The crucial role of age and site in incidence and prognosis of female neuroendocrine neoplasms in the United States: a population-based study from 2000 to 2018.

BACKGROUND: As the incidence continues to rise, global concern about neuroendocrine neoplasms (NENs) is mounting. However, little is known about how NENs affect women patients. METHODS: The annual percentage change (APC) was calculated to describe the incidence. Cox proportional hazards multivariable regression was used to identify risk factors. The nomograms were employed to estimate prognosis. RESULTS: A total of 39,237 female NENs (fNENs) cases were identified. The incidence of fNENs increased annually (APC = 4.5, 95% CI 4.1-4.8, P < 0.05), and the incidence pattern and survival outcomes showed age and site-specificity. Appendiceal, rectal, and pulmonary fNENs were major contributors to the incidence of patients younger than 40, between 40-59, and over 60 years old, respectively. The Cox proportional hazards regression model revealed that age, tumor size, grade, stage, and primary sites were closely related to survival. The worst survival outcomes appeared in breast, reproductive system, and liver fNENs for patients under 40, between 40-49, and over 50 years old, respectively. A nomogram based on these developed with higher predictive accuracy of prognosis, with a C index of 0.906 in the training cohort and 0.901 in the validation cohort. CONCLUSIONS: Our findings revealed distinct site-specific tendencies in the incidence and survival patterns among fNEN patients across various age groups. Thus, reasonable patient screening and stratification strategies should be implemented, especially for young patients.

Photothermally sensitive gold nanocage augments the antitumor efficiency of immune checkpoint blockade in immune "cold" tumors.

Introduction: Immune checkpoint blockade (ICB) has revolutionized the therapy landscape of malignancy melanoma. However, the clinical benefits from this regimen remain limited, especially in tumors lacking infiltrated T cells (known as "cold" tumors). Nanoparticle-mediated photothermal therapy (PTT) has demonstrated improved outcomes in the ablation of solid tumors by inducing immunogenic cell death (ICD) and reshaping the tumor immune microenvironment. Therefore, the combination of PTT and ICB is a promising regimen for patients with "cold" tumors. Methods: A second near-infrared (NIR-II) light-activated gold nanocomposite AuNC@SiO2@HA with AuNC as a kernel, silica as shell, and hyaluronic acid (HA) polymer as a targeting molecule, was synthesized for PTT. The fabricated AuNC@SiO2@HA nanocomposites underwent various in vitro studies to characterize their physicochemical properties, light absorption spectra, photothermal conversion ability, cellular uptake ability, and bioactivities. The synergistic effect of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy was evaluated using a mouse model of immune "cold" melanoma. The tumor-infiltrating T cells were assessed by immunofluorescence staining and flow cytometry. Furthermore, the mechanism of AuNC@SiO2@HA-induced T-cell infiltration was investigated through immunochemistry staining of the ICD-related markers, including HSP70, CRT, and HMGB1. Finally, the safety of AuNC@SiO2@HA nanocomposites was evaluated in vivo. Results: The AuNC@SiO2@HA nanocomposite with absorption covering 1064 nm was successfully synthesized. The nano-system can be effectively delivered into tumor cells, transform the optical energy into thermal energy upon laser irradiation, and induce tumor cell apoptosis in vitro. In an in vivo mouse melanoma model, AuNC@SiO2@HA nanocomposites significantly induced ICD and T-cell infiltration. The combination of AuNC@SiO2@HA and anti-PD-1 antibody synergistically inhibited tumor growth via stimulating robust T lymphocyte immune responses. Discussion: The combination of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy proposed a neoteric strategy for oncotherapy, which efficiently convert the immune "cold" tumors into "hot" ones.

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis.

ABSTRACT: As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

Combinational antitumor strategies of exosomes as drug carriers: Mini review.

Cancer therapies have made tremendous progress in the last decade, but monotherapy still has apparent limitations and lacks therapeutic efficacy. Thus, the simultaneous administration of multiple drugs has been widely explored and has shown better outcomes. Exosomes, deriving from almost all living cells, are natural nanocarriers designed to deliver drugs to tumor sites. Therefore, combinational antitumor therapies based on exosomes, such as engineered exosomes and different combinations of chemotherapeutic agents, therapeutic nucleic acids, photosensitizers, immunotherapy and phytochemicals, have considerable prospects and potential for clinical translation. Here, we summarize current strategies of cancer combination therapy in exosomes and propose opportunities and challenges in the future.