Photothermal “nano-dot” reactivate “immune-hot” for tumor treatment via reprogramming cancer cells metabolism

Biomaterials, Год журнала: 2023, Номер 296, С. 122089 - 122089

Опубликована: Март 6, 2023

Язык: Английский

---

Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer

Cancer Cell, Год журнала: 2024, Номер 42(4), С. 535 - 551.e8

Опубликована: Апрель 1, 2024

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. Here, we establish PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology genomic landscape parental tumors, reliable for drug sensitivity screening, as evidenced by both vivo models patient response. Integrative analysis dissects heterogeneity, regarding genomic/transcriptomic characteristics to seven clinically relevant drugs, well clinical associations. Pharmacogenomic identifies validates multi-gene expression signatures predicting response better stratification. Furthermore, reveal c-Jun mediator lenvatinib resistance through JNK β-catenin signaling. A compound (PKUF-01) comprising moieties veratramine (c-Jun inhibitor) synthesized screened, exhibiting marked synergistic effect. Together, our study characterizes the develops predictive biomarker panels, lenvatinib-resistant mechanism combination

Язык: Английский

---

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Язык: Английский

---

A multi‐analyte cell‐free DNA–based blood test for early detection of hepatocellular carcinoma

Hepatology Communications, Год журнала: 2022, Номер 6(7), С. 1753 - 1763

Опубликована: Март 3, 2022

Abstract The limited performance of guideline‐recommended abdominal ultrasound and serum alpha‐fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers more accurate detection early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate HelioLiver Test, multi‐analyte blood test combining cell‐free DNA methylation patterns, variables, protein tumor markers. A blinded, multicenter was performed with 247 subjects, including 122 subjects HCC 125 control chronic liver disease. Test compared AFP GALAD score as established surveillance tests. (area under receiver operating characteristic curve [AUROC] = 0.944) superior both (AUROC 0.851; p < 0.0001) 0.899; 0.0001). Using prespecified diagnostic algorithm, showed sensitivities 85% (95% confidence interval [CI], 78%–90%) any stage 76% CI, 60%–87%) (American Joint Committee on Cancer [AJCC] I II) HCC. In contrast, (≥20 ng/mL) alone (≥−0.63) lower 62% 54%–70%) 75% 67%‐82%) overall, 57% 40%–71%) 65% 49%–79%) (AJCC HCC, respectively. specificities (91%; 95% 85%–95%), (97%; 92%–99%), (94%; 88%–97%) were similar subjects. warrants further evaluation in settings.

Язык: Английский

---

High‐Z‐Sensitized Radiotherapy Synergizes with the Intervention of the Pentose Phosphate Pathway for In Situ Tumor Vaccination

Advanced Materials, Год журнала: 2022, Номер 34(13)

Опубликована: Фев. 1, 2022

In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity establishing efficient in vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) boost radiation-therapy (RT)-induced immunogenic (ICD) potent It first observed that sheet-like PLGdH can present superior X-ray deposition penetrability, exhibiting improved radiosensitization vitro vivo. Moreover, destruction cellular nicotinamide adenine dinucleotide (NADPH) nucleotide homeostasis Phy-mediated PPP intervention further amplify PLGdH-sensitized RT-mediated oxidative stress DNA damage, which correspondingly results effective ICD enhance immunogenicity irradiated cells. Consequently, Phy@PLGdH-sensitized RT successfully primes robust CD8+ -T-cell-dependent immunity potentiate checkpoint blockade immunotherapies against primary metastatic tumors.

Язык: Английский

---

The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(6), С. 3073 - 3073

Опубликована: Март 12, 2022

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It heavy, worldwide burden for mankind with high morbidity mortality. Therefore, groundbreaking research innovations are necessary. Research in space under microgravity (µg) conditions novel approach potential fight cancer develop future therapies. Space travel accompanied by adverse effects on our health, there need counteract these health problems. On cellular level, studies have shown that real (r-) simulated (s-) µg impact survival, apoptosis, proliferation, migration, adhesion as well cytoskeleton, extracellular matrix, focal adhesion, factors cells. Moreover, µg-environment induces vitro 3D tumor models (multicellular spheroids organoids) preclinical drug targeting, development, studying processes progression metastasis molecular level. This review focuses r- s-µg different types cells deriving from thyroid, breast, lung, skin, prostate cancer, tumors gastrointestinal tract. In addition, we summarize current knowledge cancerous stem The information demonstrates has become an important new technology increasing biology.

