Thyroid cancer, the most prevalent endocrine malignancy, poses significant therapeutic challenges due to its heterogeneous biological behavior. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine, is implicated in tumor progression and senescence regulation in various cancers. However, its role in thyroid cancer, particularly its interaction with the p53 signaling pathway, remains poorly understood. This study aimed to investigate the functional contribution of GDF15 to thyroid cancer progression and its regulatory mechanism in cancer cell senescence.

Public datasets and clinical specimens were analyzed to evaluate GDF15 expression patterns and their clinical significance. In vitro models were established using human thyroid cancer cell lines. GDF15 expression was modulated through siRNA-mediated silencing. RT-qPCR and Western blotting were employed to evaluate the expression levels of target molecules. Functional assays were conducted to assess proliferation (CCK-8, colony formation) and migration/invasion (transwell, cell scratch assay). Cellular senescence was evaluated by measuring β-galactosidase activity, γ-H2AX expression, and senescence-associated secretory phenotype factors. The dependency on p53 was elucidated through siRNA-mediated knockdown of p53. Mechanistic investigations were performed using RNA sequencing and Western blotting.

Compared with adjacent normal tissues, GDF15 was significantly upregulated in thyroid cancer tissues and correlated with lymph node metastasis status. Knockdown of GDF15 suppressed proliferation, migration, and invasion while inducing cellular senescence. RNA sequencing revealed that GDF15 silencing activated the p53 signaling pathway and upregulated p53 expression. Rescue experiments utilizing p53 siRNA partially reversed GDF15-mediated senescence.

GDF15 is implicated in the progression of thyroid cancer and potentially modulates cellular senescence through a p53-dependent mechanism, underscoring its dual functionality as both a pro-tumorigenic driver and a senescence regulator. These findings establish the potential of GDF15 as a therapeutic target and prognostic biomarker in thyroid cancer, providing novel insights developing senescence-centered therapeutic strategies.

Autoimmune polyglandular syndrome type 2 (APS 2) is a rare endocrinopathy characterized by primary adrenal insufficiency associated with autoimmune thyroiditis or type 1 diabetes. The diagnosis is usually delayed, and it has high mortality if undetected. Hashimoto's thyroiditis is the commonest thyroid disease associated with APS 2, while structural thyroid abnormalities or neoplasms are rarely reported. Hurthle cell adenoma (HCA) is a rare benign oncocytic tumor and may arise from long-standing chronic autoimmune thyroiditis. To date, there is no documented case of APS 2 with Hurthle cell adenoma, making this case a rarity. We present a case of a 44-year-old man with gastrointestinal symptoms, fatigue, hyperpigmentation, and weight loss for six months. The critical findings were generalized hyperpigmentation with orthostatic hypotension and electrolyte imbalance, especially hyponatremia and hyperkalemia, with low cortisol and elevated adrenocorticotropic hormone levels. These, along with bilateral adrenal atrophy on imaging and high anti-thyroid peroxidase antibodies, established a diagnosis of primary adrenal insufficiency and autoimmune thyroiditis, findings consistent with APS 2. HCA was detected on fine needle biopsy subsequently, which is a rare association in APS 2. The patient responded well to adrenal and thyroxine replacement therapy. The patient's tumor, although small and asymptomatic, was excised via hemithyroidectomy as per the American Thyroid Association guidelines. Histopathology confirmed HCA with no capsular invasion. Postoperative recovery was uneventful, and on follow-up, the patient showed significant improvement. There are two major learning points from this case. Firstly, it emphasizes the need for high clinical suspicion in diagnosing APS 2 in patients with nonspecific constitutional symptoms. Secondly, it highlights the rare but clinically significant co-occurrence of HCA with APS 2. HCA, while benign, can mimic malignancy on cytology and requires histopathological confirmation. In view of the possibility of progression of HCA to Hurthle cell carcinoma, surgical excision is the standard of care.

