at the sixth week and 88percent did so at the eighth week. Forty one percent of these patients discontinued all analgesics. Conclusions: Samarium153 EDTMP is effective in the treatment of pain in patients with bone metastases and its myelotoxicity is low to moderate. It should be considered as a therapy for this type of pain, with the precaution of performing periodical bood counts