Local Injection Of Bleomycin Research Articles

Comparative Study of TACE with Bleomycin-Lipiodol Emulsion and Percutaneous Local Bleomycin Injection in the Treatment of Giant Hepatic Hemangioma

Comparative Study of TACE with Bleomycin-Lipiodol Emulsion and Percutaneous Local Bleomycin Injection in the Treatment of Giant Hepatic Hemangioma

Diagnosis and characteristics of parotid region lesions in children

Objective:To observe the disease spectrum of the parotid region lesions in children, and clarify the outcome and prognosis of the disease by analyzing of clinical data. Method:The basic information, clinical symptoms, diagnosis results, treatment, prognosis and follow-up of 170 cases with parotid region lesions were analyzed. Result:Among 170 cases of the parotid region lesions, 83 cases（48.82%） were congenital disease, 62 cases（36.47%） were vascular mass, 17 cases（10.00%） were benign or malignant tumor, and 8 cases（4.71%） were infectious disease; 108 cases of the patients were treated with surgery, 34 of them were treated with local bleomycin injection while 28 cases were treated with both surgery and local bleomycin injection. Two cases was cured by reoperation after recurrence and 1 case had facial paralysis but recovered after 3 months of follow-up. Conclusion:The most common diseases of parotid region lesions in children were congenital disease and vascular mass. Surgery combined with bleomycin local treatment is the main therapy in parotid area and has achieved remarkable results. Oral propranolol has certain therapeutic value for parotid region hemangioma.

An Experimental Model of Anterior Urethral Stricture in Rabbits With Local Injections of Bleomycin

To develop an experimental model of anterior urethral stricture in rabbits using a bleomycin (BLM) injection technique. Thirty adult male New Zealand rabbits were randomly divided into 4 groups. In group 1 (BLM group), BLM was injected into the urethral submucosal tissue every other day through a catheter for 6 weeks at the 3-, 6-, 9-, and 12-o'clock positions of the urethra in 12 rabbits. In group 2 (phosphate-buffered saline [PBS] group), PBS was injected instead of BLM in 6 rabbits. In group 3 (stricture control group), an 8 × 20 mm urethral defect was created in 6 rabbits. In group 4 (normal group), 6 normal rabbits were included. All rabbits in the PBS group and stricture control group, as well as 6 rabbits in the BLM group, were sacrificed at 6 weeks. The remaining 6 rabbits in the BLM group were sacrificed at 10 weeks. Urethrography was performed in all rabbits before sacrifice, and the urethra was harvested for histologic analysis. All rabbits in the BLM group showed mild urethral stricture at 4 weeks and significant urethral stricture at 6 weeks, without spontaneous resolution of the stricture at 10 weeks. No urethral stricture was observed in the PBS group at 4 and 6 weeks. Histologic examination confirmed the presence of fibrosis in the BLM group without spontaneous improvement. BLM injection can induce an experimental model of anterior urethral stricture in rabbits. This simple, highly efficient, reproducible method can be carried out in any laboratory.

Successful Treatment of a Keratoacanthoma with Electrochemotherapy: A Case Report.

IntroductionFew studies have evaluated the efficacy of intralesional bleomycin injection combined with electroporation for the treatment of cutaneous tumors. However, the phenomenon that electroporation can enhance the cytotoxicity of bleomycin in vivo by 300–700 fold has been intensely investigated.Case PresentationKeratoacanthoma in an 86-year-old patient was treated with intralesional bleomycin combined with electroporation. Treatment consisted of local application of shorty and intense electric pulses followed by local injection of bleomycin. Electroporation was always well tolerated by the patient, with no significant complaints, and the tumor had completely regressed by day 71 of the follow-up.ConclusionThe results suggest that intralesional bleomycin injection combined with electroporation could represent a valid alternative therapeutic approach for the treatment of keratoacanthomas.

Treatment of Uterine Sarcoma with rAd-p53 (Gendicine) Followed by Chemotherapy: Clinical Study of TP53 Gene Therapy.

