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1.
Curr Res Transl Med ; 73(1): 103477, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39481140

RESUMEN

Burkitt lymphoma (BL) is a highly aggressive type of non-Hodgkin lymphomas that have a high likelihood of relapse and are highly refractory to initial treatment. While high-intensity chemotherapy has improved the outcomes, many adult patients still experience treatment failure, and effective salvage therapies are limited. This study retrospectively analyzed the outcomes of 21 relapsed or refractory (R/R) adult BL patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, combined or not with hematopoietic cell transplantation (HCT), across four Chinese hospitals. Patients were grouped based on treatment strategies: autologous HCT followed by CAR T-cell therapy (auto-HCT+CART group, n = 8), and CAR T-cell therapy alone (CART group, n = 13). The auto-HCT+CART group demonstrated superior outcomes, with an overall response rate (ORR) of 87.5 % and significantly higher 1-year overall survival (OS) and progression-free survival (PFS) rates compared to the CART group (p = 0.014 and p = 0.045, respectively). These findings suggest that combining auto-HCT with CAR-T therapy may enhance long-term disease control in R/R BL patients. These encouraging results highlight the need for further prospective studies to validate our data.

2.
Cancer ; 130(S17): 3054-3066, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39092590

RESUMEN

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.


Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados
3.
Cancer Biol Ther ; 25(1): 2358551, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38813753

RESUMEN

To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0-2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30-2.54, p value < .001; OS: HR = 2.49, 95% CI 1.73-3.59, p value < .001). Cox regression analysis revealed that the NRS2002 score was an independent prognostic factor for both PFS and OS. The objective response rate (ORR) in the group at nutritional risk was lower than that in the group without nutritional risk (8.33% and 19.71%, respectively, p value = .037). Patients at nutritional risk according to the NRS2002 score at initial treatment had a poorer prognosis than those without nutritional risk. The NRS2002 could be used as a preliminary index to predict the efficacy of immune checkpoint inhibitor therapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Femenino , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Supervivencia sin Progresión
4.
Oncologist ; 29(8): e1012-e1019, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38642091

RESUMEN

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.


Asunto(s)
Benzofuranos , Neoplasias Colorrectales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Benzofuranos/efectos adversos , Benzofuranos/uso terapéutico , Benzofuranos/administración & dosificación , Adulto , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Quinazolinas/administración & dosificación , China , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Pueblos del Este de Asia
5.
Angew Chem Int Ed Engl ; 63(26): e202402568, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38650435

RESUMEN

The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two-step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro-([1,1'-biphenyl]-4,4'-diyl)-dimethanaminium (OFPP) iodide which does not form low-dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP-PVK) film. Combined with the effective defect passivation, the OFPP-PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP-based perovskite solar cells exhibit a champion efficiency of 24.76 % with better device stability. Moreover, a superior efficiency of 21.04 % was achieved in a large-area perovskite module (100 cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.

6.
Medicine (Baltimore) ; 103(11): e37484, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489730

RESUMEN

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Humanos , Pronóstico , Perfilación de la Expresión Génica , Biomarcadores , Neoplasias Pulmonares/genética , Neoplasias Colorrectales/genética , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Quimiocinas/metabolismo , Apolipoproteínas E/genética , Biología Computacional , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica
7.
ACS Appl Mater Interfaces ; 16(13): 16340-16350, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38511525

RESUMEN

As an additive for perovskites, in addition to functional groups, the steric configuration of molecules is worthy of consideration because it influences perovskite crystallization, thus determining whether defect passivation is effective without any side effects. In this work, the chiral molecules l- and d-pyroglutamic acid (l-PA and d-PA) were chosen as additives for perovskite passivators to reveal the reasons for the differences in passivation between amino acids with different steric configurations. Functional groups, such as the C═O groups and N-H groups of l-PA and d-PA, can passivate the perovskite defects. However, l-PA exhibited a more distorted steric configuration, while d-PA was more planar, leading to differences in the distances between the two C═O groups. Taking the Pb-Pb bond length as a reference, the shorter distance between the two C═O groups of l-PA distorts the perovskite lattice structure, which results in poor device stability. Conversely, the similar distance between the two C═O groups of d-PA promoted the preferred orientational growth of the perovskite. Finally, the d-PA-doped device accomplished an excellent efficiency of 24.11% with an improved open-circuit voltage of 1.17 V. Furthermore, the efficiency of the unencapsulated d-PA-doped device was maintained at 93% in N2 for more than 3000 h and 74% after 500 h of operation at maximum power point tracking under continuous illumination.

