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1.
Exp Mol Pathol ; 137: 104904, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788248

RESUMO

BACKGROUND: Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities. OBJECTIVE: This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials. METHODS: Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers. CONCLUSION: Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.


Assuntos
Neoplasias Colorretais , Sistemas de Liberação de Medicamentos , Nanomedicina , Neoplasias da Próstata , Humanos , Masculino , Nanomedicina/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Nanopartículas/química , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/tratamento farmacológico , Neoplasias Pélvicas/terapia , Medicina de Precisão/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Animais
2.
Appl Opt ; 63(13): 3625-3635, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856548

RESUMO

Free-space optical communication (FSOC) systems face susceptibility to several factors, such as transmission distance, atmospheric turbulence, and alignment errors. These elements contribute to fluctuations in the signal strength reaching the receiver. The resultant signal fluctuations can result in misjudgments and an elevated bit error rate (BER). This paper proposes an adaptive decision threshold algorithm based on a sliding window (ADTSW). By estimating received signal parameters and delimiting the amplitude interval, the algorithm ensures that the decision threshold tracks signal fluctuations, thereby reducing signal misjudgment. The effectiveness of the algorithm is validated through simulations and experimentation. When the signal peak-to-peak value fluctuates, simulation results demonstrate that the proposed algorithm achieves a 1-order-of-magnitude reduction in BER compared to the traditional fixed decision threshold (FDT) method. Under the influence of weak atmospheric turbulence with different scintillation variance, both simulation and experimentation indicate a 1-order-of-magnitude reduction in BER compared to the FDT method. The ADTSW algorithm proves its capability in minimizing misjudgments, thereby effectively reducing BER and improving communication quality.

3.
Neoplasma ; 71(1): 77-87, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38506032

RESUMO

The prognosis of advanced lung adenocarcinoma (LUAD) remains unfavorable, with chemotherapy constituting a primary treatment modality. Discerning the efficacy of chemotherapy for advanced LUAD is imperative. Prior investigations have demonstrated the prognostic value of albumin and D-dimer individually for malignancies; however, the predictive capacity of albumin-to-D-dimer ratios (ADR) for advanced LUAD subjected to first-line platinum-based chemotherapy remains unexplored. A cohort of 313 patients with advanced LUAD was retrospectively examined in this study, spanning from January 2017 to January 2021. ADR threshold values were ascertained via receiver operating characteristic analysis, followed by the evaluation of the association between pretreatment ADR and clinicopathological characteristics, disease control rate (DCR), and overall response rate (ORR) pertinent to first-line chemotherapy. Prognostic factors for progression-free survival (PFS) were determined employing Cox univariate and multivariate analyses. Subsequently, survival data were illustrated utilizing the Kaplan-Meier method and scrutinized through the log-rank test across the entire and subgroup populations. ADR demonstrated a superior area under the curve (AUC) value relative to albumin and D-dimer individually and exhibited enhanced prognostic predictive capability compared to albumin-to-fibrinogen ratios (AFR) for advanced LUAD (AUC: 0.805 vs. 0.640, DeLong test: p<0.001). ADR yielded a cut-off value of 16.608. A greater proportion of non-smokers was observed within the high-ADR group (ADR>16.608) compared to the low-ADR group (ADR≤16.608). Patients in the high-ADR group displayed elevated BMI and Na+ levels and reduced neutrophil count, monocyte count, globulin, and alkaline phosphatase (all p<0.05). Notably, the high-ADR group exhibited heightened DCR (96.7% vs. 89.2%, p=0.008) and ORR rates (70.1% vs. 51.0%, p=0.001) relative to the low-ADR group. Multivariate analysis outcomes indicated that high ADR constituted an independent risk factor for PFS (hazard ratio: 0.24, p<0.001). Furthermore, patients in the high-ADR cohort displayed a significantly prolonged median PFS (254 vs. 142 days, p<0.0001) compared to their low-ADR counterparts. In subpopulations exhibiting favorable implications for PFS, as determined by multivariate analysis, high-ADR patients consistently demonstrated extended PFS durations relative to the low-ADR group (all p<0.0001). Collectively, our findings suggest that ADR constitutes a novel and promising prognostic indicator for advanced LUAD patients, surpassing the accuracy of albumin and D-dimer individually and AFR. ADR thus serves as a potent instrument for assessing treatment effects and PFS in advanced LUAD patients undergoing first-line chemotherapy.


