Application of a widely-used tropical anti-worm agent, mebendazole, in modern oncology

Although clinical trials have not been completed, it has already been confirmed that mebendazole, a well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical studies show that mebendazole notably impedes the growth of malignant and metastatic tumors such as osteosarcoma and soft tissue sarcoma, melanoma, carcinoma (lung, colorectal, breast, ovarian, hepatocellular and adrenocortical), acute myeloid leukaemia, glioblastoma multiforme and  meduloblastoma. Mebendazole can induce the depolymerization of microtubules in neoplasms and newly formed vasculature, stopping tumor growth and neoangiogenesis, along with other proposed mechanisms of action.Keywords: Anthelmintic, Mebendazole, Cancer treatment, Antimicrotubullar effect, Antineoangiogenesi

Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia

Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements. Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient and used in semi-nested PCR for the detection of preleukemic clones at birth. Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis. Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events

Infantile hepatic hemangioendothelioma: Report of two cases

We described two cases of infantile hepatic hemangioendothelioma: one with a solitary lesion and the other with multicentric lesions. Clinical presentation was with no liver symptoms in case 1, and hepatomegaly, failure to thrive, and palpable abdominal mass in case 2. Diagnostic imaging revealed single tumor formation in case 1 and multiple nodules in the liver in case 2. Dilemmas related to nature of the tumor were solved by microscopic analysis. The patient with the clinical appearance of a single lesion was successfully operated. The patient with multiple lesions in the liver tissue showed complete involution after corticotherapy

Allergic complications of L-asparaginase therapy in children with acute lymphoblastic leukaemia

Introduction. L-asparaginase (L-ASP) is one of the most effective medications for the treatment of acute lymphoblastic leukaemia (ALL) in children, and allergic reactions to the therapy are considered the most significant side effects. Objective. The aim of this study was to determine the prevalence and type of allergic reactions, as well as to identify potential risk factors for the development of allergic reactions during L-ASP therapy in children with ALL. Methods. The study encompassed 70 patients under 18 years of age, who were treated at the Institute for Child and Youth Healthcare of Vojvodina, Novi Sad in the period January 2000 - June 2009. We analyzed the frequency and type of allergic reactions during the administration of L-ASP, the onset of allergic reaction in relation to the phase of therapy of underlying disease, as well as the prevalence of allergic reactions in relation to drug administration method. Results. Allergic reaction manifested in 17 patients (24%). In 14 patients (82%) allergic reaction to L-ASP manifested as urticaria, bronchospasm or anaphylaxis, whereas a mild local reaction was observed in only three patients (18%). In a group treated, according to the high-risk protocol, the prevalence of allergic reactions was statistically significantly higher in the intermediate-risk group of patients (p<0.01), i.e. statistically significantly more frequent, as compared to the standard-risk group of patients (p<0.05). The majority of patients (11; 65%) developed allergic reactions to the 9th dose of L-ASP, i.e. the first dose during the reinduction phase. The time interval between the last L-ASP dose in the induction phase and the 1st dose in the reinduction phase was at least four weeks. With respect to administration method, the majority of patients (16; 94%) developed allergic reaction after intravenous application of L-ASP. Conclusion. Potential risk factors for the development of allergic reaction to L-ASP are a high-risk therapy group, intravenous administration route and repeated application of the drug after at least four-week cessation period

The Protective Effects of Silymarin against Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity in Rats

Silymarin is a complex of five major compounds, and silibinin is the most biologically active component of the complex. The aim of this study was to investigate, evaluate and confirm the potential cardioprotective and hepatoprotective effects of administration of silymarin, rich in silibinin, at a dose of 60 mg/kg orally for a time-span of 12 days on doxorubicin induced toxicity in male Wistar rats. The in vivo model was used to explore whether silymarin could prevent damage of liver and heart tissue induced by doxorubicin administered every other day at dose of 1.66 mg/kg intraperitoneally for twelve days. In the study the change of body weight, ECG changes, biochemical parameters of oxidative stress, serum activity of alanine and aspartate transaminase, lactate dehydrogenase, creatine kinase and histological preparations of heart and liver samples of treated animals were examined. According to physiological, pharmacological, microscopic and biochemical results, we confirmed that at the examined dose, silymarin exhibits a protective influence on the heart and liver tissue against toxicity induced by doxorubicin

Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia

Introduction Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. Methods We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1–9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient-specific primers were designed for each patient and used in semi-nested polymerase chain reaction for the detection of preleukemic clones at birth. Results Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis. Conclusion Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card-positive versus Guthrie card-negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events