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2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(5): 516-520, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38778693

RESUMO

Gastric cancer ranks as the third most prevalent malignant tumor in our nation, imposing a substantial health and economic burden. The occurrence of postoperative complications in gastric cancer not only hinders patient recovery but also significantly increases the medical expenditures of patients, contributing supplementary health economic challenges to both society and healthcare institutions. Conducting health economic analysis on postoperative complications in gastric cancer provides evidence for the formulation of health policies, offers guidance for hospital cost control, and furnishes economic insights for the development of new technologies in the prevention and treatment of complications. This paper, through a thorough review of domestic and international literature, comprehensively examines the impact of complication severity on healthcare expenses, delineates the principal contributors to healthcare costs in patients with postoperative complications, and proposes practical strategies to alleviate the health economic burden resulting from such complications. Furthermore, this study delves into and analyzes the health economic considerations associated with postoperative complications within the framework of the Diagnosis Related Groups (DRG) billing model.


Assuntos
Custos de Cuidados de Saúde , Complicações Pós-Operatórias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/economia , Complicações Pós-Operatórias/economia , Gastos em Saúde , Efeitos Psicossociais da Doença
3.
Zhonghua Zhong Liu Za Zhi ; 46(3): 211-220, 2024 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-38494768

RESUMO

Antibody-drug conjugates (ADCs) are drugs that combine monoclonal antibody drugs targeting specific antigens and small molecule cytotoxic drugs through linker molecules. ADCs combine the advantages of high specificity targeting and potent killing effects, achieving precise and efficient targeting of cancer cells. Nowadays, ADCs are one of the hotspots in cancer drug development. Human epidermal growth factor receptor 2 (HER-2) is a known oncogene that can drive the occurrence and development of various types of tumors. HER-2 is also an important tumor target for ADCs approved for solid tumors. Anti-HER-2 ADCs can not only be used to treat HER-2-positive tumors but also effectively target HER-2-low tumors. The emergence of ADCs has broken the traditional classification of HER-2 in tumors, bringing significant treatment breakthroughs for HER-2-low tumors. Anti-HER-2 ADCs are widely used in the treatment of solid tumors and have substantial evidence for HER-2-low tumors. This article presents the progress of various anti-HER-2 ADCs in HER-2-low tumors including breast cancer, gastrointestinal malignancies, urothelial carcinoma, lung cancer. And this article summarizes the current status of preclinical studies, clinical studies, and safety of anti-HER-2 ADCs in order to provide reference for the clinical use of HER-2-low tumors.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Imunoconjugados , Receptor ErbB-2 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos/uso terapêutico , Imunoconjugados/uso terapêutico , Oncogenes
4.
J Magn Reson Imaging ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294179

RESUMO

BACKGROUND: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). PURPOSE: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. STUDY TYPE: Prospective. POPULATION: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). FIELD STRENGTH/SEQUENCE: 3.0 T/reduced field of view single-shot echo-planar DTI sequence. ASSESSMENT: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. STATISTICAL TESTS: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). DATA CONCLUSION: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

5.
Artigo em Chinês | MEDLINE | ID: mdl-38296241

RESUMO

In September 8th, 2021, a male patient (aged 18 years) with severe destructive injuries of high-voltage electric burns in the head, face, and neck was admitted to General Hospital of Taiyuan Iron Steel (Group) Co., Ltd. Based on the economic theory of flaps, the flap donor site and transplantation method were optimized and evaluated before surgery, and then debridement of head, face, and neck wounds+removal of necrotic skull+free transplantation of super large latissimus dorsi myocutaneous flap+thin intermediate thickness skin graft transplantation from the left thigh was performed. The extra large flap donor site wound was sutured directly. This surgery reduced the adverse consequences of the flap donor site on the premise of ensure of repair effect. After operation, the patient's condition was stable, the flap and skin graft survived well, the repair effect of wound was well, the scar in the flap donor area was relatively mild, and the upper limb had no dysfunction.