8.
SSM Popul Health ; 25: 101630, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38405164

RESUMEN

Objective: To explore the effects of green spaces exposure on common psychiatric disorders. Methods: PubMed, Embase, Web of Science and MEDLINE were screened and articles published prior to November 15, 2023 were included. Analyses were performed on common psychiatric disorders, categorized into depression, anxiety, dementia, schizophrenia, and attention deficit hyperactivity disorder (ADHD). And the subgroup analyses were conducted for depression, anxiety, dementia, and schizophrenia. Results: In total, 2,0064 studies were retrieved, 59 of which were included in our study; 37 for depression, 14 for anxiety, 8 for dementia, 7 for schizophrenia and 5 for ADHD. Green spaces were found to benefit the moderation of psychiatric disorders (OR = 0.91, 95% CI: 0.89 to 0.92). Green spaces positively influence depression (OR = 0.89, 95% CI: 0.86 to 0.93), regardless of the cross-sectional or cohort studies. Green spaces can also help mitigate the risk of anxiety (OR = 0.94, 95%CI:0.92 to 0.96). As an important index for measuring green spaces, a higher normalized difference vegetation index (NDVI) level related to a lower level of depression (OR = 0.95, 95%CI:0.91 to 0.98) and anxiety (OR = 0.95, 95%:0.92 to 0.98). The protection was also found in dementia (OR = 0.95, 95% CI: 0.93 to 0.96), schizophrenia (OR = 0.74, 95% CI: 0.67 to 0.82), and ADHD (OR = 0.89, 95% CI: 0.86 to 0.92) results. Conclusion: Green spaces decrease the risk of psychiatric disorders, including depression, anxiety, dementia, schizophrenia, and ADHD. Further studies on green spaces and psychiatric disorders are needed, and more green spaces should be considered in city planning.

9.
PeerJ ; 11: e15995, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37719110

RESUMEN

Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years.


Asunto(s)
Neoplasias Colorrectales , Reducción Gradual de Medicamentos , Humanos , Estudios Retrospectivos , Neoplasias Colorrectales/tratamiento farmacológico , Comités de Ética en Investigación , Fluorouracilo/uso terapéutico
10.
Nutr Clin Pract ; 38(5): 1167-1174, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37461335

RESUMEN

BACKGROUND: To investigate the influencing factors of infectious complications in patients with chronic kidney disease (CKD) and provide a basis for clinical diagnosis and prognosis evaluation of CKD. METHODS: A total of 682 patients with CKD were selected and divided into CKD stage 1-5 subgroups according to their glomerular filtration rate. Infectious complications, length of hospital stay, and total cost of hospitalization were recorded. The Global Leadership Initiative on Malnutrition (GLIM) diagnostic tool was used to assess the detection rate of malnutrition among patients. Univariate and multivariate analyses were performed in patients with and without infectious complications. RESULTS: The incidence rates of infectious complications in CKD stages 1-5 were 45.6%, 22.7%, 28.3%, 30.8%, and 40.4%, respectively. The overall detection rate of malnutrition among patients based on the GLIM criteria was 16.7%. The total detection rate of severe malnutrition was 14.2%, with all patients with severe malnutrition in CKD stages 3-5. The incidences of infectious complications in patients with and without malnutrition were 62.3% and 29%, respectively. Binary multivariate logistic regression analysis shows that malnutrition is a risk factor for infectious complications in patients with CKD, who are at 2.41 times higher risk than patients without malnutrition. There were significant differences in length of hospital stay and hospitalization costs between the patients with CKD with and without infectious complications (P < 0.01). CONCLUSION: Infectious complications are relatively common in patients with CKD. As CKD advances, the incidence of infectious complications increases. Moreover, malnutrition accelerates the occurrence of infectious complications in patients with CKD.


