Ethyl acetate extract of Clausena execavata promotes growth inhibition of Burkitt's lymphoma cell line via apoptotic activities / El extracto de acetato de etilo de Clausena excavata promueve la inhibición del crecimiento de la línea celular del linfoma de Burkitt a través de actividades apoptóticas

Clausena excavata is a famous folklore medicinal plant in Asian region that is being used for the treatment of different disorders. This study investigated the cytotoxic effects of leaf extracts via MTT assay, as well as the in vitro apoptotic activities of the ethyl acetate C. excavata leaf extract (EACE) on human Burkitt's lymphoma, Raji, cell line using annexin-V-FITC/propidium iodide flow cytometric assays. Pro-apoptotic (BAX) and anti-apoptotic (BCL-2, c-MYC) gene expressions were determined via real-time quantitative PCR. Phytochemical screening was done by Gas chromatography-mass spectrometry (GC-MS). EACE has the lowest IC50 (19.3 ± 0.35 µg/mL) among extracts. EACE-treated Raji cells after 48 h underwent apoptosis as evident by loss of cell viability and increase in the percentage of early and late apoptotic cells. The results also showed EACE mediated decreased in the BCL-2 and c-MYC gene expressions and increased in the BAX gene. C. excavata is a potential treatment for Burkitt lymphoma through activation of apoptosis.

Clausena excavata es una planta medicinal tradicional famosa en la región asiática que se utiliza para el tratamiento de diferentes trastornos. Este estudio investigó los efectos citotóxicos de los extractos de hojas a través del ensayo MTT, así como las actividades apoptóticas in vitro del extracto de hoja de acetato de etilo de C. excavata (EACE) en la línea celular de linfoma de Burkitt humano, Raji, usando citometría de flujo de yoduro de anexina-V-FITC/propidio. Las expresiones génicas proapoptóticas (BAX) y antiapoptóticas (BCL-2, c-MYC) se determinaron mediante PCR cuantitativa en tiempo real. El cribado fitoquímico se realizó mediante cromatografía de gases-espectrometría de masas (GC-MS). EACE tiene el IC50más bajo (19,3 ± 0,35 µg/mL) entre los extractos. Las células Raji tratadas con EACE después de 48 h sufrieron apoptosis como es evidente por la pérdida de viabilidad celular y el aumento en el porcentaje de células apoptóticas tempranas y tardías. Los resultados también mostraron una disminución mediada por EACE en las expresiones de los genes BCL-2 y c-MYC y un aumento en el gen BAX. C. excavata es un tratamiento potencial para el linfoma de Burkitt a través de la activación de la apoptosis.

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

BACKGROUND: Patient-reportedoutcomes (PROs) that assess health-related quality of life (HRQoL) are increasingly important components of cancer care and research that are infrequently used in sub-Saharan Africa (SSA). METHODS: We administered the Chichewa Pediatric Patient-Reported Outcome Measurement Information System Pediatric (PROMIS)-25 at diagnosis, active treatment, and follow-up among pediatric lymphoma patients in Lilongwe, Malawi. Mean scores were calculated for the six PROMIS-25 HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference). Differences in HRQoL throughout treatment were compared using the minimally important difference (MID) and an ANOVA analysis. Kaplan-Meier survival estimates and Cox hazard ratios for mortality are reported. RESULTS: Seventy-five children completed PROMIS-25 surveys at diagnosis, 35 (47%) during active treatment, and 24 (32%) at follow-up. The majority of patients died (n = 37, 49%) or were lost to follow-up (n = 6, 8%). Most (n = 51, 68%) were male, median age was 10 (interquartile range [IQR] 8-12), 48/73 (66%) presented with advanced stage III/IV, 61 (81%) were diagnosed with Burkitt lymphoma and 14 (19%) Hodgkin lymphoma. At diagnosis, HRQoL was poor across all domains, except for Peer Relationships. Improvements in HRQoL during active treatment and follow-up exceeded the MID. On exploratory analysis, fair-poor PROMIS Mobility <40 and severe Pain Intensity = 10 at diagnosis were associated with increased mortality risk and worse survival, but were not statistically significant. CONCLUSIONS: Pediatric lymphoma patients in Malawi present with poor HRQoL that improves throughout treatment and survivorship. Baseline PROMIS scores may provide important prognostic information. PROs offer an opportunity to include patient voices and prioritize holistic patient-centered care in low-resource settings.

