982 research outputs found

    Senior Recital

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    A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer

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    Background: Neoadjuvant chemotherapy with concurrent docetaxel, doxorubicin and cyclophosphamide is commonly used for patients with locally advanced breast cancer. Epirubicin is another anthracycline used in breast cancer but the concurrent use of epirubicin and taxane is not well-established. We conducted a single institution, phase II study to assess the efficacy and safety of concurrent docetaxel, epirubicin and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen in breast cancer. Methods: Patients with newly diagnosed locally advanced breast cancer defined as T2 >3 cm, T3, T4 with any N, or any T with N1-3 were eligible. A chemotherapy regimen of docetaxel 75mg/m2, epirubicin 75mg/m2 and cyclophosphamide 600mg/m2 was given with filgrastim support every 3 weeks for 6 cycles. The primary end-point was pathologic complete response rate. Results: Twenty patients were enrolled from 2003 to 2006. The median age was 51 (29-70) year-old. Eight patients were premenopausal. Ten patients had positive hormone receptors. Four patients had HER2 positive receptor. Nineteen patients completed six cycles of TEC chemotherapy. The pathologic complete response rate was 25%. Eight of sixteen patients with N1-3 disease had pathological negative lymph nodes. With a median follow up of 57.5 (16-71) months, four patients relapsed including one death from recurrence. The estimated 5 year relapse-free survival was 79.3% and the 5-year overall survival was 94.7%. No patient had cardiac failure or death during treatment. The most common grade 3-4 toxicity was neutropenia (35%). Conclusion: TEC regimen is a well- tolerated and effective neoadjuvant chemotherapy regimen for locally advanced breast cancer that results in a pathologic complete response rate of 25%

    mab-31 and the TGF-β pathway act in the ray lineage to pattern C. elegans male sensory rays

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    <p>Abstract</p> <p>Background</p> <p><it>C. elegans </it>TGF-β-like Sma/Mab signaling pathway regulates both body size and sensory ray patterning. Most of the components in this pathway were initially identified by genetic screens based on the small body phenotype, and many of these mutants display sensory ray patterning defect. At the cellular level, little is known about how and where these components work although ray structural cell has been implicated as one of the targets. Based on the specific ray patterning abnormality, we aim to identify by RNAi approach additional components that function specifically in the ray lineage to elucidate the regulatory role of TGF-β signaling in ray differentiation.</p> <p>Result</p> <p>We report here the characterization of a new member of the Sma/Mab pathway, <it>mab-31</it>, recovered from a genome-wide RNAi screen. <it>mab-31 </it>mutants showed ray cell cluster patterning defect and mis-specification of the ray identity. <it>mab-31 </it>encodes a nuclear protein expressed in descendants of ray precursor cells impacting on the ray cell's clustering properties, orientation of cell division plane, and fusion of structural cells. Genetic experiments also establish its relationship with other Sma/Mab pathway components and transcription factors acting upstream and downstream of the signaling event.</p> <p>Conclusion</p> <p><it>mab-31 </it>function is indispensable in Sma/Mab signal recipient cells during sensory rays specification. Both <it>mab-31 </it>and <it>sma-6 </it>are required in ray lineage at the late larval stages. They act upstream of <it>C. elegans Pax-6 </it>homolog and repress its function. These findings suggested <it>mab-31 </it>is a key factor that can integrate TFG-β signals in male sensory ray lineage to define organ identity.</p

    Cultural orientation of self-bias in perceptual matching

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    This work was supported by grants from the Economic and Social Research Council (ES/K013424/1), the National Natural Science Foundation of China (31371017), and the Research Grants Council of Hong Kong (HKU758412H)Peer reviewedPublisher PD

    Provider-Initiated HIV Testing and Counseling: Increased Uptake in Two Public Community Health Centers in South Africa and Implications for Scale-Up

