Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

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Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

2005-02-01

We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

Successful pleurodesis with OK-432 (picibanil in preterm infants with persistent pleural effusion

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Jeong Eun Kim

2012-05-01

Full Text Available OK-432 (picibanil is an inactivated preparation of <em>Streptococcus pyogenes</em> that causes pleurodesis by inducing a strong inflammatory response. Intrapleural instillation of OK-432 has recently been used to successfully treat neonatal and fetal chylothorax. Here we report a trial of intrapleural instillation of OK-432 in two preterm infants who were born with hydrops fetalis and massive bilateral pleural effusion. Both cases showed persistent pleural effusion, refractory to conservative treatment, up to postnatal days 26 and 46, respectively. An average of 80 to 140 mL of pleural fluid was drained daily. In case 1, the infant was treated with OK-432 during the fetal period at gestation 28 weeks and 4 days of gestation, but showed recurrence of pleural effusion and progressed into hydrops. Within two to three days after OK-432 injection, the amount of pleural fluid drainage was dramatically decreased and there was no reaccumulation. We did not observe any side effects related to OK-432 injection. We suggest that OK-432 should be considered as a therapeutic option in infants who have persistent pleural effusion for more than four weeks, with the expectation of the early removal of the chest tube and a good outcome.

Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

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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

2014-01-01

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.

Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.

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Hashimoto, Masahito; Takashige, Katsuhiro; Furuyashiki, Maiko; Yoshidome, Keitaro; Sano, Ryoko; Kawamura, Yutaka; Ijichi, Shinji; Morioka, Hirofumi; Koide, Hiroyuki; Oku, Naoto; Moriya, Yoichiro; Kusumoto, Shoich; Suda, Yasuo

2008-01-01

OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.

Subpopulation of lymphocytes in patients with cancer of the head and neck

International Nuclear Information System (INIS)

Yoshida, Atsuhiro; Tomita, Kinai; Toda, Norikazu; Sekine, Kiyoshi; Mizugoe, Takanori

1978-01-01

On 31 patients with cancer of the head and neck, lymphocyte count and T- and B-cell levels were determined, and their changes following radiotherapy and the effect of picibanil on their changes were examined. 1) Lymphocyte count and T-cell count decreased remarkably following radiotherapy. B-cell count changed a little. Changes in lymphocyte count seemed chiefly to be due to changes in T-cell. 2) At 3 weeks after radiotherapy, lymphocyte count and T-cell count remained to be low in the patients who were not given picibanil, but those counts tended to increase in the patients who were given picibanil. The effect of picibanil was statistically significant in the experienced cases except those of maxillary cancer. 3) At 3 weeks after radiotherapy, T-cell count was significantly low in those who were not given picibanil and had unfavourable prognosis. 4) With 5 times repeated intramuscular injections of picibanil (0.2 KE), T-cell % and T-cell count increased in some cases. (Ueda, J.)

Treatment of lymphatic malformations with OK-432 (Picibanil): review of the literature.

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Poldervaart, Michelle T; Breugem, Corstiaan C; Speleman, Lucienne; Pasmans, Suzanne

2009-07-01

Lymphatic malformations (LM) are benign structural defects that can cause serious complications because of their size and location. Traditionally, surgical removal was the first treatment modality, but this could be associated with many complications and risks. Since Ogita introduced OK-432 (picibanil) in 1987 as a treatment method, this sclerosant has become popular. This paper is a review of the trials published so far on this topic. A literature search of English trials with 5 or more patients in it with LM who had never been treated before was done. The paper had to use the microcystic-macrocystic classification and have a mean follow-up of more than a year to be included in this review. Results were classified as "excellent" when the lesions show a regression of more than 90%, "good" when regression is more than 50%, and "poor" when shrinkage is less than 50% (this also includes no response at all). Twenty-seven percent of microcystic LMs show an excellent result; 33%, a good result; and 40%, a poor result. Of the macrocystic LMs, 88% have excellent results. Recurrence rates vary from 5% to 8%. The adverse effects are mostly mild. Most trials have a short follow-up; therefore, there are uncertainties when it comes to cure and regression. Mostly, the adverse effects of OK-432 are trivial and disappear after a week, but the need for a temporary tracheostomy has been described. Screening for allergic reactions to penicilline is needed, with the risk of anaphylactic shock in mind. It is difficult to compare the different techniques used by the authors, and none of the trials included in this study are randomized controlled trials; most are retrospective and were so-called level 4 studies. This review demonstrates that OK-432 is an effective way to treat LM. Because of a possible risk of airway obstruction, treatment should always take place in specialized treatment facilities. Macrocystic lesions show a better response to OK-432 treatment than microcystic lesions

O uso de Picibanil (OK-432 no tratamento do linfangioma de cabeça e pescoço

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Mello-Filho Francisco V.

2002-01-01

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.

OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

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Yoo, Jae Chul; Ahn, Youngjin; Lim, Yune Syung; Hah, J Hun; Kwon, Tack-Kyun; Sung, Myung-Whun; Kim, Kwang Hyun

2009-01-01

Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. Initial and the long-term response rate were equally good for lymphangioma.

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

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Aoyagi, H; Iino, Y; Takeo, T; Horii, Y; Morishita, Y; Horiuchi, R

1997-01-01

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

Efficacy of dendritic cells matured early with OK-432 (Picibanil), prostaglandin E2, and interferon-alpha as a vaccine for a hormone refractory prostate cancer cell line.