This study evaluated the efficacy of rAd-p53 (Gendicine®) followed by chemotherapy for the treatment of uterine sarcoma. Twelve cases of uterine sarcoma treated at Shengjing Hospital were retrospectively analyzed. Among the 12 patients, one had primary cancer, and 11 had recurrent cancer. For the recurrent cases, the interval between the first operation and diagnosis of recurrence, or progression-free survival time 1 (PFS1), was 1-18 months (median 3 months). All patients were treated with local application of rAd-p53 followed by chemotherapy (local injection of bleomycin and i.v. infusion of cisplatin, epirubicin, and isocyclophosphamide). Efficacy was evaluated, and the rates of complete remission (CR) and partial remission (PR) were calculated. During follow-up, PFS time 2 (PFS2) after the baseline period and overall survival (OS) time after the baseline period of rAd-p53 treatment data were obtained. The treatment resulted in one CR, seven PR, three with stable disease (SD), and one with progressive disease (PD). The remission rate (CR + PR) was 66.7%, and the responsive (CR + PR + SD) rate was 91.7%. PFS2 ranged from 2 to 62 months, with a median of 13 months, which is 10 months longer than that of PFS1; this difference was statistically significant (p = 0.0038). The OS time ranged from 6 to 62 months, with a median of 24 months. Following the combined treatment, four of the patients underwent a second debulking surgery. Of the two patients with liver metastases, one had CR of liver foci, and one had PR. Up to the follow-up date of the two patients who survived, one was tumor-free for 60 months. The PFS2 for the other patient was 39 months. This patient survived with tumor for 53 months with slow disease progression. The remaining 10 patients died. Local application of rAd-p53 combined with local injection of bleomycin and intravenous infusion of cisplatin, epirubicin and isocyclophosphamide was effective for treatment of uterine sarcoma, especially for patients with liver metastases. For patients with uterine sarcoma who do not have the opportunity for surgery, this regimen can be used as a new adjuvant therapy to obtain a surgical opportunity that allows further debulking of the tumor mass.

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers

AimElectrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. Patient and methodsForty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. ResultsThirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. ConclusionElectrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.

Discoidin Domain Receptor 2–microRNA 196a–Mediated Negative Feedback against Excess Type I Collagen Expression Is Impaired in Scleroderma Dermal Fibroblasts

Systemic sclerosis (SSc) is characterized by excess collagen deposition in the skin, due to intrinsic transforming growth factor-β (TGF-β) activation. We tried to determine the expression and the role of discoidin domain receptor 2 (DDR2) in SSc. The expression of DDR2 mRNA and protein was significantly decreased in SSc dermal fibroblasts, which was recovered by knocking down TGF-β. The knockdown of DDR2 in normal fibroblasts induced microRNA-196a expression, which led to type I collagen downregulation, indicating that DDR2 itself has a negative effect on microRNA-196a expression and inducible effect on collagen expression. In SSc fibroblasts, however, the DDR2 knockdown did not affect TGF-β signaling and microRNA-196a expression. The microRNA-196a levels were significantly decreased in normal fibroblasts treated with TGF-β and in SSc fibroblasts. Taken together our data indicate that, in SSc fibroblasts, intrinsic TGF-β stimulation induces type I collagen expression, and also downregulates DDR2 expression. This probably acts as a negative feedback mechanism against excess collagen expression, as a decreased DDR2 expression is supposed to stimulate the microRNA-196a expression and further change the collagen expression. However, in SSc fibroblasts the microRNA-196a expression was downregulated by TGF-β signaling. DDR2-microRNA-196a pathway may be a previously unreported negative feedback system, and its impairment may be involved in the pathogenesis of SSc.

Differential Contribution of Dermal Resident and Bone Marrow–Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice

Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

Successful Treatment of Refractory Wart with a Topical Activated Vitamin D in a Renal Transplant Recipient

Warts are benign proliferations of the skin and mucosa caused by infection with human papillomavirus. They are commonly treated with destructive modalities such as cryotherapy with liquid nitrogen, local injection of bleomycin, electrocoagulation, topical application of glutaraldehyde, and local and systemic interferon-β therapy. These treatment modalities often cause pain and sometimes scarring or pigmentation after treatment. We herein report a case with a right index finger wart, which was successfully treated with a topical activated vitamin D.

