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Clinics (Sao Paulo, Brazil) Aug 2014Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with... (Comparative Study)
Comparative Study
OBJECTIVE
Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with OK-432, bleomycin and surgery, and a combination of the three modalities.
METHODS
We performed a retrospective, cross-sectional study including patients treated from 1998 to 2011. The effects on macrocystic lymphangiomas and adverse reactions were evaluated. Twenty-nine children with cystic lymphangiomas without any previous treatment were included. Under general anesthesia, patients given sclerosing agents underwent puncture of the lesion (guided by ultrasound when necessary) and complete aspiration of the intralesional liquid. The patients were evaluated with ultrasound and clinical examinations for a maximum follow-up time of 4 years.
RESULTS
The proportions of patients considered cured after the first therapeutic approach were 44% in the surgery group, 29% in the bleomycin group and 31% in the OK-432 group. These proportions were not significantly different. Sequential treatment increased the rates of curative results to 71%, 74% and 44%, respectively, after the final treatment, which in our case was approximately 1.5 applications per patient.
CONCLUSION
The results of this study indicate that most patients with cystic lymphangiomas do not show complete resolution after the initial therapy, regardless of whether the therapy is surgical or involves the use of sclerosing agents. To achieve complete resolution of the lesions, either multiple operations or a combination of surgery and sclerotherapy must be used and should be tailored to the characteristics of each patient.
Topics: Bleomycin; Brazil; Child, Preschool; Combined Modality Therapy; Cross-Sectional Studies; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Infant; Injections, Intralesional; Lymphangioma, Cystic; Male; Picibanil; Punctures; Remission Induction; Retrospective Studies; Sclerosing Solutions; Treatment Outcome
PubMed: 25141107
DOI: 10.6061/clinics/2014(08)01 -
Yonsei Medical Journal Apr 2007The aim of this study was to demonstrate OK- 432 sclerotherapy efficacy for treatment of simple renal cysts.
PURPOSE
The aim of this study was to demonstrate OK- 432 sclerotherapy efficacy for treatment of simple renal cysts.
MATERIALS AND METHODS
Twenty patients with 25 symptomatic or large simple cysts were treated by ultrasonography (US)-guided percutaneous aspiration and injection of OK-432 (8 men and 12 women, mean age 63.6 years, SD 9.5). Six patients presented with flank pain, 14 presented with renal mass; renal cyst location was right, left, or bilateral sided in 9, 8, and 8 kidneys, respectively. Patients were evaluated by clinical assessment, US, or CT scan 3 months following the procedure. Complete and partial success was defined as symptom resolution with either total cyst ablation or greater than 70% reduction, respectively. Failure was defined as 30% of cyst size recurrence and/or persistent symptoms.
RESULTS
Average reduction was 93.0%. Complete and partial resolution occurred in 11 (44.0%) and 13 (52.0%) cysts, respectively. One case was defined as failure, with a 64.2% size reduction from 10.9cm to 3.9cm (volume reduction rate 95.4%). Renal pain improved in all patients, regardless of complete or partial resolution. Minor complications occurred in 3 patients, 2 developed leukocytosis and 1 had mild fever (< 38.5 degrees C) following aspiration and sclerotherapy. Successful treatment was achieved with conservative measures and NSAID therapy.
CONCLUSION
Percutaneous treatment of simple renal cysts with OK-432 sclerotherapy was found to be a safe, effective and minimally invasive procedure.
Topics: Adult; Aged; Female; Functional Laterality; Humans; Kidney Diseases, Cystic; Male; Middle Aged; Picibanil; Sclerotherapy; Treatment Outcome
PubMed: 17461526
DOI: 10.3349/ymj.2007.48.2.270 -
International Journal of Hyperthermia :... 1991We have studied the effect of a streptococcal preparation, OK-432, given alone or in combination with hyperthermia on murine tumour and normal tissues. The experimental...