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Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong; Kim, Choung-Soo

2010-09-01

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

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Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong

2010-01-01

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods. PMID:20808670

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

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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

2011-12-15

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.

Disease: H01471 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available HORS ... Ogita S, Tsuto T, Nakamura K, Deguchi E, Tokiwa K, Iwai N ... TITLE ... OK-432 therapy for lymphangioma in child...Rautio R, Rautiainen M, Airaksinen M ... TITLE ... OK-432 (Picibanil) therapy for lymphangiomas in children. ...

Prepubertal unilateral gynecomastia and the presence of 47,XXY mosaicism in breast epithelial cells

DEFF Research Database (Denmark)

Andersen, Peter Stemann; Petersen, Bodil Laub; Juul, Anders

2013-01-01

, 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...

Treatment of Lymphangiomas with OK-432 (Picibanil)

International Nuclear Information System (INIS)

Rautio, Riitta; Keski-Nisula, Leo; Laranne, Jussi; Laasonen, Erkki

2003-01-01

Purpose: To determine the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. Methods: The treatment was begun for 14 patients with lymphangioma. The age range of the patients at the time of the first injection was from 10 months to 42 years. Eleven of the lesions involved the head and neck region, two the thorax and one was localized in the extremity. Prior to treatment all patients were investigated with either magnetic resonance imaging, computed tomography, ultrasound or a combination of these modalities. The injections were performed with ultrasound and/or fluoroscopic guidance. Eight patients received OK-432 as first-line treatment; five were treated after surgery and one after medical therapy. On average, 2.2 intracystic injections were performed per patient. Nine of the lesions were macrocystic and five were mixed lesions. Results: Eleven patients showed complete or marked response to the OK-432 sclerotherapy, two patients had moderate shrinkage of their lesions and only one patient showed no response to therapy. Macrocystic lesions showed the best response to therapy. Those patients who received OK-432 as first-line treatment showed complete or marked response. Conclusion: It was found that treatment of lymphangiomas with OK-432 was safe and effective

Treatment of lymphangiomas with OK-432 (Picibanil).

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Rautio, Riitta; Keski-Nisula, Leo; Laranne, Jussi; Laasonen, Erkki

2003-01-01

To determine the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. The treatment was begun for 14 patients with lymphangioma. The age range of the patients at the time of the first injection was from 10 months to 42 years. Eleven of the lesions involved the head and neck region, two the thorax and one was localized in the extremity. Prior to treatment all patients were investigated with either magnetic resonance imaging, computed tomography, ultrasound or a combination of these modalities. The injections were performed with ultrasound and/or fluoroscopic guidance. Eight patients received OK-432 as first-line treatment; five were treated after surgery and one after medical therapy. On average, 2.2 intracystic injections were performed per patient. Nine of the lesions were macrocystic and five were mixed lesions. Eleven patients showed complete or marked response to the OK-432 sclerotherapy, two patients had moderate shrinkage of their lesions and only one patient showed no response to therapy. Macrocystic lesions showed the best response to therapy. Those patients who received OK-432 as first-line treatment showed complete or marked response. It was found that treatment of lymphangiomas with OK-432 was safe and effective.

Retiform hemangioendothelioma developed on the site of an earlier cystic lymphangioma in a six-year-old girl.

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Albertini, Anne-Fore; Brousse, Nicole; Bodemer, Christine; Calonje, Eduardo; Fraitag, Sylvie

2011-10-01

Retiform hemangioendothelioma (RH) is a rare low-grade malignancy angiosarcoma, with a high rate of local recurrence and a low metastatic risk. A 6 year-old girl with a large cervical cystic lymphangioma diagnosed by ultrasound and Doppler ultrasound, which showed a large multiloculated anechoic cyst with no flow. The lymphangioma was treated with injections of Picibanil (OK-432). The tumor regressed, but after a year, she developed a poorly limited infiltrated plaque spreading out regularly over her chest, back, and shoulder. The biopsy showed a poorly limited dermal and subcutaneous vascular proliferation composed of elongated arborising vessels lined with ovoid endothelial cells in a hobnail pattern. In addition, the deep part of the lesion showed typical features of a papillary intralymphatic angioendothelioma pattern (PILA) or Dabska tumor. The endothelial cells strongly expressed podoplanin (D2-40). A diagnosis of RH with focal areas of PILA was reached. The girl died 8 months after surgery of hypovolemic shock in a context of diffuse lymphangiomatosis with pulmonary localization. To our knowledge, RH has hardly ever been described in children. This entity exhibits a continuum with the PILA, sharing not only morphological and immunohistochemical similarities but also its ability to develop in a context of a vascular anomaly, particularly a lymphangioma. The role of Picibanil in the development of this tumor can be discussed.

Radiotherapy of medulloblastoma combined with OK-432 (Picibanil)

International Nuclear Information System (INIS)

