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1.
J Clin Med ; 13(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38730986

RESUMO

Background: Nivolumab has been shown to improve the overall survival (OS) of patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, there is a need to identify factors associated with long-term survival (beyond 2 years) in these patients. This study investigated the relationship between pretreatment factors and long-term survival in patients with R/M HNSCC treated with nivolumab. Methods: Forty-nine patients with R/M HNSCC who were treated with nivolumab were retrospectively reviewed. Baseline characteristics, clinical data, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify factors associated with long-term survival (OS ≥ 2 years). Results: The median OS in the overall cohort was 11.0 months, and the 2-year survival rate was 34.7%. Long-term survivors (OS ≥ 2 years) had significantly higher proportions of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 0 or 1, serum albumin levels ≥ 3.5 g/dL, and neutrophil-to-eosinophil ratio (NER) < 32.0 compared to non-long-term survivors. On multivariate analysis, serum albumin levels ≥ 3.5 g/dL, in addition to ECOG-PS score of 0 or 1, were independent predictors of long-term survival. Conclusions: Pretreatment serum albumin levels may be useful for predicting long-term survival in R/M HNSCC patients treated with nivolumab.

2.
Anticancer Res ; 44(1): 323-329, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159971

RESUMO

BACKGROUND/AIM: We evaluated the incidence of radiation-induced hypothyroidism and its risk factors in patients with head and neck cancer who underwent radiotherapy using simultaneous integrated boost-volumetric-modulated arc therapy (SIB-VMAT). PATIENTS AND METHODS: This retrospective study included 86 patients who received definitive radiotherapy using SIB-VMAT for head and neck cancer. The incidence of ≥ grade 2 hypothyroidism was evaluated. We also evaluated the relationships between hypothyroidism development and clinical factors and thyroid dose-volume parameters. RESULTS: During a median follow-up period of 17 months (range=3-65 months), 31 patients (36.0%, 31/86) developed grade 2 hypothyroidism requiring hormone replacement therapy. No patients experienced ≥ grade 3 hypothyroidism. The cumulative incidences of hypothyroidism at 1 and 2 years after radiation therapy were 24.5% and 38.7%, respectively, with a median onset time of 10.0 months (range=3.0-35.0 months). Thyroid volume (p=0.003), volume of the thyroid spared at 60 Gy (VS60; cut-off value, 5.16 ml; p=0.009), VS70 (cut-off value, 8.0 ml; p=0.007), VS60 equivalent dose in 2 Gy fraction (EQD2; cut-off value, 7.78 ml; p=0.001), and VS70EQD2 (cut-off value, 10.59 ml; p=0.008) were significantly associated with the development of radiation-induced hypothyroidism. CONCLUSION: Radiation-induced hypothyroidism is not rare in patients with head and neck cancer undergoing radiotherapy using SIB-VMAT. Radiation dose-volume parameters detected in this study may be useful indicators to prevent this complication.


Assuntos
Neoplasias de Cabeça e Pescoço , Hipotireoidismo , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Fatores de Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/efeitos adversos
3.
Pol J Pathol ; 74(2): 122-130, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37728471

RESUMO

CD98 is a marker of cancer stem cells, and it regulates radiosensitivity in head and neck squamous cell carcinoma (HNSCC). The current study aimed to investigate whether CD98 can be used as a prognostic factor and marker of radioresistance. CD98 immunostaining was performed using biopsy specimens collected from patients diagnosed with HNSCC. The average period of postoperative monitoring was 31.6 months. The treatment options were radiation therapy with either cisplatin or cetuximab, and surgery. The participants were divided into groups of low and high fluorescence intensity. CD98 was an independent prognostic factor of radioresistance. In total, 103 patients were treated with chemoradiotherapy or bioradiotherapy. The overall survival rates of patients receiving chemoradiotherapy or bioradiotherapy were 69.2% in the low group and 36.2% in the high group. The progression-free survival rates were 60.0% and 24.6%, respectively. CD98 expression was considered an independent prognostic factor of overall survival and progression-free survival. In total, 99 patients underwent surgical treatment. The surgery group did not differ according to CD98 expression. Via CD98 immunostaining, sensitivity to radiotherapy can be determined in advance. In HNSCC, knowledge about sensitivity to radiotherapy can significantly improve prognosis.


