Publications by authors named "Muley T"

Objective: Among the different subtypes of invasive lung adenocarcinoma, lepidic predominant adenocarcinoma (LPA) has been recognized as the lowest-risk subtype with good prognosis. The aim of this study is to provide insight into the heterogeneity within LPA tumors and to better understand the influence of other sub-histologies on survival outcome.

Methods: Overall, 75 consecutive patients with LPA in pathologic stage I (TNM 8th edition) who underwent resection between 2010 and 2022 were included into this retrospective, single center analysis.

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Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.

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Article Synopsis
  • Mammalian ribosomal RNA (rRNA) has over 220 modifications, but how these modifications are regulated across tissues and conditions is still unclear.
  • Researchers used direct RNA sequencing to analyze rRNA modifications in humans and mice, discovering tissue- and developmental stage-specific modification patterns, including new sites not previously documented.
  • They established "epitranscriptomic fingerprinting," a method enabling accurate identification of tissues and tumor types, and showed that rRNA modification patterns could effectively distinguish normal and tumor samples in lung cancer patients with minimal data.
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Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth.

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  • Lung cancer poses a significant health challenge globally, with patient survival rates varying widely, and this study explores the genetic factors affecting these outcomes through an analysis of germline polymorphisms in 1,464 lung adenocarcinoma patients after surgery.!* -
  • Researchers employed a Cox proportional hazard model to evaluate over seven million polymorphisms against overall survival over a 60-month period, considering key variables like age, sex, and disease stage.!* -
  • Six significant germline variants were identified, linked to gene expression regulation, indicating that certain minor alleles correspond to poorer survival outcomes; further research is needed to fully understand these genetic mechanisms in lung cancer prognosis.!*
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  • SIAH3, a member of the SIAH family in humans, is often silenced in various cancers like melanoma and lung adenocarcinoma, leading to worse survival for patients.
  • Inducing SIAH3 expression can decrease cancer cell growth and trigger cell death, as it shifts cellular energy production from aerobic metabolism to glycolysis.
  • SIAH3 is found in mitochondria and interacts with proteins related to mitochondrial function and other ubiquitin ligases, suggesting it plays a role as a tumor suppressor by regulating metabolism.
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Introduction: Molecular profiling of lung cancer is essential to identify genetic alterations that predict response to targeted therapy. While deep learning shows promise for predicting oncogenic mutations from whole tissue images, existing studies often face challenges such as limited sample sizes, a focus on earlier stage patients, and insufficient analysis of robustness and generalizability.

Methods: This retrospective study evaluates factors influencing mutation prediction accuracy using the large Heidelberg Lung Adenocarcinoma Cohort (HLCC), a cohort of 2356 late-stage FFPE samples.

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Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg.

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Background: Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors.

Methods: We identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015.

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Article Synopsis
  • - Histological confirmation through either CT-guided needle biopsy (CTGNB) or bronchoscopy is crucial for planning lung cancer treatment, with concerns raised about CTGNB potentially increasing pleural recurrence risk, especially considering tumor proximity to the pleura.
  • - A study of 844 lung cancer patients revealed a low pleural recurrence rate (3.2%), and while CTGNB resulted in tumors being closer to the pleura, the biopsy method itself did not significantly impact the recurrence risk.
  • - The analysis concluded that CTGNB is safe and does not increase the risk of pleural recurrence, but this finding needs to be corroborated with data from larger, multicenter studies.
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Objective: Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors.

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Background: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival.

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Introduction And Objectives: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy.

Materials And Methods: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS.

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  • Novel immunotherapies for lung cancer can reactivate the immune system for tumor cell killing, but many patients experience treatment failure, particularly women, possibly due to the immunosuppressive glycoprotein glycodelin.
  • Research shows that glycodelin from non-small-cell lung cancer (NSCLC) resembles that from amniotic fluid and interacts with immune cells, potentially affecting inflammatory responses and tumor dynamics.
  • High levels of glycodelin in tumors are linked to poor survival rates in female patients and may serve as a biomarker to identify those who won't benefit from immunotherapy, suggesting it could also be targeted for improved treatment options.
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As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization.

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Background: Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression.

Objective: To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease.

Methods: In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS).

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Background: Serum tumor markers (STM) may complement imaging and provide additional clinical information for patients with non-small cell lung cancer (NSCLC).

Objective: To determine whether STMs can predict outcomes in patients with stable disease (SD) after initial treatment.

Methods: This single-center, prospective, observational trial enrolled 395 patients with stage III/IV treatment-naïve NSCLC; of which 263 patients were included in this analysis.

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Background: Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) database indicates that early diagnosis is significantly associated with favorable outcome.

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Introduction: The tumoral immune milieu plays a crucial role for the development of non-small-cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery.

Materials And Methods: The tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining.

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Introduction: Lung cancer remains the deadliest cancer in the world, and lung cancer survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography screening can reduce mortality; however, annual screening is limited by low adherence in the United States of America and still not broadly implemented in Europe. As a result, less than 10% of lung cancers are detected through existing programs.

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To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.

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Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages.

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Introduction: Trials of CT-based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population.

Methods: We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL).

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