Rare Langerhans cell histiocytosis in children: a case report

Langerhans cell histiocytosis (LCH) is a rare disease, formally known as histiocytosis X that is characterized by abnormal proliferation of histiocytes derived from bone marrow (Langerhans cells), joined with leucocytes, eosinophils, neutrophils, lymphocytes, plasma cells and giant multi-nucleated cells causing tissue destruction. One of the first signs of LCH is oral manifestation, in some cases, the oral cavity may be the only affected area. With the chance of oral lesion incidence in LCH being 77%.Initial symptoms are generally nonspecific, which can easily cause misdiagnoses.The purpose of reporting this case is to discuss the features of LCH clinically and radiographically and in the role of the dentist when diagnosing such lesions for a proper management.An 11-year-old boy reported a complaint of swelling in the left side of the lower jaw that is asymptomatic and had been gradually increasing in size for the past 6 months without any improvements. After preforming a biopsy and diagnosing the lesion as LCH, the patient was then treated with a dose of vinblastine (6 mg/m2 intravenous bolus) for 24 weeks as a total period. Two years follow up; the patient showed no sign of recurrence and is in good general condition. In conclusion, reporting this case serves as documentation of the proper route of clinical assessment and diagnosis of LCH with the best possible treatment as guidance.

Yeast extract elicitation increases vinblastine and vincristine yield in protoplast derived tissues and plantlets in Catharanthus roseus

Abstract Catharanthus roseus (L.) G. Don, Apocynaceae, is an immensely important medicinal plant, produces a variety of anticancerous compounds. The yield of two most investigated alkaloids vinblastine and vincristine is unfortunately very low. A vast array of technologies including elicitation have recently been used to enrich Catharanthus alkaloid in culture. Yeast extract is a biotic elicitor, the polysaccharide and the peptide moiety have been recognized as a signalling element in enriching secondary metabolites. In this study, the yeast extract elicitation on vinblastine and vincristine was studied in various protoplast derived tissues and plantlets. Four different yeast extract treatments (T1 = 0.5 g/l, T2 = 1.0 g/l, T3 = 1.5 g/l and T4 = 2.0 g/l) were prepared and used. The alkaloid was quantified and a comparative account of yield were presented by the use of High performance thin layer chromatography. The yeast extract amendment in medium improved vinblastine and vincristine yield in cultivating tissues, maximum being in germinating embryos and in in vitro raised leaf. The highest yield was in T3 (1.5 mg/l) in which 22.74% vinblastine and 48.49% vincristine enrichment was noted in germinating embryos; the enhancement was however, treatment-specific. Antioxidant enzymes such as superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase activities were investigated as addition of yeast extract caused cellular stress and had enriched level of alkaloids.

Linfoma Hodgkin clássico de apresentação incomum. Relato de caso / An unusual presentation of a classic Hodgkin lymphoma. Case report

O linfoma é uma neoplasia originária do sistema linfático, a partir de células linfocitárias. A sintomatologia mais comum é febre, tosse, sudorese noturna, perda de peso, fraqueza e linfoadenopatia indolor. A etiologia ainda permanece desconhecida, tendo sido relacionada ao vírus Epstein-Barr. O diagnóstico se baseia na visualização das células de Reed-Sternberg. O esquema adriamicina, bleomicina, vinblastina e dacarbazina (ABVD) ainda é o tratamento preconizado, associado ou não à radioterapia. Relatamos um caso de linfoma de Hodgkin de apresentação atípica, cujo diagnóstico só foi possível por esplenectomia.(AU)

The lymphoma is a cancer of the lymphatic system originating from lymphocyte cells. The most common symptoms are fever, cough, night sweats, weight loss, weakness, and painless lymphadenopathy. The etiology remains unknown, having been related to the Epstein Barr virus. The diagnosis is based on visualization of Reed Sternberg cells. The adriamycin, bleomicin, vinblastine and dacarbazine (ABVD) regimen is still the preferred treatment, with or without radiation therapy. We report a case of Hodgkin's lymphoma of atypical presentation, the diagnosis of which was only possible through splenectomy.(AU)

Langerhans' cell histiocytosis diagnosed due to dermatological perianal lesion / Histiocitose de células de Langerhans diagnosticada por lesão perianal dermatológica