Assuntos
Quimiorradioterapia , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Células-Tronco Neoplásicas , Tolerância a Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína-1 Reguladora de Fusão/metabolismo
4.
Oncol Lett ; 25(4): 171, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36970606

RESUMO

Head and neck squamous cell carcinoma (HNSCC) has been identified as the sixth most common disease in the world, and its prognosis remains poor. The basic treatment of HNSCC includes a combination of chemoradiation and surgery. With the advent of immune checkpoint inhibitors, the prognosis has improved; however, the efficacy of checkpoint inhibitors is limited. L-type amino acid transporter 1 (LAT1), an amino acid transporter, is highly expressed in a cancer-specific manner. However, to the best of our knowledge, LAT1 expression in HNSCC has not been determined. Therefore, the present study aimed to examine the role of LAT1 expression in HNSCC. A total of three HNSCC cell lines (Sa3, HSC2 and HSC4) were used to investigate the characteristics of LAT1-positive cells, including their ability to form spheroids, and their invasion and migration. The present study also examined LAT1 by immunostaining of biopsy specimens from 174 patients diagnosed, treated and followed-up at Akita University (Akita, Japan) between January 2010 and December 2019, and overall survival, progression-free survival and multivariate analyses were performed. The results demonstrated that LAT1-positive cells in HNSCC were an independent prognostic factor for overall survival and progression-free survival, and were resistant to chemoradiation. Therefore, JPH203, a LAT1 inhibitor, may be effective in treating chemoradiotherapy-resistant HNSCC and may improve the prognosis of patients with HNSCC.

5.
J Appl Clin Med Phys ; 24(5): e13901, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36635847

RESUMO

BACKGROUND: Radixact Synchrony® , a real-time motion tracking and compensating modality, is used for helical tomotherapy. Control parameters are used for the accurate application of irradiation. Radixact Synchrony® uses the potential difference, which is an index of the accuracy of the prediction model of target motion and is represented by a statistical prediction of the 3D distance error. Although there are several reports on Radixact Synchrony® , few have reported the appropriate settings of the potential difference threshold. PURPOSE: This study aims to determine the optimal threshold of the potential difference of Radixact Synchrony® during respiratory tumor-motion-tracking irradiation. METHODS: The relationship among the dosimetric accuracy, motion tracking accuracy, and control parameter was evaluated using a moving platform, a phantom with a basic respiratory model (the fourth power of a sinusoidal wave), and several irregular respiratory model waveforms. The dosimetric accuracy was evaluated by gamma analysis (3%, 1 mm, 10% dose threshold). The tracking accuracy was measured by the distance error of the difference between the tracked and driven positions of the phantom. The largest potential difference for 95% of treatment time was evaluated, and its correlation with the gamma-pass ratio and distance error was investigated. The optimal threshold of the potential difference was determined by receiver operating characteristic (ROC) analysis. RESULTS: A linear correlation was identified between the potential difference and the gamma-pass ratio (R = -0.704). A linear correlation was also identified between the potential difference and distance error (R = 0.827). However, as the potential difference increased, it tended to underestimate the distance error. The ROC analysis revealed that the appropriate cutoff value of the potential difference was 3.05 mm. CONCLUSION: The irradiation accuracy with motion tracking by Radixact Synchrony® could be predicted from the potential difference, and the threshold of the potential difference should be set to ∼3 mm.


