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1.
Appl Radiat Isot ; 207: 111256, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432035

RESUMO

3D printing technology has rapidly spread for decades, allowing the fabrication of medical implants and human phantoms and revolutionizing healthcare. The objective of this study is to evaluate some radiological properties of commercially available 3D printing materials as potential tissue mimicking materials. Among fifteen materials, we compared their properties with nine human tissues. In all materials and tissues, exposure and energy absorption buildup factors were calculated for photon energies between 0.015 and 15 MeV and penetration depths up to 40 mean free path. Furthermore, the Geant4 Monte Carlo toolkit (version 10.5) was used to simulate their percentage depth dose distributions. In addition, equivalent atomic numbers, effective atomic numbers, attenuation coefficients, and CT numbers have been examined. All parameters were considered in calculating the average relative error (σ), which was used as a statistical comparison tool. With σ between 6 and 7, we found that Polylactic Acid (PLA) was capable of simulating eye lenses, blood, soft tissue, lung, muscle, and brain tissues. Moreover, Polymethacrylic Acid (PMAA) material has a σ value of 4 when modeling adipose and breast tissues, respectively. Aside from that, variations in 3D printing materials' infilling percentage can affect their CT numbers. We therefore suggest the PLA for mimicking soft tissue, muscle, brain, eye lens, lung and blood tissues, with an infill of between 92.7 and 94.3 percent. We also suggest an 89 percent infill when simulating breast tissue. Furthermore, with a 96.7 percent infill, the PMAA faithfully replicates adipose tissue. Additionally, we found that a 59 percent infill of Fe-PLA material is comparable to cortical bone. Due to the benefits of creating individualized medical phantoms and equipment, the results might be seen as an added value for both patients and clinicians.


Assuntos
Ácidos Polimetacrílicos , Impressão Tridimensional , Radiometria , Humanos , Raios gama , Poliésteres , Imagens de Fantasmas
2.
Int J Audiol ; : 1-5, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38298149

RESUMO

OBJECTIVE: This clinical note aimed to 1) describe the order-of-report (OoR) strategies used by a large sample of children who completed 2pDD testing in the free-recall condition as part of an audiological assessment of auditory processing (AP), and 2) determine if use of OoR correlated with 2pDD test performance. DESIGN: A retrospective (case-review), single observation design. STUDY SAMPLE: A convenient sample of 77 children (50 males and 27 females aged 7.0 to 17.4 years [median = 8.8 years]) referred to audiology for an AP assessment. RESULTS: The participating children used temporal more than ear or sequential OoR and showed decreased test scores with increased use of ear OoR. CONCLUSIONS: These findings suggest children referred for an AP assessment could favour a temporal OoR when completing 2pDD testing for its opportunity to rehearse the first digit pair (possibly strengthening its memory trace) prior to processing the second digit pair, while their use of an ear OoR could come at the cost detrimental ear dominance effects that reduce their test performance. Future research could consider if similar results are observed in other child populations and if preferred dichotic processing strategy could inform auditory training for children with dichotic listening deficits.

3.
Channels (Austin) ; 18(1): 2313323, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354101

RESUMO

The members of the superfamily of Transient Receptor Potential (TRP) ion channels are physiologically important molecules that have been studied for many years and are still being intensively researched. Among the vanilloid TRP subfamily, the TRPV4 ion channel is an interesting protein due to its involvement in several essential physiological processes and in the development of various diseases. As in other proteins, changes in its function that lead to the development of pathological states, have been closely associated with modification of its regulation by different molecules, but also by the appearance of mutations which affect the structure and gating of the channel. In the last few years, some structures for the TRPV4 channel have been solved. Due to the importance of this protein in physiology, here we discuss the recent progress in determining the structure of the TRPV4 channel, which has been achieved in three species of animals (Xenopus tropicalis, Mus musculus, and Homo sapiens), highlighting conserved features as well as key differences among them and emphasizing the binding sites for some ligands that play crucial roles in its regulation.


