Doxorubicin-induced second degree and complete atrioventricular block.

Doxorubicin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. Cardiotoxicity is the most important dose-limiting toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect of doxorubicin, it usually occurs many years after the treatment and relates to cumulative doxorubicin dosage. Another form of doxorubicin cardiotoxicity is arrhythmia which may occur at any time and after any dosage. However, doxorubicin-induced arrhythmia is rarely a life-threatening side effect. In this report, we present a case in which there were doxorubicin-induced life-threatening arrhythmias.     

A Turkish family with 6.7 Kb deletion associated with isolated growth hormone deficiency type 1A

Familial growth hormone deficiency type 1A is an autosomal recessive disease caused by homogenous deletions of both alleles of growth hormone gene 1 (hGH1) in various patterns. The hGH1 gene deletion is an event that probably occurs between the 5' and 3' flanking regions by unequal recombination, and results in deletion of the hGH1 gene in different patterns. Deletions are mostly 6.7 kb and rarely 7.0 kb, 7.6 kb and 45 kb in size. A four-year-old girl diagnosed with growth hormone deficiency syndrome was send to us for further evaluation. DNA samples of the patient, her parents and controls were amplified by polymerase chain reaction (PCR); furthermore, restriction endonuclease analysis was done with Sma I enzyme and the patterns were evaluated. Our gel electrophoresis results show that the gene deletion pattern of the patient represents a homogenous 6.7 kb deletion, while her parents had a heterogeneous 6.7 kb deletion pattern.     

Therapeutic Effects of AICAR and DOX Conjugated Multifunctional Nanoparticles in Sensitization and Elimination of Cancer Cells via Survivin Targeting

Purpose

Resistance to chemotherapy is one of the major problems facing current cancer research. Enhancing tumor cell response to anticancer agents increases chemotherapeutic effectiveness. We have recently addressed this issue and reported on producing multifunctional nanoparticles (Fe₃O₄@SiO₂(FITC)-FA/AICAR/DOX) aiming to overcome chemoresistance with synergetic effect of AICAR and DOX. In the present study, we demonstrated that these nanoparticles not only show enhanced cellular uptake and cytotoxic effect but can also show enhanced pro-apoptotic and anti-proliferative effects in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat and MIA PaCa-2).

Methods

The nanoparticles were examined by using flow cytometric analyses of apoptosis and cell cycle. In addition, we performed caspase-3 activity assay, which supported our flow cytometric data. Furthermore, we demonstrated the applicability of this approach in a variety of cancer types confirming the potential widespread utility of this approach.

Results

With the concept of co-delivery of AICAR and DOX in the nanoparticle formulation, the use of AICAR against survivin (BIRC5) sensitized cancer cells to DOX chemotherapy which resulted in effective cancer cell elimination. These result showed that combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent has the ability to retain and enhance therapeutic efficacy.

Conclusion

Fe₃O₄@SiO₂(FITC)-FA/AICAR/DOX nanoparticles is superior to monotherapy via the synergetic effect of AICAR and DOX and also the nanoparticle formulation could overcome issues of toxicity with targeted therapy while maintaining the potent anticancer effects of AICAR and DOX.

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Graphical Abstract Apoptosis analysis of A549 cells by flow cytometry-based PE-annexin-V / 7-ADD double staining treated with low-dose (10 μg/ml) concentration of (1) Fe3O4@SiO2(FITC)-FA (2) Fe3O4@SiO2(FITC)-FA/AICAR, (3) Fe3O4@SiO2(FITC)-FA/DOX or (4) Fe3O4@SiO2(FITC)-FA/AICAR/DOX nanoparticles. Viable cells labelled with PE-annexin-V(-)/7-ADD(-), early apoptotic cells labelled with PE-annexin-V(+)/7-ADD(-) and apoptotic cells labelled with PE-annexin-V(+)/ 7-ADD(+) in flow cytometric graphics.

     

Treatment of comorbidities besides the treatment of primary tumor may further increase effective management of cancer

For most of the patients with cancer comorbidity had independent prognostic effect. This negative influence of comorbidity on survival of cancer might be due to several mechanisms: the increased risk of death due to the comorbid condition itself, more contra-indications for anti-cancer treatment, more indications for dose reduction and a higher rate of treatment-related complications, such as infections and cardiovascular events. It is known that in some chronic diseases (e.g., coronary artery disease, hypertension, and obesity) pro-angiogenic growth factors are increased compared to controls and mostly normalized after specific treatment. We propose that increased pro-angiogenic growth factor levels in cancer patients due to comorbidities may lead to the progression of the tumors and poor prognosis. Treatment of comorbidities besides the treatment of primary tumor may further increase effective management of cancer.     

Meningitis due to Providencia stuartii

In this report, we present a case of postneurosurgical meningitis due to Providencia stuartii, which was treated successfully with meropenem therapy lasting 21 days.     

Rapid transformation of atypical myeloproliferative disorder with consistent t(8;13) to B-cell acute lymphoblastic leukemia: a case report

8p11 myeloproliferative syndrome (EMS; also known as the stem cell leukemia syndrome-SCLL) is a rare atypical myeloproliferative disorder associated with chromosomal abnormalities involving the 8p11 chromosomal band. Translocations associated with this syndrome result in the fusion of the fibroblast growth factor receptor 1 (FGFR 1) gene with various partners, resulting in ligand independent FGFR activity. The most commonly observed translocation of this syndrome is t(8;13), which results in the expression of a chimeric ZNF198-FGFR1 tyrosine kinase. Disease phenotype associated with this translocation has some typical features such as poor prognosis, and transformation to mainly acute leukemia and non-Hodgkin lymphoma; commonly with a T-cell phenotype in which obtaining and maintenance of remission is difficult by conventional chemotherapy. We hereby present a case diagnosed as atypical chronic myeloproliferative disease with consistent t(8;13)(p12;q12) and transformed rapidly to pre-B-cell acute lymphoblastic leukemia which is a rare clinical presentation.     

Rituximab-related viral infections in lymphoma patients

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.