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1.
BMC Complement Med Ther ; 24(1): 310, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160496

RESUMO

BACKGROUND: The previous effects of acupuncture-related interventions in improving chemotherapy-induced peripheral neuropathy (CIPN) symptoms and quality of life (QoL) remain unclear in terms of pairwise comparisons. AIMS: This systematic review and network meta-analysis aimed to determine the hierarchical effects of acupuncture-related interventions on symptoms, pain, and QoL associated with CIPN in cancer patients undergoing chemotherapy. METHODS: Nine electronic databases were searched, including PubMed, Embase, Cochrane Library, EBSCO, Medline Ovid, Airiti Library, China National Knowledge Infrastructure (CNKI), China Journal full-text database (CJFD), and Wanfang. Medical subject heading terms and text words were used to search for eligible randomized controlled trials published from database inception to May 2023. RESULTS: A total of 33 studies involving 2,027 participants were included. Pairwise meta-analysis revealed that acupuncture-related interventions were superior to usual care, medication, or dietary supplements in improving CIPN symptoms, CIPN pain, and QoL. Furthermore, network meta-analysis indicated that acupuncture plus electrical stimulation (acupuncture-E) had the greatest overall effect among the various interventions. The surface under the cumulative ranking curve (SUCRA) revealed that acupuncture-E ranked the highest in improving CINP symptoms. Acupuncture alone was most effective in reducing CIPN pain, and acupuncture plus moxibustion (acupuncture-M) ranked highest in enhancing QoL. CONCLUSION: This finding suggests that acupuncture-related interventions can provide patients with benefits in improving CIPN symptoms, pain, and QoL. In particular, acupuncture-E could be the most effective approach in which the provided evidence offers diverse options for cancer patients and healthcare professionals. IMPLICATION FOR THE PROFESSION AND/OR PATIENT CARE: These findings provide valuable insights into the potential benefits of acupuncture-related interventions for managing symptoms, pain, and QoL associated with CIPN in patients undergoing chemotherapy. Among the various interventions studied, overall, acupuncture-E had the most significant impact and was effective for a minimum duration of 3 weeks. On the other hand, transcutaneous electrical acupoint/nerve stimulation (TEAS) was identified as a noninvasive and feasible alternative for patients who had concerns about needles or the risk of bleeding. It is recommended that TEAS interventions should be carried out for a longer period, preferably lasting 4 weeks, to achieve optimal outcomes. TRIAL REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews. REGISTRATION NUMBER: CRD42022319871.


Assuntos
Terapia por Acupuntura , Antineoplásicos , Metanálise em Rede , Doenças do Sistema Nervoso Periférico , Qualidade de Vida , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Clin Med ; 13(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39200867

RESUMO

Background: Radiation-induced hemorrhagic cystitis (RHC) is a chronic inflammatory disease in patients undergoing radiation therapy that causes a cluster of symptoms which may have a latent period of months to years. The current non-invasive treatments include drug treatment and hyperbaric oxygen therapy (HBOT), which has been widely applied for RHC so far but with limited evidence. Thus, we conducted a systematic review and meta-analysis to clarify the effects and safety of HBOT for RHC. Methods: A systematic review and meta-analysis were utilized, searching in the databases of Embase, Pubmed, and Web of Science. The primary endpoint of the present study was complete remission of hematuria. The meta-analysis was conducted using a random effects model, and a pooled odds ratio with 95% CI was calculated. Results: A total of 317 studies were searched and fourteen articles with 556 patients were collected. The results showed that a total of 500 patients (89.9%) had symptom improvement, and the pooled results demonstrated that 55% of patients with HBOT had complete remission of hematuria (95% CI 51-59%). Conclusions: A significant improvement of symptoms when treated with HBOT was shown in this meta-analysis for patients with RHC.