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    BACKGROUND: International guidance recommends the scale up of routinely recommended, offered, and delivered health care provider-initiated HIV testing and counseling (PITC) to increase the proportion of persons who know their HIV status. We compared HIV test uptake under PITC to provider-referral to voluntary counseling and testing (VCT referral) in two primary health centers in South Africa. METHODS: Prior to introducing PITC, clinical providers were instructed to refer systematically selected study participants to VCT. After PITC and HIV rapid test training, providers were asked to recommend, offer and provide HIV testing to study participants during the clinical consultation. Participants were interviewed before and after their consultation to assess their HIV testing experiences. RESULTS: HIV test uptake increased under PITC (OR 2.85, 95% CI 1.71, 4.76), and more patients felt providers answered their questions on HIV (104/141 [74%] versus 73/118 [62%] for VCT referral; p 0.04). After three months, only 4/106 (3.8%) HIV-positive patients had registered for onsite HIV treatment. Providers found PITC useful, but tested very few patients (range 0-15). CONCLUSION: PITC increased the uptake of HIV testing compared with referral to onsite VCT, and patients reported a positive response to PITC. However, providing universal PITC will require strong leadership to train and motivate providers, and interventions to link HIV-positive persons to HIV treatment centers

    A functional Notch–survivin gene signature in basal breast cancer

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    INTRODUCTION: Basal-type, or triple-negative, breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression) is a high-risk disease for which no molecular therapies are currently available. We studied genetic signatures of basal breast cancer potentially suitable for therapeutic intervention. METHODS: We analyzed protein expression of the Notch-1 intracellular domain and survivin by immunohistochemistry in a series of basal breast cancer patients. A hierarchical clustering and overall survival analysis was carried out on a microarray mRNA database of 232 breast cancer patients. Fifteen published mRNA datasets containing estrogen receptor-negative or estrogen receptor-positive samples were subjected to meta-analysis for co-segregated gene expression. Experiments of plasmid transfection and gene silencing were carried out in estrogen receptor-negative MDA-MB-231 breast cancer cells. RESULTS: The developmental signaling regulator Notch-1 was highly expressed in breast cancer, compared with normal tissue, and was segregated with basal disease. Higher Notch-1 levels correlated with progressively abbreviated overall survival, and with increased expression of survivin, a tumor-associated cell death and mitotic regulator implicated in stem cell viability. Analysis of Pearson\u27s correlation coefficient indicated that Notch-1 and survivin co-segregated in basal breast cancer. Notch-1 stimulation in MDA-MB-231 cells increased survivin expression, whereas silencing Notch reduced survivin levels. CONCLUSIONS: A Notch-1-survivin functional gene signature is a hallmark of basal breast cancer, and may contribute to disease pathogenesis. Antagonists of Notch and survivin currently in the clinic may be tested as novel molecular therapy for these recurrence-prone patients

    An integrated method for identifying present status and risk of drought in Bangladesh

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    The occurrence and severity of agricultural droughts may not be dependent upon climatic variables alone. Rather increasingly, drought is affected by human interventions such as irrigation. Anthropogenic activity has introduced uncertainty in the assessment of current drought and future drought risk in many parts of the world; neither climatic nor remote sensing data alone are able to assess drought conditions effectively. In response, we present a simple approach to assess drought by combining a remote sensing-based drought index, the Temperature Vegetation Dryness Index (TVDI), climate data (i.e., rainfall and temperature), and field observations to evaluate recent drought conditions in northwestern Bangladesh (NWB). Applying this approach, we gained five insights: (i) the TVDI successfully indicated the drought conditions of NWB and agrees with field observations, (ii) the integrated use of TVDI and climate data (such as rainfall and temperature) provides the best understanding of the difference between meteorological drought and droughts resulting from surface moisture conditions, (iii) the TVDI results agree with rainfall data (r2 = 0.40 in March and r2 = 46 in April) in a part of the study area (NWB) where irrigation is not available, (iv) the TVDI can be used along with climate data to predict the potential risk of drought, and (v) while meteorological drought exists due to low rainfall and high temperature in this NWB in pre-monsoon season, because of widespread irrigation practices, meteorological drought is unable to trigger agricultural drought over most parts of the study area. The findings imply that there is a potential risk of drought in NWB, since any disruption of irrigation water supply could trigger a severe agricultural drought over the whole region. This is similar to what is currently observed over a small part of NW
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