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1.
J Gen Virol ; 105(1)2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189334

RESUMO

Phosphorylation and dephosphorylation of viral movement proteins plays a crucial role in regulating virus movement. Our study focused on investigating the movement protein TGBp1 of Bamboo mosaic virus (BaMV), which is a single-stranded positive-sense RNA virus. Specifically, we examined four potential phosphorylation sites (S15, S18, T58, and S247) within the TGBp1 protein. To study the impact of phosphorylation, we introduced amino acid substitutions at the selected sites. Alanine substitutions were used to prevent phosphorylation, while aspartate substitutions were employed to mimic phosphorylation. Our findings suggest that mimicking phosphorylation at S15, S18 and T58 of TGBp1 might be linked to silencing suppressor activities. The phosphorylated form at these sites exhibits a loss of silencing suppressor activity, leading to reduced viral accumulation in the inoculated leaves. Furthermore, mimicking phosphorylation at residues S15 and S18 could diminish viral accumulation at the single-cell level, while doing so at residue T58 could influence virus movement. However, mimicking phosphorylation at residue S247 does not appear to be relevant to both functions of TGBp1. Overall, our study provides insights into the functional significance of specific phosphorylation sites in BaMV TGBp1, illuminating the regulatory mechanisms involved in virus movement and silencing suppression.


Assuntos
Potexvirus , Fosforilação , Potexvirus/genética , Alanina , Substituição de Aminoácidos
2.
J Formos Med Assoc ; 122(11): 1141-1149, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37202235

RESUMO

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/terapia , Estudos Retrospectivos , Carcinoma Nasofaríngeo/terapia , Prognóstico , Inflamação
3.
J Exp Bot ; 71(22): 6932-6944, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32926136

RESUMO

NbRabF1, a small GTPase from Nicotiana benthamiana and a homolog of Arabidopsis thaliana Ara6, plays a key role in regulating Bamboo mosaic virus (BaMV) movement by vesicle transport between endosomal membranes. Reducing the expression of NbRabF1 in N. benthamiana by virus-induced gene silencing decreased the accumulation of BaMV, and with smaller infection foci on inoculated leaves, but had no effect in protoplasts. Furthermore, transient expression of NbRabF1 increased the accumulation of BaMV in inoculated leaves. Thus, NbRabF1 may be involved in the cell-to-cell movement of BaMV. The potential acyl modification sites at the second and third amino acid positions of NbRabF1 were crucial for membrane targeting and BaMV accumulation. The localization of mutant forms of NbRabF1 with the GDP-bound (donor site) and GTP-bound (acceptor site) suggested that NbRabF1 might regulate vesicle trafficking between the Golgi apparatus and plasma membrane. Furthermore, GTPase activity could also be involved in BaMV cell-to-cell movement. Overall, in this study, we identified a small GTPase, NbRabF1, from N. benthamiana that interacts with its activation protein NbRabGAP1 and regulates vesicle transport from the Golgi apparatus to the plasma membrane. We suggest that the BaMV movement complex might move from cell to cell through this vesicle trafficking route.


Assuntos
Proteínas Monoméricas de Ligação ao GTP , Potexvirus , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Potexvirus/genética , Nicotiana/metabolismo
4.
Oncologist ; 23(12): 1426-1435, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29728468

RESUMO

BACKGROUND: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Stents/normas , Idoso , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
J Clin Med ; 12(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37959348

RESUMO

BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.

6.
Life (Basel) ; 12(5)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35629353

RESUMO

OBJECTIVES: To evaluate the feasibility and safety of low energy X-ray photon intraoperative radiotherapy (IORT) as an adjuvant therapy for recurrent gynecological cancer. METHODS: Medical records of all recurrence gynecological cancer patients who underwent IORT were reviewed. RESULTS: Between January 2018 and December 2021, five women (including cervical cancer (n = 2), endometrial cancer (n = 2), and uterine leiomyosarcoma (n = 1)), who underwent IORT and surgical resection for recurrent gynecologic cancer were reviewed. A median dose of 15.62 Gy (range, 12 to 20 Gy) was used for IORT. Repeated IORT and surgical resection was performed in two women. Three women experienced local recurrence, and three women died during follow-up. The 1-year local control rate was 60%. The 2-year overall survival rate was 30%. There was no Clavien-Dindo classification grade III-V complication. CONCLUSION: IORT using low energy X-ray photon therapy seems to be feasible and safe as an adjuvant therapy in women who underwent salvage surgery for recurrent gynecologic cancer. However, large-scale prospective studies are needed to confirm our findings and evaluate its efficacy.

