Transfecting the hard-to-transfect lymphoma/leukemia cells using a simple cationic polymer nanocomplex.

Although the development of gene delivery systems via non-viral-mediated methods is advancing rapidly, it remains a challenge to deliver plasmids into hard-to-transfect cells, such as lymphoma/leukemia cells. To develop an efficient transfection method, we formulated a simple nanocomplex by incorporating poly β-amino ester (PBAE) polymers with plasmid DNAs containing a GFP reporter gene. The formed PBAE-plasmid nanocomplexes are approximately 200nm in diameter and stable under physiological conditions, but become rapidly biodegradable when pH decreases <7.

Structural messenger RNA contains cytokeratin polymerization and depolymerization signals.

We have previously shown that VegT mRNA plays a structural (translation-independent) role in the organization of the cytokeratin cytoskeleton in Xenopus oocytes. The depletion of VegT mRNA causes the fragmentation of the cytokeratin network in the vegetal cortex of Xenopus oocytes. This effect can be rescued by the injection of synthetic VegT RNA into the oocyte.

mRNA stability alterations mediated by HuR are necessary to sustain the fast growth of glioma cells.

Regulation of mRNA decay is an important mechanism controlling gene expression. Steady state levels of mRNAs can be markedly altered by changes in the decay rate. The control of mRNA stability depends on sequences in the transcript itself and on RNA-binding proteins that dynamically bind to these sequences.

Concomitant reconstruction of infrarenal aorta and inferior vena cava after en bloc resection of retroperitoneal rhabdomyosarcoma.

Adult paratesticular rhabdomyosarcoma (PRMS) with invasion of the retroperitoneum and involvement of the infrarenal aorta and inferior vena cava (IVC) is rare. We describe a 23-year-old male diagnosed with PRMS in 2008, previously treated with right orchiectomy, chemotherapy, and radiation, who presented with new onset of lower back pain. Computed tomography (CT) scan revealed a 4.

Interleukin-2 Functions in Anaplastic Large Cell Lymphoma Cells through Augmentation of Extracellular Signal-Regulated Kinases 1/2 Activation.

In addition to intrinsic genetic alterations, the effects of the extrinsic microenvironment also play a pathological role in cancer development. Altered chemokine/cytokine networks in the tumor microenvironment may contribute to the dysregulation of cellular functions in cancer cells. Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma caused by abnormal expression of anaplastic lymphoma kinase due to a chromosomal translocation.

Binary function of mRNA.

Since the discovery of messenger RNA (mRNA) over half a century ago, the assumption has always been that the only function of mRNA is to make a protein. However, recent studies of prokaryotic and eukaryotic organisms unexpectedly show that some mRNAs may be functionally binary and have additional structural functions that are unrelated to their translation product. These findings imply that some of the phenotypic features of cells and organisms can also be binary, that is, they depend both on the function of a protein and the independent structural function of its mRNA.

Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping.

Oncocytoma, chromophobe renal cell carcinoma (chRCC), and the eosinophilic variant of clear cell RCC (ccRCC) are morphologically similar tumors with significantly different clinical courses. These renal tumor subtypes show characteristic structural genetic changes; however, the mRNA expression patterns of oncocytoma and chRCC are strikingly similar. MicroRNAs (miRNA) are small RNA molecules that regulate the expression of many genes and have been shown to be useful for tumor classification and identification.

Allochimeric molecules and mechanisms in abrogation of cardiac allograft rejection.

Background: Dendritic cells are professional antigen presenting cells that perform antigen processing and antigen presentation functions and rely on the proper functioning and distribution of the endoplasmic reticulum (ER) and Golgi apparatus and of vesicular trafficking pathways. We previously developed a model system to study the mechanisms governing inhibition of chronic rejection of heart allografts.

Methods: Heterotopic cardiac transplants were placed intra-abdominally and the major histocompatibility class (MHC) class I allochimeric molecule, [α1h1/u]-RT1.

A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma.

Background: Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy.

Results: In this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL) by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK) gene in lymphoma cells.

Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo.

The objective of this study was to determine the effects of an luteinizing hormone-releasing hormone (LHRH)-I antagonist, Cetrorelix, on human multiple myeloma (MM) cells and to elucidate the mechanisms of action. We showed that LHRH-I and LHRHR-I genes were expressed in MM cell lines and primary MM cells. Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, including cell lines resistant to arsenic trioxide, bortezomib, or lenalidomide.

Transfection of shRNA-encoding Minivector DNA of a few hundred base pairs to regulate gene expression in lymphoma cells.

This work illustrates the utility of Minivector DNA, a non-viral, supercoiled gene therapy vector incorporating short hairpin RNA from an H1 promoter. Minivector DNA is superior to both plasmid DNA and small interfering RNA (siRNA) in that it has improved biostability while maintaining high cell transfection efficiency and gene silencing capacity. Minivector DNAs were stable for over 48 h in human serum, as compared with only 0.

Local control after craniospinal irradiation, intensity-modulated radiotherapy boost, and chemotherapy in childhood medulloblastoma.

Background: The current study was conducted to determine whether the use of cochlear-sparing intensity-modulated radiotherapy (IMRT) boost results in excess local failures in children with medulloblastoma.

Methods: Fifty children with a median age of 7.8 years underwent resection, craniospinal irradiation (CSI), IMRT posterior fossa (PF) and/or tumor bed (TB) boost, and cisplatin-based chemotherapy for medulloblastoma.