Assuntos
Canais de Cátion TRPV , Canais de Potencial de Receptor Transitório , Camundongos , Animais , Canais de Cátion TRPV/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Mutação , Xenopus/metabolismo , Sítios de Ligação
4.
Biochem Biophys Res Commun ; 692: 149309, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38048727

RESUMO

Poly (ADP-ribose) glycohydrolase (PARG) is an enzyme that mainly degrades poly (ADP-ribose) (PAR) synthesized by poly (ADP-ribose) polymerase (PARP) family proteins. Although PARG is involved in many biological phenomena, including DNA repair, cell differentiation, and cell death, little is known about the relationship between osteoclast differentiation and PARG. It has also not been clarified whether PARG is a valuable target for therapeutic agents in the excessive activity of osteoclast-related bone diseases such as osteoporosis. In the present study, we examined the effects of PARG inhibitor PDD00017273 on osteoclast differentiation in RANKL-induced RAW264 cells. PDD00017273 induced the accumulation of intracellular PAR and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. PDD00017273 also downregulated osteoclast differentiation marker genes such as Trap, cathepsin K (Ctsk), and dendrocyte expressed seven transmembrane protein (Dcstamp) and protein expression of nuclear factor of activated T cells 1 (NFATc1), a master regulator of osteoclast differentiation. Taken together, our findings suggest that dysfunction of PARG suppresses osteoclast differentiation via the PAR accumulation and partial inactivation of the NFATc1.


Assuntos
Osteoclastos , Ribose , Glicosídeo Hidrolases/metabolismo , Osteoclastos/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Animais , Camundongos
5.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 80(2): 175-187, 2024 Feb 20.
Artigo em Japonês | MEDLINE | ID: mdl-38030241

RESUMO

PURPOSE: The purpose of this study was to understand the PDD and OAR during electron beam therapy using lead cutout on the body surface. METHODS: The Monte Carlo code PHITS version 3.24 was used to simulate PDD and OAR. The simulation results were compared with actual measurements using a silicon diode detector to evaluate the validity of the simulation results. RESULTS: The simulated PDD and OAR parameters of the linac agreed with the measured values within 2 mm. When the lead cutout on the body surface was used, all parameters except for R100 agreed with the measured values within 2 mm. The cutout sizes of the broad-beam square irradiation fields were 3 cm for 6 MeV, 5 cm for 12 MeV, and 8 cm for 18 MeV when the lead cutout on the body surface was used. CONCLUSION: The Monte Carlo simulation was useful for understanding the PDD and OAR of the lead cutout irradiation fields, which are difficult to measure.


Assuntos
Elétrons , Planejamento da Radioterapia Assistida por Computador , Método de Monte Carlo , Simulação por Computador , Planejamento da Radioterapia Assistida por Computador/métodos , Aceleradores de Partículas , Radiometria/métodos , Dosagem Radioterapêutica
6.
Neurobiol Aging ; 135: 1-14, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38142464

RESUMO

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.


Assuntos
Doença de Alzheimer , Demência , Doença de Parkinson , Humanos , Ritmo alfa/fisiologia , Doença de Parkinson/complicações , Demência/etiologia , Córtex Cerebral/fisiologia , Descanso/fisiologia , Eletroencefalografia/métodos
8.
Int J Clin Oncol ; 29(2): 205-212, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38112832

RESUMO

BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.


Assuntos
Carcinoma de Células de Transição , Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Ácido Aminolevulínico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Cistectomia/métodos , Recidiva Local de Neoplasia/patologia , Invasividade Neoplásica
9.
Br J Neurosurg ; : 1-5, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37997374

RESUMO

AIM: The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. METHODS: A specially designed endoscope for PDD that delivers white light or blue light (375-440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. RESULTS: A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). CONCLUSION: These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.

10.
Neurobiol Dis ; 188: 106337, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37918758

RESUMO

Dementia with Lewy bodies and Parkinson's disease dementia are common neurodegenerative diseases that share similar neuropathological profiles and spectra of clinical symptoms but are primarily differentiated by the order in which symptoms manifest. The question of whether a distinct molecular pathological profile could distinguish these disorders is yet to be answered. However, in recent years, studies have begun to investigate genomic, epigenomic, transcriptomic and proteomic differences that may differentiate these disorders, providing novel insights in to disease etiology. In this review, we present an overview of the clinical and pathological hallmarks of Lewy body dementias before summarizing relevant research into genetic, epigenetic, transcriptional and protein signatures in these diseases, with a particular interest in those resolving "omic" level changes. We conclude by suggesting future research directions to address current gaps and questions present within the field.