Aoki, Yoshiro

1986-01-01

The OK-432 group consists of 8 Medulloblastoma patients, 5 Pinealoma patients and 1 Pons glioma patient, while the historical control group consists of 12 Medulloblastoma patients who have been treated only with radiation at NIRS. The frequency of the week when the value of white blood cell counts decreased below 2,500 was 13 weeks per 98 weeks of total observation period (13.3 %) in the OK-432 group. However, it was 37 weeks per 103 weeks (35.9 %) in the control group. The frequency of the week when the value of the platelet counts decreased below 10 x 10 4 was 5 weeks per 98 weeks (5.1 %) in the OK-432 group, while it was 21 weeks per 103 weeks (20.4 %) in the control group. The OK-432 group received 54.4 ± 3.3 Gy/ 34 ± 2 fractions/ 51 ± 4 days to the cerebellar tumor, except a one-year-old girl who received only a half of the radiation dose as the other patients who were older than 5 years, while the control group received 47.2 ± 7.3 Gy/ 34 ± 7 fractions/ 49 ± 10 days. In terms of TDF, the OK-432 group received 83.5 ± 8.7 and the control group received 63.5 ± 10.2, whereby the difference between the OK-432 group and the control group is statistically significant at 2 % level. To the spinal cord, the OK-432 group received 27.1 ± 3.1 Gy/ 27 ± 5 fractions/ 41 ± 9 days, while the control group received 25.4 ± 7.5 Gy/ 27 ± 13 fractions/ 43 ± 25 days. The survival rate of 8 Medulloblastoma patients treated with radiation combined with OK-432 is as follows : the relative survival rate is 75.1 % in one year, 62.5 % in 3 years and 62.5 % in 5 years, in contrast to the rate of 73.3 % in one year, 20.0 % in 3 years and 20.0 % in 5 years in the control group. (J.P.N.)

[Unsuccessful treatment with OK-432 picibanil for orbital lymphangioma].

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Lanuza García, A; Bañón Navarro, R; Llorca Cardeñosa, A; Delgado Navarro, C

2012-01-01

Lymphangioma is a malformation of the lymphatic system. The classic approach is surgery. We report a case of orbital lymphangioma in a girl who was given OK-432 to avoid surgery and its complications. OK-432 is a lyophilized mixture of group A Streptococcus pyogenes which produces a fibrosis limited to the lesion with a high cure rate. The main advantages are the easy intra-lesional application. with no scars and or damage of closed areas. Its main disadvantage is a significant local inflammatory reaction. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods.

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Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga

2010-01-01

Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

Protective action of OK-432 (Picibanil) on the radiation-induced myelosuppression

International Nuclear Information System (INIS)

Aoki, Yoshiro

1986-01-01

This report aims to examine the alleviating action of OK-432 against the radiation-induced myelosuppression in the whole body irradiated mice. The mice treated with OK-432 were given OK-432 with the dose of 5.0 KE by intraperitoneal injection 24 hours before irradiation, while the control group was given 1.0 ml of saline according to the same procedure as the OK-432 group. The fifty percent lethal dose on the 30th day after the whole body irradiation is 700R in the OK-432 group, while it is 580R in the control group. The dose reduction factor (DRF) is 1.21 in this series. The white blood cell counts decreased after irradiation with 300R in both groups. The recovery of WBC counts in the OK-432 group began at the 6th or 7th day after irradiation, while the decreased level continued until the 20th day in the control group. The WBC counts and the spleen weights were examined on the 10th day after irradiation. The WBC counts of the OK-432 group were higher than those of the control group, the difference of which was statistically significant at the 5 % level at 300R. The spleens of the OK-432 group were heavier and larger than those of the control group, the difference of which was statistically significant at the 0.1 % level for the dose range from 300 to 500R. The HE-stained spleen of the OK-432 group on the 10th day after irradiation showed the increase of hematopoietic cells in the enlarged sinus in comparison with that of the control group. The timing of OK-432 administration and the percentage of the survival of the OK-432 group on 30th day, irradiated with 600R to the whole body, were examined. The 5.0 KE of OK-432 was injected from 4 days before and upto 4 days after irradiation to each group. When OK-432 was inected from 2 days before and upto 12 hours after irradiation, the OK-432 group showed the good survival rate in comparison with the control group. (J.P.N.)

OK-432 as a sclerosing agent to treat wound-healing impairment.

Science.gov (United States)

Fasching, G; Sinzig, M

2007-12-01

We report on the application of OK-432 (picibanil) in a patient with prolonged wound healing impairment. A 13-year-old girl had suffered a polytrauma with a displaced fracture of the sacrum which required neurosurgical decompression of the sacral plexus. Postoperatively, a seroma with recurrent fistulation was seen. Excision of the wound, prolonged suction drainage and the instillation of hypertonic glucose solution did not have any effect over a period of four months postoperatively. Relying on our personal experience of the treatment of lymphangiomas using OK-432 we instilled OK-432 into the wound. Leakage stopped immediately, there was a regression of fluid accumulation and four weeks later the ultrasound examination was normal. The patient is still asymptomatic four years after treatment. OK-432 can be used effectively for the treatment of chronic wound healing impairment.

Treatment of Lymphatic Malformations With OK-432 (Picibanil) : Review of the Literature

NARCIS (Netherlands)

Poldervaart, Michelle T.; Breugem, Corstiaan C.; Speleman, Lucienne; Pasmans, Suzanne

Introduction: Lymphatic malformations (LM) are benign structural defects that call cause serious complications because of their size and location. Traditionally surgical removal was the first treatment modality, but this Could be associated with many complications and risks. Since Ogita introduced

The therapeutic effect of OK-432 (picibanil) sclerotherapy for benign neck cysts.

