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1.
Support Care Cancer ; 32(6): 336, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727753

ABSTRACT

PURPOSE: Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. METHODS: AYAs diagnosed with MBC (18-39 years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. RESULTS: Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3 years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). CONCLUSION: Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.


Subject(s)
Breast Neoplasms , Quality of Life , Humans , Female , Prospective Studies , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Adult , Young Adult , Surveys and Questionnaires , Social Support , Adolescent , Middle Aged
2.
Heliyon ; 10(9): e30015, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707411

ABSTRACT

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

3.
Carbohydr Polym ; 337: 122187, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710543

ABSTRACT

The effects of different electron beam irradiation doses (2, 4, 8 KGy) and various types of fatty acids (lauric acid, stearic acid, and oleic acid) on the formation, structure, physicochemical properties, and digestibility of starch-lipid complex were investigated. The complexing index of the complexes was higher than 85 %, indicating that the three fatty acids could easily form complexes with starch. With the increase of electron beam irradiation dose, the complexing index increased first and then decreased. The highest complexing index was lauric acid (97.12 %), stearic acid (96.80 %), and oleic acid (97.51 %) at 2 KGy radiation dose, respectively. Moreover, the microstructure, crystal structure, thermal stability, rheological properties, and starch solubility were analyzed. In vitro digestibility tests showed that adding fatty acids could reduce the content of hydrolyzed starch, among which the resistant starch content of the starch-oleic acid complex was the highest (54.26 %). The lower dose of electron beam irradiation could decrease the digestibility of starch and increase the content of resistant starch.


Subject(s)
Electrons , Fatty Acids , Solubility , Starch , Starch/chemistry , Fatty Acids/chemistry , Lauric Acids/chemistry , Rheology , Hydrolysis , Oleic Acid/chemistry , Lipids/chemistry
4.
Article in English | MEDLINE | ID: mdl-38769276

ABSTRACT

The subjective experience of time flow in speech deviates from the sound acoustics in substantial ways. The present study focuses on the perceptual tendency to regularize time intervals found in speech but not in other types of sounds with a similar temporal structure. We investigate to what extent individual beat perception ability is responsible for perceptual regularization and if the effect can be eliminated through the involvement of body movement during listening. Participants performed a musical beat perception task and compared spoken sentences to their drumbeat-based versions either after passive listening or after listening and moving along with the beat of the sentences. The results show that the interval regularization prevails in listeners with a low beat perception ability performing a passive listening task and is eliminated in an active listening task involving body movement. Body movement also helped to promote a veridical percept of temporal structure in speech at the group level. We suggest that body movement engages an internal timekeeping mechanism, promoting the fidelity of auditory encoding even in sounds of high temporal complexity and irregularity such as natural speech.

5.
Environ Microbiol ; 26(5): e16622, 2024 May.
Article in English | MEDLINE | ID: mdl-38757466

ABSTRACT

Microbial communities that reduce nitrous oxide (N2O) are divided into two clades, nosZI and nosZII. These clades significantly differ in their ecological niches and their implications for N2O emissions in terrestrial environments. However, our understanding of N2O reducers in aquatic systems is currently limited. This study investigated the relative abundance and diversity of nosZI- and nosZII-type N2O reducers in rivers and their impact on N2O emissions. Our findings revealed that stream sediments possess a high capacity for N2O reduction, surpassing N2O production under high N2O/NO3- ratio conditions. This study, along with others in freshwater systems, demonstrated that nosZI marginally dominates more often in rivers. While microbes containing either nosZI and nosZII were crucial in reducing N2O emissions, the net contribution of nosZII-containing microbes was more significant. This can be attributed to the nir gene co-occurring more frequently with the nosZI gene than with the nosZII gene. The diversity within each clade also played a role, with nosZII species being more likely to function as N2O sinks in streams with higher N2O concentrations. Overall, our findings provide a foundation for a better understanding of the biogeography of stream N2O reducers and their effects on N2O emissions.