Assuntos
Demência , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/patologia , Demência/patologia , Doença de Parkinson/patologia , Proteômica , Corpos de Lewy/patologia
11.
Appl Radiat Isot ; 200: 110978, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603966

RESUMO

This work aims to model and characterize the radiation beam of one Accuray tomotherapy equipment using the Monte Carlo Code MCNP5 (Monte Carlo N-Particle). This tomotherapy equipment is used for delivering high doses of radiation in tumor regions to kill cancer cells and shrink the tumor during radiation therapy of cancer patients, however, the radiation can damage surrounding areas and nearby organs at risk (OAR) if the radiation field is not well delimited. In particular, intensity-modulated radiotherapy treatments (IMRT) with tomotherapy equipment offer great benefits to patients allowing treatment of tumor regions without affecting surrounding areas and OAR. Nowadays, it is well known that a correct simulation of transport of radiation in tomotherapy equipment facilitates considerably the estimation of ideal doses in the tumor, surrounding regions, and OAR. For that reason, in this work, we simulated the geometry of the 6 MV ACCURAY Tomotherapy equipment of the CECAN using the MCNP5. The model includes a TomoLINAC consisting of an electron source that emits Gaussian distribution particles with an average energy of 5.7 MeV and width of 0.3 MeV. The emitted particles impact the tungsten target and pass through primary collimators and jaws that define the irradiation field in the isocenter. To validate the geometry and radiation transport in the TomoLINAC the curves of depth dose percentage (PDD) estimated by simulation and the curves measured experimentally were tuned. In the same way, the simulated transverse and longitudinal profiles were compared with the experimental results. In addition, a comparison between the qualities of the radiation beam characterized with MCNP and measured experimentally in CECAN showed a deviation of 1%. For the simulations, cylindrical detectors located inside a water phantom were considered and it was employed the tally *F8. A good agreement was observed between the PDD's curves obtained from the simulation and those measured experimentally for a field of 5 × 10 cm2 in the isocenter and SSD (distance from the source to the surface) of 85 cm. Also, the comparison between the simulated and experimental transverse profiles obtained at 1.5 cm, 10 cm and 15 cm depth with a radiation field of 5 × 40 cm2 showed very good agreement. The longitudinal profiles were estimated with the same depths as the transverse ones, but for each of them, the openings of the jaws were 5.0 cm, 2.5 cm and 1.0 cm in the longitudinal direction, which corresponds to the direction in which the patient's table moves. The comparison between the simulated and experimental longitudinal profiles showed good concordance too. Once the radiation beam of the ACCURAY tomotherapy equipment had been characterized, experimental dose measurements were made using a Cheese phantom and two A1SL ionization chambers. These results obtained experimentally were compared with those estimated with MCNP for a field of 5 × 40 cm2 at the isocenter and SAD of 85 cm and, it was concluded that both results were similar considering the regions of uncertainty. Finally, we must highlight that the modeling and characterization of the radiation beam of CECAN's ACCURAY tomotherapy equipment can be a key tool for dose estimations in different cancer treatment plans and future research.