3.
Microorganisms ; 12(6)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38930543

RESUMO

Acanthamoeba, a widely distributed free-living amoeba found in various environments, is an opportunistic pathogen responsible for causing Acanthamoeba keratitis, a condition that may lead to blindness. However, identifying the pathogenicity of Acanthamoeba is challenging due to its complex life cycle, ability to adapt to different environments, variable virulence factors, and intricate interactions with the host immune system. Additionally, the development of an effective model for studying Acanthamoeba pathogenicity is limited, hindering a comprehensive understanding of the mechanisms underlying its virulence and host interactions. The aim of this study was to develop an ex vivo model for Acanthamoeba infection using porcine eyeballs and to evaluate the pathogenicity of the Acanthamoeba isolates. Based on slit lamp and biopsy analysis, the developed ex vivo model is capable of successfully infecting Acanthamoeba within 3 days. Histopathological staining revealed that clinical isolates of Acanthamoeba exhibited greater corneal stroma destruction and invasion in this model than environmental isolates. Our results highlight the importance of an ex vivo porcine eye model in elucidating the pathogenesis of Acanthamoeba infection and its potential implications for understanding and managing Acanthamoeba-related ocular diseases.

4.
Int J Parasitol Drugs Drug Resist ; 25: 100550, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38821038

RESUMO

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.


Assuntos
Acanthamoeba castellanii , Biguanidas , Ouabaína , Biguanidas/farmacologia , Acanthamoeba castellanii/efeitos dos fármacos , Ouabaína/farmacologia , Ceratite por Acanthamoeba/parasitologia , Ceratite por Acanthamoeba/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Humanos , Sinergismo Farmacológico , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/efeitos dos fármacos , Desinfetantes/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
5.
Quant Imaging Med Surg ; 13(12): 7731-7740, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106241

RESUMO

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA. Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift. Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity. Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists.

6.
BMC Cancer ; 23(1): 568, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340337

RESUMO

PURPOSE: To investigate the survival outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line novel androgen receptor axis-targeted therapies (ARATs) and prognostic factors for patient survival. METHODS: This retrospective study obtained data from 202 patients who started abiraterone acetate or enzalutamide as first-line therapy for mCRPC between 2016 and 2021 from a single academic center. The primary endpoint was overall survival (OS) defined as the interval from the start of ARAT to death, loss to follow-up, or the end of the study period. The secondary endpoints were PSA decline, PSA nadir, and time to nadir (TTN) after ARATs. Kaplan-Meier survival analyses were applied for depicting OS. Cox proportional hazards model with inversed probability of treatment weighing-adjustment was used to validate the effect of patient, disease, and treatment response factors on OS. RESULTS: Among 202 patients, 164 patients were treated with first-line ARATs alone and 38 patients received second-line chemotherapy. The median OS was not reached in patients with first-line ARATs alone and was 38.8 months in those with subsequent chemotherapy after failure from ARATs. OS was not different between the use of abiraterone and enzalutamide, though enzalutamide showed a higher rate of PSA decline ≧ 90% (56% versus 40%, p = 0.021) and longer TTN (5.5 versus 4.7 months, p = 0.019). Multivariable analysis showed that PSA nadir > 2 ng/mL [hazard ratio (HR) 7.04, p < 0.001] and TTN<7 months (HR 2.18, p = 0.012) were independently associated with shorter OS. Patients with both of these poor prognostic factors had worse OS compared to those who had 0-1 factors (HR 9.21, p < 0.001). CONCLUSIONS: Patients with mCRPC who received first-line ARATs had better survival if they had a PSA nadir[Formula: see text]2 ng/mL or a TTN[Formula: see text]7 months. Further study is needed to determine if an early switch in therapy for those in whom neither is achieved may impact OS.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Antígeno Prostático Específico , Prognóstico , Estudos Retrospectivos , Antagonistas de Androgênios/uso terapêutico , Nitrilas/uso terapêutico , Resultado do Tratamento
7.
J Mol Cell Cardiol ; 174: 56-62, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36414111