Hepatoesplenomegalia relacionada a linfoma de Burkitt en paciente pediátrico / Hepatoesplenomegalia related to Burkitt´s lymphoma in a pediatric patient

RESUMEN El linfoma de Burkitt, se trata de un subtipo poco frecuente del linfoma no Hodgkin, con elevada frecuencia en aquellos pacientes con sida. La hepatoesplenomegalia es un signo clínico de gran importancia para el diagnóstico oportuno de algunas patologías; entre los mecanismos de formación de la hepatoesplenomegalia se encuentra la infiltración celular, ocasionada por la migración de células tumorales. Se presenta por inflamaciones debido a la presencia de infecciones por virus o bacterias las cuales son muy comunes en pacientes con sida. Se presentó un caso de un paciente masculino de 4 años, diagnosticado con VIH positivo, con la configuración correspondiente de criterios clínicos en clasificación C para sida. El cual desarrolló a nivel de cavidad oral un Burkitt primario, que se acompañó de hepatoesplenomegalia. Se pretendió describir la relación y el comportamiento de este tipo de linfoma con la hepatoesplenomegalia, así como la repercusión a nivel del sistema estomatognático, a nivel sistémico y el plan de tratamiento. Por el cuadro clínico e inmunológico del paciente estudiado, se planteó un pronóstico reservado por presentar un cuadro clínico infrecuente, en el que se observó Burkitt; tanto a nivel del sistema estomatognático como a nivel abdominal. Se hizo necesario realizar un diagnóstico oportuno y certero para iniciar el tratamiento a tiempo, se comenzó inmediatamente con tratamiento (AU).

ABSTRACT Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin lymphoma, with high frequency in those patients with AIDS. Hepatosplenomegaly is a clinical sign of great importance for the timely diagnosis of some pathologies; cellular infiltration is found among the mechanisms of hepatosplenomegaly formation; it is caused by the migration of tumor cells. It emerges by inflammations due to the presence of infections by virus or bacteria which are very common in patients with AIDS. The authors present the case of a male patient, aged 4 years, with a positive HIV diagnosis, and the correspondent configuration of clinical criteria in C classification for AIDS, who developed a primary Burkitt lymphoma at the level of oral cavity We present the case of a 4-year-old male patient diagnosed with HIV positive, with the corresponding configuration of clinical criteria in classification C for AIDS; who developed a primary LB at the oral cavity level that was accompanied by hepatosplenomegaly. The authors pretended to describe the relation and behavior of this kind of lymphoma with hepatosplenomegaly, and also the repercussion at the stomatognathic level, at the systemic level and the treatment plan. Due to the clinical and immunological characteristics of the studied patient a reserved prognosis was given because of presenting infrequent clinical characteristics in which a Burkitt was observed both, at the stomatognathic and at the abdominal level. It was necessary to make an opportune and accurate diagnosis to begin the treatment on time (AU).

Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets.

B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of resistance to chemotherapeutic drugs and/or relapse. During drug-induced apoptosis, Yin Yang 1 (YY1) transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of YY1 in reversing drug resistance in B-NHLs; and (2) identify YY1 transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that YY1 binds the promoter of the BIRC5/survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between YY1 and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt's lymphomas cells, demonstrated that YY1 silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) YY1 and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs; (2) YY1 strongly binds to the survivin promoter, hence survivin may be suggested as YY1 transcriptional target; (3) YY1 silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both YY1 and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.

Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line.

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma.

