E. Valle Rodríguez
Full Text Available Introducción: El linfangioma es una malformación del sistema linfático. El abordaje clásico ha sido la cirugía. El OK-432 (Picibanil tiene acción esclerosante y se está utilizando cómo primer escalón terapéutico. El objetivo es aportar un nuevo caso de linfangioma tratado con OK-432 y hacer una revisión de la literatura. Material y método: Aportamos un varón de 16 años con un linfangioma cervical macroquístico de 10 x 6 cm tratado con una dosis de OK-432. Resultados: A las 16 semanas del tratamiento, el tamaño del linfangioma era de 6 x 2 cm, siendo clínicamente inapreciable. Discusión: El tratamiento con OK-432 tiene una alta tasa de curación, con una baja tasa de recidiva y una fibrosis circunscrita a la lesión. En relación con la cirugía, se evitan cicatrices y posibles lesiones de estructuras vitales.Introduction: Lymphangioma is a malformation of the lymphatic system. The classic approach is surgery. OK-432 (Picibanil has sclerosing action and is being used as the first therapeutic step. The objective was to report a new case of lymphangioma treated with OK-432 and to review the literature. Material and method: We report the case of a 16-year-old man with a 10x6-cm macrocystic cervical lymphangioma treated with a dose of OK-432. Results: At 16 weeks of treatment, the size of the lymphangioma was 6x2 cm and it was clinically unappreciable. Discussion: OK-432 treatment has a high cure rate, low recurrence rate, and fibrosis circumscribed to the lesion. Compared to surgery, scars and possible harm to vital structures are avoided.
Full Text Available The effect of Picibanil, a streptococcal agent, on the development of liver injury after operations for urogenital cancer was studied retrospectively in the light of serum alanine aminotransferase (ALT activity. The series comprised 32 cases receiving Picibanil and 33 controls with otherwise comparable clinical backgrounds. Picibanil reduced the incidence of postoperative ALT rise over 50 U/l within 6 weeks but increased it thereafter. The increase in ALT activity after 6 weeks was relatively small and was seen more often in patients given blood transfusions. It was interpreted as retardation and suppression of ALT rise and as being related to the induction of interferon or to immunopotentiation. Other antihepatotoxic effects of Picibanil, due to its antioxidant activity, for example, may also account for the prevention of the early postoperative rise in ALT activity.
Alonso, Juan; Barbier, Luis; Alvarez, Julio; Romo, Laura; Martín, Jesús C; Arteagoitia, Iciar; Santamaría, Joseba
Cervical cystic lymphangioma (CCL) is a rare and benign tumour involving congenital and cystic abnormalities derived from lymphatic vessels. The most accepted treatment continues to be surgical excision. However, when this infiltrates vital neurovascular neck structures, complete excision is difficult and if only partial, the recurrence rate is very high. The most frequently used alternative treatment is to inject sclerosants into the lesion. The use of these techniques has reported good results in children; however, there are few references thereof with regard to adults. We are reporting on a cervical cystic lymphangioma in a male aged 22, treated with an intra-lesion injection of 20 cc with 0.01 mg/cc dilution of OK-432 (picibanil) in physiological serum. Sole complications were fever and local reaction where the solution was injected. One month after treatment the lymphangioma had totally remitted and sixteen months later continues in remittance.
Mello-Filho Francisco V.
Full Text Available Introdução e Objetivo: O Linfangioma Cérvico-Facial (LCF é geralmente um tumor volumoso, envolvendo estruturas importantes da face e do pescoço. A terapia habitualmente recomendada é a retirada cirúrgica, porém, esta é geralmente seguida de seqüelas importantes, causando deformidade da região. Com o objetivo de avaliarmos uma terapêutica alternativa, analisamos a eficiência do Picibanil (OK 432 no tratamento de LCF em crianças. Forma de Estudo: Clínico retrospectivo. Material e Método: Estudo retrospectivo de seis crianças com diagnóstico de LCF tratadas com OK-432 no HCFMRP-USP no período de 1997 a 2001. Foram analisadas as seguintes características dos LCF: dimensões, tipos de cistos e volume aspirado. Avaliamos, também, o número de aplicações de OK 432 com os respectivos intervalos de tempo utilizados, sua evolução, intercorrências e o resultado final do tratamento. Resultados: Os LCFs apresentavam de oito a 15cm em seu maior diâmetro, na ocasião da primeira consulta, sendo o tipo de cisto mais freqüentemente encontrado o tipo macro cisto. O volume de liquido aspirado variou de dois a 60 ml e o número de aplicações de uma a cinco vezes em intervalos variáveis de um mês a um ano. Em todos os pacientes ocorreu regressão da massa tumoral, sendo que em três houve o desaparecimento total do LCF. A única intercorrência observada foi febre em media de 38.2º C em todos pacientes. Conclusão: O OK 432 é uma droga segura, eficaz e que pode ser utilizada como medida de primeira escolha no tratamento do LCF.
