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Hongwei Wang

Publications and source records attributed to Hongwei Wang.

42 records · Page 3Linked to original sources

Linking molecular diagnostics to molecular therapeutics: targeting the PI3K pathway in breast cancer.

Modulation of the signaling pathways that are aberrant in cancer cells has the potential to provide an effective nontoxic approach to patient management in a broad range of cancers. This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Support for the concept of targeting products of fusion genes found in specific cancers was first provided by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia where the RARalpha all-trans retinoic acid target is the target of multiple different chromosomal rearrangements. In breast cancer, trastuzumab, which alters the function of the HER2 proto-oncogene overexpressed in a portion of breast cancers, provides an additional example of targeting specific molecular aberrations present in cancer cells. Although the target for these signal transduction modulators is functional in normal cells, acceptable therapeutic indices sufficient to prevent tumor growth without unacceptable toxicities have been observed. Whether STI-571 and other signal transduction modulators also target the stroma, and specifically the neovasculature, in addition to the tumor remains an open question. The presence of the target in the cancer cells or in the surrounding stroma appears to be required but not sufficient for the action of molecular therapeutics. Thus, linking molecular diagnostics to identify patients where the target is amplified or activated and driving the pathophysiology of the patients' tumor to effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for breast cancer patients. This review will focus on the phosphatidylinositol 3-kinase pathway and novel molecules targeting this pathway to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast cancer.

Animals↗

Targeting PI3K-AKT pathway for cancer therapy.

The phosphatidilinositol 3-kinase/protein kinase B (PI3K-AKT) pathway presents an exciting new target for molecular therapeutics. While exhibiting great promise, additional preclinical and clinical studies will be required to determine how best to target this pathway to improve patient outcome. A number of questions need to be answered prior to the implementation into patient care practices. As described below, the PI3K-AKT pathway regulates a broad spectrum of cellular processes, some of which are necessary to maintain normal physiological functions, which potentially contribute to the toxicity of the drugs targeting the pathway. Elucidation of the precise function of the PI3K-AKT isoforms, could promote the development of isoform specific approaches to provide a selective action on tumor cells. However, whether this will be possible due to conservation of structural domains is not yet clear. Inhibition of the PI3K-AKT pathway at multiple sites or a combination with inhibitors of different signaling pathways may allow the development of an acceptable therapeutic index for cancer management. Further, inhibition of the PI3K-AKT pathway combined with conventional chemotherapy or radiation therapy may provide a more effective strategy to improve patient outcome. As molecular therapeutics target the underlying defects in patient tumors, molecular diagnostics are required to identify patients with particular genetic aberrations in the pathway. It will be critical to provide adequate therapeutic strategies tailored to each patient. In addition, patients with different genetic backgrounds or in different health conditions could respond adversely to particular therapeutics. Therefore, identification of patients for particular drugs based on the underlying genetic defects in the tumor as well as the characteristics of the host would be of benefit for improving patient outcome. Linking the targeted therapeutics to molecular imaging approaches will determine appropriate biologically relevant dose for patients. It will also define expected tumor responsiveness and eventually will improve efficacy and decrease toxicity. In this regard, personalized molecular medicine is likely to soon provide effective cancer treatment.

Animals↗

[Cloning and functional analysis of promoter pagC from attenuated Salmonella typhimurium].

This study describes the cloning and function of promoter pagC (P(pagC)) from Salmonella typhimurium. The expression plasmid containing the in vivo-inducible promoter pagC and HGV-NS3 gene was introduced into the attenuated Salmonella typhimurium SL7207 to investigate the function of P(pagC). The expressed HGV-NS3 protein was detectable by SDS-PAGE and Western blotting in the recombinant bacteria in the presence of low concentration of Mg2+ (<50 mmol/L). When the concentration of Mg2+ reached to 50 mmol/L, the amount of expressed HGV-NS3 was decreased significantly. The recombinant bacteria were multiplied in LB medium containing 50 mmol/L of Mg2+ and used as a DNA vaccine to orally inoculate C57 mice for three times. The results of serum antibodies, T lymphocyte proliferative response and cytotoxic T lymphocyte response of immunized mice showed that the oral vaccine could iuduce strong humoral and cellular immune responses in mice, which indicates that the P(pagC) is a strong in vivo-inducible promoter and can be used in attenuated Salmonella typhimurium to construct an effective oral vaccine.

Animals↗

Confirmation of existence of a new syndrome: LAPS syndrome.

In l998, Hopkin et al. described a new disorder characterized by progressive laryngotracheal stenosis, short stature, and arthropathy. We provide extensive clinical information on two additional unrelated patients with this distinctive disorder and propose the name LAPS syndrome, to reflect the most consistently recognized features, namely, Laryngotracheal stenosis, Arthropathy, Prognathism, and Short stature.

Abnormalities, Multiple↗

Exploring nursing education in the People's Republic of China, Japan and Turkey.

The global nursing shortage has caused competition and cooperation between countries desperate for registered nurses (RNs), and has led to an increase in migration and international recruitment of nurses. Some nursing diplomas or degrees earned in one country may not be transferable to another. As a result, there is growing interest in common standards and competencies of entry-level nurses to guide future registered nurse agreements between countries or multi-country licensure programs. An exploratory study was conducted to investigate how entry-level nurses are educated throughout the world. The researchers sent a nursing education questionnaire to nurse educators in eleven countries inviting them to participate in the study. Nurse educators from The People's Republic of China, Japan and Turkey were the first to agree to participate in the study. They responded to questions about their country's nursing history, types of nursing programs, use of national nursing licensing examination, and social and political influences on nursing education. The nurse researchers did an analysis and comparison of the nursing education in each country.

China↗