Publications by authors named "Lin Bo-Wen"

Clarifying the inceptive pathophysiology of hypertensive heart disease helps to impede the disease progression. Through coarctation of the infrarenal abdominal aorta (AA), we induced hypertension in minipigs and evaluated physiological reactions and morpho-functional changes of the heart. Moderate aortic coarctation was achieved with approximately 30 mmHg systolic pressure gradient in minipigs.

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This multicenter study explored the survival benefits of upfront primary tumor resection (PTR) followed by first-line cetuximab plus chemotherapy in real-world patients with wild-type metastatic colorectal cancer (mCRC). Treatment options for mCRC include chemotherapy, targeted therapy, immunotherapy, and surgery. The efficacy of upfront PTR in managing mCRC remains unclear.

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Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge.

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Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers.

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Article Synopsis
  • A multicenter study assessed the survival benefits of combining metastasectomy with first-line cetuximab-based chemotherapy in patients with wild-type metastatic colorectal cancer (mCRC), measuring overall survival (OS) and progression-free survival (PFS) as primary endpoints.
  • Of the 758 enrolled patients, the study found that those who underwent metastasectomy had significantly better OS (54.9 months) and PFS (21.0 months) compared to those who did not, highlighting the importance of this surgical intervention in treatment outcomes.
  • The analysis also identified that patients receiving 14 or more treatment cycles had improved survival rates and higher chances of undergoing metastasectomy, suggesting this as an optimal treatment duration for maximizing outcomes in m
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Multigene mutations in colorectal cancer (CRC), including KRAS, BRAF, and p53, afford high metastatic ability and resistance to EGFR-targeting therapy. Understanding the molecular mechanisms regulating anti-EGFR-resistant CRC metastasis can improve CRC therapy. This study aimed to investigate the effects of IL-8 and the activation of KRAS on reactive oxygen species (ROS) production and metastasis of hyperlipidemia-associated CRC harboring mutations of KRAS and p53.

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Article Synopsis
  • Malnutrition is a frequent issue in patients with metastatic colorectal cancer (mCRC) undergoing targeted therapy and chemotherapy, leading to increased toxicity and lower survival rates.
  • This study analyzed data from 758 patients treated with cetuximab and chemotherapy, separating them into groups that did or did not receive supplemental home parenteral nutrition (HPN).
  • Results showed that the HPN group had higher rates of successful surgeries, longer treatment durations, and improved overall and progression-free survival compared to the non-HPN group, suggesting HPN may enhance treatment outcomes for certain mCRC patients.
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  • Metastasis, the spread of cancer to other parts of the body, is a key factor in the high mortality rates of colorectal cancer, with nuclear TYRO3 receptor identified as a major predictor of poor patient outcomes.
  • The study reveals that the kinase activity of nuclear TYRO3 and its effect on matrix metalloproteinase-2 (MMP-2) are crucial for promoting metastasis, while emphasizing that this process does not require a ligand to function.
  • Researchers found that the interaction between TYRO3, MMP-2, and bromodomain-containing protein 3 (BRD3) can lead to drug resistance and enhanced metastasis, suggesting that targeting this pathway could help improve treatment outcomes for colorectal cancer
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Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo.

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Aim: The OPTIM1SE study observed long-term real-world outcomes of cetuximab-based infusional 5-fluorouracil (5-FU) regimens for first-line treatment of metastatic colorectal cancer (mCRC) across Asia-Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice.

Methods: OPTIM1SE was a prospective, open-label, observational study. Patients with untreated KRAS wild-type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records.

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Background: The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC.

Methods: We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching.

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Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort.

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Objective: To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post-stenotic dilatation (PSD) porcine model.

Methods: The porcine abdominal aorta (AA) was moderately coarctated to induce overt flow turbulence in the downstream region and to lead to dilatation in time periods between four and twelve weeks. We propose a new metric, fluctuation intensity (FI), to quantify turbulent fluctuations of pulsatile aortic flow measured within twenty minutes post-coarctation.

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Background: Colorectal cancer (CRC), the most common cancer type, causes high morbidity and mortality. Patients who develop drug resistance to oxaliplatin-based regimens have short overall survival. Thus, identifying molecules involved in the development of oxaliplatin resistance is critical for designing therapeutic strategies.