Asunto(s)
Desnutrición , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/diagnóstico , Desnutrición/complicaciones , Desnutrición/diagnóstico , Desnutrición/epidemiología , Tiempo de Internación , Hospitalización , Evaluación Nutricional , Estado Nutricional
11.
Pathol Oncol Res ; 29: 1611070, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37151353

RESUMEN

Background: Waldenström macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton's tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression. Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse. Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy.


Asunto(s)
ADN Tumoral Circulante , Linfoma de Células B , Macroglobulinemia de Waldenström , Humanos , Masculino , Persona de Mediana Edad , Ascitis , ADN Tumoral Circulante/genética , Progresión de la Enfermedad , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/genética , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico
12.
J Int Med Res ; 51(4): 3000605231162443, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37032598

RESUMEN

Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Neoplasias de los Tejidos Blandos , Masculino , Humanos , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/terapia , Radiofármacos , Fluorodesoxiglucosa F18 , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/terapia , Inmunoterapia , Estudios Retrospectivos , Carga Tumoral , Pronóstico
13.
Cancer Control ; 30: 10732748231169396, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37039746

RESUMEN

OBJECTIVE: We investigated the prognostic value of cyclin-dependent kinase 5 (CDK5) in a true population-based cohort of patients with colon cancer. METHODS: 1. Immunohistochemical (IHC) staining was used to retrospectively analyse the expression of CDK5 in colon cancer tissue samples of 296 patients. The χ2 test, Kaplan-Meier method and Cox proportional regression model were used to analyse the difference between the patients with differential expression of CDK5 and with different stages (metastatic and nonmetastatic); 2. The number of tumour-infiltrating lymphocytes (TILs) in tumour sections was determined, and its relationship with prognosis was explored. RESULTS: 1. Among 296 patients stained for CDK5, 18 cases (6.09%) showed negative expression, 77 cases (26.01%) showed weak expression (+1), 124 cases (41.89%) showed medium positive expression (2+), and 77 cases (26.01%) showed strong positive expression (3+). The expression of CDK5 was neither related to mismatch repair nor TILs (p > .05). In non-metastatic patients, longer progression-free survival (PFS) and cancer-specific survival (CSS) were observed in patients with high CDK5 expression (2+ or 3+) than low CDK5 expression (- or 1+), while in metastatic disease, the opposite was true (p < .001). 2. TILs in 226 patients were detected in the study. Among them, 115 cases (50.88%) showed a low number of TILs (TILs-L), and 111 cases (49.12%) showed a high number of TILs (TILs-H). Patients with a TIL ratio greater than .2 had a significantly better CSS (p < .001) or PFS (p = .008) than patients with a lower TIL ratio. By multivariate analysis, TILs-H was a protective factor for CSS, however failed to reach a significant difference (hazard ratio: .59, 95% CI: .33∼1.06, p = .079), and so was the PFS (HR: .65, 95% CI: .29∼1.43, p = .279). CONCLUSION: High expression of CDK5 indicates a good prognosis in nonmetastatic colon cancer, while it is the opposite in metastatic colon cancer, and the expression of CDK5 is unrelated to TILs. Patients with TIL-H have a better prognosis, with a proper cut-off value of 20% for colon cancer.


Asunto(s)
Carcinoma , Neoplasias del Colon , Humanos , Linfocitos Infiltrantes de Tumor/patología , Estudios Retrospectivos , Quinasa 5 Dependiente de la Ciclina , Pronóstico , Neoplasias del Colon/patología , Carcinoma/patología
14.
BMC Med ; 21(1): 132, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37013584

RESUMEN

BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , Oxaliplatino/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación hacia Abajo , ARN Largo no Codificante/genética , MicroARNs/metabolismo , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo
15.
Sci Rep ; 13(1): 3185, 2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36823199

RESUMEN

Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.