7.
J Colloid Interface Sci ; 628(Pt B): 877-885, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36029601

RESUMO

Composite solid-state electrolyte (CSSE) with integrated strengths avoids the weaknesses of organic and inorganic electrolytes, and thus become a better choice for all-solid-state lithium battery (ASSLB). However, the poor dispersion of inorganic fillers and the organic/inorganic nature difference leads to their interface incompatibility, which greatly destroys the performance of CSSE and ASSLB. Herein, silane coupling agent (SCA) aminopropyl triethoxysilane (ATS) is introduced to tailor the organic/inorganic interfaces in CSSE by the common chemical bridging effect of SCA and the special amino effect (hydrogen bond and lone pair electron effects). It is found that the hydrogen bond interaction between -NH2 and polyethylene oxide (PEO) enhances their interface interaction. And the lone pair electrons on nitrogen atom allow it to react with solvent acetonitrile and promote the uniform dispersion of ceramic fillers. Moreover, the lone pair electrons can complex with Li+, which promotes the dissociation of Li salts, uniforms Li+ diffusion and inhibits the Li dendrite. Thanks to the above merits, the interface compatibility and stability of organic/inorganic CSSE are much enhanced by innovatively introducing ATS, showing high ionic conductivity and superior mechanical/thermal stability. The ASSLB with this modified CSSE exhibits excellent electrochemical performance with a reversible capacity of 140.9 mAh g-1 and a capacity retention of 94.4% after 280 cycles. These achievements offer a new insight into improving the stability of organic/inorganic CSSE interface and promoting their applicability into ASSLB.


Assuntos
Lítio , Silanos , Lítio/química , Sais , Eletrólitos/química , Acetonitrilas , Polietilenoglicóis , Solventes
8.
Bioengineering (Basel) ; 9(5)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35621491

RESUMO

BACKGROUND: Protecting cardiac function in patients with advanced left-breast cancer receiving radiation therapy (RT) with regional nodal irradiation (RNI) is an important issue. Modern RT techniques can limit cardiac exposure. The aim of this study was to explore the association be-tween cardiac dose and cardiac function. METHODS: Between 2017 and 2020, we retrospectively reviewed left-breast cancer patients who received adjuvant RT, including RNI with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT). Left ventricular ejection fraction (LVEF) was assessed by echocardiography before RT and 1 year after RT to detect any early deterioration in cardiac systolic function. RESULTS: A total of 30 eligible patients were enrolled. The median follow-up time from the initiation of RT was 3.9 years (range 0.6-5 years). Seventeen patients received VMAT, and the other 13 patients received HT. The median RT dose was 55 Gray (Gy), and the mean heart dose was 3.73 Gy (range 1.95-9.36 Gy). The median LVEF before and after RT was 68% and 68.5%, respectively. No obvious deterioration was found. There was no association between cardiac dose (mean heart dose, V5-V30) and LVEF (change in values or post-RT). CONCLUSIONS: For left-breast cancer patients undergoing RT with RNI, VMAT, or HT can be used to limit cardiac exposure. Cardiac function as evaluated by LVEF revealed no obvious deterioration after RT in our patients, and no association was found between cardiac dose and LVEF in those treated with either VMAT or HT in early cardiac surveillance.

9.
Case Rep Otolaryngol ; 2022: 5877106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204045

RESUMO

Background: To explore spotted temporal lobe necrosis (TLN) and changes in brain magnetic resonance imaging (MRI) after image-guided radiotherapy (IGRT) in a patient with nasopharyngeal carcinoma (NPC). Case presentation: a 57-year-old male was diagnosed with stage III NPC, cT1N2M0, in 2017. He underwent concurrent chemoradiation therapy (CCRT) with cisplatin (30 mg/m2) and 5- fluorouracil (5-FU, 500 mg/m2) plus IGRT with 70 Gy in 35 fractions for 7 weeks. The following MRI showed a complete response in the NPC. However, the patient suffered from fainting periodically when standing up approximately 3 years after CCRT. Neck sonography showed mild atherosclerosis (< 15%) of bilateral carotid bifurcations and bilateral small-diameter vertebral arteries, with reduced flow volume. The following MRI showed a 9 mm × 7 mm enhancing lesion in the right temporal lobe without locoregional recurrence, and TLN was diagnosed. The lesion was near the watershed area between the anterior temporal and temporo-occipital arteries. The volume of the necrotic lesion was 0.51 c.c., and the mean dose and Dmax of the lesion were 64.4 Gy and 73.7 Gy, respectively. Additionally, the mean dose, V45, D1 c.c. (dose to 1 ml of the temporal lobe volume), D0.5 c.c. and Dmax of the right and left temporal lobes were 11.1 Gy and 11.4 Gy, 8.5 c.c. and 6.7 c.c., 70.1 Gy and 67.1 Gy, 72.0 Gy and 68.8 Gy, and 74.2 Gy and 72.1 Gy, respectively. Conclusion: Spotted TLN in patients with NPC treated by IGRT may be difficult to diagnose due to a lack of clinical symptoms and radiological signs. Endothelial damage may occur in carotid and vertebral arteries within the irradiated area, affecting the small branches supplying the temporal lobe and inducing spotted TLN. Future research on the relationship between vessels and RT or CCRT and the development of TLN is warranted.

10.
Cancers (Basel) ; 13(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34680189

RESUMO

BACKGROUND: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI. METHODS: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed. RESULTS: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5-V20, whole-lung mean dose, lung parameters of V5-V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose. CONCLUSIONS: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available.