The global burden of cancer is increasing tremendously, particularly among individuals aged 60 years and older, and has emerged as a critical public health concern. Cancer vaccine-induced immunity can recognize and eliminate tumor cells with high specificity and low toxicity. Nevertheless, immunosenescence increases the risk and severity of cancers in elderly individuals while impairing vaccine-induced immunity. Furthermore, much oncology research has predominantly focused on adults, often neglecting the potential contributions of aging individuals to tumor progression. Elucidating the interactions between the immunosenescent microenvironment and tumorigenesis can inspire the development of more effective cancer vaccines tailored to the characteristics of elderly individuals, thereby alleviating the global cancer burden. In this review, we analyze how the immunosenescent microenvironment impacts tumor development and summarize existing strategies aimed at enhancing cancer vaccine efficacy, drawing inspiration from insights into immunosenescence. We believe that this review will inspire efforts toward creating individualized cancer vaccines for the elderly.

With global aging accelerating, cancer incidence among older adults is rapidly increasing. Individuals aged ≥65 years now represent 64% of new cancer cases and 71.3% of cancer-related deaths worldwide. This population exhibits a distinct immune imbalance-driven by tumor-induced immunosuppression, immunosenescence, and inflammaging-which contributes to poor tolerance of standard therapies and suboptimal outcomes with PD-1/PD-L1 inhibitors. As an emerging immunotherapeutic strategy, oncolytic viruses (OVs) selectively infect tumor cells, induce immunogenic cell death (ICD), and activate the cGAS-STING pathway. Although clinical data in elderly patients with esophageal, lung, or pancreatic cancer are scarce, promising outcomes have been reported in melanoma/sarcoma subgroups, including objective response rates of 26.4-32.9% and a median duration of response of 33.7 months, highlighting the potent antitumor potential of OVs. However, age-related immunological vulnerability-manifesting across different frailty stages as reflected by G8 scoring-may predispose elderly patients to immune overload, cytokine storm, and impaired tolerance, while this group remains underrepresented in OV trials. Systematic studies in this context are lacking. This review highlights the immunological characteristics of aging, emphasizes the importance of addressing immunological vulnerability across different age stages (G8 scoring), and outlines emerging challenges and future directions for OV-based therapies tailored to frail elderly populations.

Glioma, the most prevalent primary brain tumor, exhibits dysregulated ribosome biogenesis closely linked to malignant behavior. However, the role of ribosome biogenesis in glioma and prognosis remains incompletely understood. This study aimed to construct a molecular signature based on ribosome biogenesis-related genes to predict patient survival and therapeutic response in glioma.

Utilizing The Cancer Genome Atlas (TCGA) glioma cohort data, we constructed a ribosome biogenesis-related genes (RBRGs) signature using LASSO regression and multivariate Cox analyses, and subsequently validating its prognostic value in independent cohorts. We systematically evaluated the signature's associations with clinicopathological features, tumor immunity, genomic instability, tumor stemness, and therapeutic sensitivity. The oncogenic role of the key gene UTP20 was experimentally validated in U87 and U251 glioma cell lines through MTS, colony formation, and transwell assays.

We established a four-gene RBRGs signature (NOP10, UTP20, SHQ1, and PIH1D2). Elevated RBRGs score significantly correlated with shortened overall survival and adverse clinical characteristics, including advanced age, high WHO grade, IDH wild-type status, and absence of 1p/19q codeletion. A nomogram incorporating the RBRGs score demonstrated excellent predictive performance (C-index = 0.841). RBRGs-associated genes were enriched in immune regulatory pathways. The high-risk group exhibited increased infiltration of immunosuppressive cells (macrophages, myeloid-derived suppressor cells [MDSCs], and cancer-associated fibroblasts [CAFs]), upregulation of immunosuppressive checkpoints, and resistance to immunotherapy. Furthermore, the RBRGs signature correlated with genomic alterations, heterogeneity, tumor stemness, and therapeutic sensitivity. Crucially, UTP20 knockdown significantly suppressed glioma cell proliferation and invasion in vitro.