The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin model

ObjectivesThere is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine...

Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

Sticker's sarcoma (also known as transmissible venereal tumor) is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT), treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

Ganglioneuroblastoma in a cat: A rare neoplasm treated with electrochemotherapy

An 8-year-old male castrated cat was referred for sudden onset of lameness. Physical examination revealed a 1 × 2 × 1 cm mass originating from a footpad of the right hind leg. A diagnosis of ganglioneuroblastoma was suggested by the tumour appearance following histopathological staining with haematoxylin and eosin and haematoxylin/van Gieson. Immunohistochemical staining for glial fibrillary acidic protein (GFAP), vimentin, neuron-specific enolase (NSE), neurofilament and S100 further confirmed the diagnosis. The staging process did not indicate metastatic spread. The cat was treated with three sessions of electrochemotherapy (ECT) 1 week apart, following local injection of bleomycin. The tumour had completely regressed within 1 week of the third ECT application and remained in remission for 402 days at which time a small recurrence was noted. The animal was given a further session of ECT using intra-lesional cisplatin and again went into remission. It remained tumour free at 450 days. Electrochemotherapy is considered a safe and effective treatment for localised neoplasms of cats and dogs and warrants further investigation.

Effects of Wenyang Chubi Decoction on connective tissue growth factor and collagen-Ⅰ in a mouse model of scleroderma

To study the effects of Wenyang Chubi Decoction (WYCBD), a compound traditional Chinese herbal medicine, on connective tissue growth factor (CTGF) and collagen-I (COL-I) in a mouse model of scleroderma. Scleroderma was induced in BALB/c mice by daily local injection of bleomycin for three weeks and the mice were randomly divided into untreated, WYCBD-treated and normal saline (NS) treated groups, with another group of BALB/c mice as normal control. WYCBD and NS were given orally for one month respectively. Histopathology in the skin and lungs of the mice were examined. The CTGF and COL-I expressions in the skin or skin lesions were detected by immunohistochemical Elivision assay. The expression levels of CTGF and COL-I in the untreated group were significantly higher than those in the normal control group (P<0.05). Compared with the NS-treated group, the WYCBD-treated group had significant improvement in the skin and lung histopathology and remarkably decreased expression levels of CTGF and COL-I (P<0.05). Scleroderma mice showed high expressions of CTGF and COL-I in the skin. WYCBD had the effects of decreasing the CTGF and COL-I expressions and improving the skin fibrosis.

Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: a preliminary study in a spontaneous feline model

Feline soft tissue sarcomas are spontaneous, rapidly growing, and aggressive neoplasms that mimic their human counterpart. The purpose of this study was to evaluate the feasibility and efficacy of electrochemotherapy (ECT) in an adjuvant fashion for the treatment of feline sarcomas, and the possibility of repeated treatments in the case of recurrence. Cats with fibrosarcoma (FSA) were assigned to receive surgery or surgery plus ECT. Feline patients recruited in the ECT study were enrolled in a microscopic arm (39 patients) or a macroscopic arm (19 patients) on the basis of their tumor status (absence or presence of gross disease). Patients received local injection of bleomycin followed by bursts of eight biphasic pulses at a voltage of 1,300 V/cm for postoperative and of 800 V/cm for intraoperative treatments. The median time to recurrence was 4 months for cats treated with surgery alone, 19 months for the postoperative cohort, and 12 months for the intraoperative group. Moreover, ten patients with recurring neoplasms were retreated and experienced responses lasting 6 to 28+ months. Side effects were minimal. Of interest, the metastatic rate (1.7%) in our patients was negligible: only one cat had distant spread. The results suggest that ECT is a well tolerated and potentially useful addition to surgery in controlling high-grade sarcomas. On the basis of these results, additional evaluations are warranted in pets and in humans.