Assuntos
Neoplasias , Radioterapia de Intensidade Modulada , Humanos , Imagens de Fantasmas , Movimento (Física) , Radiometria , Neoplasias/radioterapia
6.
J Interv Card Electrophysiol ; 66(4): 981-989, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36336724

RESUMO

BACKGROUND: The distal hemisphere of a balloon is generally cooled during cryoapplication. However, a wide ablation area can be acquired after cryoballoon ablation. This study aimed to evaluate the extent of ice formation on two types of balloon surfaces through experimental and simulation studies. METHODS: A standard cryoballoon (SCB; Arctic Front Advance Pro, Medtronic) and novel cryoballoon (NCB; POLARx, Boston Scientific) were frozen for 240 s in 36 °C normal saline solution to observe ice formation on the balloon surface. Pieces of porcine tissue were placed between the upper and lower sides of the balloon, and the balloon was frozen in the horizontal direction for 240 s in 20 attempts (10 for SCB and NCB each). The measured areas of ice formation were evaluated and compared between the upper and lower sides of each balloon. RESULTS: Ice formation was greater on the lower side of the balloon than on the upper side. A larger area of ice formation in the tissue slab was observed on the lower side than on the upper side in both balloons, and the ice formation extended to the proximal hemisphere on the lower side of the balloon. The ice formation area in the NCB was significantly larger than that in SCB. CONCLUSIONS: Ice formation was significantly greater on the lower side of the cryoballoon than on the upper side and extended to the proximal hemisphere of the balloon, which might facilitate the acquisition of a wide ablation area on the left atrial posterior wall after cryoballoon ablation. Different ice formation after cryoballoon ablation Greater ice formation on the lower side of cryoballoon and an extensive ice formation in the proximal hemisphere, especially in novel cryoballoon.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Animais , Suínos , Gelo , Fibrilação Atrial/cirurgia , Átrios do Coração/cirurgia , Veias Pulmonares/cirurgia , Resultado do Tratamento
7.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 79(1): 46-51, 2023 Jan 20.
Artigo em Japonês | MEDLINE | ID: mdl-36418062

RESUMO

Confirmation of patient information is required to ensure the safety of radiation therapy. The purpose of this study was to construct a system that facilitates radiation therapy operations by linking a radiation therapy information system to a smartphone. By linking a smartphone to a radiation therapy operation support system, without using a PC terminal, we were able to input information about the patient's position and fixation into images taken with a smartphone. In addition, patient information could be directly linked into the radiation therapy information system. In addition, patient information could be verified in the irradiation room by synchronizing the smartphone with the radiation therapy support system. The questionnaire was highly evaluated in terms of radio reception, usability, visibility and barcode reading. In this study, by linking a smartphone to a radiotherapy information system, it was possible to construct a system that facilitates radiotherapy operations by checking and registering patient information at hand.


Assuntos
Radiocirurgia , Smartphone , Humanos , Inquéritos e Questionários , Extremidade Superior
8.
Pathol Oncol Res ; 28: 1610450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061142

RESUMO

Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens. Methods: We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival. Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor. Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.


Assuntos
Neoplasias de Cabeça e Pescoço , Glicoproteínas de Membrana , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Glicoproteínas de Membrana/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
9.
In Vivo ; 36(5): 2218-2223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099093

RESUMO

BACKGROUND/AIM: To investigate the effect of polaprezinc (antioxidant) administration and hyperbaric oxygen therapy on radiation-induced intestinal injury. MATERIALS AND METHODS: Forty-five C57BL/6J mice underwent total body radiation of 2 Gy. Polaprezinc was given in 12 mice, hyperbaric oxygen in 12 mice, and both in 12 mice. The other 9 mice did not undergo any treatment. Mice were sacrificed 2, 4, and 6 h after radiation, and 9 specimens (3 each from the duodenum, jejunum, and ileum) were harvested. Apoptotic intestinal crypt cells were histologically evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Apoptotic cell number per 1,000 crypt cells was 31.0±6.7 at 2 h, 28.4±5.2 at 4 h, and 32.9±5.1 at 6 h in the mice group treated by radiation alone. Both polaprezinc administration and hyperbaric oxygen therapy significantly suppressed apoptosis. Although the effect of polaprezinc administration on suppressing apoptosis became less over time (4.9±5.7 and 19.4±13.2 at 2 and 6 h, respectively), that of hyperbaric oxygen therapy was stable regardless of time (23.6±4.8 and 25.8±4.1 at 2 and 6 h). Administration of both polaprezinc and hyperbaric oxygen showed a significant synergetic or additive effect on suppressing apoptosis at 6 h (11.4±10.5, p<0.0035 vs. polaprezinc, p<0.0001 vs. hyperbaric oxygen). CONCLUSION: Both polaprezinc administration and hyperbaric oxygen therapy are effective in relieving radiation-induced small intestinal damage, and a synergistic or additive effect is expected when using both.