RESUMO

OBJECTIVE: Arterial thrombosis may be initiated by endothelial inflammation or denudation, activation of blood-borne elements or the coagulation system. Tissue factor (TF), a central trigger of the coagulation cascade, is regulated by the pro-inflammatory NF-κB-dependent pathways. Sirtuin 6 (SIRT6) is a nuclear member of the sirtuin family of NAD+-dependent deacetylases and is known to inhibit NF-κB signaling. Its constitutive deletion in mice shows early lethality with hypoglycemia and accelerated aging. Of note, the role of SIRT6 in arterial thrombosis remains unknown. Thus, we hypothesized that endothelial SIRT6 protects from arterial thrombosis by modulating inhibition of NF-κB-associated pathways. APPROACH AND RESULTS: Using a laser-induced carotid thrombosis model, in vivo arterial occlusion occurred 45% faster in 12-week-old male endothelial-specific Sirt6-/- mice as compared to Sirt6fl/fl controls (n ≥ 9 per group; p = 0.0012). Levels of procoagulant TF were increased in animals lacking endothelial SIRT6 as compared to control littermates. Similarly, in cultured human aortic endothelial cells, SIRT6 knockdown increased TF mRNA, protein and activity. Moreover, SIRT6 knockdown increased mRNA levels of NF-κB-associated genes tumor necrosis factor alpha (TNF-α), poly [ADP-ribose] polymerase 1 (PARP-1), vascular cell adhesion molecule 1 (VCAM-1), and cyclooxygenase-2 (COX-2); at the protein level, COX-2, VCAM-1, TNF-α, and cleaved PARP-1 remained increased after Sirt6 knockdown. CONCLUSIONS: Endothelium-specific Sirt6 deletion promotes arterial thrombosis in mice. In cultured human aortic endothelial cells, SIRT6 silencing enhances TF expression and activates pro-inflammatory pathways including TNF-α, cleaved PARP-1, VCAM-1 and COX-2. Hence, endogenous endothelial SIRT6 exerts a protective role in experimental arterial thrombosis.


Assuntos
Sirtuínas , Trombose , Animais , Humanos , Masculino , Camundongos , Células Cultivadas , Ciclo-Oxigenase 2 , Células Endoteliais , NF-kappa B , Inibidores de Poli(ADP-Ribose) Polimerases , Sirtuínas/genética , Trombose/genética , Fator de Necrose Tumoral alfa , Molécula 1 de Adesão de Célula Vascular/genética
8.
PLoS One ; 17(4): e0266604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385553

RESUMO

PURPOSE: Image-guided radiation therapy (IGRT) is used to precisely deliver radiation to a tumour to reduce the possible damage to the surrounding normal tissues. Clinics use various quality assurance (QA) equipment to ensure that the performance of the IGRT system meets the international standards set for the system. The objective of this study was to develop a low-cost and multipurpose module for evaluating image quality and dose. METHODS: A multipurpose phantom was designed to meet the clinical requirements of high accuracy, easy setup, and calibration. The outer shell of the phantom was fabricated using acrylic. Three dimensional (3D) printing technology was used to fabricate inner slabs with the characteristics of high spatial resolution, low-contrast detectability, a 3D grid, and liquid-filled uniformity. All materials were compatible with magnetic resonance (MR). Computed tomography (CT) simulator and linear accelerator (LINAC) modules were developed and validated. RESULTS: The uniformity slab filled with water is ideal for the assessment of Hounsfield units, whereas that filled with wax is suitable for consistency checks. The high-spatial-resolution slab enables measurements with a resolution up to 5 lp/cm. The low-contrast detectability slab contains rods of 5 different sizes that can be clearly visualised. These components meet the American College of Radiology (ACR) standards for QA of CT simulators and LINACs. CONCLUSIONS: The multifunctional phantom module meets the ACR recommended QA guidelines and is suitable for both LINACs and CT-sim. Further measurements in an MR simulator and an MR linear accelerator (MR-LINAC) will be arranged in the future.