Abstract Langerhans' cell histiocytosis is a rare disease characterized by proliferation of Langerhans cells in the body. It affects mainly males, predominantly in childhood. Ulcerated plaques are one of the cutaneous forms of presentation. Diagnostic confirmation is done through immunohistochemistry. As therapeutic options, topical corticosteroids and chemotherapy are good choices. The case is reported of a male patient, aged 14, with perianal ulceration. He consulted a coloproctologist, who performed a biopsy of the region and started local triamcinolone applications. Immunohistochemistry diagnosed Langerhans' cells histiocytosis. Further investigation revealed diabetes insipidus, osteolytic lesions in the skull and lower limbs, enlarged liver, and encephalic alterations. Chemotherapy was started with Vinblastine, with significant improvement of the lesions.

Resumo A histiocitose de células de Langerhans é uma doença rara caracterizada pela proliferação de células de Langerhans no corpo. A doença afeta principalmente os homens, predominantemente na infância. Placas ulceradas são uma das formas cutâneas de apresentação. A confirmação diagnóstica é feita através de análise imuno-histoquímica. Como opções terapêuticas, corticosteroides tópicos e quimioterapia são boas escolhas. O caso aqui relatado é de um paciente do sexo masculino, com idade de 14 anos, com ulceração perianal. Ele consultou um coloproctologista, que realizou uma biópsia da região e iniciou o tratamento com aplicações locais de triancinolona. A análise imunohistoquímica diagnosticou histiocitose de células de Langerhans. Outros exames revelaram diabetes insipidus, lesões osteolíticas no crânio e nos membros inferiores, aumento do fígado e alterações encefálicas. A quimioterapia foi iniciada com vimblastina, com melhora significativa das lesões.

Vinblastine enhances the expression of tumor resistance gene abcb4 in zebrafish / 基础医学与临床

Objective To explore the effects of vinblastine on abcb4 tumor resistance gene expression in early development zebrafish and lay an important foundation for multi-drug resistant antineoplastic screening in zebrafish model.Methods Zebrafish embryos of 0.5~1.5 hours post-fertilization were exposured to different concentrations of vinblastine, and then calculated the IC50 of vinblastine.Zebrafish embryos of 0.5~1.5 hours post-fertilization were treated with different concentrations of vinblastine and embryo culture medium respectively, and then observed zebrafish embryo development in 24~120 hours post-fertilization and recorded the number of death, hatch and malformation.Evaluating the impact of vinblastine on abcb4 gene expression in zebrafish with quantitative real-time PCR and whole-mount in situ hybridization by collecting zebrafish embryos exposed to different concentrationsof vinblastine.Results Vinblastine IC50 in zebrafish embryos was 3.08 μmol/L.The mRNA level of abcb4 gene in vinblastine treated embryos was significantly increased compared to blank control group.Moreover, abcb4 gene positive hybridization signals were found in the small intestine of zebrafish embryos after 120 hours post-fertilization and also found in the brain and heart of zebrafish embryos by the method of whole-mount in situ hybridization.Conclusions Vinblastine can significantly increase the expression level of abcb4 tumor resistancegene in early development zebrafish embryos, which indicates that zebrafish can be used as a tumor resistant drug screening model.

Concentration Determination and Pharmacokinetics of Vinblastine in Rat Plasma by HPLC-MS/MS / 中国药师