Subject(s)
Bacteria , Nitrous Oxide , Rivers , Nitrous Oxide/metabolism , Rivers/microbiology , Rivers/chemistry , Bacteria/genetics , Bacteria/classification , Bacteria/metabolism , Geologic Sediments/microbiology , Oxidation-Reduction , Phylogeography , Phylogeny , Microbiota
6.
J Dermatol Sci ; 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38749796

ABSTRACT

BACKGROUND: Ultraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized. OBJECTIVE: To explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis. METHODS: HaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes. RESULTS: After UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition. CONCLUSION: Our study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.

9.
Nanotechnology ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38759630

ABSTRACT

Due to the suitable bandgap structure, efficient conversion rates of photon to electron, adjustable optical bandgap, high electron mobility/aspect ratio, low defects, and outstanding optical and electrical properties for device design, III-V semiconductors have shown excellent properties for optoelectronic applications, including photodiodes, photodetectors, solar cells, photocatalysis, etc. In particular, III-V nanostructures have attracted considerable interest as a promising photodetector platform, where high-performance photodetectors can be achieved based on the geometry-related light absorption and carrier transport properties of III-V materials. However, the detection range from Ultraviolet to Terahertz including broadband photodetectors of III-V semiconductors still have not been more broadly development despite significant efforts to obtain the high performance of III-V semiconductors. Therefore, the recent development of III-V photodetectors in a broad detection range from Ultraviolet to Terahertz, and future requirements are highly desired. In this review, the recent development of photodetectors based on III-V semiconductor with different detection range is discussed. First, the bandgap of III-V materials and synthesis methods of III-V nanostructures are explored, subsequently, the detection mechanism and key figures-of-merit for the photodetectors are introduced, and then the device performance and emerging applications of photodetectors are provided. Lastly, the challenges and future research directions of III-V materials for photodetectors are presented. .

10.
Sci Rep ; 14(1): 11217, 2024 05 16.
Article in English | MEDLINE | ID: mdl-38755208

ABSTRACT

Our preliminary investigation has identified the potential of serum fucosylated extracellular vesicles (EVs) miR-4732-5p in the early diagnosis of lung adenocarcinoma (LUAD) by a fucose-captured strategy utilizing lentil lectin (LCA)-magnetic beads and subsequent screening of high throughput sequencing and validation of real-time quantitative polymerase chain reaction (RT-qPCR). Considering the relatively complicated procedure, expensive equipment, and stringent laboratory condition, we have constructed an electrochemical biosensor assay for the detection of miR-4732-5p. miR-4732-5p is extremely low in serum, down to the fM level, so it needs to be detected by highly sensitive electrochemical methods based on the Mg2+-dependent DNAzyme splitting nucleic acid lock (NAL) cycle and hybridization chain reaction (HCR) signal amplification. In this study, signal amplification is achieved through the dual amplification reactions using NAL cycle in combination with HCR. In addition, hybridized DNA strands bind to a large number of methylene blue (MB) molecules to enhance signaling. Based on the above strategy, we further enhance our signal amplification strategies to improve detection sensitivity and accuracy. The implementation of this assay proceeded as follows: initially, miR-4732-5p was combined with NAL, and then Mg2+-dependent DNAzyme splitted NAL to release auxiliary DNA (S1) strands, which were subsequently captured by the immobilized capture probe DNA (C1) strands on the electrode surface. Following this, abundant quantities of DNA1 (H1) and DNA2 (H2) tandems were generated by HCR, and S1 strands then hybridized with the H1 and H2 tandems through base complementary pairing. Finally, MB was bonded to the H1 and H2 tandems through π-π stacking interaction, leading to the generation of a signal current upon the detection of a potential capable of inducing a redox change of MB by the electrode. Furthermore, we evaluated the performance of our developed electrochemical biosensor assay. The results demonstrated that our assay is a reliable approach, characterized by its high sensitivity (with a detection limit of 2.6 × 10-17 M), excellent specificity, good accuracy, reproducibility, and stability. Additionally, it is cost-effective, requires simple operation, and is portable, making it suitable for the detection of serum fucosylated extracellular vesicles miR-4732-5p. Ultimately, this development has the potential to enhance the diagnostic efficiency for patients with early-stage LUAD.