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The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, we illustrated the relationships between germline eVariants, TME-based immune response eGenes, and clinical outcomes.

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Article Synopsis
  • Colorectal cancer (CRC) is a common cancer globally, and identifying risk factors for tumor recurrence is crucial for patient treatment and survival after surgery.
  • Researchers developed a prediction algorithm using four machine learning models (logistic regression, random forest, CART, and support vector machine) based on clinicopathological data from 1,073 patients with stage II and III CRC.
  • The logistic regression model showed the best predictive accuracy (AUC of 0.678), while several significant risk factors for tumor recurrence were identified, including chemotherapy, tumor stage, lymph node involvement, and various invasion types.
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Systemic characterization of genomic alterations into signaling pathways helps to understand the molecular pathogenies of colorectal cancer; however, their clinical implications remain unclear. Here, 128 patients with metastatic colorectal cancer (mCRC) receiving targeted next generation sequencing were retrospectively enrolled to analyze the impact of altered oncogenic pathways on clinical outcome. The datasets from Memorial Sloan Kettering Cancer Center were used for validation.

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Article Synopsis
  • Recent advances in therapeutic options for metastatic colorectal cancer (mCRC) have complicated treatment decision-making despite improvements from oncology guidelines.
  • A consensus paper was developed over three years with expert discussions to fill gaps in international guidelines, focusing on real-world practices in Taiwan for better mCRC management.
  • The resulting recommendations include criteria for patient treatment plans based on fitness for treatment, molecular characteristics, and specific patient profiles, enhancing the approach to mCRC care in Taiwan.
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Tumor heterogeneity results in more than 50% of hypermutated cancers failing to respond to standard immunotherapy. There are numerous challenges in terms of drug resistance, therapeutic strategies, and biomarkers in immunotherapy. In this study, we analyzed primary tumor samples from 533 cancer patients with six different cancer types using deep targeted sequencing and gene expression data from 78 colorectal cancer patients, whereby driver mutations, mutational signatures, tumor-associated neoantigens, and molecular cancer evolution were investigated.

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The analysis of cell-free DNA (cfDNA) is rapidly emerging as a powerful approach to guide the clinical care of cancer patients. Several comprehensive cfDNA assays designed to detect mutations across several genes are now available. Here, we analyzed the use of a cfDNA panel in colorectal cancer (CRC) patients.

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Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse effect that causes delayed treatment and poor prognosis among colorectal cancer (CRC) patients. However, its mechanism remains elusive, and no effective treatment is available. We employed a prospective cohort study of adult patients with pathologically confirmed stage III CRC receiving adjuvant chemotherapy with an oxaliplatin-based regimen for investigating OIPN.

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Background: Certain sequences of genomic mutations can lead to cancer formation and affect treatment outcomes and drug resistance. We constructed a cancer evolutionary tree using bulk-targeted deep sequencing to explore the impact of sequential and co-occurring somatic mutations on patients with stage III colorectal cancer (CRC).

Methods: A total of 108 stage III CRC patients from National Cheng Kung University Hospital (NCKUH) were recruited for this study between Jan.

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Article Synopsis
  • This study evaluates the safety and effectiveness of regorafenib for metastatic colorectal cancer in a Taiwanese group within the larger CORRELATE study, which included participants from multiple countries.
  • Involving 128 Taiwanese patients with a median age of 64, the study found high rates of dose reductions and interruptions, with a notable incidence of hand-foot-skin reactions affecting about a third of participants.
  • The results showed a median overall survival of 11.64 months and progression-free survival of 2.17 months, aligning with previous findings from clinical trials involving Asian patients.
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Microsatellite instability (MSI) is reflective of a deficient mismatch repair (dMMR) system, which is mostly associated with the methylation of mismatch repair (MMR) genes and BRAF mutations in sporadic colorectal cancers (CRCs). We performed a retrospective study to analyze the clinicopathological features of dMMR CRCs and their association with the BRAF V600E mutation. The incidence of dMMR CRCs in our cohort was 7.

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