Publications by authors named "Liam Chung"

Background And Objectives: Due to heterogeneous characteristics of primary cancers, the efficacy of pulmonary metastasectomy (PM) in nonprimary lung cancers has not been investigated. This study aims to investigate the clinical outcomes of PM for non-primary lung cancer.

Methods: A systematic search for meta-analyses on PM for nonprimary lung cancers was conducted, encompassing publications up to January 3, 2024.

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Background: Anti-programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 antibodies are efficacious in various malignancies.

Objectives: This study presents the first results of ipilimumab-nivolumab in invasive mucinous or non-mucinous lepidic adenocarcinoma (invasive mucinous adenocarcinoma (IMA) or invasive non-mucinous lepidic adenocarcinomas (INLA), respectively) of the lung.

Design: Dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) is a prospective, open-label, multicenter (1016 US sites), multi-cohort phase II trial of ipilimumab (1 mg/kg intravenously (IV) every 6 weeks) plus nivolumab (240 mg IV every 2 weeks).

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  • The SWOG S1609 DART trial investigated the effectiveness of dual therapy with ipilimumab and nivolumab in patients with vulvar cancers, showing initial promising results.
  • In this phase II clinical trial involving 16 patients, the objective response rate was 18.8%, with some patients exhibiting durable responses and stable disease.
  • Adverse effects were common, including diarrhea and fatigue, with 25% of patients experiencing severe side effects, highlighting the need for ongoing studies to identify response and resistance markers.
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  • - Invasive mucinous adenocarcinoma (IMA) of the lung has unique features such as multicentric lesions and low distant metastasis but a poor prognosis, with median survival under a year.
  • - While treatment options are limited, lung transplantation in selected IMA patients has shown improved survival, but with high rates of recurrence often linked to the primary tumor.
  • - A notable case of bilateral lung transplantation using cardiopulmonary bypass for stage ⅣA lung-limited IMA achieved 15 months of stable health without disease recurrence or organ rejection, and IMA's characteristics and outcomes are discussed in relation to prior classifications and other lung transplantation cases.
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  • The study assesses the effectiveness of a dual checkpoint inhibition therapy (ipilimumab and nivolumab) on advanced non-epithelial ovarian cancers (NEOCs) in patients who have no other effective treatments available.
  • In a clinical trial involving 17 patients, the therapy showed a 25% overall response rate in those with granulosa cell tumors, with some patients experiencing significant progression-free survival and overall survival benefits.
  • However, the therapy had serious side effects, leading to treatment discontinuation in 18% of participants and no positive responses noted in carcinosarcoma cases.
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  • Dual inhibition using ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) was tested on patients with desmoid tumors in a phase II clinical trial to assess efficacy and safety in treating these rare solid tumors.
  • The study involved 16 patients, with an overall response rate (ORR) of 18.8%, and a clinical benefit rate (CBR) of 62.5%, indicating decent stability and response to treatment over an average of 19.4 months of progression-free survival (PFS).
  • Adverse events were common, with fatigue, nausea, and hypothyroidism reported, highlighting the need for careful monitoring during treatment.
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Background: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported.

Methods: We retrospectively investigated the medical records of patients diagnosed with lung IMA.

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Introduction: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival.

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Background: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA-based MRD detection to predict recurrence in a real-world cohort of primarily early-stage non-small cell lung cancer (NSCLC) patients treated with curative intent.

Methods: Longitudinal plasma samples were collected post curative-intent treatment from 36 patients with stage I-IV NSCLC.

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Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck.

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Activins, members of the TGF-beta superfamily, have been isolated and identified in the endocrine system, but have not been substantially investigated in the context of the immune system and endocrine-unrelated cancers. Here, we demonstrated that tumor-bearing mice had elevated systemic activin levels, which correlated directly with tumor burden. Likewise, cancer patients have elevated plasma activin levels compared to healthy controls.