Assuntos
Adenocarcinoma de Pulmão , Produtos de Degradação da Fibrina e do Fibrinogênio , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Estudos Retrospectivos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Albuminas/uso terapêutico
4.
Nano Lett ; 23(11): 5035-5041, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37235534

RESUMO

Highly anisotropic materials show great promise for spatial control and the manipulation of polaritons. In-plane hyperbolic phonon polaritons (HPhPs) supported by α-phase molybdenum trioxide (MoO3) allow for wave propagation with a high directionality due to the hyperbola-shaped isofrequency contour (IFC). However, the IFC prohibits propagations along the [001] axis, hindering information or energy flow. Here, we illustrate a novel approach to manipulating the HPhP propagation direction. We experimentally demonstrate that geometrical confinement in the [100] axis can guide HPhPs along the forbidden direction with phase velocity becoming negative. We further developed an analytical model to provide insights into this transition. Moreover, as the guided HPhPs are formed in-plane, modal profiles were directly imaged to further expand our understanding of the formation of HPhPs. Our work reveals a possibility for manipulating HPhPs and paves the way for promising applications in metamaterials, nanophotonics, and quantum optics based on natural van der Waals materials.

5.
Langenbecks Arch Surg ; 409(1): 22, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157060

RESUMO

PURPOSE: This study aimed to identify the risk factors impacting long-term outcomes in patients diagnosed with sigmoid colon cancer with urinary bladder involvement. METHODS: A comprehensive analysis was conducted on a retrospective cohort of 118 patients who underwent multivisceral resection for sigmoid colon cancer with urinary bladder involvement between June 2002 and May 2017. Univariate and multivariate analyses were employed to identify risk factors associated with long-term outcomes. RESULTS: Among the included patients, 10 (8.5%) experienced grade III-IV complications according to Clavien-Dindo classification, with 4 (3.4%) presenting anastomotic leaks. The postoperative mortality was 0.8%. R0 resection was achieved in 108 (91.6%) patients. Adjuvant chemotherapy was administrated to only 31 patient (26.3%). Local recurrence was observed in 8 (6.8%) cases. Risk factors for local recurrence-free survival and disease-free survival were CCI>3, grade III-IV postoperative complications according to Clavien-Dindo classification, positive resection margins, stage III of the disease, additional resected organs (excluding colon and bladder) and the absence of adjuvant chemotherapy. The same risk factors, with the exception of CCI, were associated with overall survival. CONCLUSION: This study highlights that negative resection margins, a postoperative period without grade III-IV complications, and the implementation of adjuvant chemotherapy are crucial factors contributing to improve overall, disease-free and local recurrence-free survival in patients with sigmoid colon cancer with urinary bladder involvement.


Assuntos
Neoplasias do Colo Sigmoide , Humanos , Neoplasias do Colo Sigmoide/cirurgia , Bexiga Urinária , Estudos Retrospectivos , Margens de Excisão , Intervalo Livre de Doença , Complicações Pós-Operatórias/epidemiologia , Recidiva Local de Neoplasia , Fatores de Risco
6.
Nano Lett ; 22(20): 8060-8067, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36214538

RESUMO

Dielectric metasurfaces governed by bound states in the continuum (BIC) are actively investigated for achieving high-quality factors and strong electromagnetic field enhancements. Traditional approaches reported for tuning the performance of quasi-BIC metasurfaces include tuning the resonator size, period, and structure symmetry. Here we propose and experimentally demonstrate an alternative approach through engineering slots within a zigzag array of elliptical silicon resonators. Through analytical theory, three-dimensional electromagnetic modeling, and infrared spectroscopy, we systematically investigate the spectral responses and field distributions of the slotted metasurface in the mid-IR. Our results show that by introducing slots, the electric field intensity enhancement near the apex and the quality factor of the quasi-BIC resonance are increased by a factor of 2.1 and 3.3, respectively, in comparison to the metasurface without slots. Furthermore, the slotted metasurface also provides extra regions of electromagnetic enhancement and confinement, which holds enormous potential in particle trapping, sensing, and emission enhancement.


