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1.
Ann Med ; 56(1): 2383959, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39086168

RESUMEN

BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.


Asunto(s)
Quimioradioterapia , Ciclobutanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Compuestos Organoplatinos , Radioterapia de Intensidad Modulada , Humanos , Masculino , Anciano , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Ciclobutanos/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Estimación de Kaplan-Meier
2.
Prostate ; 84(14): 1336-1343, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39031050

RESUMEN

BACKGROUND: There are no population-level studies assessing 18F-fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System. METHODS: Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate-specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging. RESULTS: Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0-0.5 ng/mL, 21% for >0.5-1.0, 54% for >1.0-2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07-7.96; men on ADT only OR: 4.42, 95% CI: 1.73-11.26) and use of ADT (OR: 3.94, 95% CI: 1.32-11.75), and White (all men OR: 2.22, 95% CI: 1.20-4.17) predicted positive fluciclovine PET/CT. CONCLUSION: This real-world study assessing 18F-fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.


Asunto(s)
Ácidos Carboxílicos , Ciclobutanos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Ciclobutanos/uso terapéutico , Anciano , Recurrencia Local de Neoplasia/diagnóstico por imagen , Persona de Mediana Edad , Estados Unidos , Antígeno Prostático Específico/sangre , United States Department of Veterans Affairs , Antagonistas de Andrógenos/uso terapéutico
3.
BMC Med ; 22(1): 252, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886794

RESUMEN

BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.


Asunto(s)
Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclobutanos , Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclobutanos/administración & dosificación , Ciclobutanos/uso terapéutico , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Anciano , Taxoides/uso terapéutico , Taxoides/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Resultado del Tratamiento , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Hidrocarburos Aromáticos con Puentes
4.
ESMO Open ; 9(5): 103448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38718704

RESUMEN

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.


Asunto(s)
Radioisótopos de Carbono , Ácidos Carboxílicos , Colina , Ciclobutanos , Radioisótopos de Galio , Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Prospectivos , Anciano , Ácidos Carboxílicos/farmacología , Ácidos Carboxílicos/uso terapéutico , Radioisótopos de Galio/farmacología , Colina/farmacología , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Radioisótopos de Carbono/farmacología , Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Isótopos de Galio , Radiofármacos/farmacología , Anciano de 80 o más Años , Receptores Androgénicos/metabolismo
5.
Medicine (Baltimore) ; 103(21): e38183, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38788019

RESUMEN

BACKGROUND: We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. RESULTS: This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. CONCLUSIONS: Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Teorema de Bayes , Bevacizumab , Resistencia a Antineoplásicos , Recurrencia Local de Neoplasia , Metaanálisis en Red , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Supervivencia sin Progresión , Ensayos Clínicos Fase III como Asunto , Ciclobutanos/uso terapéutico , Antineoplásicos/uso terapéutico , Inmunoterapia/métodos , Terapia Molecular Dirigida/métodos , Carbolinas , Compuestos Heterocíclicos de 4 o más Anillos
6.
Oncologist ; 29(5): e635-e642, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38431781

RESUMEN

BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.


Asunto(s)
Ciclobutanos , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/mortalidad , Femenino , Terapia Neoadyuvante/métodos , Pronóstico , Persona de Mediana Edad , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/farmacología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano , Neutrófilos/metabolismo , Biomarcadores de Tumor/sangre , Linfocitos/metabolismo , Plaquetas/patología , Estudios Retrospectivos
7.
Nucl Med Commun ; 45(6): 526-535, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38517329

RESUMEN

BACKGROUND: According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. OBJECTIVE: To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. METHODS: We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. RESULTS: The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. CONCLUSION: 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.


Asunto(s)
Antagonistas de Andrógenos , Ácidos Carboxílicos , Ciclobutanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Ácidos Carboxílicos/uso terapéutico , Ciclobutanos/uso terapéutico , Masculino , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Anciano , Persona de Mediana Edad , Antagonistas de Andrógenos/uso terapéutico , Nivel de Atención , United States Department of Veterans Affairs , Estados Unidos , Guías de Práctica Clínica como Asunto , Anciano de 80 o más Años , Recurrencia
8.
Future Med Chem ; 14(19): 1375-1402, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36069190

RESUMEN

Since they were first synthesized in 1965 by Treibs and Jacob, squaraine dyes have revolutionized the polymethine dyes' 'universe' and their potential applications due to their indisputable physical, chemical and biological properties. After 30 years and up to the present, various research teams have dedicated themselves to studying the squaraines' photodynamic therapy application using in vitro and in vivo models. The various structural modifications made to these compounds, as well as the influence they have shown to have in their phototherapeutic activity, are the main focus of the present review. Finally, the most evident limitations of this class of dyes, as well as future perspectives in the sense of hypothetically successfully overcoming them, are suggested by the authors.