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Kim, Myung Gu; Kim, Sun Gon; Lee, Jun Ho; Eun, Young Gyu; Yeo, Seung Geun

2008-12-01

In general, benign neck cysts are treated by surgical excision. This can present technical difficulties and frequent recurrences, because of insufficient surgery. Sclerosing agents such as OK-432 have been tested for the nonsurgical treatment of these cysts. We have assessed the efficacy of OK-432 sclerotherapy for benign neck cysts. The study group consisted of 75 patients (42 men, 33 women) diagnosed with and treated for benign neck cysts between March 2001 and December 2007 by intralesional injection of OK-432. The liquid content of each cyst was aspirated as much as possible, and the same volume of OK-432 solution was injected. Patients were assessed by ultrasonography or computerized tomography, and therapeutic outcomes and adverse effects were evaluated by patient age, sex, cyst type, and number of injections. Of the 75 treated patients, 31 (41.3%) showed total shrinkage, seven (9.3%) showed near-total shrinkage (>90% of cyst volume), five (6.6%) showed marked shrinkage (>70% of cyst volume), and 17 (22.7%) showed partial shrinkage (<70% of cyst volume). No response was seen in 15 patients (20%). Despite repeated sclerotherapy, eight patients (10.7%) showed recurrences. Minor adverse effects of therapy included fever, localized pain, and odynophagia but these complications spontaneously disappeared within several days. OK-432 sclerotherapy is a safe and effective primary alternative to surgery in patients with benign neck cysts.

Primary treatment of pediatric plunging ranula with nonsurgical sclerotherapy using OK-432 (Picibanil).

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Roh, Jong-Lyel; Kim, Hyo Sun

2008-09-01

Although surgery is the first choice of therapy for plunging ranula, it is associated with technical difficulties, morbidity and recurrence. Plunging ranula may be also primarily treated with nonsurgical sclerotherapy, but there is little experience in pediatric patients. We, therefore, assessed the efficacy of OK-432 sclerotherapy for pediatric plunging ranula. Nine children with plunging ranula were prospectively treated with intracystic injections of OK-432. At the outpatient clinic, the ranula was punctured in the neck and aspirated mucus was replaced with 0.1-0.2mg OK-432 solution. The size of the ranula was compared before and after sclerotherapy. Total or nearly total shrinkage was observed in 6 of 9 patients; marked reduction (>50% of original size) in 2; and partial reduction (<50% of original size) in 1. At a mean follow-up of 26 months after last sclerotherapy, recurrence was observed in only 1 patient; this patient showed complete response after reinjection of OK-432 solution. No significant complications were observed, with only fever and mild local pain observed in 4 patients for 2-4 days after treatment. OK-432 sclerotherapy is safe and effective in the treatment of pediatric plunging ranula. Sclerotherapy may become a primary treatment modality prior to surgery.

Whole abdominal irradiation for ovarian cancer in combined treatment with OK-432 picibanil

International Nuclear Information System (INIS)

Morita, Shinroku; Arai, Tatsuo; Tsunemoto, Hiroshi

1986-01-01

One hundred seventeen patients with postoperative ovarian cancer who were treated with whole abdominal irradiation by the open-field technique were analyzed as to the effectiveness of combined therapy with or without OK-432. OK-432, 0.2 to 2.0 (KE) (kev) daily, has been used to prevent bone marrow suppression since 1978 at NIRS. Cumulative five-year survival rates were 63.6 % in the OK-432 group (37 patients) and 54.5 % in the NON-OK-432 group (34 patients). The complete rates of previously arranged treatment schedules were 81 % and 66 % in the two groups, respectively, as we originally intended. (author)

Development of cancer immunotherapy

International Nuclear Information System (INIS)

Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y.

1999-04-01

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

Randomized controlled study on the effect of adjuvant immunotherapy with OK-432 on malignant gliomas

International Nuclear Information System (INIS)

Shibata, Shobu; Mori, Kazuo; Moriyama, Tadayoshi; Tanaka, Keisei; Moroki, Jiro.

1985-01-01

During periods from January, 1981 to December, 1983, 51 patients (31 malignant astrocytomas, 17 glioblastomas, and others 3) were treated with radiochemotherapy using Nimustine hydrochloride, ACNU (group B) and radiochemoimmunotherapy with Picibanil, OK-432 (group A) by randomized controlled study. Group A consisted of 24 patients and group B of 27 patients. The differences in the background of the two groups were not statistically significant. Survival curves of both groups were shown by the Kaplan-Meier method. The postoperative survival rate at 1 year and 2 years were 70 % and 30 %, respectively, equal in both groups, and the differences between groups A and B were not statistically significant by the Cox-Mantel test. The side effects by group B therapy were most prominent in the bone marrow, and severe leukopenia occurred. However, group A therapy suppressed leukopenia after 2 months. Immunological parameters, such as purified protein derivative skin reaction test did not change, but streptococcal Su-polysaccharide skin reaction test became positive after group A therapy. (author)

[Severe iatrogenic airway obstruction due to lingual lymphangioma].

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Segado Arenas, A; Flores González, J-C; Rubio Quiñones, F; Quintero Otero, S; Hernández González, A; Pantoja Rosso, S

2011-09-01

Lymphangioma of the tongue is a rare and benign tumour involving congenital and cystic abnormalities derived from lymphatic vessels. Treatment modalities include surgery and a large number of different intralesional injections of sclerosing agents. Presently, OK-432 (Picibanil(®)) is the preferred sclerosant and when administered intralesionally will result in inflammation, sclerosis, and cicatricial contraction of the lesion. We report a case of microcystic lymphangioma of the tongue in a 5-year-old boy treated with an intralesional injection of OK-432. In the immediate postoperative period, the patient suffered severe diffuse swelling, progressive upper airway obstruction with inspiratory stridor, and respiratory distress requiring emergency fiberoptic nasotracheal intubation. Although OK-432 injections are found to be safe and effective as a first line of treatment for lymphangiomas, local swelling with potentially life-threatening airway compromise should be anticipated, especially when treating lesions near the upper airway. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Intrapleural chemo- and hyperthermotherapies for malignant pleural effusion: a randomized prospective study.