Assuntos
Queimaduras por Corrente Elétrica , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Masculino , Queimaduras por Corrente Elétrica/cirurgia , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/cirurgia , Cicatrização , Adolescente
6.
Clin Oncol (R Coll Radiol) ; 36(1): 39-45, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37977903

RESUMO

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Etoposídeo , Estudos Prospectivos , Carboplatina/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptores ErbB , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Radiol Artif Intell ; 5(6): e220259, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074778

RESUMO

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

8.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 41(10): 846-849, 2023 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-37935552

RESUMO

Objective: To understand the epidemiological characteristics of suspected occupational diseases cases, and to track the subsequent diagnosis of suspected cases in Hubei Province from 2020 to 2021, and to provide theoretical basis for the supervision of suspected occupational diseases. Methods: In April 2022, the data of suspected occupational diseases cases and occupational diseases in Hubei Province from 2020 to 2021 were collected by the Occupational Diseases and Health Risk Factors Information Surveillance System. The distribution and diagnosis of suspected occupational diseases cases were analyzed. We investigated undiagnosed suspected occupational diseases by telephone. Results: From 2020 to 2021, a total of 1872 cases of suspected occupational diseases in 6 categories and 18 species were reported in Hubei Province. The top three suspected occupational diseases were suspected occupational noise deafness (36.75%, 688/1872), suspected coal worker's pneumoconiosis (33.07%, 619/1872) and suspected silicosis (20.99%, 393/1872). The diagnosis rate of suspected occupational diseases was 33.60% (629/1872). The rate of confirmed diagnosis was 63.59% (400/629). The diagnosis rate (26.86%, 456/1698) and rate of confirmed diagnosis (55.48%, 253/456) of suspected occupational diseases detected by occupational health examination were the lowest. The diagnosis rate of suspected occupational diseases detected by comprehensive medical institutions and private medical institutions were lower than disease prevention and control institutions and occupational disease prevention center (P<0.05). The main reasons for not entering the diagnostic procedure included that workers were not informed that they were diagnosed as suspected occupational diseases (31.55%, 124/393), workers were unwilling to apply for occupational disease diagnosis (18.56%, 73/393), and some workers planned to apply for diagnosis but had not yet applied (10.69%, 42/393) . Conclusion: Occupational noise deafness, coal worker's pneumoconiosis and silicosis are the main diseases of suspected occupational diseases in Hubei Province. In order to increase the diagnosis rate and confirmed diagnosis rate of suspected occupational diseases, it is suggested to strengthen management and supervision from the aspects of case management, information warning and worker notification.


Assuntos
Antracose , Minas de Carvão , Surdez , Perda Auditiva Provocada por Ruído , Doenças Profissionais , Pneumoconiose , Silicose , Humanos , Pneumoconiose/epidemiologia , Seguimentos , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Antracose/epidemiologia , China/epidemiologia
9.
JAMA Netw Open ; 6(9): e2333933, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37707811

RESUMO

Importance: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials. Objective: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST). Design, Setting, and Participants: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer with no pathologic evidence of residual disease following standard NST enrolled from March 6, 2017, to November 9, 2021. Validated PRO measures were administered at baseline and 6, 12, and 36 months post-radiotherapy. Data were analyzed from January to February 2023. Interventions: PRO measures included the Decision Regret Scale (DRS), Functional Assessment of Cancer Therapy-Lymphedema (FACT-B+4), and Breast Cancer Treatment Outcomes Scale (BCTOS). Main Outcomes and Measures: Changes in PRO measure scores and subscores over time. Results: Among 31 patients, the median (IQR) age was 61 (56-66) years, 26 (84%) were White, and 26 (84%) were non-Hispanic. A total of 15 (48%) had triple-negative disease and 16 (52%) had ERBB2-positive disease. Decisional comfort was high at baseline (median [IQR] DRS score 10 [0-25] on a 0-100 scale, with higher scores indicating higher decisional regret) and significantly increased over time (median [IQR] DRS score at 36 months, 0 [0-20]; P < .001). HRQOL was relatively high at baseline (median [IQR] FACT-B composite score 121 [111-134] on a 0-148 scale, with higher scores indicating higher HRQOL) and significantly increased over time (median [IQR] FACT-B score at 36 months, 128 [116-137]; P = .04). Perceived differences between the affected breast and contralateral breast were minimal at baseline (median [IQR] BCTOS score 1.05 [1.00-1.23] on a 1-4 scale, with higher scores indicating greater differences) and increased significantly over time (median [IQR] BCTOS score at 36 months, 1.36 [1.18-1.64]; P < .001). At 36 months postradiotherapy, the cosmetic subscore was 0.45 points higher than baseline (95% CI, 0.16-0.74; P = .001), whereas function, pain, and edema subscores were not significantly different than baseline. Conclusions and Relevance: In this nonrandomized phase 2 clinical trial, analysis of PROs demonstrated an overall positive experience for trial participants, with longitudinal improvements in decisional comfort and overall HRQOL over time and minimal lasting adverse effects of therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02945579.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Estudos Prospectivos , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Medidas de Resultados Relatados pelo Paciente
10.
J Anim Physiol Anim Nutr (Berl) ; 107(6): 1368-1375, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37539819