Asunto(s)
Anemia , Antineoplásicos , Neoplasias , Trombocitopenia , Femenino , Humanos , Estudios Retrospectivos , Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Trombocitopenia/tratamiento farmacológico , Anemia/complicaciones
16.
PLoS One ; 18(1): e0280474, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36652446

RESUMEN

OBJECTIVE: The aim of the current study was to explore the association between age and outcomes in breast cancer. METHODS: Patients during 2010-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and breast cancer-specific death (BCSD) were taken as endpoints. The restrict cubic spline graph (RCS) was used to explore the relationship between age and outcomes in patients, and the cumulative incidence of BCSD and non-BCSD was calculated using the Gray method. Age-specific gene expression profiles were studied using RNA sequence data from the Cancer Genome Atlas (TCGA) database to explore whether there were young age-related gene or gene sets. RESULTS: A total of 142,755 patients with breast cancer were included. The hazard ratio (HR) of OS for Patients with stage I-III breast cancer was roughly stable before 53 years old and increased significantly after that, and the HR of BCSD for these patients showed a U-shaped distribution when plotted against age, with patients younger than 50 years and patients older than 70 years experiencing the worst survival. Further stratified analysis according to molecular subtype revealed that the U-shaped distribution of the HR of BCSD with was only found in the Hormone receptor-positive/HER2-negative (HoR+/HER2-) subgroup. The cumulative incidence plots showed that young age was associated with worse BCSD in the breast cancer patients with stage I-III and HoR+/HER2- subgroup. In stage IV breast cancer, there was a linearity of the relationship between poor OS and increasing age. We failed to find any differentially expressed age-specific genes between 20-40 years and 41-60 years groups in 258 patients with stage I-III and HoR+/HER2- subtype. CONCLUSION: Young age could predict worse BCSD of patient with stage I-III and HoR+/HER2- breast cancer. The escalating therapy was recommended to young age breast cancer with stage I-III and HoR+/HER2- subtype.


Asunto(s)
Neoplasias de la Mama , Humanos , Persona de Mediana Edad , Adulto Joven , Adulto , Femenino , Neoplasias de la Mama/metabolismo , Estadificación de Neoplasias , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Programa de VERF , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Hormonas , Pronóstico
17.
Clin Lung Cancer ; 24(3): e141-e151, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36639280

RESUMEN

BACKGROUND: The standard surgical procedure for ≤ 2 cm non-small cell lung cancer (NSCLC), including the number of lymph nodes sampled (nLN) and surgical modality, remains controversial. This study was designed to determine the optimal cohort in which sublobectomy could be an alternative to lobectomy. MATERIALS (OR PATIENTS) AND METHODS: Patients from 1998 to 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of nLN was identified using a restrictive cubic spline graph (RCS). Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). The COX proportional hazard regression model was used to identify the influence of clinical and demographic variables on survival, and propensity score matching (PSM) was used to balance differences in baseline characteristics. Finally, we used an external cohort from a single-center medical institution to verify the conclusions drawn from the SEER database. RESULTS: A total of 6150 patients were included. The sublobectomy subgroup included segmentectomy (308, 5.0%) and wedge resection (1611, 26.2%). The cutoff value for nLN was 7. In the nLN ≥7 subgroup of the PSM cohort, the CSS of segmentectomy and wedge resection was close to that of the lobectomy subgroup (P = .12), whereas in the nLN <7 subgroup, the CSS of the lobectomy subgroup was significantly higher than that of the sublobectomy with P < .001). Surgical methods, nLN, age, sex, and differentiated grade were independent predictors of CSS. External cohort validation: A total of 1106 patients from the Affiliated Jinhua Hospital of Zhejiang University School of Medicine between 2013 and 2020 were included. The grouping criteria were consistent with the SEER database. In the nLN≥7 subgroup, sublobectomy had a survival outcome similar to that of lobectomy (P = .81). CONCLUSION: Sublobectomy and nLN < 7 were strongly associated with poorer CSS for early-stage NSCLC. On the premise of nLN ≥ 7, sublobectomy could provide similar survival outcomes to lobectomy for these patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Neumonectomía/métodos , Estadificación de Neoplasias , Carcinoma Pulmonar de Células Pequeñas/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología
18.
ACS Nano ; 17(3): 2802-2812, 2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36700840

