Bi-weekly Chemotherapy of Paclitaxel and Cisplatin in Patients with Metastatic or Recurrent Esophageal Cancer

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m2) followed by cisplatin (50 mg/m2). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC

<p>Abstract</p> <p>Background</p> <p>RET/PTC (rearranged in transformation/papillary thyroid carcinomas) gene rearrangements are the most frequent genetic alterations identified in papillary thyroid carcinoma. Although it has been established that RET/PTC kinase plays a crucial role in intracellular signaling pathways that regulate cellular transformation, growth, and proliferation in thyroid epithelial cells, the upstream signaling that leads to the activation of RET/PTC is largely unknown. Based on the observation of high levels of PLD expression in human papillary thyroid cancer tissues, we investigated whether PLD plays a role in the regulating the RET/PTC-induced STAT3 activation.</p> <p>Methods</p> <p>Cancer tissue samples were obtained from papillary thyroid cancer patients (n = 6). The expression level of PLD was examined using immunohistochemistry and western blotting. Direct interaction between RET/PTC and PLD was analyzed by co-immunoprecipitation assay. PLD activity was assessed by measuring the formation of [³H]phosphatidylbutanol, the product of PLD-mediated transphosphatidylation, in the presence of <it>n</it>-butanol. The transcriptional activity of STAT3 was assessed by m67 luciferase reporter assay.</p> <p>Results</p> <p>In human papillary thyroid cancer, the expression levels of PLD2 protein were higher than those in the corresponding paired normal tissues. PLD and RET/PTC could be co-immunoprecipitated from cells where each protein was over-expressed. In addition, the activation of PLD by pervanadate triggered phosphorylation of tyrosine 705 residue on STAT-3, and its phosphorylation was dramatically higher in TPC-1 cells (from papillary carcinoma) that have an endogenous RET/PTC1 than in ARO cells (from anaplastic carcinoma) without alteration of total STAT-3 expression. Moreover, the RET/PTC-mediated transcriptional activation of STAT-3 was synergistically increased by over-expression of PLD, whereas the PLD activity as a lipid hydrolyzing enzyme was not affected by RET/PTC.</p> <p>Conclusion</p> <p>These findings led us to suggest that the PLD synergistically functions to activate the STAT3 signaling by interacting directly with the thyroid oncogenic kinase RET/PTC.</p

Layer Engineered MXene Empowered Wearable Pressure Sensors for Non-Invasive Vital Human–Machine Interfacing Healthcare Monitoring

Pressure sensors with high flexibility and sensitivity face significant challenges in meeting the delicate balance and synergy among suitable active sensing electrode materials, substrates, and their device geometry design. In this contribution, layer-engineered delaminated Ti-MXene (DL-Ti3C2Tx) is introduced, which has relatively wider interlayer spacing through intercalated large organic molecules and accordion-like open internal microstructure than the narrower pristine Ti3C2Tx MXene (Ti-MXene), graphene/carbon nanotube&apos;s interlayer spacing suitably fulfill the high sensitivity and flexibility requirement through accessible electronic pathways under the external pressure. Notably, a milder in-situ ambient condition etching is performed to eliminate the associated safety risks for a flexible personal healthcare monitoring pressure sensor. DL-Ti3C2Tx MXene-empowered, flexible pressure sensor demonstrates a broad range of sensitivities up to a very high-pressure of 20.8kPa at a sensitivity of 242.3 kPa−1 with a fast response and recovery time (<300ms). A twofold increase in pressure sensitivity performance of DL-Ti3C2Tx MXene than that of Ti-MXene, graphene can be attributed to the engineered wider interlayer distance among the delaminated DL-Ti3C2Tx MXene layers causing a facile interlayer atomic movements, contacts, and reversible compressibility. The current economical, scalable DL-Ti3C2Tx MXene flexible pressure sensor can provide future safe personal healthcare artificial intelligence with real-time tracking ability. © 2023 Wiley-VCH GmbH.FALS

A 1.2-V 1.5-Gb/s 72-Mb DDR3 SRAM

A 1.2-V 72-Mb double data rate 3 (DDR3) SRAM achieves a data rate of 1.5 Gb/s using dynamic self-resetting circuits [5]. Single-ended main data lines halve the data line precharging power dissipation and the number of data lines. Clocks phase shifted by 0 , 90 , and 270 are generated through the proposed clock adjustment circuits. The proposed clock adjustment circuits make input data sampled with optimized setup/hold window. On-chip input termination with the linearity error of 4.1% is developed to improve signal integrity at higher data rates. A 1.2-V 1.5-Gb/s 72-Mb DDR3 SRAM is fabricated in a 0.10- m CMOS process with five metals. The cell size and the chip size are 0.845 m2 and 151.1 mm2, respectively.Published versio