Assuntos
Radioterapia Guiada por Imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aceleradores de Partículas , Imagens de Fantasmas , Impressão Tridimensional , Radioterapia Guiada por Imagem/métodos
9.
Microbiol Spectr ; 9(3): e0051221, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34935418

RESUMO

Acanthamoeba castellanii is a free-living, pathogenic ameba found in the soil and water. It invades the body through ulcerated skin, the nasal passages, and eyes and can cause blinding keratitis and granulomatous encephalitis. However, the mechanisms underlying the opportunistic pathogenesis of A. castellanii remain unclear. In this study, we observed that commensal bacteria significantly reduced the cytotoxicity of the ameba on mammalian cells. This effect occurred in the presence of both Gram-positive and Gram-negative commensals. Additionally, commensals mitigated the disruption of cell junctions. Ex vivo experiments on mouse eyeballs further showed that the commensals protected the corneal epithelial layer. Together, these findings indicate that A. castellanii is pathogenic to individuals with a dysbiosis of the microbiota at infection sites, further highlighting the role of commensals as a natural barrier during parasite invasion. IMPORTANCE Acanthamoeba castellanii, an opportunistic protozoan widely present in the environment, can cause Acanthamoeba keratitis and encephalitis in humans. However, only a few reports describe how the ameba acts as an opportunistic pathogen. Our study showed that the normal microbiota interfered with the cytotoxicity of Acanthamoeba, persevered during Acanthamoeba invasion, and reduced corneal epithelium peeling in the mouse eyeball model. This suggests that commensals may act as a natural barrier against Acanthamoeba invasion. In future, individuals who suffer from Acanthamoeba keratitis should be examined for microbiota absence or dysbiosis to reduce the incidence of Acanthamoeba infection in clinical settings.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Acanthamoeba castellanii/fisiologia , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Ceratite por Acanthamoeba/microbiologia , Animais , Córnea/microbiologia , Córnea/parasitologia , Epitélio/parasitologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Simbiose
10.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34876527

RESUMO

Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease.


Assuntos
Anticorpos/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Antígenos Embrionários Estágio-Específicos/imunologia , Animais , Linhagem Celular Tumoral , Terapia Baseada em Transplante de Células e Tecidos , Regulação da Expressão Gênica , Humanos , Imunoterapia , Imunoterapia Adotiva , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Medicine (Baltimore) ; 100(38): e27241, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559123

RESUMO

ABSTRACT: The study's aim was to determine if there was an association between gastric morphology and gastroesophageal reflux (GER). Few published studies have investigated the relationship between gastric morphology and the risk of GER.A total of 777 patients were randomly selected from 3000 to 3300 patients who presented at a medical center in Taipei for annual health checkups from early 2008 through to late 2010 and underwent a series of radiographs of the upper gastrointestinal tract (UGI). GER was recorded during the real-time fluoroscopic study. Thirty-nine participants had a follow-up endoscopy, and another 164 participants were followed up by a second UGI series 12 +/ -1.5 months later, from late 2008 through to early 2022. All participants completed a lifestyle and symptom questionnaire. The variables included current smoking and alcohol consumption. Participants who had heartburn and dysphagia were included in the study. Additionally, all participants underwent a limited physical examination which recorded age, sex, body mass index, and total cholesterol and triglyceride levels.All participants were classified into types 1 to 6 based on the gastric morphology determined from the first UGI. Cascade stomach is recognized by characteristic findings on UGI. Gastric types 2 and 3 tend to appear as cascade stomachs and were significantly associated with GER (P < .05) compared with the other groups. Morphologic type 5 appeared as an elongated sac extending downward into the pelvic cavity and was less likely to develop GER (P < .001). The results of follow-up studies by UGI and endoscopy were similar to those of the first UGI. Gastric morphologic type 2 was significantly associated, and type 5 was usually not associated, with GER and erosive esophagitis (P < .05) compared with the other groups, by both UGI and endoscopy.Gastric morphologic types 2 and 3, with cascade stomach, might provide a relatively easy method for the development of the GER phenomenon. Gastric morphologic type 5 appeared as an elongated sac that might reduce the incidence of the GER phenomenon. The study suggested that gastric morphologic type could influence the occurrence of GER.