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Chen, Wen-Jun; Yuan, Shao-Fei; Yan, Qing-Yuan; Xiong, Jian-Ping; Wang, Sen-Ming; Zheng, Wei-E; Zhang, Wu; Sun, Hong-Yu; Chen, Hua; Wu, Li-Li

2012-02-01

The current prospective randomized study was designed to evaluate the safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil) plus hyperthermotherapy in patients with malignant pleural effusion (MPE). A total of 358 patients with MPE due to end-stage malignancies were enrolled and randomly divided into two groups, A and B: the intrapleural combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea, vomiting or anorexia, bone marrow depression, and pyrexia were similar in both groups. Patients in Group A (with hyperthermotherapy) showed a significantly higher overall response (93.4%) compared to those in Group B (79.8%, χ(2) = 43.11, p .05). After treatment, the quality of life scores were significantly increased in both groups as compared to prior treatment (p < .05). In conclusion, our study suggests that combined intrapleural cisplatin and OK-432 followed by hyperthermotherapy are more effective in the control of MPE and improve patients' quality of life.

Development of cancer immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y

1999-04-01

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.

Primary Effusion Lymphoma Involving both Pleural and Abdominal Cavities in a Patient with Hepatitis B Virus-related Liver Cirrhosis

Directory of Open Access Journals (Sweden)

Pei-Ying Hsieh

2007-01-01

Full Text Available Primary effusion lymphoma (PEL is an unusual form of non-Hodgkin's lymphoma, which is characterized by lymphomatous effusion in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV. We describe a 54-year-old man with HIV-negative PEL, with a history of hepatitis B virus-related liver cirrhosis. Both abdominal and pleural cavities were involved; no solid tumor masses were found and bone marrow investigations were normal. The ascites and pleural effusion contained numerous pleomorphic lymphoid cells. Immunophenotyping was positive for CD138. Chromosome study showed complex cytogenetics. The genomic human herpesvirus-8 was detected in the lymphoma cells. It is postulated that the immuno-suppressed state in this patient may have been caused by cirrhosis. The patient received four cycles of chemotherapy of CHOP and Picibanil (OK-432 intraperitoneal administration. However, no durable remission was achieved. Adefovir failed to halt the progressive liver failure after the development of YMDD mutant related to lamivudine. He died of sepsis and hepatic failure.

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

Science.gov (United States)

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Increased tumor uptake of 67Ga citrate following a course of picibanil (NSC-B116209)

International Nuclear Information System (INIS)

Okuyama, Shinichi; Matsuzawa, Taiju; Mishina, Hitoshi.

1979-01-01

Exposure to exponential dose schedules of OK-432, penicillin-inactivated preparation of streptococcus hemolyticus (NSC-B116209), resulted in an increased retention of 67 Ga citrate. Its uptake in footpad tumors of AH 109A was also increased. The results may suggest that pretreatment with OK-432 would increase tumor uptake of 67 Ga citrate and help scintigraphic delineation of malignancies in man. It may probably augment tumor concentration of anticancer chemotherapeutics, too. Thus, the tumor affinitive property of OK-432 can be taken advantage of in anticancer strategy as well as cancer detection by 67 Ga scanning. (author)

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

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Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Directory of Open Access Journals (Sweden)

Arnt-Ove Hovden

Full Text Available Dendritic cells (DC used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

OK-432 (Picibanil) sclerotherapy for recurrent dislocation of the temporomandibular joint in elderly edentulous patients: Case reports.

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Matsushita, Kazuhiro; Abe, Takae; Fujiwara, Toshikatsu

2007-09-01

Dislocation of the temporomandibular joint (TMJ) is a thorny problem not only for a patient but also a doctor. Especially for the elderly edentulous patients, it is very hard to treat the condition although there are many surgical and non-surgical procedures. We successfully treated it in two elderly edentulous patients by injection of OK-432 as a sclerosing agent.

Alleviating action of OK-432 (Picibanil) on the myelosuppression in medulloblastoma patients induced by whole axis irradiation

International Nuclear Information System (INIS)

Aoki, Yoshiro

1982-01-01

The test subjects termed as OK-432 group which consist of 4 patients of Medulloblastoma and 2 of Pinealoma, underwent the whole axis irradiation in combination with OK-432. The control group consisting of 9 Medulloblastoma patients was subjected to the same radiation treatment without OK-432. Six of the nine patients (66.7%) irradiated showed the decrease of peripheral white blood cell counts down to 2,500, whereas, only two of six patients showed a similar decrement in OK-432 group. Three of the nine patients (33.3%) in the control group showed the decrease of white blood cell down to 2,000, but only one of the six patients in OK-432 group. The neutrophil counts decreased below the level of 1,000 in three of the nine patients (33.3%) in the control group, but none in the OK-432 group. The platelet counts decreased below the level of 100,000 in five of the nine patients (55.6%) in the control group during the irradiation period, but only one patient in the OK-432 group showed a decrease down to 100,000 counts. Three of the nine patients (33.3%) in the control group had to be stopped irradiation due to the severe leukopenia and thrombocytopenia, in contrast to the OK-432 group, which completed whole axis irradiation without interruption. These results seem to indicate that OK-432 alleviated the myelosuppression induced in patients by whole axis irradiation. This alleviating action of OK-432 is considered to be applicable to the treatment of Medulloblastoma patients. (J.P.N.)