Objective:To establish an HPLC-MS/MS method for the determination of vinblastine in rat plasma. Methods:Aceto-nitrile was used to precipitate protein in the samples after the addition of internal standard, and then the concentration was analyzed by HPLC/MS/MS. All the separations were carried out on an Ultimate C18 column (150 mm × 2. 1 mm, 5. 0 μm). The mobile phase was composed of acetonitrile and 10 mmol·L-1 ammoniumacetate (containing 0. 1% formic acid) (49 ∶51) and was pumped at a flow rate of 0. 3 ml·min-1 under 40 °C. The detection was performed with multiple reactions monitoring (MRM) using electrospray ioniza-tion (ESI). The precursor/product ion transitions were monitored at m/z 811. 4→m/z 224. 2 (positive ion mode) for vinblastine and m/z 825. 4→m/z 807. 4(positive ion mode) for internal standard vincristine. Results:Good linearity of vinblastine was obtained with-in the range of 0. 457-950 ng·ml-1(r=0. 997 1). The lower limit of quantification was 0. 457 ng·ml-1. The extraction recoveries were within the range of 89. 15%-95. 28%. The precision of intra-and inter-day was not more than 7. 95%. T1/2 of vinblastine in rats was (5. 86 ± 2. 37) h, and AUC(0-t) and AUC(0-∞) was (68. 45 ± 14. 51) and (95. 03 ± 33. 09)μg·L-1 ·h, respectively. Conclu-sion:The method is fast, sensitive and accurate, which provides research basis for the development of vinblastine and transporters re-search in medicine. The concentration of vinblastine in rats is low, and the half-life is long.

Study on content of terpenoid indole alkaloids and transcriptional differences for covalent orca3/g10h in double-gene transgenic hairy roots of Catharanthus roseus / 中草药

Objective: In order to improve the content of terpenoid indole alkaloids (TIAs), orca3/g10h genes were introduced to the hairy roots in Catharanthus roseus. Methods: Bivalent expression vector CAMBIA1304+ +orca3 + g10h was constructed and introduced into Agrobacterium rhizogenes strain and transformed into C. roseus to obtain transgenic hairy roots. RT-qPCR was used to study the transcriptional differences of relative genes referred to the biosynthesis pathway of TIAs. Then HPLC was used to study TIAs content in the transgenic hairy roots of C. roseus, including vinblastine, vincristine, and ajmalicine. Results: The transcriptional level of genes that linked to biosynthesis of TIAs in the transgenic hairy roots of C. roseus, asα, ggpps, g10h, str, tdc, cpr, sgd, and dat, were all expressed higher than those of the nontransgenic roots. HPLC results showed that modified hairy root of C. roseus owned more total TIAs production, 58.23 mg/g, the number was larger than that of common roots in C. roseus as many as 27.5 times. On the other hand, the average content of vinblastine and vincristine was also more than the common roots in C. roseus. Among them, vinblastine content was the most. The number of production got 51.30 mg/g, which was as many as 197.3 times of the common root of C. roseus. Conclusion: Orca3/g10h double-gene transgenic hairy root of C. roseus can increase TIAs content efficiently.

Study on Anti-tumor Effects of Vinblastine Hydrophilic Group Modified Cationic Liposomes in Tumor-bearing Mice / 中国药房

OBJECTIVE:To study the anti-tumor effects of Vinblastine (VLB) hydrophilic group modified cationic liposomes in tumor-bearing mice. METHODS:Tumor-bearing model were induced by inoculating yellow ascites of S180 ascites tumor mice. Tumor-bearing mice were randomly divided into model group,VLB sulfate injection group,VLB liposomes group,VLB hydrophil-ic group modified liposomes group,VLB cationic liposomes group and VLB hydrophilic group modified cationic liposomes group, i.e. group A,B,C,D,E and F,with 18 mice in each group. Group A was given normal saline intravenously via mice tail,other groups were given VLB 1.5 mg/kg every 2 days for consecutive 5 times. The anti-tumor effects of different VLB preparations were compared,using living conditions,survival time,tumor volume and weight,and tissue pathological section as indexes. RE-SULTS:Compared with group A,B,C,D and E,the mice of group F were more active,and had longer survival time,smaller tumor volume and lighter tumor weight,with statistical significance(P<0.05). The tissue pathological section of mice in group F indicated that coagulation necrosis,disintegration,and dissolution of tumor cell nucleus. CONCLUSIONS:VLB hydrophilic group modified cationic liposomes have obvious anti-tumor effect,which are better than other VLB preparations.

Sudden hearing loss in a patient of Hodgkin’s lymphoma following vinblastine chemotherapy: a rare case report and review of the literature.

Ototoxicity is a well-known complication of certain chemotherapeutic agents. There have been few reports of ototoxicity following administration of vincristine. However, vinblastine has seldom been implicated causing ototoxicity. We report a case of sudden bilateral hearing loss in a 32-year-old male patient of classical Hodgkin’s lymphoma following standard adriamycin, bleomycin, vinblastine, dacarbazine chemotherapy.