We have studied the effect of a streptococcal preparation, OK-432, given alone or in combination with hyperthermia on murine tumour and normal tissues. The experimental tumour was a spontaneous non-immunogenic fibrosarcoma FSa-II transplanted in the foot of C3Hf/Sed mice. Local hyperthermia was achieved by immersing the mouse foot into a constant temperature water bath (42-45 degrees C) for various lengths of time. Tumour response was studied by analysing the tumour growth (TG) time. Various doses of OK-432 (1-5 KE/mouse) were injected locally into the tumour. Local administration of OK-432 alone (without hyperthermia) had no effect on the TG time. Thermal enhancement ratio (TER) for combined treatment was independent of drug dose greater than or equal to 2 KE, and the mean TER was 1.48 +/- 0.27 (95% CL). The TER was greater for 6 mm tumours than for 4 mm tumours, and it was greatest if the time interval between hyperthermia and drug administration was 3 h or less. There was no effect if the drug was administrated 4 days before hyperthermia, but its application 9 days prior to hyperthermia caused a slight prolongation of the TG time of non-heated tumours, and a reduction in the TG time of heated tumours. Normal-tissue response was studied by scoring the peak foot reaction and RD50 (the treatment time to induce a specified response in one-half of the treated animals). The effect of OK-432 on the thermal response of the foot was also studied at various temperatures. The mean TER was 1.11 +/- 0.07. Local administration of OK-432 failed to modify significantly the kinetics of thermotolerance. Present experiments demonstrated that OK-432 after local administration enhanced the thermal response of murine tumour and normal tissues. This enhancement was greater for the tumour than for the normal tissue, resulting in a favourable differential effect between normal and malignant tissues (the average therapeutic gain was 1.33 +/- 0.19).
Topics: Animals; Combined Modality Therapy; Hot Temperature; Mice; Mice, Inbred C3H; Picibanil; Sarcoma, Experimental; Temperature; Time Factors
PubMed: 2051067
DOI: 10.3109/02656739109004982 -
International Journal of Hyperthermia :... 1991It has previously been demonstrated that the local administration of OK-432 (Picibanil) enhances the response of a murine tumour and normal tissue to elevated...
It has previously been demonstrated that the local administration of OK-432 (Picibanil) enhances the response of a murine tumour and normal tissue to elevated temperatures. The experimental animals were C3Hf/Sed mice and the tumours were the fourth generation isotransplants of a spontaneous non-immunogenic fibrosarcoma, FSa-II. The thermal enhancement ratio was greater for the tumour than for normal tissue, resulting in a favourable differential effect between normal and malignant tissues. Further studies were conducted to disclose the mechanism of OK-432 induced thermal enhancement. Although OK-432 showed a slight direct cytotoxic activity against tumour cells in vitro, the in vivo antitumour effect of combined OK-432 and hyperthermia treatments was greater than the effect expected from in vitro cytotoxicity, indicating the involvement of the host-mediated mechanisms. Whole body irradiation (WBI), which suppressed the host's immune reaction, did not affect the thermal enhancement mediated by OK-432, suggesting that radiosensitive cells (sensitive to WBI) were not involved in this process. As expected, the i.v. injections of the anti-mouse T-cell serum did not have any effect on the thermal enhancement of OK-432. The administration of blockers of the reticuloendothelium system, i.e. silica or trypan blue, did not inhibit the OK-432 induced thermal enhancement. Moreover, local intratumoural injections of normal or OK-432 induced macrophages showed no effect on tumour growth. The thermal enhancement by OK-432 was eliminated following treatments with anti-(asialo GM1) globulin. Despite the fact that the cytotoxic effect of anti-(asialo GM1) globulin was not selective to natural killer (NK) cells, all the experimental results indicated that NK cells were probably attributable to thermal enhancement by OK-432 in vivo. The NK cell activity was stimulated when the OK-432 was locally administered with hyperthermia.