Local Bleomycin Injection in the Treatment of Lymphangioma

We report here our experience with local bleomycin injection in lymphangioma. Nine patients with lymphangioma were treated with locally injected bleomycin and followed prospectively. We performed an ultrasound study in all cases to delineate the size, location, nature, and number of compartments of the cyst prior to the injection. Under ultrasound guidance, the content of the cystic cavity was aspirated and 1 - 3 mg/kg bleomycin were injected. The patients were revisited monthly. No attempt at re-injection was made as long as the mass continued to decrease in size. Patients consisted of 4 boys and 5 girls aged between 14 days and 6 years. The localisation of the mass was cervical in 6, cervical, sublingual, and lingual in 1, axillary in 1 and axillary and thoracic in 1. In six children, the mass disappeared totally after a single injection. In one patient a second injection was needed, and surgical excision was performed in two patients with residual solid component. No complication related to bleomycin was seen. Local application of bleomycin in children with lymphangioma is a simple, safe, and effective method. In the majority of cases, total healing may be achieved with a single injection.

Transcatheter Arterial Embolization in the Treatment of Extensive Maxillofacial Hemangioma in Children

Infantile hemangioma frequently occurs in the maxillofacial region as an extensive mass involving many vital structures. As such, many children are found to have an unresectable hemangioma at the initial diagnosis. In the present study transcatheter arterial embolization (TAE) alone or in combination with surgery and local injection of bleomycin A has been attempted to improve the treatment of these lesions. The results of evaluating the effectiveness and therapeutic role of TAE in these extensive maxillofacial hemangiomas in children are presented. We retrospectively analyzed the records of 17 children with maxillofacial hemangioma treated between 1997 and 2004. Altogether, 17 patients (11 boys, 6 girls) were diagnosed as having an extensive maxillofacial hemangioma based on its clinical manifestation, color Doppler ultrasonography, and sometimes computed tomography. They underwent selective TAE alone or TAE followed by surgical excision. For the children with Kasabach-Merritt syndrome, systemic corticosteroid therapy was administered first. All the children had an excellent response after TAE treatment without obvious complications, and the size of the hemangioma body markedly decreased. Local injection of bleomycin A was then undertaken in four children and surgical removal in five. All the children achieved successful disappearance of the hemangioma, with no recurrence during the follow-up period of 5 to 86 months. TAE is thus a reliable and effective therapeutic choice for extensive maxillofacial hemangioma in children, alone or as a preoperative adjunctive measure. It improves the feasibility of complete resection and effects the disappearance of these potentially dangerous bulky tumors with little bleeding and few complications.

Increased expression of p53 and p21 (Waf1/Cip1) in the lesional skin of bleomycin-induced scleroderma

Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive deposition of extracellular matrix in the affected skin as well as various internal organs, vascular injury and immune abnormality; however, the etiology of SSc remains still unknown. We previously established an experimental mouse model for scleroderma by repeated local injections of bleomycin, a DNA damaging agent. In this study, we examined the induction of apoptosis and the expression of p53, p21 (Waf1/Cip1), and proliferating cell nuclear antigen (PCNA) in the lesional skin following bleomycin exposure in this model. Dermal sclerosis was induced by alternate day's injections of bleomycin for 4 weeks. TUNEL assay showed that apoptotic cells began to appear at 1 week after bleomycin exposure, and were prominently detected at 3-4 weeks. Immunohistochemical examination showed increased expression of p53 and p21 mainly in the infiltrating mononuclear cells at 2 weeks after bleomycin treatment. Bleomycin treatment markedly enhanced PCNA expression at 1-2 weeks, mainly in mesenchyme, as compared with control phosphate buffered saline treatment. Reverse transcriptase-polymerase chain reaction analysis showed that the expression of p53 and p21 mRNA was concurrently upregulated at 1-2 weeks after bleomycin treatment. Taken together, coordinate increased levels of p53 and p21 preceded the maximal induction of apoptosis and dermal sclerosis. Our findings suggest that apoptotic processes are involved in the pathophysiology of bleomycin-induced scleroderma, which may be mediated, in part, by the upregulation of p53 and p21.