Anti-Cancer and Anti-Proliferation Activity of Ethyl Asetat Extract From Ant Nest (Myrmecodia pendans) in Burkitt's Lymphoma Cancer Cells

Objective: To determine the activity of anti-cancer and anti-proliferation of ethyl acetate fraction of ant nest plants (Myrmecodia pendans) in Burkitt's Lymphoma cancer cells. Material and Methods: The study was conducted in a pure laboratory experimental method using Burkitt's Lymphoma cancer cell culture. Gradual research begins with the determination, extraction and fractionation of ant nest plants, to test for proliferation barriers. Data analysis using two-way ANOVA followed by Post Hoc LSD test with a significance level of 95%. Pearson correlation test was conducted. Results: The results of testing the inhibition of Burkitt's Lymphoma cell proliferation with ethyl acetate extract treatment showed that there was inhibition of cell growth based on the concentration given, starting from the lowest concentration of 15.625 µg/mL. Likewise, the incubation time factor of 24, 48, and 72 hours showed that the longer the incubation time, the greater the inhibition of cell growth. Antiproliferation analysis of flavonoid ethyl acetate extract based on concentration and incubation time on absorption of optical density Burkitt's Lymphoma was statistically significant (p = 0.00). Conclusion: Ant nest ethyl acetate extract has the effect of proliferation inhibition on Burkitt's lymphoma cells.

Ibrutinib significantly inhibited Bruton's tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model.

Pediatric and adult patients with recurrent/refractory Burkitt lymphoma (BL) continue to have poor outcomes, emphasizing the need for newer therapeutic agents. Bruton's tyrosine kinase (BTK) is activated following B-cell receptor stimulation and in part regulates normal B-cell development. Ibrutinib, a selective and irreversible BTK inhibitor, has been efficacious in chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström's macroglobulinemia, and marginal zone lymphoma. In this study, we investigated the efficacy of ibrutinib alone and in selective adjuvant combinations against BL in-vitro and in a human BL xenografted immune-deficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mouse model. Our data demonstrated that phospho-BTK level was significantly reduced in BL cells treated with ibrutinib (p < 0.001). Moreover, we observed a significant decrease in cell proliferation as well as significant decrease in IC50 of ibrutinib in combination with dexamethasone, rituximab, obinutuzumab, carfilzomib, and doxorubicin (p < 0.001). In-vivo studies demonstrated ibrutinib treated mice had a significantly prolonged survival with median survival of mice following ibrutinib treatment (32 days) (24 days) (p < 0.02). In conclusion, our findings demonstrate the significant in-vitro and preclinical in-vivo effects of ibrutinib in BL. Based on our preclinical results in this investigation, there is an on-going clinical trial comparing overall survival in children and adolescents with relapsed/refractory BL treated with chemoimmunotherapy with or without ibrutinib (NCT02703272).

Triptolide induces mitochondria-mediated apoptosis of Burkitt's lymphoma cell via deacetylation of GSK-3ß by increased SIRT3 expression.

Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with rapid growth and dissemination propensity. Triptolide (TP), an active component extracted from Chinese herb Tripterygium wilfordii Hook f., has broad-spectrum anti-tumor activities. This study aimed to explore the in vitro and in vivo anti-cancer effects of TP on BL and the potential molecular mechanisms. In this study, the in vitro anti-tumor activity of TP was determined by CCK-8 and flow cytometry assays in Raji, NAMALWA and Daudi cells. The expression of SIRT3, phosphorylation and acetylation of glycogen synthase kinase-3ß (GSK-3ß) were analyzed by Western blot assay. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured apoptosis related protein using Western blot assay. BL xenograft model in NOD/SCID mice were established to evaluate the in vivo anti-cancer effect of TP. We discovered that TP inhibited BL cell growth and induced apoptosis in a dose-dependent manner. Loss of SIRT3 provides growth advances for BL cells. However, TP could up-regulate SIRT3 expression, which resulted in suppression of BL cells proliferation. GSK-3ß was activated by SIRT3-mediated deacetylation, which subsequently induced mitochondrial translocation and accumulation of Bax and decrease of mitochondrial membrane potential. Anti-tumor studies in vivo showed that TP (0.36 mg/kg) inhibited the growth of BL xenografts in NOD/SCID mice with an inhibitory rate of 73.13%. Our data revealed that TP triggered mitochondrial apoptotic pathway in BL by increasing SIRT3 expression and activating SIRT3/GSK-3ß/Bax pathway. This study indicated that TP is a potential anti-cancer Chinese herbal medicine against BL.

Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda.