11.
ACS Appl Mater Interfaces ; 12(12): 13923-13930, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32150372

RESUMO

Increasing attention has been paid to layered high-Ni oxides with high capacity as a promising cathode for high-energy lithium-ion batteries. However, the undesirable microcracks in secondary particles usually occur due to the volume changes of anisotropic primary grains during cycles, which lead to the decay of electrochemical performance. Here, for the first time, a functional electrolyte with di-sec-butoxyaluminoxytriethoxysilane additive integrating the functions of silane and aluminate is proposed to in situ form the binder-like filler between anisotropic primary grains for mitigating the microcracks of high-Ni oxides. It is demonstrated that Li-containing aluminosilicate as a glue layer between the gaps of grains and as a coating layer on the surface of the grains is generated, and these features further enhance the interfacial bonding and surface stability of anisotropic primary grains. Consequently, the microcracks along with side reactions and phase transitions of high-Ni oxides are mitigated. As anticipated, the electrochemical performance and thermal stability of high-Ni oxides are improved, and there is also a capacity retention of 75.4% even after 300 cycles and large reversible capacity of ∼160 mA h g-1 at 5 C. The functional electrolyte offers a simple, efficient, and scalable method to promote the electrochemical properties and applicability of high-Ni oxide cathodes in high-energy lithium-ion batteries.

12.
Sci Rep ; 9(1): 8885, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222096

RESUMO

Specifications about the size and stiffness of healthy salivary glands with ultrasound (US) are not available for Asian people. Using a Toshiba Apolio 500 US platform, we determined the size (including anterior-posterior median length, median paramandibular depth dimension, and cranio-caudal height) and hardness of 100 healthy submandibular and parotid glands in volunteers without a history of disease affecting the salivary glands or post-radiation, and compared the dimensions to those of 36 parotid glands and 37 submandibular glands in post-irradiated patients. The dimensions of the parotid and submandibular glands were significantly correlated with body weight. However, the dimension of the parotid glands was not significantly correlated with that of patients with prior radiation; the shear wave velocity (SWV) significantly increased (1.99 m/s versus 2.43 m/s, p-value < 0.01). The dimension of the submandibular glands was significantly correlated with prior radiation, where the SWV also significantly increased (2.32 m/s versus 2.50 m/s, p-values < 0.01). We find that US is a useful tool for assessment of the reference dimensions and hardness of major salivary glands that may be altered by irradiation.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Glândulas Salivares/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Salivares/anatomia & histologia
13.
Radiat Oncol ; 14(1): 90, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146741

RESUMO

BACKGROUND: To evaluate the practicality of NS-21 cream with regard to its skin-related toxicity in patients with head and neck cancer (HNC) who are undergoing concurrent chemoradiation therapy (CCRT) or radiotherapy (RT). METHODS: Between July 2015 and November 2017, 30 HNC patients who underwent RT or CCRT were randomly allocated to receive either NS-21 or control treatment on their irradiated skin three times per day, starting at the initiation of RT or CCRT and ending 2 weeks after the completion of RT or until the appearance of grade 3 acute radiation dermatitis (ARD). Dermatitis was recorded weekly according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Skin humidity was monitored by a digital moisture meter. The generalized estimating equation (GEE) and logit link function method were used for statistical analysis. RESULTS: No serious adverse events were observed in either group. Itching dermatitis occurred on the right lower neck in one patient of the NS-21 group during the 3rd week of CCRT, but the severity was mild. The median skin moisture value at the time of the final treatment was significantly different between the study and control groups (30.6 vs. 27.3, p = 0.013). Additionally, there was an inverse relationship between skin moisture and ARD grade (B = -0.04, p = 0.005). The incidence of ARD at the time of the last treatment was not significantly different between the study and control groups (6.7% vs 26.7%, p = 0.165). The risk of grade 3 ARD for skin that had received an irradiation dose of 47-70 Gy was higher than that of skin that had received an irradiation dose ≤46 Gy (OR = 31.06, 95% CI =5.95-162.21, p < 0.001). Nevertheless, the risk of ARD was not significantly different between the groups (OR = 0.38, 95% CI = 0.08-1.74, p = 0.212). CONCLUSIONS: NS-21 was well tolerated and effective for the maintenance of skin moisture; however, there was no statistically significant reduction in the risk of ARD in HNC patients undergoing RT or CCRT when compared with HNC patients in the control group. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Far Eastern Memorial Hospital ( FEMH-IRB , 104048-F), Registered 1st June 2015.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Fenilacetatos/uso terapêutico , Radiodermite/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Dermatológicos/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenilacetatos/administração & dosagem , Radiodermite/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Resultado do Tratamento
14.
Medicine (Baltimore) ; 94(20): e862, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25997064

RESUMO

Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m) and 5-Fluorouracil (500 mg/m) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 10 /µL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection.Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation.


Assuntos
Falso Aneurisma/etiologia , Doenças da Aorta/etiologia , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Stents/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada , Evolução Fatal , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
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