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Filename: drivers/Session_files_driver.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
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Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
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Although targeting the Ras/Raf/MEK pathway remains a promising anticancer strategy, mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors in clinical development are likely to be limited in their ability to produce durable clinical responses due to the emergence of acquired drug resistance. To identify potential mechanisms of such resistance, we established MEK inhibitor-resistant clones of human HT-29 colon cancer cells (HT-29R cells) that harbor the B-RafV600E mutation. HT-29R cells were specifically resistant to MEK inhibition in vitro and in vivo, with drug-induced elevation of MEK/ERK and their downstream targets primarily accountable for drug resistance. We identified MEK1(F129L) mutation as a molecular mechanism responsible for MEK/ERK pathway activation. In an isogenic cell system that extended these findings into other cancer cell lines, the MEK1(F129L) mutant exhibited higher intrinsic kinase activity than wild-type MEK1 [MEK1(WT)], leading to potent activation of ERK and downstream targets. The MEK1(F129L) mutation also strengthened binding to c-Raf, suggesting an underlying mechanism of higher intrinsic kinase activity. Notably, the combined use of Raf and MEK inhibitors overcame the observed drug resistance and exhibited greater synergy in HT-29R cells than the drug-sensitive HT-29 parental cells. Overall, our findings suggested that mutations in MEK1 can lead to acquired resistance in patients treated with MEK inhibitors and that a combined inhibition of Raf and MEK may be potentially useful as a strategy to bypass or prevent drug resistance in the clinic.
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http://dx.doi.org/10.1158/0008-5472.CAN-10-4351 | DOI Listing |
J Int Med Res
December 2024
Department of Oncology Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with the poorest prognosis among all types of lung cancer. Developing an effective comprehensive strategy remains a key focus. We herein present the first documented case of a 68-year-old man with limited-stage SCLC who has maintained a complete response (CR) for over 30 months to date.
View Article and Find Full Text PDFAIDS Res Hum Retroviruses
December 2024
Department of Infectious Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
This study focuses on HIV-1-infected women of childbearing age in Liangshan Prefecture and analyses their HIV-1 RNA and HIV-1 DNA genotypic drug resistance to provide a theoretical basis and technical support for monitoring the spread of resistant strains and formulating and optimizing antiretroviral therapy regimens. The study subjects were HIV-1-infected women of childbearing age who were followed up in the county of Liangshan Prefecture from January to September 2023. Peripheral venous blood samples were collected from each subject.
View Article and Find Full Text PDFBiopolymers
January 2025
Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India.
Dipeptides were constructed using hydrophobic amino acid residues following AMP prediction. After that Boc-modification was performed on the screened peptides and finally Boc-Phe-Trp-OMe and Boc-Trp-Trp-OMe were synthesized. Even though no inhibition zones were observed in agar well diffusion assays, minimum inhibitory concentration (MIC) analysis revealed anti-bacterial activity against both Gram-positive and Gram-negative bacteria, with MIC ranging from 230 to 400 μg/mL.
View Article and Find Full Text PDFCell Oncol (Dordr)
December 2024
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Background: Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited treatment options. Lenvatinib, a tyrosine kinase inhibitor, has shown promise but is often undermined by the development of drug resistance.
Methods: Utilizing high-throughput sequencing, we investigated the molecular mechanisms underlying lenvatinib resistance in HCC cells, with a focus on metabolic pathways.
AMB Express
December 2024
Department of Laboratory Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine (The First Hospital of Changsha), Central South University, No. 311, Yingpan Road, Changsha, 410005, Hunan, China.
Antibiotic resistance by methicillin-resistant Staphylococcus aureus (MRSA) is an urgent threat to human health. The biofilm and persister cells formation ability of MRSA and Staphylococcus epidermidis often companied with extremely high antimicrobial resistance. Pinaverium bromide (PVB) is an antispasmodic compound mainly used for irritable bowel syndrome.
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