RESUMEN

An electron-transport layer with appropriate energy alignment and enhanced charge transfer is critical for perovskite solar cells (PSCs). In addition, interface stress and lattice distortion are inevitable during the crystallization process of perovskite. Herein, IT-4F is introduced into PSCs at the buried SnO2 and perovskite interface, which assists in releasing the residual stress in the perovskite layer. Meanwhile, the work function of SnO2/IT-4F is lower than that of SnO2, which facilitates charge transfer from perovskite to ETL and consequently leads to a significant improvement in the power conversion efficiency (PCE) to 23.73%. The VOC obtained is as high as 1.17 V, corresponding to a low voltage deficit of 0.38 V for a 1.55 eV bandgap. Consequently, the device based on IT-4F maintains 94% of the initial PCE over 2700 h when stored in N2 and retains 87% of the initial PCE after operation for 1000 h.

19.
Small ; 19(11): e2206952, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36541718

RESUMEN

All-inorganic perovskite CsPbI3 contains no volatile organic components and is a thermally stable photoactive material for wide-bandgap perovskite solar cells (PSCs); however, CsPbI3 readily undergoes undesirable phase transitions due to the hygroscopic nature of the ionic dopants used in commonly used hole transport materials. In the current study, the popular donor material PM6 in organic solar cells is used as a hole transport layer (HTL). The benzodithiophene-based backbone-conjugated polymer requires no dopant and leads to a higher power conversion efficiency (PCE) than 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-OMeTAD). Moreover, PM6 also shows priorities in hole mobility, hydrophobicity, cascade energy level alignment, and even defect passivation of perovskite films. With PM6 as the dopant-free HTL, the PSCs achieve a champion PCE of 18.27% with a competitive fill factor of 82.8%. Notably, the present PCE is based on the dopant-free HTL in CsPbI3 PSCs reported thus far. The PSCs with PM6 as the HTL retain over 90% of the initial PCE stored in a glovebox filled with N2 for 3000 h. In contrast, the PSCs with Spiro-OMeTAD as the HTL maintain ≈80% of the initial PCE under the same conditions.

20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 51(5): 594-602, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36581574

RESUMEN

OBJECTIVE: To evaluate the effect of resection of primary lesion and chemotherapy on survival of patients with metastatic colorectal neuroendocrine carcinoma (CRNEC). METHODS: Clinical data of 393 patients with metastatic CRNECs between January 2010 and December 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, including 171 patients who received resection of primary lesion and 221 patients who did not undergo surgery. With the propensity score matching method 172 non-operated patients were selected as controls. Kaplan-Meier method and Log-rank test were used to evaluate the survival differences, while the prognostic factors were analyzed by Cox proportional-hazards model. Metastatic CRNEC patients from January 2001 to December 2021 in Affiliated Jinhua Hospital, Zhejiang University School of Medicine were selected for validation. RESULTS: Compared with non-operated patients, patients who received resection had longer cause-specific survival ( P<0.05). Patients with resected positive lymph nodes>8 had a poorer prognosis compared to those with resected positive lymph nodes≤8 ( P<0.05). Multivariate analysis showed that gender, location of primary lesion and treatments were independent risk factors for cause-specific survival in patients with metastatic CRNEC (all P<0.05). For metastatic CRNEC patients with resection of primary lesion, rectal neuroendocrine carcinoma, positive resected lymph nodes≤8 and resection of primary lesion combined with chemotherapy were associated with better cause-specific survival (all P<0.05). CONCLUSIONS: Patients with metastatic CRNEC may benefit from resection of primary lesion, and resection of primary lesion combined with chemotherapy might be the better strategy for metastatic CRNECs. The number of positive lymph nodes resected is correlated with the prognosis of patients.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias Colorrectales , Humanos , Estadificación de Neoplasias , Pronóstico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugía , Modelos de Riesgos Proporcionales
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