Assuntos
Refluxo Gastroesofágico/fisiopatologia , Estômago/anatomia & histologia , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Refluxo Gastroesofágico/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estômago/fisiopatologia
12.
ACS Chem Biol ; 16(8): 1526-1537, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34369155

RESUMO

The globo-series glycosphingolipids (SSEA3, SSEA4, and Globo H) were shown to express in many cancers selectively, and a combination of anti-SSEA4 and anti-Globo H antibodies was able to suppress tumor growth in mice inoculated with breast cancer cell lines. To further understand the effect, we focused on the combined effect of the two antibodies in target binding and antibody-dependent cellular cytotoxicity (ADCC) in vitro. Here, we report that the binding of anti-Globo H antibody (VK9) to MDA-MB231 breast cancer cells was influenced by anti-SSEA4 antibody (MC813-70), and a combination of both antibodies induced a similar effect as did anti-SSEA4 antibodies alone in a reporter-based ADCC assay, indicating that SSEA4 is a major target in breast cancer due to its higher expression than Globo H. Furthermore, we showed that a homogeneous anti-SSEA4 antibody (chMC813-70-SCT) designed to maximize the ADCC activity can be used to isolate a subpopulation of natural killer (NK) cells that exhibit an ∼23% increase in killing the target cells as compared to the unseparated NK cells. These findings can be used to predict a therapy outcome based on the expression levels of antigens and evaluate therapeutic antibody development.


Assuntos
Anticorpos/imunologia , Antígenos Glicosídicos Associados a Tumores/imunologia , Neoplasias da Mama/metabolismo , Antígenos Embrionários Estágio-Específicos/imunologia , Animais , Antígenos Glicosídicos Associados a Tumores/metabolismo , Linhagem Celular Tumoral , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Receptores de IgG/metabolismo , Antígenos Embrionários Estágio-Específicos/metabolismo
13.
Cancers (Basel) ; 13(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071587

RESUMO

BACKGROUND: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT. METHODS: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan-Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms. RESULTS: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT > 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis. CONCLUSIONS: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

14.
Med Dosim ; 46(4): 360-363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33903006

RESUMO

Stereotactic ablative radiotherapy (SABR) aims to deliver high doses of radiation to kill cancer cells and shrink tumors in less than or equal to 6 fractions. However, organ motion during treatment is a challenging issue for this kind of technique. We develop a control system via Bluetooth technology to simulate and correct body motion during SABR. METHODS: Radiation doses were analyzed, and the radiation damage protection capability was checked by external beam therapy 3 (EBT3) films irradiated by a linear accelerator. A wireless signal test was also performed. A validation was performed with 8 previously treated patient respiratory pattern records and 8 healthy volunteers. RESULTS: The homemade simulation system consisted of 2 linear actuators, one movable stage with a maximal moving distance of 6.5 cm × 12.5 cm × 5 cm to simulate the respiratory pattern of 8 patients precisely with a median error of 0.36 mm and a maximal motion difference of 1.17 mm, and 3.17 and chipset transited signals to display them as a waveform. From the test with 8 volunteers, the chip could detect deep respiratory movement up to 3 cm. The effect of the chip on a radiation dose of 400 monitor units (MUs) by 6 MV photons and 200 MUs by 10 MV photons showed high penetration rates of 98.8% and 98.6%, respectively. CONCLUSIONS: We invented a tubeless and wireless respiratory gating detection chip. The chip has minimal interference with the treatment angles, good noise immunity and the capability to easily penetrate a variety of materials. The simulation system consisting of linear actuators also successfully simulates the respiratory pattern of real patients.