Assuntos
Campos Eletromagnéticos , Silício , Vibração , Espectrofotometria Infravermelho , Eletricidade
7.
Nat Mater ; 20(12): 1663-1669, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34675374

RESUMO

Wavelength-selective thermal emitters (WS-EMs) are of interest due to the lack of cost-effective, narrow-band sources in the mid- to long-wave infrared. WS-EMs can be realized via Tamm plasmon polaritons (TPPs) supported by distributed Bragg reflectors on metals. However, the design of multiple resonances is challenging as numerous structural parameters must be optimized simultaneously. Here we use stochastic gradient descent to optimize TPP emitters (TPP-EMs) composed of an aperiodic distributed Bragg reflector deposited on doped cadmium oxide (CdO) film, where layer thicknesses and carrier density are inversely designed. The combination of the aperiodic distributed Bragg reflector with the designable plasma frequency of CdO enables multiple TPP-EM modes to be simultaneously designed with arbitrary spectral control not accessible with metal-based TPPs. Using this approach, we experimentally demonstrated and numerically proposed TPP-EMs exhibiting single or multiple emission bands with designable frequencies, line-widths and amplitudes. This thereby enables lithography-free, wafer-scale WS-EMs that are complementary metal-oxide-semiconductor compatible for applications such as free-space communications and gas sensing.

8.
BMC Urol ; 22(1): 63, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439980

RESUMO

BACKGROUND: Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. CASE PRESENTATION: A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. CONCLUSIONS: Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.


Assuntos
Hemangioma , Ureter , Neoplasias Ureterais , Adulto , Erros de Diagnóstico/efeitos adversos , Feminino , Tecido de Granulação/patologia , Hemangioma/complicações , Hemangioma/diagnóstico , Hemangioma/cirurgia , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Masculino , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia
9.
Nano Lett ; 21(19): 7921-7928, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34534432

RESUMO

The hyperbolic phonon polaritons supported in hexagonal boron nitride (hBN) with long scattering lifetimes are advantageous for applications such as super-resolution imaging via hyperlensing. Yet, hyperlens imaging is challenging for distinguishing individual and closely spaced objects and for correlating the complicated hyperlens fields with the structure of an unknown object underneath. Here, we make significant strides to overcome each of these challenges. First, we demonstrate that monoisotopic h11BN provides significant improvements in spatial resolution, experimentally resolving structures as small as 44 nm and those with sub 25 nm spacings at 6.76 µm free-space wavelength. We also present an image reconstruction algorithm that provides a structurally accurate, visual representation of the embedded objects from the complex hyperlens field. Further, we offer additional insights into optimizing hyperlens performance on the basis of material properties, with an eye toward realizing far-field imaging modalities. Thus, our results significantly advance label-free, high-resolution, spectrally selective hyperlens imaging and image reconstruction methodologies.


Assuntos
Microscopia , Fônons , Processamento de Imagem Assistida por Computador
10.
Plant Cell ; 30(6): 1220-1242, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29802214

RESUMO

The unfolded protein response (UPR) is a highly conserved response that protects plants from adverse environmental conditions. The UPR is elicited by endoplasmic reticulum (ER) stress, in which unfolded and misfolded proteins accumulate within the ER. Here, we induced the UPR in maize (Zea mays) seedlings to characterize the molecular events that occur over time during persistent ER stress. We found that a multiphasic program of gene expression was interwoven among other cellular events, including the induction of autophagy. One of the earliest phases involved the degradation by regulated IRE1-dependent RNA degradation (RIDD) of RNA transcripts derived from a family of peroxidase genes. RIDD resulted from the activation of the promiscuous ribonuclease activity of ZmIRE1 that attacks the mRNAs of secreted proteins. This was followed by an upsurge in expression of the canonical UPR genes indirectly driven by ZmIRE1 due to its splicing of Zmbzip60 mRNA to make an active transcription factor that directly upregulates many of the UPR genes. At the peak of UPR gene expression, a global wave of RNA processing led to the production of many aberrant UPR gene transcripts, likely tempering the ER stress response. During later stages of ER stress, ZmIRE1's activity declined, as did the expression of survival modulating genes, Bax inhibitor1 and Bcl-2-associated athanogene7, amid a rising tide of cell death. Thus, in response to persistent ER stress, maize seedlings embark on a course of gene expression and cellular events progressing from adaptive responses to cell death.


Assuntos
Morte Celular/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Resposta a Proteínas não Dobradas/fisiologia , Zea mays/citologia , Zea mays/metabolismo , Morte Celular/genética , Estresse do Retículo Endoplasmático/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resposta a Proteínas não Dobradas/genética , Zea mays/genética
11.
Nature ; 512(7513): 194-7, 2014 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-25043035

RESUMO

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.