Reproducibility and performance of virtual karyotyping with SNP microarrays for the detection of chromosomal imbalances in formalin-fixed paraffin-embedded tissues.

Background: Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues.

Using oligonucleotide aptamer probes for immunostaining of formalin-fixed and paraffin-embedded tissues.

For tissue immunostaining, antibodies are currently the only clinically validated and commercially available probes. Aptamers, which belong to a class of small molecule ligands composed of short single-stranded oligonucleotides, have emerged as probes over the last several decades; however, their potential clinical value has not yet been fully explored. Using cultured cells and an RNA-based CD30 aptamer, we recently demonstrated that the synthetic aptamer is useful as a specific probe for flow cytometric detection of CD30-expressing lymphoma cells.

Downregulation of RhoA and changes in T cell cytoskeleton correlate with the abrogation of allograft rejection.

Proper actin cytoskeleton architecture and dynamics are indispensable for events in the immunological response such as T cell migration, redistribution of T cell receptors, and interaction with antigen presenting cells. Thus, T cell activation, downstream signaling events and effector functions are all actin-dependent. Actin cytoskeleton architecture and dynamics are regulated by proteins belonging to the superfamily of small GTP-binding proteins, such as RhoA GTPase.

Synergistic growth inhibition of anaplastic large cell lymphoma cells by combining cellular ALK gene silencing and a low dose of the kinase inhibitor U0126.

Abnormal expression of anaplastic lymphoma kinase (ALK) gene is an important pathogenic factor for anaplastic large cell lymphoma (ALCL). To study the function of ALK, an inducible short hairpin RNA (shRNA) system was stably introduced into cultured human ALCL cells. Inducing shRNA expression in the generated cells resulted in cellular ALK gene silencing and led to inactivation of multiple signaling pathways and growth arrest.

Ototoxicity after intensity-modulated radiation therapy and cisplatin-based chemotherapy in children with medulloblastoma.

Purpose: To report the incidence of Pediatric Oncology Group (POG) Grade 3 or 4 ototoxicity in a cohort of patients treated with craniospinal irradiation (CSI) followed by posterior fossa (PF) and/or tumor bed (TB) boost using intensity-modulated radiation therapy (IMRT).

Methods And Materials: From 1998 to 2006, 44 patients with medulloblastoma were treated with CSI followed by IMRT to the PF and/or TB and cisplatin-based chemotherapy. Patients with standard-risk disease were treated with 18 to 23.

Bone marrow stromal cells from myeloma patients support the growth of myeloma stem cells.

It has been well documented that bone marrow stromal cells (BMSCs) of multiple myeloma patients play a pivotal role in supporting the growth of mature myeloma cells. With evolving concepts concerning the presence of myeloma stem (initiating) cells, we aimed this investigation to specifically address the supportive role of BMSCs for myeloma stem cell growth in vitro and in vivo. BMSC lines were derived from myeloma or control patients (myeloma or control BMSCs).

Computer-assisted quantitative evaluation of therapeutic responses for lymphoma using serial PET/CT imaging.

Rationale And Objectives: Molecular imaging modalities such as positron emission tomography (PET)/computed tomography (CT) have emerged as an essential diagnostic tool for monitoring treatment response in lymphoma patients. However, quantitative assessment of treatment outcomes from serial scans is often difficult, laborious, and time consuming. Automatic quantization of longitudinal PET/CT scans provides more efficient and comprehensive quantitative evaluation of cancer therapeutic responses.

Diagnosis of uncertain primary tumors with the Pathwork tissue-of-origin test.

Clinical workup of metastatic malignancies of unknown origin is an arduous and expensive process, which is reported to be unsuccessful in up to 30% of cases. Global gene expression-based molecular testing may offer accurate classification of metastatic tumors in which a primary site has not been identified. Recently, the US FDA cleared the Pathwork((R)) tissue-of-origin test, which is a gene expression microarray-based test that quantifies the molecular similarity of tumor specimens to 15 known tissue types.

Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma.

Background: Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma (DLBCL). Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related) and PCM using array-based comparative genomic hybridization.

p38 Mitogen-activated protein kinase and hematologic malignancies.

Context: p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in responses ranging from apoptosis to cell cycle, induction of expression of cytokine genes, and differentiation. This plethora of activators conveys the complexity of the p38 pathway. This complexity is further complicated by the observation that the downstream effects of p38 MAPK activation may be different depending on types of stimuli, cell types, and various p38 MAPK isoforms involved.

Unique biomechanical interactions between myeloma cells and bone marrow stroma cells.

We observed that BMSCs (bone marrow stromal cells) from myeloma patients (myeloma BMSCs) were significantly stiffer than control BMSCs using a cytocompression device. The stiffness of myeloma BMSCs and control BMSCs was further increased upon priming by myeloma cells. Additionally, myeloma cells became stiffer when primed by myeloma BMSCs.

Central venous pressure versus pulmonary artery catheter-directed shock resuscitation.

Previously, we developed a protocol for shock resuscitation of severe trauma patients to reverse shock and regain hemodynamic stability during the first 24 intensive care unit (ICU) hours. Key hemodynamic measurements of cardiac output and preload were obtained using a pulmonary artery catheter (PAC). As an alternative, we developed a protocol that used central venous pressure (CVP) to guide decision making for interventions to regain hemodynamic stability [mean arterial pressure (MAP) >or= 65 mmHg and heart rate (HR) View Article and Find Full Text PDF