Topics: Animals; Combined Modality Therapy; Cytotoxicity, Immunologic; Fibrosarcoma; Hyperthermia, Induced; Immunotherapy, Adoptive; In Vitro Techniques; Killer Cells, Natural; Lymphocyte Depletion; Macrophages; Mice; Mice, Inbred C3H; Picibanil; T-Lymphocytes
PubMed: 1919160
DOI: 10.3109/02656739109034977 -
The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep.American Journal of Physiology.... Aug 2010Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is...
Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 +/- 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide.
Topics: Animals; Blood Pressure; Brain; Cardiovascular System; Cerebral Infarction; Electroencephalography; Female; Fetal Blood; Fetal Movement; Gestational Age; Heart Rate; Hemodynamics; Infusions, Parenteral; Nitrites; Picibanil; Pleura; Pregnancy; Respiratory Mechanics; Seizures; Sheep; Time Factors; Vascular Resistance; Vasodilation
PubMed: 20484698
DOI: 10.1152/ajpregu.00116.2010 -
International Immunopharmacology Mar 2024Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular...
Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.
Topics: Carcinoma, Hepatocellular; Hyperthermia, Induced; Liver Neoplasms; Neoplasm Recurrence, Local; Picibanil; Retrospective Studies; Toll-Like Receptor 4; Antineoplastic Agents; Animals; Mice; Cell Line, Tumor; Radiofrequency Ablation; Mice, Inbred C57BL; Nucleotidyltransferases; Membrane Proteins; Male
PubMed: 38442584
DOI: 10.1016/j.intimp.2024.111769 -
Cancer Immunology, Immunotherapy : CII 1989In this report the mechanism of therapeutic activity of OK-432 for the treatment of peritoneal carcinomatosis was investigated by correlating effector-cell augmentation...
In this report the mechanism of therapeutic activity of OK-432 for the treatment of peritoneal carcinomatosis was investigated by correlating effector-cell augmentation with therapeutic activity in rats bearing MADB-106 carcinomatosis. Tumor cells were injected i.p. and the treatment with OK-432 was initiated 5 days later with 0.5, 1, 5 or 10 KE/animal of OK-432 injected i.p. semiweekly. Significant therapeutic activity was observed at all doses examined with greater prolongation of survival noted at the higher doses of OK-432. Animals treated with 0.5 KE/animal had a prolongation of the median survival time from 14 days for saline-treated animals to 17 days for the OK-432 treated animals (P less than 0.0008), while animals treated with higher doses had much longer periods of survival, some animals being tumor-free at 185 days. In the same studies, natural killer (NK) cell, lymphokine-activated killer cell, cytotoxic T lymphocyte, and macrophage tumoricidal/cytostatic activities were measured 7 days and 14 days following tumor injection (2 days and 9 days after initiation of immunotherapy). OK-432 had immunostimulatory activity in most of the assays of immune function examined and this correlated with host survival, including augmentation of peritoneal and peripheral blood cytotoxic T lymphocyte activity on day 14, peritoneal and alveolar macrophage activity on day 7 and day 14, as well as natural killer cell activity on day 14. These results suggest that the therapeutic doses are also immunomodulatory doses for the effector cells mentioned above. We suggest, therefore, that immunological monitoring may help to optimize treatment protocols for the treatment of peritoneal and perhaps pleural effusions with OK-432.
Topics: Adjuvants, Immunologic; Animals; Biological Products; Carcinoma; Cell Line; Cytotoxicity, Immunologic; Female; Killer Cells, Natural; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Peritoneal Neoplasms; Picibanil; Rats; Rats, Inbred F344; T-Lymphocytes, Cytotoxic
PubMed: 2784999
DOI: 10.1007/BF00199909 -
Cancer Immunology, Immunotherapy : CII Apr 2014Radiofrequency ablation therapy (RFA) is a radical treatment for liver cancers and induces tumor antigen-specific immune responses. In the present study, we examined the...