BACKGROUND: Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (eBL). EBV control was improved by magnesium (Mg2+) supplementation in XMEN, an X-linked genetic disease associated with Mg2+ deficiency, high circulating EBV levels (viral loads), and EBV-related lymphomas. We, therefore, investigated the relationship between Mg2+ levels and EBV levels and eBL in Uganda. METHODS: Plasma Mg2+ was measured in 45 women with low or high circulating EBV levels, 40 pediatric eBL cases, and 79 healthy children. Mg2+ uptake by T-lymphocytes was evaluated in samples from healthy donors. RESULTS: Plasma Mg2+ deficiency (plasma level <1.8 mg/dl) was more likely in women with high- vs. low-EBV levels (76.0% vs. 35%; odds ratio [OR] 11.3, 95% CI 2.14-60.2), controlling for age, and in eBL cases than controls (42.0% vs. 13.9%; OR 3.61, 95% CI 1.32-9.88), controlling for sex, age group, and malaria status. Mg2+ uptake by T-lymphocytes was related to extracellular Mg2+ concentration. INTERPRETATION: Plasma Mg2+ deficiency is associated with high EBV levels and eBL.

Data supporting the functional role of Eleven-nineteen Lysine-rich Leukemia 3 (ELL3) in B cell lymphoma cell line cells.

The data presented here are related to the research article entitled "Selective expression of the transcription elongation factor ELL3 in B cells prior to ELL2 drives proliferation and survival" (Alexander et al., 2017) [1]. The cited research article characterizes Eleven-nineteen Lysine-rich Leukemia 3 (ELL3) expression in the B cell compartment and functional dependence in B lymphoma cell lines. This data report describes the mRNA expression pattern in a panel of cell lines representing the B cell compartment, supplementing the protein expression data presented in the associated research report. In addition, a reanalysis is presented of publicly available mRNA expression data from primary murine B cells to reveal dynamic regulation of the ELL family members post LPS stimulation (Barwick et al., 2016) [2]. The effect of ELL3 depletion on cell morphology, latent Epstein Barr Virus (EBV) lytic replication and differentiation markers in a Burkitt's lymphoma (BL) cell line cells are presented.

The role of traditional healers in the diagnosis and management of Burkitt lymphoma in Cameroon: understanding the challenges and moving forward.

BACKGROUND: Burkittlymphoma(BL) is the most common childhood cancer in Cameroon with a reported incidence of 3 per 100,000 children under 15 years in the Northwest region. Treatment at three Baptist mission hospitals has a recorded cure rate of over 50%. Traditional medicine(TM) is recognized by the national health system, but its scope is undefined and entraps children with BL. The aim of this study was to investigate the attitudes and practices of parents and traditional healers (TH) towards TM in children with BL in order to develop recommendations for an integrative approach and improved access to life-saving treatment for children with BL. METHODS: This is a descriptive case series of children diagnosed with BL treated at Banso, Mbingo, and Mutengene Baptist Hospitals between 2003 and 2014. A questionnaire was used to obtain the following information: demographic information, religion, the rate of use of TM, reasons why guardians chose to use TM, the diagnoses made by the TH, treatment offered, and the type of payment requested, based on the accounts of patient caregivers. Data was analyzed using Center for Disease Control Epi Info 7. RESULTS: Three hundred eighty-seven questionnaires were completed by parents/guardians. 55% had consulted a TH, of whom 76.1% consulted the TH as first choice. Common diagnoses provided by TH included liver problem, abscess, witchcraft, poison, hernia, side pain, mushroom in the belly and toothache. Methods of management included massage, cuts, concoctions, and incantations. The fee for these services included chickens, farm tools, and cash ranging from 200FCFA (0.4USD) to 100,000FCFA(200USD). The choice of TM was based on accessibility, failed clinic/hospital attendance, recommendation of relatives, and belief in TM. CONCLUSIONS: TH are involved in BL management in Cameroon. TH are ignorant about BL, resulting in non-referral, and thus delay in diagnosis and treatment. Collaboration with TH could reduce late diagnosis and improve cure rates of BL and other childhood cancers.

Puzzling and ambivalent roles of malarial infections in cancer development and progression.

Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

Correlation between the overexpression of Yin Yang 1 and the expression levels of miRNAs in Burkitt's lymphoma: A computational study.