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BACKGROUND To evaluate the role of double-lung transplantation (DLT) for lung cancer, the survival outcomes of patients who underwent DLT for lung cancer and the incidence of de novo lung cancer after DLT were assessed. MATERIAL AND METHODS Data from all cases reported in the literature were pooled for analysis and additional data were collected from the Organ Procurement Transplantation Network (OPTN) registry. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) of patients who underwent DLT for lung cancer were determined.

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Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed.

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Technological advances have progressively enhanced the survival rate of lung transplant recipients and expanded its indications for various diseases, including the recent coronavirus disease 2019 (COVID-19). However, according to the International Society for Heart and Lung Transplantation, lung cancer constituted a mere 0.1% of the indications for lung transplantation over the past two decades.

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Laryngotracheal stenosis (LTS) is pathologic fibrotic narrowing of the larynx and trachea characterized by hypermetabolic fibroblasts and CD4+ T cell-mediated inflammation. However, the role of CD4+ T cells in promoting LTS fibrosis is unknown. The mTOR signaling pathways have been shown to regulate the T cell phenotype.

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The interleukin-4 (IL-4) cytokine plays a critical role in modulating immune homeostasis. Although there is great interest in harnessing this cytokine as a therapeutic in natural or engineered formats, the clinical potential of native IL-4 is limited by its instability and pleiotropic actions. Here, we design IL-4 cytokine mimetics (denoted Neo-4) based on a de novo engineered IL-2 mimetic scaffold and demonstrate that these cytokines can recapitulate physiological functions of IL-4 in cellular and animal models.

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The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4-expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis.

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Most clinically evaluated chimeric antigen receptor (CAR)-based cell therapies are generated from autologous immune cells. However, there are several limitations to autologous cell therapy, including low availability, poor quality of starting cellular material and limited expansion capability. Recently, induced pluripotent stem cell (iPSC)-derived allogeneic cell therapy platforms have gained popularity, as they seek to overcome many of the challenges inherent to current autologous cell therapies.

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Network controllability asserts a perspective that the structure-the location of edges that connect nodes-of the network contains important information about fundamental characteristics of our ability to change the behavior that evolves on these networks. It can be used, for example, to determine the parts of the system that when influenced by outside controlling signals, can ultimately steer the behavior of the entire network. One of the challenges in utilizing the ideas from network controllability on real systems is that there is typically more than one potential solution (often many) suggested by the topology of the graph that perform equally well.

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The avascular nature of cornea tissue limits its regenerative potential, which may lead to incomplete healing and formation of scars when damaged. Here, we applied micro- and ultrafine porcine urinary bladder matrix (UBM) particulate to promote type 2 immune responses in cornea wounds. Results demonstrated that UBM particulate substantially reduced corneal haze formation as compared to the saline-treated group.

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Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (Min) enterotoxigenic (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas.

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Objective/hypothesis: Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis-associated gene expression in iLTS mice.

Study Design: Prospective controlled animal study.

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Senescent cells (SnCs) are implicated in the pathogenesis of age-related diseases including osteoarthritis (OA), in part via expression of a senescence-associated secretory phenotype (SASP) that includes immunologically relevant factors and cytokines. In a model of posttraumatic OA (PTOA), anterior cruciate ligament transection (ACLT) induced a type 17 immune response in the articular compartment and draining inguinal lymph nodes (LNs) that paralleled expression of the senescence marker p16INK4a (Cdkn2a) and p21 (Cdkn1a). Innate lymphoid cells, γδ+ T cells, and CD4+ T cells contributed to IL-17 expression.

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YAP is a transcriptional coactivator of the Hippo signaling pathway that has largely been studied for its role in the regulation of organ size during development. Several studies have shown that YAP is upregulated in cancer cells, and more recently in the T regulatory (Treg) subset of CD4+ cells. These observations suggest that the transcriptional co-activator may promote tumor persistence and progression.

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Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. We found increased numbers of interleukin 17 (IL17)-producing γδ T cells and CD4 T helper 17 (T17) cells as well as senescent stromal cells in the fibrotic capsules.

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