Cellular and molecular mechanisms of bleomycin‐induced murine scleroderma: current update and future perspective

Scleroderma is a fibrotic condition characterized by immunologic abnormalities, vascular injury and increased accumulation of matrix proteins in the skin. Although the aetiology of scleroderma is not fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, macrophages and fibroblasts, via a number of mediators. Cytokines, chemokines and growth factors secreted by inflammatory cells and mesenchymal cells (fibroblasts and myofibroblasts) play an important role in the fibrotic process of scleroderma. Recently, we established a murine model of scleroderma by repeated local injections of bleomycin. Dermal sclerosis was induced in various mouse strains, although the intensity of dermal sclerosis varied among various strains. Histopathological and biochemical analysis demonstrated that this experimental murine scleroderma reflected a number of aspects of human scleroderma. Further investigation of the cellular and molecular mechanisms of inflammatory reaction, fibroblast activation and extracellular matrix deposition following dermal injury by bleomycin treatment will lead to the better understanding of the pathophysiology and the exploration of effective treatment against scleroderma. This review summarizes recent progress of the cellular and molecular events in the pathogenesis of bleomycin-induced scleroderma; moreover, further perspective by using this mouse model has been discussed.

Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma

Background: Interleukin-13 (IL-13) has been implicated in the pathogenesis of fibrotic conditions. Previously, a murine model for scleroderma has been established by repeated local injections of bleomycin. This animal model enabled us to study local expression and production of IL-13 in skin lesions during disease progression. Methods: Dermal sclerosis (DSc) was induced by repeated subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4 expressions were examined by RT-PCR, ELISA and immunohistochemistry. Results: RT-PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical localization showed in skin lesions expression of IL-13 on infiltrating inflammatory cells, including mononuclear cells and possibly mast cells, increased with DSc progression. IL-13 protein production was also significantly increased. In skin lesions, IL-13 receptor (IL-13R) α2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Rα2, but not IL-13Rα1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Rα1 and IL- 13Rα2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin. Conclusion: These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma.

Possible Role of Apoptosis in the Pathogenesis of Bleomycin-Induced Scleroderma

To elucidate the role of apoptosis in cutaneous sclerosis, we examined the induction of apoptosis and expression of Fas, Fas ligand, as well as caspase-3 in a murine model of bleomycin-induced scleroderma. Dermal sclerosis was induced by local injections of bleomycin (1 mg per mL) in C3H/HeJ mice. Induction of apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling) assay and DNA gel electrophoresis. TUNEL positivity was prominently detected on keratinocytes and infiltrating mononuclear cells, but not endothelial cells and fibroblasts, in the lesional skin. DNA fragmentation revealed laddering at 3 to 4 wk following bleomycin treatment. Immunohistochemistry showed increased expression of Fas in infiltrating mononuclear cells at early phases following bleomycin exposure, whereas constitutive expression in fibroblasts. Fas ligand expression was increased in mononuclear cells as well as fibroblasts in the sclerotic skin. Results of reverse transcription-polymerase chain reaction analysis revealed that expression of Fas ligand mRNA was upregulated and reached a maximum at 3 wk, whereas Fas mRNA was continuously detected. mRNA expression as well as activity of caspase-3 was also enhanced at 3 wk. Administration of neutralizing anti-Fas ligand antibody together with local bleomycin treatment reduced the development of dermal sclerosis, associated with the reduction of TUNEL-positive mononuclear cells and also with the blockade of apoptosis. Caspase-3 activity in the lesional skin was also significantly reduced after anti-Fas ligand treatment. These findings suggest that excessive apoptosis, which is mediated by Fas/Fas ligand pathway and caspase-3 activation, is involved in the pathogenesis of bleomycin-induced scleroderma, possibly by playing an inflammatory role.