Assuntos
Carnosina , Oxigenoterapia Hiperbárica , Lesões por Radiação , Animais , Carnosina/análogos & derivados , Intestino Delgado , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organometálicos , Compostos de Zinco
10.
Diagn Cytopathol ; 50(8): 394-403, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35567786

RESUMO

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials. METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 µm2 ) and perimeter (34.1 ± 6.1 µm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns. CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Citometria de Fluxo , Humanos , Antígeno Ki-67 , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias
11.
Cancers (Basel) ; 14(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35626162

RESUMO

Patients with cancer are concerned about the effects of the COVID-19 vaccination. We conducted an online survey on the COVID-19 vaccination status and side effects among patients with cancer in Japan between 8 and 14 August 2021. We included 1182 female patients with cancer aged 20-70 years and registered on an online patient website. Of the patients, 944 had breast cancer, 216 had gynecological cancer, 798 were undergoing drug/radiation therapy, and 370 were in follow-up. At the time of the survey, 885 patients had already received at least one dose. Of these, 580 had also received their second dose. The incidence rate of side effects was equivalent to previous reports. In patients with breast cancer, problems such as the onset or worsening of lymphedema or axillary lymphadenopathy metastasis requiring differential diagnosis were encountered following vaccination. A total of 768 patients were concerned about the vaccine at some point, and 726 consulted with their attending physicians about the timing or side effects of the vaccination. Of the 110 patients undergoing chemotherapy or radiation therapy, 75 adjusted the timing of the vaccination based on their therapy. The cross-analysis revealed that 81% of those who consulted their physician had received at least one dose of the COVID-19 vaccination compared with 65% of those who had not consulted their physician. Consulting with a physician about the COVID-19 vaccination was found to alleviate the concerns of patients with cancer and encourage them to get vaccinated.

12.
Asian Pac J Cancer Prev ; 23(4): 1271-1278, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35485685

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are assessed by the ratio of the area of lymphocytes infiltrating the stroma. TILs are important in breast cancer and malignant melanoma and are being established as a marker of prognosis and sensitivity to chemotherapy. This has resulted in various therapies being developed in fields such as breast cancer. However, the evaluation of TILs in head and neck squamous cell carcinoma (HNSCC) is not progressing, and the prognosis is still poor. Thus, investigating whether or not the evaluation of TILs is also effective in HNSCC and prognoses can be predicted with just biopsy samples alone is required. METHODS: This study included 153 patients who were diagnosed with HNSCC between January 2010 and December 2019, underwent treatment, and could be followed up thereafter at our institution. RESULTS: TILs, overall survival (OS), and progression-free survival (PFS) were evaluated in all patients, the chemoradiotherapy arm, and the surgery arm. The cut-off value for TILs was 50%. In all patients, OS was 69.8% and 40.2% (P = 0.01) and PFS was 58.4% and 31.6% (P = 0.003) in the high and low TIL groups, respectively. Multivariate analyses revealed that TILs independently predicted prognosis. In the chemoradiotherapy arm, OS was 70.8% and 31.6% (P = 0.012) and PFS was 63.4% and 20.3% (P = 0.001) in the high and low TIL groups, respectively. No significant differences were noted in the surgery arm. CONCLUSIONS: In HNSCC, TILs can be used as a prognosis predictor and chemoradiotherapy biomarker. Assessments can be performed just with hematoxylin-eosin staining and is very simple. This will greatly contribute to report personalized therapy progress. Further evaluations and, thus, prospective clinical multicenter trials are needed to use TILs in clinical practice for HNSCC.