Assuntos
Adaptação Fisiológica/genética , Altitude , DNA/genética , Variação Genética , Hominidae/genética , Animais , Povo Asiático/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Frequência do Gene , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Tibet
12.
Nano Lett ; 19(11): 7725-7734, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31650843

RESUMO

Hyperbolic phonon polaritons (HPhPs) are generated when infrared photons couple to polar optic phonons in anisotropic media, confining long-wavelength light to nanoscale volumes. However, to realize the full potential of HPhPs for infrared optics, it is crucial to understand propagation and loss mechanisms on substrates suitable for applications from waveguiding to infrared sensing. We employ scattering-type scanning near-field optical microscopy (s-SNOM) and nano-Fourier transform infrared (FTIR) spectroscopy, in concert with analytical and numerical calculations, to elucidate HPhP characteristics as a function of the complex substrate dielectric function. We consider propagation on suspended, dielectric and metallic substrates to demonstrate that the thickness-normalized wavevector can be reduced by a factor of 25 simply by changing the substrate from dielectric to metallic behavior. Moreover, by incorporating the imaginary contribution to the dielectric function in lossy materials, the wavevector can be dynamically controlled by small local variations in loss or carrier density. Counterintuitively, higher-order HPhP modes are shown to exhibit the same change in the polariton wavevector as the fundamental mode, despite the drastic differences in the evanescent ranges of these polaritons. However, because polariton refraction is dictated by the fractional change in the wavevector, this still results in significant differences in polariton refraction and reduced sensitivity to substrate-induced losses for the higher-order HPhPs. Such effects may therefore be used to spatially separate hyperbolic modes of different orders and for index-based sensing schemes. Our results advance our understanding of fundamental hyperbolic polariton excitations and their potential for on-chip photonics and planar metasurface optics.

13.
Am J Hum Genet ; 93(2): 249-63, 2013 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-23849776

RESUMO

Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Predisposição Genética para Doença , Genoma , Mutação , Adulto , Criança , Feminino , Heterogeneidade Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Linhagem
14.
J Investig Med ; : 10815589241252356, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38644377

RESUMO

Recent studies have introduced the weight-adjusted waist circumference index (WWI) as a viable obesity indicator that may better reflect centripetal obesity and its associated risks. In examining the connection between WWI and prostate-specific antigen (PSA), this study leveraged data from the National Health and Nutrition Examination Survey 2003-2010, including 5732 participants. Our initial analysis indicated a significant positive association between WWI and PSA levels. However, subsequent models that adjusted for covariates such as age, race, and a range of metabolic and cardiovascular health-related factors revealed that the strength and significance of this relationship were attenuated. Model 1 showed a highly significant correlation (p < 0.0001). Yet, in Model 2, which accounted for age and race, the association softened (p = 0.0520). Moreover, when a full spectrum of health covariates was included in Model 3, the association was no longer significant (p = 0.9775). These findings suggest that while an unadjusted correlation exists, its potential use as a diagnostic predictor is limited without considering the broader health context. Therefore, it is crucial to review such data with multiple considerations in mind, and extensive attention should be paid to the evaluation of covariates.

15.
Front Immunol ; 15: 1428920, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015566

RESUMO

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplay between anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Ferroptose , Mitocôndrias , Neoplasias , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Mitocôndrias/metabolismo , Animais , Metástase Neoplásica
16.
Front Med (Lausanne) ; 11: 1418800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966532

RESUMO

Background: Potential uncertainties and overtreatment exist in adjuvant chemotherapy for triple-negative breast cancer (TNBC) patients. Objectives: This study aims to explore the performance of deep learning (DL) models in personalized chemotherapy selection and quantify the impact of baseline characteristics on treatment efficacy. Methods: Patients who received treatment recommended by models were compared to those who did not. Overall survival for treatment according to model recommendations was the primary outcome. To mitigate bias, inverse probability treatment weighting (IPTW) was employed. A mixed-effect multivariate linear regression was employed to visualize the influence of certain baseline features of patients on chemotherapy selection. Results: A total of 10,070 female TNBC patients met the inclusion criteria. Treatment according to Self-Normalizing Balanced (SNB) individual treatment effect for survival data model recommendations was associated with a survival benefit (IPTW-adjusted hazard ratio: 0.53, 95% CI, 0.32-8.60; IPTW-adjusted risk difference: 12.90, 95% CI, 6.99-19.01; IPTW-adjusted the difference in restricted mean survival time: 5.54, 95% CI, 1.36-8.61), which surpassed other models and the National Comprehensive Cancer Network guidelines. No survival benefit for chemotherapy was seen for patients not recommended to receive this treatment. SNB predicted older patients with larger tumors and more positive lymph nodes are the optimal candidates for chemotherapy. Conclusion: These findings suggest that the SNB model may identify patients with TNBC who could benefit from chemotherapy. This novel analytical approach may provide debiased individual survival information and treatment recommendations. Further research is required to validate these models in clinical settings with more features and outcome measurements.