The RBRGs signature was successfully developed and validated as an independent prognostic biomarker and predictor of therapeutic response in glioma, highlighting its extensive association with tumor heterogeneity. Furthermore, this study identified UTP20 as a key oncogenic driver that facilitates glioma progression.

Occupational risks contribute substantially to the global burden of pneumoconiosis, chronic obstructive pulmonary disease (COPD), tracheal-bronchus-and-lung (TBL) cancer, and asthma; however, comprehensive, up-to-date global, regional, and national estimates remain limited.

Data from the Global Burden of Disease Study (GBD) 2021 were analyzed to quantify the burden of these diseases attributable to occupational exposure across 204 countries between 1990 and 2021, stratified by sex, age, socio-demographic index (SDI), and geographic region.

In 2021, occupational risks led to 30,546 deaths due to pneumoconiosis, 285,628 deaths due to COPD, 585,451 deaths due to TBL (the highest among the four diseases), and 18,315 deaths due to asthma, with disability-adjusted life years (DALYs) of 1.8, 6.1, 12.6, and 0.4 million, respectively. Male patients exhibited higher burdens of all diseases, reflecting greater exposure to male-dominated industries. Geographically, middle SDI regions had the highest absolute cases for pneumoconiosis and COPD, high-SDI regions for TBL cancer, and low-middle SDI regions for asthma. While age-standardized rates declined for most outcomes over time, the absolute burdens increased owing to population growth and aging, with demographic factors driving up to 80% of the increase in total cases. Health inequities persisted, with lower SDI regions bearing a disproportionate burden, despite modest improvements in absolute inequalities.

These findings highlight the need for strengthened occupational health regulations, targeted interventions in high-risk regions, and policies addressing population dynamics to mitigate the impact of workplace exposure on respiratory health.

This study evaluated the short-term safety and effectiveness of percutaneous transhepatic biliary drainage (PTBD) for a malignant hilar biliary obstruction (MHBO).

The data from 112 patients with MHBO who underwent PTBD between January 2019 and June 2024 were analyzed retrospectively. All MHBO was confirmed pathologically. Technical success was defined as the placement of a drainage tube within the biliary tract. Clinical success was defined as a decrease in the total bilirubin level of ≥20% within seven days post-procedure. The 30-day morbidity, mortality, and re-intervention were documented. One interventional radiologist with 15 years of experience performed all procedures.

The average age was 62.6±12.3 years (range, 28-91 years), and the female-to-male ratio was 2:3. The most common etiology of MHBO was cholangiocarcinoma (68.8%). The Bismuth-Corlette classification scores were as follows: type 1 (17.9%), type 2 (23.2%), type 3A (25.9%), type 3B (16.0%), and type 4 (17.0%). The technical success rate was 99.1%; 41.4% of PTBD were bilateral, and 82% were internal-external drainage. Preoperative drainage and palliative drainage were indicated in 28.6% and 71.4% of cases, respectively. Biliary stents were implanted in 39 patients (35.1%), including 51.3% unilateral stents, 23.1% Y-stents, 20.5% kissing stents, and 5.1% T-stents. The clinical success rate was 69.6%. The minor complication rate was 18.8%. The 30-day re-intervention and mortality rates were 24.1% and 1.8%, respectively.

PTBD was safe and effective in managing MHBO. Further study of this specific subgroup and long-term follow-up is warranted.

Pancreatic cancer is a highly lethal malignancy often diagnosed at an advanced stage. Gastroparesis, marked by delayed gastric emptying, may be a potential risk factor or early indicator. Despite this, little is known about the association between gastroparesis and pancreatic cancer.

This retrospective cohort study analyzed the data from the Nationwide Inpatient Sample (2016-2021), encompassing 207,629,866 hospitalizations. Adult hospitalizations with a diagnosis of pancreatic cancer, and with or without a diagnosis of gastroparesis, were identified using International Classification of Diseases, Tenth Revision codes. Multivariable logistic regression was used to assess the association between gastroparesis and pancreatic cancer, adjusting for demographic and clinical variables.