RESUMO

Weaning is a critical period in raising pigs. Novel animal feed additives that promote gut health and regulate immune function of piglets without antibiotics are needed. In this study, we aimed to test the ability of mesobiliverdin IXα-enriched microalgae (MBV IXα-enriched microalgae) to eliminate reliance on antibiotics to promote intestinal health in piglets. Eighty 28-day-old weaned piglets were randomly allocated to four groups each with four replicate pens and five piglets per pen. The dietary treatments were a basal diet as control (NC), basal diet plus 0.05% tylosin (PC), basal diet plus 0.1% or 0.5% MBV IXα-enriched microalgae as low (MBV-SP1) or high (MBV-SP2) dose respectively. All treated animals showed no significant differences in live weight, average daily gain and feed efficiency compared to control animals. Histological examination showed that MBV-SP1 and particularly MBV-SP2 increased the ratio of villus height to crypt depth in the jejunum and ileum compared to NC (p < 0.05). Similarly, tylosin treatment also increased villi lengths and the ratio of villus height to crypt depth in the jejunum and ileum compared to the NC (p < 0.05). MBV-SP1 and particularly MBV-SP2 reduced the levels of inflammatory cytokines interleukin-6 and tumour necrosis factor-alpha in the small intestine. MBV-SP2 and tylosin similarly reduced the lipid peroxidation marker (TBARS value) in the duodenum and ileum. In conclusion, feed supplementation with MBV IXα-enriched microalgae improved gut health by villus height and production of immunomodulators that correlated with down-regulated secretion of inflammatory cytokines.


Assuntos
Suplementos Nutricionais , Microalgas , Animais , Suínos , Desmame , Tilosina/farmacologia , Antibacterianos/farmacologia , Dieta/veterinária , Citocinas , Ração Animal/análise
13.
Radiol Imaging Cancer ; 5(4): e230009, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37505106

RESUMO

Purpose To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, 181 women diagnosed with stage I-III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting in 930 features per scan. Radiomic features were compared between pCR and non-pCR groups by using Wilcoxon rank sum test. To build a multivariable predictive model, logistic regression with elastic net regularization and cross-validation was performed for texture feature selection using 119 participants (median age, 52 years [range, 26-77 years]). An independent testing cohort of 62 participants (median age, 48 years [range, 23-74 years]) was used to evaluate and compare the models by area under the receiver operating characteristic curve (AUC). Results Univariable analysis identified 15 T1, 10 T2, and 12 PD radiomic features at midtreatment that predicted pCR with an AUC greater than 0.70 in both the training and testing cohorts. Multivariable radiomics models of maps acquired at midtreatment demonstrated superior performance over those acquired at baseline, achieving AUCs as high as 0.78 and 0.72 in the training and testing cohorts, respectively. Conclusion SyMRI-based radiomic features acquired at midtreatment are potentially useful for identifying early NAST responders in TNBC. Keywords: MR Imaging, Breast, Outcomes Analysis ClinicalTrials.gov registration no. NCT02276443 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Houser and Rapelyea in this issue.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Mama
14.
J Am Coll Surg ; 237(1): 101-108, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36856291

RESUMO

BACKGROUND: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion. STUDY DESIGN: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with <2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt. RESULTS: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were White (69.2%) and non-Hispanic/Latino (84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+BC). Mean tumor size was 2.4 cm (range 0.9 to 5.0) before NST and 0.7 cm (range 0 to 1.8) after NST. Seven patients (53.8%) had residual disease identified on VACB; the remaining 6 (46.2%) comprised the feasibility cohort. At a median follow-up of 44.3 months (range 41.3 to 51.3) there was no ipsilateral breast tumor recurrence in this cohort. CONCLUSIONS: These early data suggest that omission of breast surgery in patients with invasive TNBC and HER2+BC with no evidence of residual disease on standardized VACB after NST is potentially feasible. Results from the expansion phase of this clinical trial will be reported per protocol prespecified analyses.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Estudos Prospectivos , Estudos de Viabilidade , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
15.
Biomolecules ; 13(3)2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36979346