17.
Trials ; 25(1): 438, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956698

RESUMO

BACKGROUND: Colon cancer is a global health concern, ranking fifth in both new diagnoses and deaths among tumors worldwide. Surgical intervention remains the primary treatment for localized cases, with a historical evolution marked by a focus on short-term outcomes. While Japan pioneered radical tumor removal with a systematic categorization of lymph nodes (D1, D2, D3), the dissemination of Japanese practices to the West was delayed until 90th of last century. Discrepancies between Japanese D3 dissection and the CME with CVL principle persist, with variations in longitudinal margins and recommended procedures. Non-randomized trials indicate the superiority of D3 over D2, but a consensus is lacking. METHODS: This prospective, international, multicenter, randomized controlled trial employs a two-arm, parallel-group, open-label design to rigorously compare the 5-year overall survival outcomes between D2 and D3 lymph node dissection in stage II-III right colon cancer. Building on prior studies, the trial aims to address existing knowledge gaps and provide a comprehensive evaluation of the outcomes associated with D3 dissection. The study population comprises patients with right colon cancer, ensuring a focused investigation into the specific context of this disease. The trial design emphasizes its global scope and collaboration across multiple centers, enhancing the generalizability of the findings. DISCUSSION: This study's primary objective is to elucidate the potential superiority in 5-year overall survival benefits of D3 lymph node dissection compared to the conventional D2 approach in patients with stage II-III right colon cancer. By examining this specific subset of patients, the research aims to contribute valuable insights into optimizing surgical strategies for improved long-term outcomes. The trial's international and multicenter nature enhances its applicability across diverse populations. The outcomes of this study may inform future guidelines and contribute to the ongoing discourse surrounding the standardization of colon cancer surgery, particularly in the context of right colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200834. Registered on June 27, 2017.


Assuntos
Neoplasias do Colo , Excisão de Linfonodo , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Estudos Prospectivos , Resultado do Tratamento , Fatores de Tempo , Estadiamento de Neoplasias , Metástase Linfática , Linfonodos/patologia , Linfonodos/cirurgia , Colectomia/efeitos adversos , Colectomia/métodos
18.
Front Oncol ; 14: 1244693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686198

RESUMO

Background: Colorectal cancer is among the most common cancers in the world, and splenic flexure colon cancer accounts for about 2-5% of them. There is still no consensus on the surgical treatment of splenic flexure colon cancer (SFCC), and the extent of surgical resection and lymph node dissection for SFCC is still controversial. Aim: To compare the postoperative and long-term oncologic outcomes of extended right colectomy (ERC), segmental colectomy (SC) and left colectomy (LC) for SFCC. Method: Up to March 2024, retrospective and prospective studies of ERC, SC, and LC for SFCC were searched through databases. Pooled weighted/standardized mean difference (WMD/SMD), odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated using a fixed effects model or random effects model, and meta-analysis was performed using Stata. Results: This meta-analysis includes 5,918 patients from 13 studies with more lymph node harvest (OR:6.29; 95%Cl: 3.66-8.91; Z=4.69, P=0), more operation time (WMD: 22.53; 95%Cl: 18.75-26.31; Z=11.68, P=0), more blood loss (WMD:58.44; 95%Cl: 20.20-96.68; Z=2.99, P=0.003), longer hospital stay (WMD:1.74; 95%Cl: 0.20-3.29; Z=2.21, P=0.03), longer time to return to regular diet (WMD:3.17; 95%Cl: 2.05-4.30; Z=5.53, P=0), longer first flatus time (WMD:1.66; 95%Cl: 0.96-2.37; Z=4.61, P=0) in ERC versus SC. More lymph node harvest (WMD: 3.52; 95% Cl: 1.59-5.44; Z=3.58, P=0) in ERC versus LC and LC versus SC (WMD: 1.97; 95% CI: 0.53-3.41; Z=2.68, P=0.007), respectively. There is no significant difference between anastomotic leakage, postoperative ileus, total postoperative complication, severe postoperative complication, wound infection, reoperations, R0 resection, postoperative mortality, 5-year overall survival (OS), 5-year disease-free survival (DFS) in three group of patients. In LC versus SC and ERC versus LC, there is no difference between operation time, blood loss, hospital stay, return to regular diet, and first flatus. Conclusion: In the included studies, SC and LC may be more advantageous, with fewer postoperative complications and faster recovery. ERC harvests more lymph nodes, but there is no significant difference in long-term OS and DFS between the three surgical approaches. Given that the included studies were retrospective, more randomized controlled trials are needed to validate this conclusion.