12.
Anticancer Res ; 43(8): 3615-3621, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37500129

RESUMO

BACKGROUND/AIM: Photodynamic diagnosis (PDD)-assisted transurethral resection of a bladder tumor (PDD-TURBT) in a patient receiving 5-aminolevulinic acid improved the detection of micro- and flat lesions of the bladder. This study used real-world data in Japan to examine the diagnostic accuracy of PDD-assisted targeted biopsies and white-light (WL) random biopsies and reevaluated the necessity of random biopsies. PATIENTS AND METHODS: A total of 133 patients diagnosed with bladder cancer who underwent TURBT from April 2020 to March 2022 were included in the study. Biopsy specimens obtained from 407 flat lesions or normal-like lesions, excluding biopsies from elevated lesions and TUR specimens, were used to analyze diagnostic accuracy in PDD and WL findings. RESULTS: The respective sensitivities, specificities, and negative predictive values of PDD vs. WL findings were 81.4% vs. 54.0% (p=0.0039), 70.4% vs. 81.4% (p=0.0012), and 96.4% vs. 90.6% (p=0.0144), indicating that PDD was useful for a diagnosis of exclusion. Combining the PDD and WL findings improved the detection of malignant flat lesions. Ten (PDD-positive and WL-negative) specimens from 9 patients were diagnosed as malignant. The results of PDD-assisted targeted biopsy provided an accurate assessment of the risk classification for recurrence and progression of non-muscle invasive bladder cancer (NMIBC) as defined by the Japanese Urological Association (JUA) guidelines. CONCLUSION: For NMIBC treatment, a more accurate diagnosis is important for postoperative treatment decisions. PDD-assisted targeted biopsy may be necessary and sufficient for diagnosis of flat lesions in patients with bladder cancer for treatment decision making based on JUA risk classification.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/patologia , População do Leste Asiático , Ácido Aminolevulínico , Neoplasias da Bexiga Urinária/patologia , Biópsia , Fármacos Fotossensibilizantes
13.
Neurol Int ; 15(2): 743-749, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37368330

RESUMO

OBJECTIVES: Arithmetic errors in the financial context have been investigated mainly in cognitively normal Parkinson's disease (PD) patients and mildly impaired PD (PD-MCI) individuals. The aim of this study was to examine arithmetic errors in the financial context across neurocognitive disorders. METHODS: Four hundred and twenty older adults from Greece were divided into four groups (110 patients with a diagnosis of Alzheimer's disease (AD), 107 patients with a diagnosis of mild cognitive impairment (MCI), 109 healthy controls and 94 Parkinson's disease dementia (PDD) patients). Their ages ranged from 65 to 98 years (M = 73.96, SD = 6.68), and the sample had a mean of 8.67 (SD = 4.08) years of education. For each of the AD patients, a counterpart matched by age, educational attainment and gender was selected from a larger group of participants. RESULTS: Overall, the results reveal that healthy older adults did not commit arithmetic errors, but AD patients reported procedural errors in their responses to both questions. A high frequency of procedural errors was found in MCI patients' responses to the first question, while the errors in their responses to the second question cannot be categorized. Finally, in PDD patients, place value errors were reported for the first question, while more magnitude errors were made when responding to the second question. CONCLUSIONS: These findings support that arithmetic errors within financial contexts are not the same across neurocognitive disorders, and numerical representations are not impaired not only in PDD, but also in AD and MCI. This information could be useful in cognitive assessments performed by neurologists and neuropsychologists as these types of errors may be indicators of specific brain pathologies.

14.
Radiol Phys Technol ; 16(3): 414-421, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37294521

RESUMO

A radiotherapy bolus is a tissue-equivalent material placed on the skin to adjust the surface dose of megavoltage X-ray beams used for treatment. In this study, the dosimetric properties of two 3D-printed filament materials, polylactic acid (PLA) and thermoplastic polyether urethane (TPU), used as radiotherapy boluses, were investigated. The dosimetric properties of PLA and TPU were compared with those of several conventional bolus materials and RMI457 Solid Water. Percentage depth-dose (PDD) measurements in the build-up region were performed for all materials using 6 and 10 MV photon treatment beams on Varian linear accelerators. The results showed that the differences in the PDDs of the 3D-printed materials from the RMI457 Solid Water were within 3%, whereas those of the dental wax and SuperFlab gel materials were within 5%. This indicates that PLA and TPU 3D-printed materials are suitable radiotherapy bolus materials.