Wada, Hisashi; Isobe, Midori; Kakimi, Kazuhiro; Mizote, Yu; Eikawa, Shingo; Sato, Eiichi; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Yamasaki, Makoto; Miyata, Hiroshi; Matsushita, Hirokazu; Udono, Heiichiro; Seto, Yasuyuki; Yamada, Kazuhiro; Nishikawa, Hiroyoshi; Pan, Linda; Venhaus, Ralph; Oka, Mikio; Doki, Yuichiro; Nakayama, Eiichi
We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule. Nine patients were immunized with 0.25 mg each of three 30-mer and a 32-mer long NY-ESO-1 OLP mixed with 0.2 KE Picibanil OK-432 and 1.25 mL Montanide ISA-51. The primary endpoints of this study were safety and NY-ESO-1 immune responses. Five to 18 injections of the NY-ESO-1 OLP vaccine were well tolerated. Vaccine-related adverse events observed were fever and injection site reaction (grade 1 and 2). Two patients showed stable disease after vaccination. An NY-ESO-1-specific humoral immune response was observed in all patients and an antibody against peptide #3 (121-150) was detected firstly and strongly after vaccination. NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients.
Kakimi, Kazuhiro; Isobe, Midori; Uenaka, Akiko; Wada, Hisashi; Sato, Eiichi; Doki, Yuichiro; Nakajima, Jun; Seto, Yasuyuki; Yamatsuji, Tomoki; Naomoto, Yoshio; Shiraishi, Kenshiro; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Oka, Mikio; Pan, Linda; Hoffman, Eric W; Old, Lloyd J; Nakayama, Eiichi
We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients. Copyright © 2011 UICC.
徐茂磊; 张艳丽; 周玲; 张静; 姚庆收; 杨小平
目的 评估OK432作为佐剂制备的内皮细胞疫苗体内抗肿瘤转移的作用.方法 以OK432为佐剂,体外混合人脐静脉内皮细胞(HUVEC),制备HUVEC-OK432疫苗.雄性健康BALB/c小鼠尾静脉注射肝癌细胞5×105建立肝癌肺转移模型,皮下注射HUVEC-OK432疫苗,分别在预防性和治疗性免疫中评价HUVEC-OK432疫苗抗肿瘤转移活性;皮内注射5×104肝癌细胞建立皮内肿瘤血管模型,皮下注射HUVEC-OK432疫苗,评价HUVEC-OK432疫苗抑制肿瘤新生血管的活性;采用ELISA的方法测定小鼠免疫血清中HUVEC抗体水平;采用细胞毒T淋巴细胞(CTL)实验考察HUVEC-OK432疫苗诱导的细胞免疫应答水平.结果 肺转移模型结果显示,在预防性和治疗性免疫中,HUVEC-OK432免疫均能有效降低小鼠肺上的肿瘤转移灶数目(P＜0.01);皮内肿瘤血管模型的结果显示,HUVEC-OK432免疫能显著降低肿瘤新生血管的数目(116.5±20.6 vs 45.0±8.9,P＜0.01);ELISA测定抗体的结果显示,HUVEC-OK432初次免疫后1周小鼠即产生了高滴度的特异性HUVEC抗体,随免疫次数的增加抗体水平不断升高,且该抗体在体外可以显著抑制HUVEC细胞的增殖;CTL实验的结果表明,HUVEC-OK432免疫组淋巴细胞体外有明显的特异性杀伤HUVEC的作用.结论 HUVEC-OK432疫苗免疫可以有效诱导小鼠产生靶向内皮细胞的免疫应答,从而有效抑制小鼠肝癌细胞转移.
Andersen, Peter Stemann; Petersen, Bodil Laub; Juul, Anders
, and sclerotherapy with Picibanil (OK-432) was attempted without any detectable effect on size. The mass was later excised. The pathological examination revealed mammary gland tissue suggestive of idiopathic gynecomastia. FISH revealed 47, XXY mosaicism in the abnormal breast epithelial cells, but not in peripheral...
Miyauchi, M; Murata, M; Fukushima, A; Sato, T; Nakagawa, M; Fujii, T; Koseki, N; Chiba, N; Kashiwazaki, Y
Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a potent adjuvant and has been shown to possess antitumor activity in many non-clinical and clinical studies. As there are no approved BCG-CWS formulations for cancer therapy, we investigated the potential for cancer immunotherapy of SMP-105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we compared the effects of drakeoland squalane-based SMP-105 emulsions on IFN-γ production in rats and evaluated their ability to induce skin reaction in guinea pigs. Both emulsions had the same activity in both experiments. We selected squalane as base material and produced two types of squalane-based formulations (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water emulsions. Although the vialed emulsion showed the same pattern of distribution as a usual homogenized emulsion, the pumped emulsion showed more uniform distribution than the other two emulsions. Whereas both emulsions enhanced strong delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped emulsion induced slightly smaller edema. Data on oil droplet size distribution suggest that few micrometer oil droplet size might be appropriate for oil-in-water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was stronger than that of some of the launched toll-like receptor (TLR) agonists (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited antitumor effectiveness, while Immunobladder had almost the same effect as SMP-105 at the highest dose, but needed about 10 times the amount of SMP-105. These findings first indicate that SMP-105 has great potential in cancer immunotherapy.
Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y
To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.
Bund, Dagmar; Buhmann, Raymund; Gökmen, Füsun; Kremser, Andreas; Dreyssig, Julia; Kolb, Hans Jochem; Schmetzer, Helga Maria
Animal-models are the basis of DC-based human immunotherapies. We describe the standardization of a canine-DC-generation protocol using different cytokines and characterize the quality and functional repertoire of the obtained canine-DCs. DCs were generated from healthy dog-PBMCs under serum-free and serum-containing conditions. DC-quality and -quantity was determined by FACS studying the expression-profiles of DC-/costimulatory- and maturation-antigens before/after culture with canine and human monoclonal-antibodies (cmabs/hmabs). Individual DCAgs-(DC-antigens)-expression-profiles were found before and after culture depending on the agents' mode-of-action. With at least one of three serum-free methods (Ca-Ionophore, Picibanil, Cytokines) sufficient DC-amounts were generated. So, canine-DCs can be regularly generated under serum-free conditions and hmabs additionally to cmabs qualify for staining/quantification of canine-cells/DCs. The canine-DCs were functional, shown by T-cell-activation, -proliferation and antigen-specific CTL-responses. In summary, successful, quantitative DC-generation is possible with serum-free methods. DC-based T-cell-vaccination-strategies evaluated for e.g. AML-patients can be tested in the dog and estimated in clinical studies for DC-vaccination-strategies.
Park, Kwang Hwan; Lee, Jongseok; Choi, Woo Jin; Lee, Jin Woo
The purpose of this study was to evaluate the clinical outcomes and usefulness of OK-432 (Picibanil) sclerotherapy as a new option in the conservative treatment of patients with malleolar bursitis of the ankle. Retrospectively, we reviewed a total of 20 consecutive patients (20 feet) in whom OK-432 sclerotherapy had been performed between March 2009 and June 2010. After aspiration of fluid in the malleolar bursal sac, 0.05 mg of OK-432 was injected into the malleolar bursal sac. We evaluated the clinical outcomes and side effects at the following time points: 2 weeks, 1 month, 3 months, 6 months, and 1 year after OK-432 sclerotherapy. The responses to the treatment were assessed according to the degree of fluctuation, shrinkage of the bursal sac, and soft tissue swelling. Complete resolution was observed in 19 patients (95%) after the first or second application of OK-432 sclerotherapy, and a partial response was observed in 1 patient (5%) after a second application of OK-432 sclerotherapy. The physical component scores of SF-36 improved from 70.0 ± 6.8 to 76.5 ± 7.3 at the last follow-up (P = .0002). OK-432 sclerotherapy was a useful procedure for patients not responding to the usual conservative treatment of malleolar bursitis of the ankle. Level IV, retrospective case series.
Full Text Available La escleroterapia convencional con esclerosantes líquidos se utiliza desde hace muchos años en el tratamiento de las malformaciones vasculares venosas, linfáticas y de bajo flujo, siendo eficaz sólo en aquéllas de reducido tamaño como complemento pre o postoperatorio. El uso de esclerosantes líquidos tiene la limitación de la dilución e inactivación progresiva en un gran volumen hemático, de la irregular distribución del esclerosante sobre el endotelio, del manejo del esclerosante una vez inyectado y de su imperceptibilidad al eco-Doppler. A su vez, tanto el etanol como el morruato sódico -esclerosantes más habitualmente utilizados- producen importantes efectos secundarios. Por el contrario, la utilización de esclerosantes, concretamente polidocanol, en microespuma mejora significativamente el procedimiento, ya que la microespuma desplaza la sangre en lugar de mezclarse y diluirse con ella, facilita un reparto homogéneo del esclerosante sobre la superficie endotelial, y finalmente la ecogenicidad de las microburbujas, que la hacen directamente visible junto con su consistencia manejable, hacen que pueda distribuirse más fácilmente a lo largo de la zona tratada. Se comenta la experiencia sobre 50 pacientes con malformaciones vasculares venosas o de bajo flujo, tratadas con esta nueva forma de esclerosante. Asimismo, se revisa y protocoliza el uso de OK-432 (picibanil como tratamiento esclerosante de elección de las malformaciones vasculares linfáticas, especialmente las macroquísticas.Traditional sclerotherapy with liquid sclerosants has been used for many years in the treatment of venous, lymphatic and low flow vascular malformations; it is efficient only with those vascular malformations of reduced size as a pre or post-operational complement. The use of liquid sclerosants has the limitations of their dilution and progressive inactivation in a great haematic volume, the irregular distribution of the sclerosant on the
Eikawa, Shingo; Kakimi, Kazuhiro; Isobe, Midori; Kuzushima, Kiyotaka; Luescher, Immanuel; Ohue, Yoshihiro; Ikeuchi, Kazuhiro; Uenaka, Akiko; Nishikawa, Hiroyoshi; Udono, Heiichiro; Oka, Mikio; Nakayama, Eiichi
Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response. Copyright © 2012 UICC.