Anti-tumor mechanisms of microtubule inhibitors / 国际药学研究杂志

Microtubules are a type of dynamic filamentous cytoskeletal protein, and a major component of centrosome. The regular dynamic changes in microtubules are the guarantees of mitosis. Microtubule inhibitors can promote or inhibit tubulin assembly, interfere cell mitosis and the normal structure and function of the spindle, resulting in the inhibition of cell proliferation and tumor specific therapeutic effect. Microtubule inhibitors, targeting different sites, are the key components of chemotherapeutic regiments for various solid tumors, and dozens of microbule inhibitors are already available in market or under clinical study. Including a brief description of the progress in paclitaxel, vinblastine and colchicine, this review systematically introduces the mechanism of a class of microtubule inhibitors.

Anti-Tumor mechanisms of microtubule inhibitors / 国际药学研究杂志

Microtubules are a type of dynamic filamentous cytoskeletal protein, and a major component of centrosome. The regular dynamic changes in microtubules are the guarantees of mitosis. Microtubule inhibitors can promote or inhibit tubulin assembly, interfere cell mitosis and the normal structure and function of the spindle, resulting in the inhibition of cell proliferation and tumor specific therapeutic effect. Microtubule inhibitors, targeting different sites, are the key components of chemotherapeutic regiments for various solid tumors, and dozens of microbule inhibitors are already available in market or under clinical study. Including a brief description of the progress in paclitaxel, vinblastine and colchicine, this review systematically introduces the mechanism of a class of microtubule inhibitors.

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15 percent to 20 percent of general patients and between 35 percent and 40 percent of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86 percent and 70 percent, respectively. The disease-free survival was approximately 60 percent at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported.

Monoclonal antibody against human stathmin 1 in combination with vinblastine inhibits proliferation of K562 cell lines / 基础医学与临床

Objective To investigate the effects of monoclonal antibody against stathmin 1 in combination with vinblastine on the proliferation of K562 cells. Methods K562 cells were treated with monoclonal antibody against stathmin 1, vinblastine alone or with their combination, 24, 48, 72, 96 hours later, inhabitation rate was studied by MTT assay;The apoptosis was analyzed by invert microscope and flow cytometry with Annexin V/PI. Results The quantity decreased and shape, size changed after treatment with different concentration of experimental groups. Monoclonal antibodies against stathmin 1 and vinblastine used alone or in combination both inhibited the proliferation of K562 cells,the inhibition ratio of their combination is higher (P <0. 05) ,and a synergistic effect of the two agents was noted in their combined action ( P < 0. 05 ). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P <0. 05). Conclusion Monoclonal antibody against stathmin 1 and vinblastine used alone or in combination both can inhibite proliferation of K562 cells and induce apoptsis. A synergistic effect is observed between the monoclonal antibodies against stathmin 1 and vinblastine in their inhibition of K562 cell proliferation.

Preparation and evaluation of vinblastine PCL-PEG-PCL nanoparticles / 中国药科大学学报

Aim:To prepare vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles,and to study their physicochemi-cal properties and in vitro antitumor activity.Methods: PCL-PEG_(6000)-PCL triblock copolymer was prepared by ring-opening polymerization,and vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles was prepared by coprecipita-tion.The morphous,particle size,polydisperse index,particle yield,the drag-loading content,the encapsulation ef-ficiency and in vitro release rate of these vinblastine-loaded nanoparticles were determined.The cytotoxicity of vinblastine-loaded nanoparticles to K562/A02 leukimia cell line was determined by MTT assay.Results: It was found using transmission electron microscopy(TEM)that the nanoparticles exhibited a spherical shape with core-shell structure.The particle sizes of the nanoparticles obtained by dynamic light scattering were(185 ± 2.7)nm.The drug loading content and the encapsulation efficiency were determined to be 28.83% and 86.52%,re-spectively.In vitro release study revealed that more than 70% of accumulative release of entrapped vinblastine was reached in 9 hr and that nearly complete release was achieved in 24 hr.The inhibition of vinblastine-loaded nanoparticles to K562/A02 cell line was significantly increased as compared with that of the same dose of sulfate vinblastine solution.Conclusions: PCL-PEG-PCL nanoparticles could be used as a carrier of vinblastine,and the prepared nanoparticles exhibited a spherical shape,high encapsulation efficiency,relevant stablity and sustained-release properties.The eytotoxicity of vinblastine to K562/A02 cell line was significantly increased when it was encapsulated in PCL-PEG-PCL nanoparticles.