Among 603,075 hospitalizations of patients with pancreatic cancer, 6,095 (1.0%) had gastroparesis compared to 0.7% of the hospitalizations with non-pancreatic cancer patients (p<0.001). Among the pancreatic cancer patients, those with gastroparesis were younger (mean age 65.55±11.61 vs. 68.46±11.44 years; p<0.001) and more likely to be female (54.2% vs. 45.8%; p<0.001). Patients with gastroparesis experienced longer hospital stays (8.48±8.30 days vs. 5.70±5.70 days; p<0.001) and higher total charges ($86,385.90±$105,352.67 vs. $63,250.12±$78,421.65; p<0.001). Gastroparesis was linked to an increased odds of pancreatic cancer (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.08-1.16) and reduced in-hospital mortality (OR 0.51, 95% CI 0.44-0.58; p<0.001).

Gastroparesis is associated with higher odds of pancreatic cancer but a lower risk of in-hospital mortality from pancreatic cancer hospitalizations. Although causal and temporal relationships cannot be established because of the cross-sectional nature of the dataset.

This retrospective analysis examined the efficacy and safety of combined endostatin and definite chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.

The current study was a retrospective analysis of esophageal squamous cell carcinoma patients treated with endostatin combined with definitive chemoradiotherapy. The patients received induction chemotherapy or concurrent chemotherapy. The endostatin dose was 30 mg/d from days one to five of each induction cycle. During concurrent therapy, the endostatin dose was 30 mg/d concomitant with radiotherapy at 60-68 Gy delivered in 2.0-2.2 Gy/d fractions.

The objective response and disease control rates were 82.76% and 84.48%, respectively. The one-year, two-year, and three-year overall survival rates were 91.83%, 86.43%, and 73.86%, respectively. The one-year, two-year, and three-year progress-free survival rates were 74.09%, 62.16%, and 61.95%, respectively. The most common grade 3 and 4 adverse events were esophagitis (31.03%), anemia (12.07%), pneumonia (12.07%), leukopenia (10.34%), neutropenia (8.62%) and thrombocytopenia (8.62%).

A combination of endostatin with definite chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma achieved high response rates, progress-free survival rates, and overall survival rates. The toxicity was acceptable. Nevertheless, additional prospective randomized controlled clinical trials will be needed to confirm the superiority of this treatment strategy.

Smoking status, health literacy challenges and chronic diseases may influence the diagnostic evaluation of patients presenting with lung cancer symptoms (LCSs) in general practice. This study aimed to (1) analyse associations between smoking status, health literacy, chronic disease and having completed diagnostic imaging amongst patients with LCSs in Danish general practice and (2) investigate how these factors interact in relation to the completion of diagnostic imaging, by examining effect modification and causal mediation. Patient/material and methods: In 2022, a random sample of 100,000 individuals aged ≥ 20 years from the Danish population was invited to participate in a survey about symptoms and healthcare seeking. This study included individuals aged ≥ 40 years who reported general practitioner (GP) contact with LCSs. Questionnaire data included health literacy, chronic disease and smoking status. Register data included socioeconomics, prescription drugs and diagnostic imaging. Descriptive statistics, multivariable logistic regression and causal mediation models were applied.

Of the 2,252 patients who had contacted their GP with LCSs, 22% had completed diagnostic imaging. Formerly smoking increased odds of diagnostic imaging compared to never smoking, whereas current smoking had no influence. No associations or mediations were demonstrated between health literacy, chronic disease and diagnostic imaging. Effect modification was implied by varying impact of health literacy on diagnostic imaging depending on smoking status, yet the results were limited by power.

Initiatives targeting awareness of the risk of overlooking cancer symptoms amongst high-risk patients presenting in general practice may improve the chance of timely diagnosis of lung cancer.