A growing number of studies have highlighted the role of microRNAs (miRNAs or miRs) in the development and progression of cancer. In particular, the aberrant expression of cancer-related proteins, such as oncogenes and tumor suppressors has been shown to correlate with the modulation of the expression of specific miRNAs. In the present study, we aimed to determine which downregulated miRNAs may be involved in modulating the expression of the oncogenic transcription factor, Yin Yang 1 (YY1). YY1 has been reported to be overexpressed in several malignancies and our previous studies have highlighted the significant correlation between the levels of YY1 and aggressive behavior in non-Hodgkin's lymphoma (NHL). A total of 57 miRNAs that are potentially capable of targeting YY1 was identified through in silico approaches. The search of publicly available NHL datasets, including paired mRNA and miRNA data (GSE23026) highlighted a significant correlation (Pearson's correlation, r>0.5) between the expression levels of YY1 and the expression levels of a limited set of miRNAs, including miR-363, miR-200a, miR-23b, miR-15a and miR-15b. Intriguingly, both hsa-miR-363 and hsa-miR-200a belong to the top 20 miRNAs that were found to be downregulated in Burkitt's lymphoma (BL) tissue compared to normal tissue. Although further validation studies are warranted, the identification of these two miRNAs associated with the upregulation of YY1 in BL may provide further insight into the pathogenesis of this tumor and may contribute to more personalized and targeted treatment approaches for patients with this disease.

Marsdenia tenacssima extract and its functional components inhibits proliferation and induces apoptosis of human Burkitt leukemia/lymphoma cells in vitro and in vivo.

Burkitt lymphoma is a fast growing non-Hodgkin lymphoma that occurs primarily in young males. The causes of Burkitt lymphoma include chromosome rearrangement and virus infection, but accurate and complete reasons remain to be discovered. The available treatment for Burkitt lymphoma is chemotherapy and radiation therapy. It is a highly aggressive B-cell neoplasm with not all patients cured, in spite of current therapies. This study evaluated the effects of traditional Chinese medicine Marsdenia tenacssima (MTE) and its component compound Tenacigenoside A (TGTA) and 11α-O-benzoyl-12ß-O-acetyltenacigenin B (TGTB) on human Burkitt lymphoma growth. It was observed that MTE, TGTA or TGTB inhibited cell growth and induced apoptosis of Burkitt lymphoma cells in culture. In lymphoma bearing NOD/SCID nude mice, both TGTA and TGTB inhibited tumor growth and improved animal survival. TGTA and TGTB significantly increased tumor cell apoptosis on lymphoma bearing mice, primarily through down-regulation of BCL2 and BCL-XL and up-regulation of BID.

Clinicopathological features of double-hit B-cell lymphomas with MYC and BCL2, BCL6 or CCND1 rearrangements.

Double-hit (DH) lymphomas are B-cell lymphomas characterized by chromosomal rearrangements, specifically of MYC and either BCL2, BCL6 or CCND1. We reviewed 22 cases of DH lymphomas. BCL2/MYC DH lymphomas constituted the majority of these DH lymphomas (17 cases; 77%), followed by BCL6/MYC (2 cases; 9%) lymphomas. Assessing morphological features using the 2008 World Health Organization classification system, 15 cases (68%) were determined to be B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BCLU) (10 cases; 45%), or as DLBCL (5 cases; 23%), and 2 cases (9%) were classified as morphologically untransformed follicular lymphoma. Burkitt lymphoma was rare (1 case; 5%) among DH lymphomas. Nineteen cases were treated with R-CHOP or a high dose chemotherapy regimen. After a median follow-up of 11 months, 7 patients had died, and the 1-year survival rate was 62.5%. High dose chemotherapy did not improve the outcome. We suggest that screening of genetic variations to detect DH lymphomas is required in diagnosing all lymphomas, even those determined morphologically to be follicular lymphoma.

Anticancer activities of selected species of North American lichen extracts.

Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0 /G1 stage, and caused apoptosis in a dose-dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs.

Diseases mimicking intussusception: diagnostic dilemma.

