Biomedical subjects

Jerry C Cheng

Publications and source records attributed to Jerry C Cheng.

6 recordsLinked to original sources

PubMed2005

Role of cyclic AMP response element binding protein in human leukemias.

Acute myeloid leukemia (AML) in adults has a 20% 5-year disease-free survival despite treatment with aggressive cytotoxic chemotherapy. Previous work from our laboratory demonstrated that the majority of patients with acute lymphoid and myeloid leukemia overexpress CREB in the bone marrow. CREB overexpression is associated with poor initial outcome of clinical disease in AML patients. CREB is a transcription factor that functions in glucose homeostasis, growth-factor-dependent cell survival, and memory. Signaling by hematopoietic growth factors, such as GM-CSF, results in activation of CREB and up-regulation of CREB target genes. To study its role in hematopoiesis, we overexpressed CREB in leukemia cell lines and in mice. CREB overexpression resulted in increased survival and proliferation of myeloid cells and blast-transformation of bone marrow progenitor cells from transgenic mice expressing CREB in the myeloid lineage. CREB transgenic mice also develop myeloproliferative disease after 1 year. Thus, CREB acts as a protooncogene to regulate hematopoiesis and contributes to the leukemia phenotype. Our results suggest that CREB-dependent pathways may serve as targets for directed therapies in leukemia in the future.

Acute Disease↗

PubMed2005

The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia.

CREB is a transcription factor that functions in glucose homeostasis, growth factor-dependent cell survival, and memory. In this study, we describe a role of CREB in human cancer. CREB overexpression is associated with increased risk of relapse and decreased event-free survival. CREB levels are elevated in blast cells from patients with acute myeloid leukemia. To understand the role of CREB in leukemogenesis, we studied the biological consequences of CREB overexpression in primary human leukemia cells, leukemia cell lines, and transgenic mice. Our results demonstrate that CREB promotes abnormal proliferation and survival of myeloid cells in vitro and in vivo through upregulation of specific target genes. Thus, we report that CREB is implicated in myeloid cell transformation.

ATP-Binding Cassette Transporters↗

PubMed2004

The emerging role of RNA interference in the design of novel therapeutics in oncology.

RNA interference (RNAi) has emerged as the tool of choice for studying gene function. Dubbed the "breakthrough of the year" in 2002 by the journal Science, RNAi is a naturally occurring host defense mechanism that mediates the sequence-specific degradation of target mRNA transcripts and their protein products. The specificity of RNAi makes it an ideal tool for targeted therapeutics against unique fusion oncogene sequences. RNAi may also be effective against viral-mediated oncogenesis and has the potential to enhance tumor sensitivities to existing chemotherapy. The current interest in the success of RNAi-based therapies will depend on the delivery systems that protect the silencing apparatus from endogenous nucleases, sustain tissue-specific expression of the small-interfering RNAs, and prevent the activation of a destructive nonspecific host immune response.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2004

Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary.

A 14-year-old girl was found to have a large, non-tender breast mass with anemia and thrombocytopenia. The diagnosis of an undifferentiated carcinoma of unknown primary was made after open breast biopsy of the mass with negative immunohistochemical studies for breast malignancies. Further evaluation showed extensive metastatic disease affecting the bone marrow, ribs, liver, and brain with magnetic resonance imaging evidence of carcinomatous meningitis. Despite 2 months of chemotherapy and intensive supportive care, the patient died of severe lactic acidosis and disseminated intravascular coagulation after exaggerated menstrual bleeding. The association of severe lactic acidosis and undifferentiated carcinoma of unknown primary in an adolescent has not been previously described.

Acidosis, Lactic↗

PubMedDate not supplied

RNA interference and human disease.

The completion of the human genome project has left researchers searching for an efficient method to study gene function in mammalian cells. RNA interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing (PTGS) mechanism mediated by double-stranded RNA (dsRNA). The dsRNA is processed into small duplex RNA molecules of approximately 21-22 nucleotides (nts) termed small interfering RNAs (siRNAs) by a RNase III enzyme called Dicer. Interaction of siRNAs with a multi-protein complex, termed the RNA-induced silencing complex (RISC), results in sequence specific association of the activated RISC complex with the cognate RNA transcript. This interaction leads to sequence-specific cleavage of the target transcript. Originally discovered in Caenorhabditis elegans, the study of RNAi in mammalian cells has blossomed in the last couple of years with the discovery that introduction of siRNA molecules directly into somatic mammalian cells circumvents the non-specific response vertebrate cells have against larger dsRNA molecules. Emerging as a powerful tool for reverse genetic analysis, RNAi is rapidly being applied to study the function of many genes associated with human disease, in particular those associated with oncogenesis and infectious disease. This review summarizes the mechanism of RNAi and provides an overview of its current applications in medicine.

Animals↗

PubMedDate not supplied

Improved documentation of wound care with a structured encounter form in the pediatric emergency department.

OBJECTIVE: Accurate and complete documentation may enhance reimbursement and compliance with financial intermediary regulations, protect against litigation, and improve patient care. We measured the effect of introduction of a structured encounter form on the completeness of documentation of pediatric wound management in a teaching hospital. METHODS: The Children's Hospital Emergency Department introduced a structured encounter form for use in the documentation of wound care in place of the existing free-text dictation method. Attending physicians and trainees, all unaware of the study, had the option of using the form in place of free-text dictation for patients with lacerations requiring closure. We abstracted 100 consecutive free-text dictations from patients treated before the form's introduction. Following a 3-month run-in period, we abstracted 100 consecutive structured wound records. We compared the 2 chart types for completeness of documentation based on 20 predetermined criteria relevant to pediatric wound care. RESULTS: Overall completeness of documentation improved with structured forms (80% vs 68% for free text, P < .001), with significant improvements in 6 of 20 individual criteria. Trainees demonstrated improvement in documentation with the structured form, with the greatest improvements among senior-level residents. Documentation of the general physical examination worsened with structured charting. DISCUSSION: In an academic pediatric emergency department, the use of a structured complaint-specific form improved overall completeness of wound-care documentation. Structured encounter forms may provide for more standardized documentation for a variety of pediatric chief complaints, thereby facilitating communication and ultimately transition to template-driven systems in anticipation of an electronic medical record.

California↗