Treatment of lymphangiomas of the head and neck in children by intralesional injection of OK-432 (Picibanil).

Science.gov (United States)

Brewis, C; Pracy, J P; Albert, D M

2000-04-01

The treatments previously used for lymphangiomas of the head and neck in children-surgery and intralesional injection of sclerosants-are associated with significant morbidity. A new treatment-intralesional injection of OK-432-was used for lymphangiomas of the head and neck in 11 children. The results were total shrinkage in two, marked shrinkage in two, slight shrinkage in five and no response in two. The results were not affected by previous surgery nor by whether aspiration prior to injection was possible. There were no recurrences in those children in whom shrinkage occurred and no child had subsequent surgery following injection. The results of this series support those of previous series showing that OK-432 injection is an effective and safe treatment for lymphangiomas of the head and neck in children.

Alleviating action of OK-432 (Picibanil) on the myelosuppression in Medulloblastoma patients induced by whole axis irradiation

Energy Technology Data Exchange (ETDEWEB)

Aoki, Yoshiro (National Inst. of Radiological Sciences, Chiba (Japan))

1982-11-01

The test subjects termed as OK-432 group which consist of 4 patients of Medulloblastoma and 2 of Pinealoma, underwent the whole axis irradiation in combination with OK-432. The control group consisting of 9 Medulloblastoma patients was subjected to the same radiation treatment without OK-432. Six of the nine patients (66.7%) irradiated showed the decrease of peripheral white blood cell counts down to 2,500, whereas, only two of six patients showed a similar decrement in OK-432 group. Three of the nine patients (33.3%) in the control group showed the decrease of white blood cell down to 2,000, but only one of the six patients in OK-432 group. The neutrophil counts decreased below the level of 1,000 in three of the nine patients (33.3%) in the control group, but none in the OK-432 group. The platelet counts decreased below the level of 100,000 in five of the nine patients (55.6%) in the control group during the irradiation period, but only one patient in the OK-432 group showed a decrease down to 100,000 counts. Three of the nine patients (33.3%) in the control group had to be stopped irradiation due to the severe leukopenia and thrombocytopenia, in contrast to the OK-432 group, which completed whole axis irradiation without interruption. These results seem to indicate that OK-432 alleviated the myelosuppression induced in patients by whole axis irradiation. This alleviating action of OK-432 is considered to be applicable to the treatment of Medulloblastoma patients.

New Combined Medical Treatment With Etilefrine and Octreotide for Chylothorax After Esophagectomy

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Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

2015-01-01

Abstract Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies. Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing. In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct. PMID:26656358

Sclerotherapy for lymphatic malformations in children: a scoping review.

Science.gov (United States)

Churchill, Paige; Otal, Damanjot; Pemberton, Julia; Ali, Abdullah; Flageole, Helene; Walton, J Mark

2011-05-01

This scoping review assesses the literature and summarizes the current evidence on sclerotherapy for the treatment of lymphatic malformations in pediatric patients. A comprehensive search of published and unpublished literature was conducted using multiple databases. Title, abstract, and full-text screening was conducted by 2 independent clinicians. All discrepancies were resolved during consensus meetings. A total of 182 articles were retrieved. Forty-four articles were removed as duplicates, and 11 articles were added after reviewing prominent studies. After full-text abstraction, 44 articles and 2 conference proceedings (N = 882 patients) were included in the final results. Twelve articles were classified as level II and 34 articles as level IV evidence. Picibanil (OK-432) was the primary agent used in most included studies. Postinjection symptoms with OK-432 were primarily fever, swelling, and erythema at the site. Life-threatening complications were uncommon and involved postinjection swelling of cervical lesions causing airway compromise. The literature regarding sclerotherapy for lymphatic malformations is of a low level of evidence and suffers from a lack of standardization. Randomized clinical trials focused on OK-432, bleomycin, or alcoholic solution of zein; standardized dosing protocols; and consistent and reliable outcome reporting will be necessary for further development of treatment guidelines. Copyright © 2011 Elsevier Inc. All rights reserved.

New Combined Medical Treatment With Etilefrine and Octreotide for Chylothorax After Esophagectomy: A Case Report and Review of the Literature.

Science.gov (United States)

Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

2015-12-01

Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies.Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing.In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct.

[Treatment of lymphangioma with OK-432 infiltration].

Science.gov (United States)

Rodríguez, J; Cáceres, F; Vargas, P

2012-10-01

The management of lymphangioma using sclerotherapy has proven to be an effective therapeutic. Our aim was to evaluate the therapeutic efficacy of OK-432 (Picibanil) in patients with lymphagioma. The study was performed from November 2010 to July 2011. Fifteen patients of both genders were diagnosed with lymphangioma, 12 days to 12 years old. All patients were infiltrated with OK-432. The studied variables were: previous surgery, localization, type of lymphangioma, number of effective injections, reduction of mass valued as excellent (100% reduction), good (reduction > 50%) and bad (reduction < 50%), presence of recurrence and complications. 40% of pacients had prior surgery and 53.3% were located in the cervical-face region. The type of macrocystic lymphangioma was present in 40% of the series, mixed type in 46.6% and microcystic type in 13.4%. The number of effective infiltrations were 3. In 6 cases (40%) the result was excellent in 5 cases (33.4%) the result was good and in 4 cases (26.6%). We had 1 recurrence (6.6%) and we haven't had complications. Injection of OK-432 in macrocystic lymphangioma and mixed had a safe therapeutic modality with satisfactory results. So it is a valid alternative to conventional surgery.