Assuntos
Neoplasias da Mama , Neoplasias de Cabeça e Pescoço , Biomarcadores , Neoplasias da Mama/patologia , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
13.
Anticancer Res ; 41(11): 5793-5802, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732453

RESUMO

BACKGROUND/AIM: To evaluate the incidence and grade of radiation pneumonitis after volumetric modulated arc therapy (VMAT) performed for the treatment of non-small cell cancer (NSCLC). PATIENTS AND METHODS: Fifty consecutive non-surgical candidates with NSCLC underwent VMAT. Thirty-five patients had stage-III tumors and 15 had recurrent tumors. The prescribed radiation dose for the gross tumor and the elective nodal area was 69 Gy in 30 fractions and 51 Gy in 30 fractions, respectively. RESULTS: Radiation pneumonitis developed in 38 patients (76%, 38/50), and grade ≥2 radiation pneumonitis developed in 11 patients (22%, 11/50). The percentage of lung volume that received a dose in excess of 5 Gy (V5), V10, V20, V30, and the mean lung dose (MLD) in the bilateral and ipsilateral lung were significantly associated with the development of grade ≥2 radiation pneumonitis. CONCLUSION: The incidence and degree of radiation pneumonitis are acceptable following treatment of NSCLC with VMAT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Doses de Radiação , Pneumonite por Radiação/diagnóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
14.
Dev Biol ; 478: 155-162, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256037

RESUMO

In vertebrate embryos, the kidney primordium metanephros is formed from two distinct cell lineages, Wolffian duct and metanephric mesenchyme, which were classically grouped as intermediate mesoderm. Whereas the reciprocal interactions between these two cell populations in kidney development have been studied extensively, the mechanisms generating them remain elusive. Here, we show that the mouse cell lineage that forms nephric mesenchyme develops as a subpopulation of Tbx6-expressing mesodermal precursor derivatives of neuro-mesodermal progenitors (NMPs) under the condition of bone morphogenetic protein (BMP)-signal-dependent Osr1 expression. The Osr1-expressing nephric mesenchyme precursors were confirmed as descendants of NMPs because they were labeled by Sox2 N1 enhancer-EGFP. In Tbx6 mutant embryos, nephric mesenchyme changed its fate into neural tissues, which reflected its NMP origin. In Osr1 mutant embryos, the specific region of the Tbx6-expressing mesoderm precursor, which normally expresses Osr1 and develops into the nephric mesenchyme, instead expressed the somite marker FoxC2. BMP signaling activated Osr1 expression in a region of TBX6-expressing mesoderm and elicited nephric mesenchyme development. This study suggested a new model of cell lineage segregation during gastrulation.


Assuntos
Gastrulação , Rim/embriologia , Mesoderma/embriologia , Células-Tronco/fisiologia , Proteínas com Domínio T/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Linhagem da Célula , Fatores de Transcrição Forkhead/metabolismo , Células-Tronco Mesenquimais/fisiologia , Mesoderma/citologia , Camundongos , Células-Tronco Neurais/fisiologia , Organogênese , Transdução de Sinais , Somitos/citologia , Somitos/fisiologia
15.
Case Rep Oncol ; 14(1): 13-16, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613236

RESUMO

We report a 49-year-old male with castration-resistant prostate cancer (CRPC) with oligometastasis diagnosed by 11C-choline positron emission tomography-computed tomography (PET/CT) and treated with target radiotherapy. In the diagnosis of CRPC (serum prostate-specific antigen [PSA] level of 6.53 ng/mL after maximum androgen blockade (MAB) therapy, high-dose brachytherapy, and external beam radiotherapy), 11C-choline PET/CT detected one tiny obturator lymph node metastasis which fluorodeoxyglucose PET/CT could not detect. He underwent intensity-modulated radiation therapy and MAB was restarted. The PSA value decreased and reached nadir (0.091 ng/mL) after 6 months. The time to PSA progression was 10 months. The choline PET/CT finding and the corresponding local treatment could play an important role in the management sequence of oligoprogressive CRPC.