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC-5

Ds. The tissue extracts and transfectant controls of PLD1/PLD2 were applied to SDS-PAGE for Western blotting with antibodies directed against PLD and β-actin. (B) Immunohistochemistry of PLD in normal and cancerous tissue. PLD2 was highly expressed in papillary thyroid cancer tissue () compared to faintly stained normal thyroid tissue (). () Negative isotype control with preimmune mouse IgG1. Original magnification, 100×. (C) Expression of RET/PTC-1 in malignant papillary thyroid cancer tissue. After the normal and cancer tissues were lysed and the total RNA was isolated, RT-PCR was performed with the primers specific to the human RET/PTC1 and GAPDH. After the PCR amplification, the products were separated by agarose gel electrophoresis and visualized using ethidium bromide staining. The results are representative of three independent experiments.<p><b>Copyright information:</b></p><p>Taken from "Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC"</p><p>http://www.biomedcentral.com/1471-2407/8/144</p><p>BMC Cancer 2008;8():144-144.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2412888.</p><p></p

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC-0

Ds. The tissue extracts and transfectant controls of PLD1/PLD2 were applied to SDS-PAGE for Western blotting with antibodies directed against PLD and β-actin. (B) Immunohistochemistry of PLD in normal and cancerous tissue. PLD2 was highly expressed in papillary thyroid cancer tissue () compared to faintly stained normal thyroid tissue (). () Negative isotype control with preimmune mouse IgG1. Original magnification, 100×. (C) Expression of RET/PTC-1 in malignant papillary thyroid cancer tissue. After the normal and cancer tissues were lysed and the total RNA was isolated, RT-PCR was performed with the primers specific to the human RET/PTC1 and GAPDH. After the PCR amplification, the products were separated by agarose gel electrophoresis and visualized using ethidium bromide staining. The results are representative of three independent experiments.<p><b>Copyright information:</b></p><p>Taken from "Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC"</p><p>http://www.biomedcentral.com/1471-2407/8/144</p><p>BMC Cancer 2008;8():144-144.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2412888.</p><p></p

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC-2

Ndicated, 10 min before the end of the treatment, cells were incubated with 0.3% -butanol. Radioactivity incorporated into PtdBut was measured as described in Methods. Each bar shows mean ± SE of at least of three independent experiments. * < 0.05, when compared with none-treated ARO cells. # < 0.05, when compared with pervanadate-treated ARO cells. (B) ARO and TPC-1 cells were treated with the various concentrations of pervanadate for 30 min as indicated. Whole cell lysates were analyzed by SDS-PAGE and Western blotting with antibodies against phosphorylated STAT3 (Y705), RET and PLD2. To confirm equal amounts of protein were loaded, the blots were reproved using an antibody against total STAT3 and β-actin. (C) TPC-1 cells were pretreated with -butanol for indicated concentrations or 2% -butanol and then treated with 10 μM pervanadate for 30 min. Cell extracts were analyzed by SDS-PAGE and Western blotting with antibodies against phosphoY705-STAT3 and STAT3. (D, E) ARO cells were transiently transfected with mock vector and RET/PTC1 (D) or RET/PTC3 (E) expression plasmids. At 24 h transfection, the cells were untreated or treated with 50 μM pervanadate for 30 min, and then total cell lysates were prepared and blotted with anti-phosphoY705-STAT3, anti-STAT3 and anti-RET antibodies. The figure is representative of at least three separate experiments.<p><b>Copyright information:</b></p><p>Taken from "Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC"</p><p>http://www.biomedcentral.com/1471-2407/8/144</p><p>BMC Cancer 2008;8():144-144.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2412888.</p><p></p

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC-1

Munoprecipitated with anti-RET (upper panel) or anti-flag (lower panel) antibodies, and then immunoprecipitants were analyzed by Western blotting with anti-flag or anti-RET antibodies. The efficiency of immune-precipitant was measured with anti-RET and anti-flag antibodies (each bottom panel). (B) TPC-1 cells were transfected with RET/PTC1 expression plasmid, and whole cell lysate was immnunoprecipitated with antibodies directed against RET and normal IgG. Immunoprecipitates were analyzed by Western blotting with anti-PLD antibody (upper panel). The efficiency of immune-precipitant was measured with anti-RET antibody (bottom panel). One percent of cell extracts from sample was used as a control of protein input. (C) HEK293 cells were transfected with various combinations of plasmids encoding an empty vector, RET/PTC1 plus either flag-tagged wild-type (wt)- or lipase inactive mutant (KRM)- PLD2. Cell lysates were immunoprecipitated with anti-flag antibody, and then immunoprecipitants were analyzed by Western blotting with anti-RET antibody (upper panel). The efficiency of immune-precipitant was measured with anti-flag antibody (bottom panel).<p><b>Copyright information:</b></p><p>Taken from "Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC"</p><p>http://www.biomedcentral.com/1471-2407/8/144</p><p>BMC Cancer 2008;8():144-144.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2412888.</p><p></p