OK-432 sclerotherapy of cervical chylous lymphocele after neck dissection.

Science.gov (United States)

Roh, Jong-Lyel; Park, Chan Il

2008-06-01

Postoperative cervical chylous lymphoceles are extremely rare circumscribed collections of lymph which are usually treated by drainage or surgical exploration, but rarely by sclerotherapy. We investigated the efficacy of OK-432 (Picibanil, Chungai Pharmaceutical Co., Tokyo, Japan) sclerotherapy in the treatment of cervical lymphocele after neck dissection. Four patients with postoperative lymphocele who could not be cured by repeated percutaneous needle aspiration and pressure dressing were treated with intralesional injection of 0.1-0.2 mg OK-432 after aspiration of fluid. The aspirated fluid was assessed biochemically and cytologically, and regular palpation and ultrasonography/computed tomography were used to evaluate outcomes and recurrences. Two patients with chyle leak during neck dissection had lymphoceles in the left supraclavicular region 3 weeks later. The other two patients had lymphoceles on the right neck 9 and 12 months, respectively, after neck dissection. All aspirated fluids were chylous in origin without tumor cells. OK-432 sclerotherapy scored all four lesions with no major complications except for fever and local pain for several days. No lymphocele recurrences or metastatic cancers were observed in any patient for >1 year after sclerotherapy. Intralesional injection of OK-432 may be a safe and effective alternative to surgical exploration in the treatment of cervical lymphocele after neck dissection.

Percutaneous sclerotherapy of massive macrocystic lymphatic malformations of the face and neck using fibrin glue with OK-432 and bleomycin.

Science.gov (United States)

Chen, W-l; Huang, Z-q; Chai, Q; Zhang, D-m; Wang, Y-y; Wang, H-j; Wang, L; Fan, S

2011-06-01

Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Vaccination with OK-432 followed by TC-1 tumor lysate leads to significant antitumor effects.

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Chen, I-Ju; Yen, Chih-Feng; Lin, Kun-Ju; Lee, Chyi-Long; Soong, Yung-Kuei; Lai, Chyong-Huey; Lin, Cheng-Tao

2011-07-01

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4(+) T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4(+) T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer.

OK-432 sclerotherapy for malleolar bursitis of the ankle.

Science.gov (United States)

Park, Kwang Hwan; Lee, Jongseok; Choi, Woo Jin; Lee, Jin Woo

2013-10-01

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.

Treatment of Primary Fetal Hydrothorax with OK-432 (Picibanil): Outcome in 14 Fetuses and a Review of the Literature.

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O'Brien, Brooke; Kesby, Greg; Ogle, Robert; Rieger, Ingrid; Hyett, Jon A

2015-01-01

Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432. A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009). Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range. OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs. © 2014 S. Karger AG, Basel.

Successful treatment of refractory hepatic lymphorrhea after gastrectomy for early gastric cancer, using surgical ligation and subsequent OK-432 (Picibanil) sclerotherapy.

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Tanaka, Kouji; Ohmori, Yukinari; Mohri, Yasuhiko; Tonouchi, Hitoshi; Suematsu, Mina; Taguchi, Yukiko; Adachi, Yukihiko; Kusunoki, Masato

2004-01-01

Postoperative hepatic lymphorrhea is a very rare complication after abdominal surgery. Hepatic lymphorrhea, not containing chyle, involves an internal lymph fistula between the lymphatic channels toward the cisterna chyli and the peritoneal cavity. Over the past 20 years, 17 cases have been reported in Japan. Here, we report a further case, of a patient with successfully treated intractable hepatic lymphorrhea following gastrectomy for early gastric cancer. We review 18 cases, including the present case, with respect to the management of postoperative lymphorrhea refractory to conventional medical treatment.

Metallothionein induction: a measure of radioprotective action

Energy Technology Data Exchange (ETDEWEB)

Matsubara, J.

1988-08-01

Mice treated to induce metallothionein (MT) synthesis in the liver prior to irradiation were resistant to radiation; this also was true of mice that had a portion of skin surgically removed or an immunomodulator administered. Mice given Mn, Cd or Zn subcutaneously prior to irradiation showed increased tolerance to an LD50 level (6-8 Gy) of x rays compared with controls that received no pretreatments (p less than 0.01). All the mice were evaluated during a 30-d postirradiation period. Weight loss in control mice peaked two weeks after irradiation, whereas body weight in mice pretreated with Mn continued to increase after irradiation with x rays. The normal level of MT in mouse liver (25 micrograms g-1 tissue) increased to 70 micrograms g-1 liver tissue in mice irradiated with 6.3-Gy x rays. However, following subcutaneous injection of Cd, Mn or Zn, or intraperitoneal injection of OK-432 (Picibanil, a killed streptococcal preparation, MT levels in liver increased by a factor of 2-8 compared to irradiated that were not treated with the reagents listed above. The mortality rate of mice with a surgically excised 2 X 2-cm2 portion of dorsal skin or of those administered OK-432 was lower than that of controls, and MT levels in liver (150-400 micrograms g-1 tissue) were higher than those of irradiated mice that were not surgically treated. These results suggest that the body's protective action against radiation correlates with the biosynthesis of MT, or that MT acts as a scavenger of radiation-induced peroxides.

Treatment of lymphatic malformations of head and neck with OK-432 sclerotherapy induce systemic inflammatory response.