Язык: Английский

---

AADAC protects colorectal cancer liver colonization from ferroptosis through SLC7A11-dependent inhibition of lipid peroxidation

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Сен. 26, 2022

Oxidative stress is a highly active metabolic process in the liver, that poses great threats to disseminated tumor cells during their colonization. Here, we aimed investigate how colorectal cancer (CRC) overcome lipid peroxidation sustain metastatic colonization liver.Orthotopic liver metastasis (CRLM) and CRC mouse models were constructed determine roles of AADAC The levels detected or tissues. overexpression LMs its clinical relevance analyzed. oncogenic role was evaluated cell experiments.Compared with primary tumors (PTs), metastases (LMs) showed significantly lower glutathione oxidized (GSH/GSSG) ratio higher malondialdehyde (MDA) CRLM patients orthotopic models. Inhibition by liproxstatin-1 promoted RNA-seq results revealed as most upregulated metabolism related gene compared PTs. Analyses datasets patient model samples confirmed PTs, correlated poor prognosis. proliferation, facilitated reducing ROS accumulation, which led ferroptosis. Mechanistically, SLC7A11 activating NRF2 inhibit peroxidation, thereby protecting from ferroptosis.AADAC protects ferroptosis inhibiting an SLC7A11-dependent manner, thus effectively promoting growth liver. Together, our findings suggest can act prognostic indicator potential therapeutic target for CRLM.

Язык: Английский

---

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation

Chemical Society Reviews, Год журнала: 2022, Номер 52(1), С. 47 - 96

Опубликована: Ноя. 25, 2022

This review overviews the landscape of nanomedicine-aided cancer radio-immunotherapy in a “from bench to clinic” manner.

Язык: Английский

---

A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

ACS Nano, Год журнала: 2023, Номер 17(12), С. 11537 - 11556

Опубликована: Июнь 5, 2023

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially abnormal metabolism cells, long underestimated. We propose an enhanced ferroptosis-activating pattern via regulating glycometabolism construct nanoplatform named PMVL, which composed lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with camouflage PD-L1 inhibiting peptide-modified cell membrane. This work reveals that mixed valence (VIV VV) in PMVL triggers due self-cyclic alteration V, process generates •OH lipid peroxide accumulation → depletes glutathione (GSH) peroxidase (GPX4) deactivation (VV VIV). Notably, LND strengthens by dual suppression glycolysis (decreasing ATP supply) pentose phosphate pathway NADPH production), causing anabatic GSH consumption. Besides, inhibited less intracellular lactic alleviates acidity microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro vivo data demonstrate glycometabolism-intervention-enhanced boosted immunity activation, potentially providing opportunities possibilities synergetic therapy.

Язык: Английский

---

Artificial intelligence in liver cancers: Decoding the impact of machine learning models in clinical diagnosis of primary liver cancers and liver cancer metastases

Pharmacological Research, Год журнала: 2023, Номер 189, С. 106706 - 106706

Опубликована: Фев. 20, 2023

Liver cancers are the fourth leading cause of cancer-related mortality worldwide. In past decade, breakthroughs in field artificial intelligence (AI) have inspired development algorithms cancer setting. A growing body recent studies evaluated machine learning (ML) and deep (DL) for pre-screening, diagnosis management liver patients through diagnostic image analysis, biomarker discovery predicting personalized clinical outcomes. Despite promise these early AI tools, there is a significant need to explain 'black box' work towards deployment enable ultimate translatability. Certain emerging fields such as RNA nanomedicine targeted therapy may also benefit from application AI, specifically nano-formulation research given that they still largely reliant on lengthy trial-and-error experiments. this paper, we put forward current landscape along with challenges management. Finally, discussed future perspectives how multidisciplinary approach using could accelerate transition medicine bench side clinic.

Язык: Английский

---