Histiocitose de células de Langerhans: doença de Letterer-Siwe - importância do diagnóstico dermatológico em dois casos / Langerhans cell histiocytosis: Letterer-Siwe disease - the importance of dermatological diagnosis in two cases

A histiocitose de células de Langerhans é proliferação clonal de células fenotipicamente semelhantes às células de Langerhans. Anteriormente denominada Letterer-Siwe, é a forma mais comum e mais grave dessa enfermidade, acometendo sobretudo crianças até os dois anos de idade. São apresentados dois casos dessa rara doença, diagnosticados após parecer dermatológico, destacando-se seus aspectos mais característicos.

Langerhans cell histiocytosis is defined as a clonal proliferation of Langerhans phenotypic-like cells. Letterer-Siwe disease is the most common and serious of these entities, affecting mainly infants up to two years of age. We present two cases of this rare disease, diagnosed after dermatological examination, highligthing its typical aspects.

Isolation and Purification of Vinblastine and Vincristine from Gatharanthus Roseus by Macroporous Adsorption Resin / 中国中医药信息杂志

Objective To optimize the technological parameters of separation and purification of vinblastine and vincristine from Gatharanthus Roseus. Methods Different types of macroporous adsorption resin were used to separate and purify vinblastine and vincristine from Gatharanthus Roseus, eluting with different concentration of alcohol aqueous and velocities, combined with silica gel column chromatography, the process was monitored by HPLC. Results AB-8 type resin showed better comprehensive adsorption property, 90% alcohol aqueous and 1.5 BV/h velocities were used to elute. Ratio adsorption quantity was achieved to 74.5 mg/g. Through silica gel column chromatography, the purity of vincristine was achieved to 97.26% and the purity of vinblastine was achieved to 94.18%. Conclusions The process is simple and reasonable with good reproducibility. It is effective to enrich highly purified vinblastine and vincristine.

Comparison of NP Regimen and TP Regimen in Treatment of Advanced Breast Cancer / 医学研究杂志

0.05).Conclusion Both PTX plus DDP and NVB plus DDP are effective to advanced breast cancer.There are no significant difference between the two groups.The two regimens can be applied to the first line chemotherapy.

Effect of Vinblastine on the Proliferation and Nitric Oxide Secretion of RAW264.7 Cells / 中国药房

OBJECTIVE:To explore the effect of vinblastine(VBL)on the proliferation and nitric oxide(NO)secretion of RAW264.7 cells. METHODS:MTT and flow cytometry were used to evaluate the inhibition effect of VBL on the proliferation of RAW264.7 cells and blockade effect of VBL on cell cycle distribution,respectively. The change of protein expression of cyclin B1 was detected by Western blot method. Griess kit was adopted to test the effect of VBL on LPS- induced NO secretion of cell. RESULTS:VBL can inhibit the proliferation and NO secretion of RAW264.7 cells,arrest cells in G2～M phase and reduce the levels of cyclin B1 in a concentration- dependent manner(P

A Case of Inappropriate ADH Secretion Secondary to Vinblastine Therapy

Inappropriate secretion of antidiuretic hormone (ADH) secondary to vincristine therapy has been reported frequently. But there has been five previous reports of vinblastine associated SIADH in the world and in 4 reports, bleomycin and cis-platinum were used along with vinblastine together. Because penetration of vinka alkaloids into CSF of humans is known to be poor, it has been suggested that lowering the osmotic threshold for vasopressin release induces SIADH in humans. In our case, the patient did not receive cis-platinum during chemotherapy. From this we concluded that vinblastine alone can induce SIADH without nephrotoxicity of cis-platinum. We experienced a case of inappropriate ADH secretion secondary to vinblastine therapy in a 5- month-old male infant who has been taking vinblastine due to Langerhans cell histiocytosis. We report this case with a brief review of related literatures.