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Närkiö-Mäkelä, Mervi; Mäkelä, Teppo; Saarinen, Pia; Salminen, Päivi; Julkunen, Ilkka; Pitkäranta, Anne

2011-01-01

Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1β, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

Metallothionein induction: a measure of radioprotective action

International Nuclear Information System (INIS)

Matsubara, J.

1988-01-01

Mice treated to induce metallothionein (MT) synthesis in the liver prior to irradiation were resistant to radiation; this also was true of mice that had a portion of skin surgically removed or an immunomodulator administered. Mice given Mn, Cd or Zn subcutaneously prior to irradiation showed increased tolerance to an LD50 level (6-8 Gy) of x rays compared with controls that received no pretreatments (p less than 0.01). All the mice were evaluated during a 30-d postirradiation period. Weight loss in control mice peaked two weeks after irradiation, whereas body weight in mice pretreated with Mn continued to increase after irradiation with x rays. The normal level of MT in mouse liver (25 micrograms g-1 tissue) increased to 70 micrograms g-1 liver tissue in mice irradiated with 6.3-Gy x rays. However, following subcutaneous injection of Cd, Mn or Zn, or intraperitoneal injection of OK-432 (Picibanil, a killed streptococcal preparation, MT levels in liver increased by a factor of 2-8 compared to irradiated that were not treated with the reagents listed above. The mortality rate of mice with a surgically excised 2 X 2-cm2 portion of dorsal skin or of those administered OK-432 was lower than that of controls, and MT levels in liver (150-400 micrograms g-1 tissue) were higher than those of irradiated mice that were not surgically treated. These results suggest that the body's protective action against radiation correlates with the biosynthesis of MT, or that MT acts as a scavenger of radiation-induced peroxides

Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

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Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

2009-01-01

To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

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Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

2015-04-01

To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

Effects of various drugs on recovery of immunological function after x-ray irradiation

International Nuclear Information System (INIS)

Fukuda, Sakae; Komori, Shoichiro; Aramaki, Shojiro; Tamai, Kazunori; Fuyuno, Kikuo

1977-01-01

X-ray of 300 R was irradiation to the whole bodies of mice aged 6 to 8 weeks, and 0.2 mg of Cepharanthin, 0.2 mg of Leucon, 0.2 ml of Cytochrome-C, and 0.01 KE of Picibanil were given intraperitoneally for seven days from the next day of the irradiation. Three days after the administration of these drugs, 0.1 ml of 7% picrylchloride ethanol solution was painted on the shaven abdomen and its sensitization was examined. Next, 0.02 to 0.03 ml of 1% picrylchloride olive solution was painted on both ears 7 days after that, and swelling of them was measured with the thickness of ears 24 hours after the painting. Moreover, the sensitization was discussed from a viewpoint of the number of leukocyte and lymphocute. Delayed-type skin reaction which was an index of cellular immunity was influenced fairly by the whole body irradiation of x-ray, but it recovered from the damage 20 to 30 days after the irradiation, showing rebound-like phenomenon. Recovery of delayed-type skin reaction and the number of lymphocyte showed almost the same pattern. Accordingly, it was suspected that the number of lymphocyte was directly proportional to cellular immunological competence of the individual. Out of four drugs, there was not a drug particularly which activated delayed-type skin reaction. In contrast with this, Leucon and Cytochrome-C significantly inhibited the recovery. It was recognized that four drugs had a tendency to promote the recovery of the number of leucocyte, but they decreased it conversely from a viewpoint of percentage of lymphocyte. Therefore, it was suspected that the subject of this would be an increase of leukocyte except lymphocyte. (Ueda, J.)

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

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Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

2015-05-01

Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

Evaluation of OK-432 Injection Therapy as Possible Primary Treatment of Intraoral Ranula.

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Kono, Michihide; Satomi, Takafumi; Abukawa, Harutsugi; Hasegawa, On; Watanabe, Masato; Chikazu, Daichi

2017-02-01

A ranula is a pseudocyst caused by mucous extravasation from the sublingual gland. Recently, a sclerosing agent, OK-432 (picibanil), has been reported to be highly effective for treating lymphangioma and cervical cystic lesions. The present study assessed the effectiveness of OK-432 injection therapy for intraoral ranula to clarify whether it can be used as the primary treatment. The present study was a retrospective clinical study of patients with intraoral ranula who received OK-432 injection therapy from 2005 to 2015. The ranula size was measured on computed tomography or magnetic resonance imaging studies. We dissolved 1 Klinische Einheit (KE) unit of OK-432 powder in normal saline equal to the aspiration volume. The primary endpoint was the treatment results. The secondary endpoints were the relation between the treatment results and the lesion length and aspiration volume. A total of 23 patients received OK-432 injection therapy for an intraoral ranula. The mean lesion size was 19.96 mm. The mean aspiration volume was 2.14 mL. The number of injections was 1 to 4 (mean 1.70). The treatment results were complete regression (CR) in 18 (78.2%), partial regression (PR) in 3 (13.0%), and no response (NR) in 2 (8%) patients after the last injection. The overall efficacy rate was 91.2% (21 of 23). No serious complications were observed. The lesion length and aspiration volume of the CR group was 17.38 mm and 1.40 mL, respectively. The lesion length and aspiration volume of the PR/NR group was 29.20 mm and 4.80 mL, respectively. The PR/NR group lesions were significantly larger than the CR group lesions. OK-432 injection therapy for intraoral ranula is safe and effective compared with other surgical therapies. This therapy could potentially become a primary treatment of intraoral ranula. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.