Assuntos
Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Humanos , Movimento (Física) , Movimento , Aceleradores de Partículas , Respiração
15.
Biomolecules ; 11(2)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672169

RESUMO

Humira is a monoclonal antibody that binds to TNF alpha, inactivates TNF alpha receptors, and inhibits inflammation. Neonatal Fc receptors can mediate the transcytosis of Humira-TNF alpha complex structures and process them toward degradation pathways, which reduces the therapeutic effect of Humira. Allowing the Humira-TNF alpha complex structures to dissociate to Humira and soluble TNF alpha in the early endosome to enable Humira recycling is crucial. We used the cytoplasmic pH (7.4), the early endosomal pH (6.0), and pKa of histidine side chains (6.0-6.4) to mutate the residues of complementarity-determining regions with histidine. Our engineered Humira (W1-Humira) can bind to TNF alpha in plasma at neutral pH and dissociate from the TNF alpha in the endosome at acidic pH. We used the constant-pH molecular dynamics, Gaussian accelerated molecular dynamics, two-dimensional potential mean force profiles, and in vitro methods to investigate the characteristics of W1-Humira. Our results revealed that the proposed Humira can bind TNF alpha with pH-dependent affinity in vitro. The W1-Humira was weaker than wild-type Humira at neutral pH in vitro, and our prediction results were close to the in vitro results. Furthermore, our approach displayed a high accuracy in antibody pH-dependent binding characteristics prediction, which may facilitate antibody drug design. Advancements in computational methods and computing power may further aid in addressing the challenges in antibody drug design.


Assuntos
Adalimumab/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/química , Simulação por Computador , Citoplasma/metabolismo , Desenho de Fármacos , Histidina/química , Antígenos de Histocompatibilidade Classe I/química , Humanos , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Inflamação , Simulação de Dinâmica Molecular , Distribuição Normal , Ligação Proteica , Conformação Proteica , Receptores Fc/química
16.
Front Oncol ; 11: 617007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777756

RESUMO

PURPOSE: Beam angle optimization is a critical issue for modern radiotherapy (RT) and is a challenging task, especially for large body sizes and noncoplanar designs. Noncoplanar RT techniques may have dosimetric advantages but increase the risk of mechanical collision. We propose a software solution to accurately predict colliding/noncolliding configurations for coplanar and noncoplanar beams. MATERIALS AND METHODS: Individualized software models for two different linear accelerators were built to simulate noncolliding gantry orientations for phantom/patient subjects. The sizes and shapes of the accelerators were delineated based on their manuals and on-site measurements. The external surfaces of the subjects were automatically contoured based on computed tomography (CT) simulations. An Alderson Radiation Therapy phantom was used to predict the accuracy of spatial collision prediction by the software. A gantry collision problem encountered by one patient during initial setup was also used to test the validity of the software. Results: In the comparison between the software estimates and on-site measurements, the noncoplanar collision angles were all predicted within a 5-degree difference in gantry position. The confusion matrix was calculated for each of the two empty accelerator models, and the accuracies were 98.7% and 97.3%. The true positive rates were 97.7% and 96.9%, while the true negative rates were 99.8% and 97.9%, respectively. For the phantom study, the collision angles were predicted within a 5-degree difference. The software successfully predicted the collision problem encountered by the breast cancer patient in the initial setup position and generated shifted coordinates that were validated to correspond to a noncolliding geometry. CONCLUSION: The developed software effectively and accurately predicted collisions for accelerator-only, phantom, and patient setups. This software may help prevent collisions and expand the range of spatially applicable beam angles.

17.
Holist Nurs Pract ; 33(4): 230-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192835

RESUMO

Young adults rarely use pharmacotherapy to cease smoking. This prospective experimental study was performed using a nonpharmacotherapy design. Smoking cessation education combined with auricular acupressure may be more attractive. The key factor for superior smoking cessation was the decrease of nicotine dependence in the early stage of smoking cessation.