Radiofrequency ablation therapy (RFA) is a radical treatment for liver cancers and induces tumor antigen-specific immune responses. In the present study, we examined the antitumor effects of focal OK-432-stimulated dendritic cell (DC) transfer combined with RFA and analyzed the functional mechanisms involved using a murine model. C57BL/6 mice were injected subcutaneously with colon cancer cells (MC38) in their bilateral flanks. After the establishment of tumors, the subcutaneous tumor on one flank was treated using RFA, and then OK-432-stimulated DCs were injected locally. The antitumor effect of the treatment was evaluated by measuring the size of the tumor on the opposite flank, and the immunological responses were assessed using tumor-infiltrating lymphocytes, splenocytes and draining lymph nodes. Tumor growth was strongly inhibited in mice that exhibited efficient DC migration after RFA and OK-432-stimulated DC transfer, as compared to mice treated with RFA alone or treatment involving immature DC transfer. We also demonstrated that the antitumor effect of this treatment depended on both CD8-positive and CD4-positive cells. On the basis of our findings, we believe that combination therapy for metastatic liver cancer consisting of OK-432-stimulated DCs in combination with RFA can proceed to clinical trials, and it is anticipated to be markedly superior to RFA single therapy.
Topics: Adenocarcinoma; Adjuvants, Immunologic; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Catheter Ablation; Cell Movement; Colorectal Neoplasms; Combined Modality Therapy; Dendritic Cells; Female; Interferon-gamma; Lymphatic Metastasis; Lymphocyte Depletion; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Inbred C57BL; Phagocytosis; Picibanil; Subcutaneous Tissue; T-Lymphocyte Subsets; Tumor Burden
PubMed: 24384836
DOI: 10.1007/s00262-013-1514-7 -
Journal of Translational Medicine Jan 2017Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the...
BACKGROUND
Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.
METHODS
We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.
RESULTS
Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.
CONCLUSIONS
The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.
Topics: Animals; Cell Line, Tumor; Cell Polarity; Combined Modality Therapy; Cytokines; Disease Models, Animal; Female; Kaplan-Meier Estimate; Mammary Neoplasms, Animal; Mice, Inbred BALB C; Microwaves; Picibanil; Survival Analysis; T-Lymphocytes, Cytotoxic; Th1 Cells
PubMed: 28137271
DOI: 10.1186/s12967-017-1124-9 -
Hinyokika Kiyo. Acta Urologica Japonica Feb 1991Primary retroperitoneal tumors are reported to account for 0.2% of all malignancies. Furthermore, 10-20% of all primary retroperitoneal tumors are liposarcomas. Up to... (Review)
Review
Primary retroperitoneal tumors are reported to account for 0.2% of all malignancies. Furthermore, 10-20% of all primary retroperitoneal tumors are liposarcomas. Up to 1989, 213 cases of retroperitoneal liposarcoma have been reported in the Japanese literature to our knowledge. Mixed type liposarcomas were rare, and composed 13.8% of all retroperitoneal liposarcomas in this series. We described here a case of retroperitoneal mixed type liposarcoma. A 50-year-old man was admitted to our department with a mass in the left abdomen. Computed tomography and aortography revealed a huge and hypovascular tumor in the retroperitoneal cavity, not containing fat tissue. It was diagnosed as a retroperitoneal tumor and treated surgically. The tumor and the left kidney were encapsulated and could be removed en bloc. The size and weight of the tumor were 28 x 18 x 12 cm and 3,100 g, respectively. Histological examination of the mass proved it to be a mixed type liposarcoma. He was administered OK-432 as adjuvant therapy. After 11 months, bone metastasis to the vertebra appeared. Moreover, lung metastasis also occurred and he died of the disease 15 months after the operation.
Topics: Combined Modality Therapy; Humans; Liposarcoma; Male; Middle Aged; Neoplasm Metastasis; Picibanil; Retroperitoneal Neoplasms; Tomography, X-Ray Computed; Urography
PubMed: 2048492
DOI: No ID Found