16.
Sci Rep ; 11(1): 1110, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441739

RESUMO

In mammalian testes, undifferentiated spermatogonia (Aundiff) undergo differentiation in response to retinoic acid (RA), while their progenitor states are partially maintained by fibroblast growth factors (FGFs). Sertoli valve (SV) is a region located at the terminal end of seminiferous tubule (ST) adjacent to the rete testis (RT), where the high density of Aundiff is constitutively maintained with the absence of active spermatogenesis. However, the molecular and cellular characteristics of SV epithelia still remain unclear. In this study, we first identified the region-specific AKT phosphorylation in the SV Sertoli cells and demonstrated non-cell autonomous specialization of Sertoli cells in the SV region by performing a Sertoli cell ablation/replacement experiment. The expression of Fgf9 was detected in the RT epithelia, while the exogenous administration of FGF9 caused ectopic AKT phosphorylation in the Sertoli cells of convoluted ST. Furthermore, we revealed the SV region-specific expression of Cyp26a1, which encodes an RA-degrading enzyme, and demonstrated that the increased RA levels in the SV region disrupt its pool of Aundiff by inducing their differentiation. Taken together, RT-derived FGFs and low levels of RA signaling contribute to the non-cell-autonomous regionalization of the SV epithelia and its local maintenance of Aundiff in the SV region.


Assuntos
Túbulos Seminíferos/metabolismo , Células de Sertoli/metabolismo , Tretinoína/metabolismo , Animais , Diferenciação Celular , Epitélio/fisiologia , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/análise , Regeneração , Ácido Retinoico 4 Hidroxilase/genética , Ácido Retinoico 4 Hidroxilase/metabolismo , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/crescimento & desenvolvimento , Células de Sertoli/fisiologia , Células de Sertoli/transplante , Transdução de Sinais , Espermatogênese , Tretinoína/farmacologia , Regulação para Cima
17.
J Vasc Interv Radiol ; 31(9): 1475-1482.e2, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800663

RESUMO

PURPOSE: To evaluate the effects of hepatic artery embolization (HAE) on the expression of programmed cell death 1 ligand 1 (PD-L1) in an orthotopic rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: A rat HCC model was established in Sprague-Dawley rats with the RH7777 cell line. Six animals each were assigned to receive HAE or sham treatment. Liver tissues were harvested 24 h after the procedure. Immunohistochemistry (IHC) was used to compare expression of PD-L1 and hypoxia-inducible factor (HIF)-1α in the intratumoral and peritumoral regions and normal liver tissue. In vitro cell culture study was performed for 24 h under normoxic and hypoxic conditions, and protein expression of PD-L1 and HIF-1α and the effects of HIF-1α inhibitors were assessed. RESULTS: IHC showed that PD-L1- and HIF-1α-positive areas were significantly larger in the HAE group vs the sham group in intratumoral (P = .006 and P < .001, respectively) and peritumoral regions (both P < .001). The expression of PD-L1 positively correlated with HIF-1α expression in the intratumoral region (r2 = 0.551; P < .001). In vitro cell culture study revealed that protein expression of PD-L1 and HIF-1α were significantly higher when cells were incubated under hypoxic vs normoxic conditions (P = .028 and P = .010, respectively). PD-L1 expression was suppressed significantly when the HIF-1α inhibitor rapamycin was added to the culture medium (P = .024). CONCLUSIONS: HAE enhances intratumoral and peritumoral PD-L1 expression in a rat HCC model. The HIF-1α pathway is a possible mechanism underlying increased intratumoral PD-L1 expression after HAE.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Artéria Hepática , Neoplasias Hepáticas Experimentais/terapia , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Microambiente Tumoral , Regulação para Cima
18.
Breast Cancer ; 27(2): 236-242, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31617073