Assuntos
Radiometria , Planejamento da Radioterapia Assistida por Computador , Raios X , Dosagem Radioterapêutica , Radiometria/métodos , Poliésteres , Impressão Tridimensional , Água , Imagens de Fantasmas
15.
Children (Basel) ; 10(5)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37238392

RESUMO

(1) Background: The study deepens the diagnosis of "pervasive developmental disorder not otherwise specified" (PDD-NOS), a subthreshold diagnosis introduced in DSM-IV and then absorbed into the broader spectrum disorder of autism in DSM 5. The presence of people still attributed with a diagnosis of PDD-NOS can cause confusion in the understanding of this disorder, which is no longer present in the current diagnostic system. This review aims to gain a deeper understanding of the characteristics and boundaries of diagnosis, its use within the scientific community, and the long-term stability of that diagnosis. (2) Methods: The Prisma method was used to carry out the literature review; the scientific papers were selected using scientific search engines, including SCOPUS, PUBMED, and PsychINFO. Twenty-three articles were finally selected, and a meticulous reading was carried out in relation to the research questions. (3) Results: Four cross-cutting categories were identified: (1) diagnosis; (2) differential diagnosis; (3) prognosis; and (4) comorbidity. (4) Conclusions: Limits have emerged regarding the consistency, sensitivity, and the stability of PDD-NOS. The inclusion of this diagnosis within the broader autism spectrum disorder category coined in DSM-5 appears applicable.

16.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 79(5): 453-461, 2023 May 20.
Artigo em Japonês | MEDLINE | ID: mdl-36927669

RESUMO

PURPOSE: To investigate fundamental dosimetric properties of surface dose, exit dose, and beam profile of the brass mesh bolus for 4, 6, and 10 MV high-energy photon beams in radiation therapy. METHODS: Surface dose and exit dose in the water-equivalent phantom were measured, and percent depth doses (PDDs) were calculated with no bolus, one layer of brass mesh, two layers of brass mesh bolus, three layers of brass mesh bolus, and 0.5 cm tissue-equivalent (TE) bolus. Exit dose was measured at a phantom thickness of 10 cm. Beam profiles were measured at phantom depths of 0 cm and 10 cm. All dosimetry was performed for 4, 6, and 10 MV photon beams using a linear accelerator. RESULTS: The surface dose at a phantom depth of 0 cm increased to 37.3%, 36.3%, and 31.0% for 4, 6, and 10 MV, respectively, with the brass mesh bolus compared to the case of no bolus. The surface dose decreased with one layer of brass mesh bolus compared to that with the 0.5 cm TE bolus. On the other hand, the exit dose increased to 22.0%, 23.1%, and 22.8% for 4, 6, and 10 MV, respectively, with the brass mesh bolus compared to the case of no bolus. The beam profile at the depth of 0 cm showed oscillations, and the difference between the maximum and minimum doses was up to 13.1% with one layer of brass mesh bolus. CONCLUSION: It was suggested that the brass mesh bolus not only increases the surface dose but also has different properties from the conventional TE bolus.


Assuntos
Radiometria , Telas Cirúrgicas , Cobre , Zinco , Dosagem Radioterapêutica
17.
Cancer Rep (Hoboken) ; 6(2): e1709, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053937

RESUMO

BACKGROUND: Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme in poly(ADP-ribose) (PAR) metabolism and a potential anticancer target. Many drug candidates have been developed to inhibit its enzymatic activity. Additionally, PDD00017273 is an effective and selective inhibitor of PARG at the first cellular level. AIMS: Using human colorectal cancer (CRC) HCT116 cells, we investigated the molecular mechanisms and tumor biological aspects of the resistance to PDD00017273. METHODS AND RESULTS: HCT116RPDD , a variant of the human CRC cell line HCT116, exhibits resistance to the PARG inhibitor PDD00017273. HCT116RPDD cells contained specific mutations of PARG and PARP1, namely, PARG mutation Glu352Gln and PARP1 mutation Lys134Asn, as revealed by exome sequencing. Notably, the levels of PARG protein were comparable between HCT116RPDD and HCT116. In contrast, the PARP1 protein levels in HCT116RPDD were significantly lower than those in HCT116. Consequently, the levels of intracellular poly(ADP-ribosyl)ation were elevated in HCT116RPDD compared to HCT116. Interestingly, HCT116RPDD cells did not exhibit cross-resistance to COH34, an additional PARG inhibitor. CONCLUSION: Our findings suggest that the mutated PARG acquires PDD00017273 resistance due to structural modifications. In addition, our findings indicate that PDD00017273 resistance induces mutation and PARP downregulation. These discoveries collectively provide a better understanding of the anticancer candidate PARG inhibitors in terms of resistance mechanisms and anticancer strategies.