19.
Arch Immunol Ther Exp (Warsz) ; 71(1): 19, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566162

RESUMO

In recent years, the incidence of colorectal cancer (CRC) and breast cancer (BC) has increased worldwide and caused a higher mortality rate due to the lack of selective anti-tumor therapies. Current chemotherapies and surgical interventions are significantly preferred modalities to treat CRC or BC in advanced stages but the prognosis for patients with advanced CRC and BC remains dismal. The immunotherapy technique of chimeric antigen receptor (CAR)-T cells has resulted in significant clinical outcomes when treating hematologic malignancies. The novel CAR-T therapy target antigens include GUCY2C, CLEC14A, CD26, TEM8/ANTXR1, PDPN, PTK7, PODXL, CD44, CD19, CD20, CD22, BCMA, GD2, Mesothelin, TAG-72, CEA, EGFR, B7H3, HER2, IL13Ra2, MUC1, EpCAM, PSMA, PSCA, NKG2D. The significant aim of this review is to explore the recently updated information pertinent to several novel targets of CAR-T for CRC, and BC. We vividly described the challenges of CAR-T therapies when treating CRC or BC. The immunosuppressive microenvironment of solid tumors, the shortage of tumor-specific antigens, and post-treatment side effects are the major hindrances to promoting the development of CAR-T cells. Several clinical trials related to CAR-T immunotherapy against CRC or BC have already been in progress. This review benefits academicians, clinicians, and clinical oncologists to explore more about the novel CAR-T targets and overcome the challenges during this therapy.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Receptores de Antígenos Quiméricos , Humanos , Feminino , Neoplasias da Mama/terapia , Imunoterapia Adotiva/métodos , Neoplasias Colorretais/terapia , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Tumoral , Moléculas de Adesão Celular , Receptores Proteína Tirosina Quinases , Proteínas dos Microfilamentos , Receptores de Superfície Celular , Receptores de Enterotoxina
20.
Front Oncol ; 13: 1189370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546423

RESUMO

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a first-line screening and diagnostic tool for prostate cancer, aiding in treatment selection and noninvasive radiotherapy guidance. However, the manual interpretation of MRI data is challenging and time-consuming, which may impact sensitivity and specificity. With recent technological advances, artificial intelligence (AI) in the form of computer-aided diagnosis (CAD) based on MRI data has been applied to prostate cancer diagnosis and treatment. Among AI techniques, deep learning involving convolutional neural networks contributes to detection, segmentation, scoring, grading, and prognostic evaluation of prostate cancer. CAD systems have automatic operation, rapid processing, and accuracy, incorporating multiple sequences of multiparametric MRI data of the prostate gland into the deep learning model. Thus, they have become a research direction of great interest, especially in smart healthcare. This review highlights the current progress of deep learning technology in MRI-based diagnosis and treatment of prostate cancer. The key elements of deep learning-based MRI image processing in CAD systems and radiotherapy of prostate cancer are briefly described, making it understandable not only for radiologists but also for general physicians without specialized imaging interpretation training. Deep learning technology enables lesion identification, detection, and segmentation, grading and scoring of prostate cancer, and prediction of postoperative recurrence and prognostic outcomes. The diagnostic accuracy of deep learning can be improved by optimizing models and algorithms, expanding medical database resources, and combining multi-omics data and comprehensive analysis of various morphological data. Deep learning has the potential to become the key diagnostic method in prostate cancer diagnosis and treatment in the future.

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