Subject(s)
Adenocarcinoma of Lung , Biosensing Techniques , Electrochemical Techniques , Extracellular Vesicles , Lung Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/blood , Biosensing Techniques/methods , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/blood , Adenocarcinoma of Lung/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Electrochemical Techniques/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Early Detection of Cancer/methods , Female , Male , Middle Aged
11.
Front Oncol ; 14: 1393074, 2024.
Article in English | MEDLINE | ID: mdl-38812781

ABSTRACT

Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.

12.
Nano Lett ; 24(21): 6247-6254, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38709758

ABSTRACT

Two-dimensional (2D) semiconductors possess exceptional electronic, optical, and magnetic properties, making them highly desirable for widespread applications. However, conventional mechanical exfoliation and epitaxial growth methods are insufficient in meeting the demand for atomically thin films covering large areas while maintaining high quality. Herein, leveraging liquid metal oxidation reaction, we propose a motorized spin-coating exfoliation strategy to efficiently produce large-area 2D metal oxide (2DMO) semiconductors with high crystallinity, atomically thin thickness, and flat surfaces on diverse substrates. Moreover, we realized a 2D gallium oxide-based deep ultraviolet solar-blind photodetector featuring a metal-semiconductor-metal structure, showcasing high responsivity (8.24 A W-1) at 254 nm and excellent sensitivity (4.3 × 1012 cm Hz1/2 W-1). This novel liquid-metal-based spin-coating exfoliation strategy offers great potential for synthesizing atomically thin 2D semiconductors, opening new avenues for future functional electronic and optical applications.

13.
iScience ; 27(5): 109818, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38766356

ABSTRACT

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

15.
Nat Commun ; 15(1): 3097, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600111

ABSTRACT

The chemical transformations of methane (CH4) and carbon dioxide (CO2) greenhouse gases typically have high energy barriers. Here we present an approach of strategic coupling of CH4 oxidation and CO2 reduction in a switched microbial process governed by redox cycling of iron minerals under temperate conditions. The presence of iron minerals leads to an obvious enhancement of carbon fixation, with the minerals acting as the electron acceptor for CH4 oxidation and the electron donor for CO2 reduction, facilitated by changes in the mineral structure. The electron flow between the two functionally active microbial consortia is tracked through electrochemistry, and the energy metabolism in these consortia is predicted at the genetic level. This study offers a promising strategy for the removal of CH4 and CO2 in the natural environment and proposes an engineering technique for the utilization of major greenhouse gases.


Subject(s)
Greenhouse Gases , Greenhouse Gases/analysis , Carbon Dioxide/analysis , Oxidation-Reduction , Iron , Methane/metabolism , Minerals
16.
Front Immunol ; 15: 1368516, 2024.
Article in English | MEDLINE | ID: mdl-38601146

ABSTRACT

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.


Subject(s)
HMGB1 Protein , Myocardial Infarction , Mice , Animals , Humans , Interleukin-6/metabolism , Adiponectin/genetics , Adiponectin/metabolism , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Feedback , Myocardial Infarction/metabolism , Macrophages/metabolism , Adipocytes/metabolism
17.
Front Pharmacol ; 15: 1380277, 2024.
Article in English | MEDLINE | ID: mdl-38628645

ABSTRACT

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1ß, TGF-ß, and IL-8 in the ileum, as well as IL-1ß and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

18.
World J Hepatol ; 16(3): 439-451, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38577529

ABSTRACT

BACKGROUND: Sterol O-acyltransferase 1 (SOAT1) is an important target in the diagnosis and treatment of liver cancer. However, the prognostic value of SOAT1 in patients with hepatocellular carcinoma (HCC) is still not clear. AIM: To investigate the correlation of SOAT1 expression with HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer. METHODS: The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC. Overall survival and disease-specific survival were explored based on TCGA-LIHC data. Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. In addition, the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy. RESULTS: SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell-cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells. CONCLUSION: Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment, which is helpful for the development of new strategies for immunotherapy and metabolic therapy.

19.
Exp Hematol Oncol ; 13(1): 37, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570883

ABSTRACT

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

20.
JAMA Oncol ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602683

ABSTRACT

Importance: Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. Objective: To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Design, Setting, and Participants: Participants were enrolled in the Young Women's Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. Main Outcomes and Measures: The 5- and 10- year cumulative incidence of SPBC. Results: In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Conclusions: Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

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