RESUMO

BACKGROUND: Obesity is associated with an increased risk for developing breast cancer and poor cancer-related outcomes. Endocrine therapy is a key part of treatment for breast cancer, but can result in weight gain. This study examined the efficacy of a structured group intervention during adjuvant endocrine therapy for obese patients with breast cancer. The intervention involved a combination of proper nutrition, exercise, and group coaching. METHODS: Participants were patients with breast cancer who were undergoing adjuvant endocrine therapy and exhibited apparent weight gain while undergoing therapy, or had a diagnosis of abnormal lipid metabolism. We conducted a single-arm prospective study with a combined intervention. The intervention comprised 15 min of nutrition education, a 30-min group health coaching program, and three 45-min group aerobic exercise sessions. We evaluated participants' parameters (e.g., body weight, body mass index [BMI], cholesterol, psychological distress) at baseline, and at 1, 3, and 6 months after the intervention. RESULTS: At 1 month after the intervention, there were significant reductions in body weight (p < 0.01), BMI (p < 0.01), triglyceride levels (p < 0.05), total cholesterol levels (p < 0.01), psychological distress (p < 0.05), and cancer-related fatigue (p < 0.01). At 3 and 6 months after the intervention, we observed further reductions in body weight, BMI, and triceps skinfold thickness. CONCLUSION: Our study showed that a short-term structured intervention helped modify dietary and exercise behaviors and promote health among breast cancer survivors, and resulted in favorable changes in participants' body weight.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer , Obesidade/prevenção & controle , Adulto , Idoso , Terapia por Exercício/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Obesidade/etiologia , Estudos Prospectivos , Aumento de Peso/efeitos dos fármacos
19.
In Vivo ; 34(1): 331-337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882496

RESUMO

BACKGROUND/AIM: Traditionally, the radiotherapy of oesophageal cancer has been conformal radiotherapy (CRT). We sought to compare dosimetric parameters of conformal radiotherapy (CRT) with those of two treatment planning systems for hybrid-volumetric modulated arc therapy (h-VMAT) for the treatment of oesophageal cancer. PATIENTS AND METHODS: In 11 patients, we compared: i) planning target volume coverage, ii) dose to organs at risk, and iii) the dose rate (DR) of the three techniques. We evaluated two treatment planning systems: i) Eclipse and ii) RayStation. RESULTS: The Conformity Index of the CRT plan was significantly higher for the h-VMAT plans, compared to all other parameters. Normal lung tissue volumes receiving >5, 13, or 20 Gy were lower with the RayStation plan compared to Eclipse. The volume of cardiac tissue receiving >40 Gy was highest with the CRT plan. The minimum DR in VMAT was lowest for the RayStation plan (49.5 MU/min). CONCLUSION: The h-VMAT plan using RayStation is the appropriate choice for reducing lung dose.


Assuntos
Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica
20.
Clin Exp Dent Res ; 5(5): 485-490, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31687181

RESUMO

Objectives: Oral infection control is important for patients undergoing cardiac valve replacement (CVR) as prophylaxis for postoperative complications. This study examined the changes in oral health status by preoperative periodontal treatment and its effects on postsurgical complications in CVR patients. Material and methods: We recruited 64 patients undergoing CVR who received preoperative periodontal treatment at our hospital as the intervention group and retrospectively reviewed the medical records of 38 patients who had undergone CVR surgery without dental intervention as the control group. Oral health status was assessed at the first visit to our dental office, 1 day before surgery, and >7 days after surgery. Days of high fever, antibiotics use, and postoperative hospitalization were recorded for the intervention and control groups for statistical comparisons. Results: In the intervention group, oral health status significantly improved from the initial visit to >7 days after surgery. There were significantly fewer days of high fever (>37.5°C) in the intervention group than in the control group, with comparable results for other events. Conclusions: This study's findings suggest that preoperative periodontal treatment can improve oral health status surrounding CVR surgery and could be the contributor of the reduction in the risk of postoperative infection.


Assuntos
Antibacterianos/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Assistência Odontológica/normas , Doenças das Valvas Cardíacas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Taxa de Sobrevida
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