BACKGROUND: Intussusception is a common abdominal emergency in early childhood. The aim of this study was to describe the diseases mimicking intussusception and to discuss the causes and management of these conditions. METHODS: Seven patients who were initially diagnosed as having intussusception on abdominal ultrasonography but who had a final diagnosis of diseases other than intussusception were reviewed retrospectively. RESULTS: Two patients with ileocolic intussusception underwent ultrasonography-guided reduction with a hydrostatic method but the ultrasonographic findings persisted. At surgery, only edematous ileocecal valve and mesenteric lymphadenopathy were observed. In three patients with Henoch-Schönlein purpura, initial abdominal ultrasonography showed intussusception. The patients with no sign of obstructive symptoms were managed conservatively with a diagnosis of intramural hemorrhage and on follow up the ultrasonographic findings of intussusception was resolved. One patient with the target sign on computed tomography and ultrasonography of the abdomen underwent ileocolic resection and end-to-end anastomosis due to a tumor in the cecum. There was no evidence of intussusception. One patient with a cyst in the right lower quadrant accompanying intussusception on ultrasonography of the abdomen underwent ultrasonography-guided reduction but the ultrasonographic findings persisted. On exploration, only cecal duplication cyst without intussusception was detected. Cecal resection including the cyst and end-to-end ileocolic anastomosis were performed. CONCLUSIONS: Ultrasonography, color Doppler ultrasonography, barium or hydrostatic enema and computed tomography are helpful in diagnosing intussusception, but patients with radiologic findings of intussusception should be evaluated on symptoms and clinical findings before surgical intervention. Also, other diseases mimicking intussusception should be kept in mind in the differential diagnosis.

Regulation of the MIR155 host gene in physiological and pathological processes.

MicroRNAs (miRNAs), a family of small nonprotein-coding RNAs, play a critical role in posttranscriptional gene regulation by acting as adaptors for the miRNA-induced silencing complex to inhibit gene expression by targeting mRNAs for translational repression and/or cleavage. miR-155-5p and miR-155-3p are processed from the B-cell Integration Cluster (BIC) gene (now designated, MIR155 host gene or MIR155HG). MiR-155-5p is highly expressed in both activated B- and T-cells and in monocytes/macrophages. MiR-155-5p is one of the best characterized miRNAs and recent data indicate that miR-155-5p plays a critical role in various physiological and pathological processes such as hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular disease, and Down syndrome. In this review we summarize the mechanisms by which MIR155HG expression can be regulated. Given that the pathologies mediated by miR-155-5p result from the over-expression of this miRNA it may be possible to therapeutically attenuate miR-155-5p levels in the treatment of several pathological processes.

A Study of Clinical Features of Acute Tumor Lysis Syndrome in Children

PURPOSE: Tumor lysis syndrome is characterized by hyperuricemia, hyperphosphatemia, hypetkalemia and hypocalcemia due to destruction of tumor cells. The purpose of this study is bi estimate in children the incidence, onset time, differences in outcomes between hemodialysis and conservative therapy, and predictive factor of tumor lysis syndrome before treatment with chernotherapy. METHODS: Subjects were 108 children who had received induction chemotherapy from January 1993 to December 1998. We reviewed 12 patients who developed turnor lysis syndrorne, and retrospectively analyzed their data on WBC, Hb, platelet, LDH, uric acid, phosphorus, potassiurr., calcium, BUN and creatinine. RESULTS: Tumor lysis syndrome was observed in 12(11.1%) cases. Seven out of 12 patient:; (58A%) were in the age group of 6 to 10 years. The incidence of tumor lysis syndrome was 9.4% in acute leukemia, 30.8% in malignant lymphoma and 6.5% in solid tumor. Before chemotherapy, tumor lysis syndrome occurred in 3 cases(25.0%). Nine cases(75.0%) developed after initiation of chemotherapy. LDH was significantly higher in the group with tumor lysis syndrome(2790.8+/-1882.1U/L) than the group without(777.6+/-618.5U/L)(P<0.05). Of 12 patients, there were increased levels of phosphorus and uric acid in 11 cases, creatinine in 9 cases, potassium in 6 cases, and calcium was decreased in 8 cases. There was no death during treatment. Duration of treatment until improvement was longer in the hemodialysis group(7.62.7 days) than in thi conservative therapy group(5.71.5 days). CONCLUSION: Turnor lysis syndrome occurred mostly within 24-48 hours after chernotherapy of acute lymphocytic leukemia and Burkitt's lymphoma. LDH before chemotherapy was helpful in predicting the occurrence of turnor lysis syndrome in children.