Assuntos
Acupressão/normas , Educação em Saúde/normas , Abandono do Hábito de Fumar/métodos , Acupressão/métodos , Acupuntura Auricular/métodos , Acupuntura Auricular/normas , Orelha/fisiologia , Educação em Saúde/métodos , Humanos , Masculino , Abandono do Hábito de Fumar/psicologia , Taiwan , Adulto Jovem
18.
Hu Li Za Zhi ; 66(3): 46-58, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31134600

RESUMO

BACKGROUND: Fatigue is the most common symptom in head and neck cancer patients who receive concurrent chemoradiotherapy (CCRT). However, evidence of the effects of acupoint interventions on fatigue and heart rate variability in these patients is unclear. PURPOSE: To evaluate the effect of an acupoint intervention on fatigue and heart rate variability in head and neck cancer patients receiving CCRT. METHODS: This randomized controlled trail applied repeated measures, and used permuted block randomization to randomly assign the participants into the acupoint and control groups. Participants in both groups received usual care. In addition, participants in the acupoint group received transcutaneous electrical acupoint stimulation and auricular acupressure for a period of six weeks. Data were collected using the brief fatigue inventory and a heart rate variability device at baseline and during the 1st, 2nd, 3rd, and 6th weeks of the study. RESULTS: The generalized estimating equation analysis found a significant group-by-time interaction for fatigue on the 6th week of acupoint stimulation (p = .036). No significant differences in group-by-time interaction were found for the standard deviation of normal to normal intervals (SDNN), low frequency (LF), high frequency (HF), or LF/HF ratio (p > .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study supports the accessibility and feasibility of the acupoint intervention. No adverse effects were observed. The six-week transcutaneous electrical acupoint stimulation and auricular acupressure may be used to improve fatigue in head and neck cancer patients currently receiving CCRT.


Assuntos
Pontos de Acupuntura , Neoplasias de Cabeça e Pescoço/terapia , Quimiorradioterapia , Fadiga/prevenção & controle , Frequência Cardíaca/fisiologia , Humanos , Resultado do Tratamento
19.
J Appl Clin Med Phys ; 18(6): 114-122, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960724

RESUMO

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications.


Assuntos
Neoplasias Encefálicas/cirurgia , Neuroma Acústico/cirurgia , Planejamento de Assistência ao Paciente/normas , Radiocirurgia/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Algoritmos , Tronco Encefálico/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
20.
Oncotarget ; 7(28): 44224-44235, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27317764

RESUMO

We investigated the outcomes and the associated clinical-pathological factors in patients with prostate cancer (PCa) undergoing salvage intensity modulated radiation therapy (IMRT) for post-radical-prostatectomy (RP) biochemical failure. We report clinical outcomes of post-RP salvage IMRT, and describe chronic toxicity in these patients.Fifty patients with PCa underwent post-RP salvage IMRT. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Clinical-pathological and toxicity information were collected. The prostate cancer-specific survival (PCSS), disease-free survival (DFS), and biochemical-failure-free survival (BFFS) were calculated. Prognostic factors were analyzed for their association with disease control.The median follow-up time was 74 months. The 5-year PCSS, DFS, and BFFS after salvage IMRT were 95%, 88%, and 60%, respectively. Two patients (4%) experienced late gastrointestinal toxicity ≥ grade 3, and 5 patients (10%) had late genitourinary toxicity ≥ grade 3. On multivariate analysis, post-RP prostate-specific antigen (PSA) nadir ≤0.1 ng/ml (P=0.018) and PSA ≤0.5 ng/ml at salvage IMRT (P=0.016) were independent factors predicting better BFFS. Patients with both post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT had a 5-year BFFS of 83% as compared with 43% in other patients (P=0.001).In conclusion, with hormonal therapy in most PCa patients, the addition of salvage IMRT for post-RP biochemical failure can achieve a good outcome with low toxicity. Patients with a post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT could benefit the most from salvage IMRT.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Resultado do Tratamento
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