RESUMO

BACKGROUND: Connexins (Cxs) are proteins that help cells to communicate with the extracellular media and with the cytoplasm of neighboring cells. Despite their importance in several human physiological and pathological conditions, their pharmacology is very poor. In the last decade, some molecules derived from aminoglycosides have been developed as inhibitors of Cxs hemichannels. However, these studies have been performed in E. coli, which is a very simple model. Therefore, our main goal is to test whether these molecules have similar effects in mammalian cells. METHODS: We transfected HeLa cells with the human Cx46tGFP and characterized the effect of a kanamycin-derived molecule (KI04) on Cx46 hemichannel activity by time-lapse recordings, changes in phosphorylation by Western blot, localization by epifluorescence, and possible binding sites by molecular dynamics (MD). RESULTS: We observed that kanamycin and KI04 were the most potent inhibitors of Cx46 hemichannels among several aminoglycosides, presenting an IC50 close to 10 µM. The inhibitory effect was not associated with changes in Cx46 electrophoretic mobility or its intracellular localization. Interestingly, 5 mM DTT did not reverse KI04 inhibition, but the KI04 effect completely disappeared after washing out KI04 from the recording media. MD analysis revealed two putative binding sites of KI04 in the Cx46 hemichannel. RESULTS: These results demonstrate that KI04 could be used as a Cx46 inhibitor and could help to develop future selective Cx46 inhibitors.


Assuntos
Aminoglicosídeos , Escherichia coli , Animais , Humanos , Células HeLa , Escherichia coli/metabolismo , Conexinas/metabolismo , Antibacterianos , Canamicina/farmacologia , Mamíferos/metabolismo
17.
NPJ Breast Cancer ; 9(1): 2, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627285

RESUMO

Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient's diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient's tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.

18.
Br J Radiol ; 96(1142): 20211326, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35451861

RESUMO

Screening mammography identifies early-stage breast cancers and is associated with reduced breast cancer mortality. An unintended consequence of breast screening is the detection and diagnosis of multiple incidental benign and malignant breast lesions, including the heterogenous group of incidental benign (B3) lesions with uncertain biological outcomes and malignant potential, for which management remains controversial. Recent shifts toward more conservative management approaches, including the identification of patients who can undergo observation after vacuum-assisted excision, has gained interest. This commentary provides an overview of incidental B3 lesions and summarizes the current management paradigms for them.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Mamografia , Detecção Precoce de Câncer , Mama/diagnóstico por imagem , Mama/patologia , Diagnóstico Diferencial
19.
J Endocrinol Invest ; 46(5): 893-901, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36376545

RESUMO

BACKGROUND: Tall cell variant (TCV) of papillary thyroid cancer (PTC) is the most common aggressive subtype of PTC. The factors that affect survival of patients with TCV remain unclear. We aimed to develop a model to predict the cancer-specific survival (CSS). METHODS: A total of 1615 patients diagnosed with TCV between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and randomized into training and validation cohorts (7:3). A predictive nomogram for predicting CSS was constructed by Cox proportional hazards regression and validated by concordance index (C-index), calibration curve, and decision curve analyses (DCA). A risk classification system was built based on the total nomogram scores of each case. RESULTS: A nomogram was constructed including five independent prognostic factors (age, tumor size, T stage, M stage, and extent of surgery) associated with CSS in TCV patients. Various validations proved that the nomogram model had good consistency and discrimination for TCV prognosis. The risk classification system could perfectly classify TCV patients into three risk groups with significantly different CSS. Compared with traditional AJCC TNM staging system, the nomogram could better predict CSS in TCV patients. CONCLUSIONS: A nomogram and corresponding risk classification system were developed for predicting CSS in TCV patients. The model has excellent performance and can be used to help clinicians make accurate prognostic assessment and individualized treatment.


Assuntos
Nomogramas , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Bases de Dados Factuais , Neoplasias da Glândula Tireoide/diagnóstico , Prognóstico
20.
AJR Am J Roentgenol ; 220(4): 512-523, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36321982

RESUMO

Contrast-enhanced mammography (CEM) is an emerging functional breast imaging technique that entails the acquisition of dual-energy digital mammographic images after IV administration of iodine-based contrast material. CEM-guided biopsy technology was introduced in 2019 and approved by the U.S. FDA in 2020. This technology's availability enables direct sampling of suspicious enhancement seen only on or predominantly on recombined CEM images and addresses a major obstacle to the clinical implementation of CEM technology. The literature describing clinical indications and procedural techniques of CEM-guided biopsy is scarce. This article describes our initial experience in performing challenging CEM-guided biopsies and proposes a step-by-step procedural algorithm designed to proactively address anticipated technical difficulties and thereby increase the likelihood of achieving successful targeting.


Assuntos
Neoplasias da Mama , Mamografia , Humanos , Feminino , Mamografia/métodos , Mama/diagnóstico por imagem , Biópsia , Meios de Contraste , Imagem Multimodal , Neoplasias da Mama/diagnóstico por imagem
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