Assuntos
Neoplasias Colorretais , Glicosídeo Hidrolases , Humanos , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Genômica
18.
Jpn J Clin Oncol ; 53(4): 343-348, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585780

RESUMO

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor. METHODS: We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. RESULTS: Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. CONCLUSIONS: The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor.


Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Análise Custo-Benefício , Fármacos Fotossensibilizantes , Estudos Retrospectivos , População do Leste Asiático , Ressecção Transuretral de Bexiga , Neoplasias da Bexiga Urinária/patologia , Atenção à Saúde , Recidiva Local de Neoplasia/patologia
19.
Life (Basel) ; 12(12)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36556469

RESUMO

This work aims to prepare pure Chlorin e6 (Ce6) and establish Ce6-mediated photodynamic therapy (Ce6-PDT) as a better therapy option for canine tumors as well as mouse tumor models. Five dogs suffering from various cancers were treated with Ce6-PDT from one to several times. After receiving the Ce6 (2.5 mg/kg) for 3 h, tumors were illuminated superficially or interstitially with 660 nm light. Two dogs underwent Ce6-guided fluorescence imaging by photodynamic diagnosis (PDD). Cell proliferation and apoptosis were detected by the 4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and western blot assay, respectively. Ce6-PDT efficacy was also determined using melanoma and pancreatic cancer mouse models. Two veterinary patients with mammary carcinoma and histiocytic sarcoma had their tumors significantly diminished and showed improved health after receiving Ce6-PDT. Moreover, in the cases of canine tumors, the adjunctive use of Ce6-PDD revealed cancers that were not visible with white light viewing and provided a visual contrast from surrounding tissues. Also, in vivo, Ce6-PDT remarkably reduced melanoma and pancreatic tumors in the mouse model. These findings could pave the way for a better understanding of the underlying processes of Ce6-PDT, making it an effective and safe candidate for use in human and veterinary applications to abolish various cancers.

20.
Cureus ; 14(9): e29623, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36320964

RESUMO

Introduction Communication is the exchange of information through speaking, writing, and other mediums. Speech is the expression of thoughts in spoken words. Language is the principal method that humans use for relaying information; consisting of words conveyed by speech, writing, or gestures. Language is the conceptual processing of communication. Problems in communication or oral motor function are called speech and language disorders. Developmental delay is diagnosed when a child does not attain normal developmental milestones at the expected age. Speech and/or language disorders are amongst the most common developmental difficulties in childhood. Such difficulties are termed 'primary' if they have no known etiology, and 'secondary' if they are caused by another condition such as hearing and neurological impairment, and developmental, behavioral, or emotional difficulties. Objectives The objective of our study was to observe the risk factors for speech and language delay in the children presenting to the speech therapy clinic of a tertiary care hospital in a large urban center. Methodology A cross-sectional study was conducted on 150 children presenting at the speech therapy clinic of Lahore General Hospital from July to August 2021. A well-designed questionnaire was used to collect data about the sociodemographic profile, and biological, developmental, and environmental risk factors of speech and language delay in children. SPSS, version 25 (IBM Corp., Armonk, NY) was used to enter and analyze the data. Results Parents or caretakers of a total of 98 male and 52 female children took part in this study aged 2-11 years. The average age of speech and language delay among the children was 5.65 years, 66.7% of which went to normal school while 31.3% went to special school; 66.7% were from urban areas. Around 60% had middle ear infections, and 34.7% were found to have oropharyngeal anomalies. A history of intrapartum complications was found in 68.4% of children; 46.7% of children had a history of use of a pacifier and 38% had a history of thumb sucking. Nearly 39% of children belonged to a multilingual family environment and 66.7% had a family history of screen viewing for more than two hours. Conclusion The major risk factors contributing to speech and language delay in children are family history of speech and language delay, prolonged sucking habits, male gender, oropharyngeal anomalies, hearing problems, and middle ear infections. Measures should be taken to educate people regarding risk factors, courses, and management of speech and language delay in children.

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