Asunto(s)
Ciclobutanos , Fotoquimioterapia , Colorantes , Ciclobutanos/química , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Colorantes Fluorescentes/química , Estructura Molecular , Fenoles
9.
Int J Oncol ; 60(5)2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35315502

RESUMEN

Ovarian cancer is the most lethal gynecological cancer type in the United States. The success of current chemotherapies is limited by chemoresistance and side effects. Targeted therapy is a promising future direction for cancer therapy. In the present study, the efficacy of co­targeting IL­6 and IL­8 in human ovarian cancer cells by bazedoxifene (Baze) + SCH527123 (SCH) treatment was examined. ELISA, cell viability, cell proliferation, cell migration, cell invasion, western blotting and peritoneal ovarian tumor mouse model analyses were performed to analyze the expression levels of IL­6 and IL­8, tumor growth, tumor migration and invasion, and the possible pathways of human ovarian cancer cell lines (SKOV3, CAOV3 and OVCAR3) and patient­derived OV75 ovarian cancer cells. Each cell line was treated by monotherapy or combination therapy. The results demonstrated that IL­6 and IL­8 were secreted by human ovarian cancer cell lines. Compared with the DMSO control, the combination of IL­6/glycoprotein 130 inhibitor Baze and IL­8 inhibitor SCH synergistically inhibited cell viability in ovarian cancer cells. Baze + SCH also inhibited cell migration and invasion, suppressed ovarian tumor growth and inhibited STAT3 and AKT phosphorylation, as well as survivin expression. Therefore, co­targeting the IL­6 and IL­8 signaling pathways may be an effective approach for ovarian cancer treatment.


Asunto(s)
Benzamidas/farmacología , Ciclobutanos/farmacología , Indoles/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Animales , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclobutanos/administración & dosificación , Ciclobutanos/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Indoles/administración & dosificación , Indoles/uso terapéutico , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Ratones , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico
10.
South Med J ; 114(11): 703-707, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34729614

RESUMEN

OBJECTIVES: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. METHODS: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. RESULTS: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. CONCLUSIONS: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.


Asunto(s)
Ácidos Carboxílicos/administración & dosificación , Ciclobutanos/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/estadística & datos numéricos , Neoplasias de la Próstata/diagnóstico , Anciano , Ácidos Carboxílicos/uso terapéutico , Ciclobutanos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/epidemiología , Recurrencia , Estudios Retrospectivos
11.
Biochem Pharmacol ; 194: 114677, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34265280

RESUMEN

New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC1381 presented comparable affinity with HDAC1, 2, 3, 6, 8 and 11. Besides, the inhibition activity of HDACs was dose-dependently inhibited by MCC1381. Particularly, a strong binding affinity was observed between MCC1381 and HDAC6 by microscale thermophoresis analysis. MCC1381 decreased the expression of HDAC6, inversely correlated with the increase of acetylated HDAC6 substrates, acetylation p53 and α-tubulin. Furthermore, MCC1381 arrested the cell cycle at the G2/M phase, induced the generation of reactive oxygen species and collapse of the mitochondrial membrane potential. MCC1381 exhibited in vivo anti-cancer activity in xenografted zebrafish. Collectively, MCC1381 extended cytotoxicity towards P-gp-resistant leukemia cancer cells and may act as a pan-HDACs inhibitor, indicating that MCC1381 is a novel candidate for cancer therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Ciclobutanos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Leucemia/enzimología , Micotoxinas/farmacología , Animales , Apoptosis/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Ciclobutanos/química , Ciclobutanos/uso terapéutico , Relación Dosis-Respuesta a Droga , Células HCT116 , Células HEK293 , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas/química , Humanos , Leucemia/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Micotoxinas/uso terapéutico , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Pez Cebra
12.
Bioconjug Chem ; 32(7): 1223-1231, 2021 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-34170116

RESUMEN

Targeting vectors bound to a chelator represent a significant fraction of radiopharmaceuticals used nowadays for diagnostic and therapeutic purposes in nuclear medicine. The use of squaramides as coupling units for chelator and targeting vector helps to circumvent the disadvantages of several common coupling methods. This review gives an overview of the use of squaric acid diesters (SADE) as linking agents. It focuses on the conjugation of cyclic chelators, e.g., DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), as well as hybrid chelators like AAZTA5 (6-pentanoic acid-6-amino-1,4-diazepine tetracetic acid) or DATA5m (6-pentanoic acid-6-amino-1,4-diazapine-triacetate) to different targeting vectors, e.g., prostate-specific membrane antigen inhibitors (KuE; PSMAi), fibroblast activation protein inhibitors (FAPi), and monoclonal antibodies (mAbs). An overview of the synthesis, radiolabeling, and in vitro and in vivo behavior of the described structures is given. The unique properties of SADE enable a fast and simple conjugation of chelators to biomolecules, peptides, and small molecules under mild conditions. Furthermore, SA-containing conjugates could not only display similar in vitro characteristics in terms of binding affinity when compared to reference compounds, but may even induce beneficial effects on the pharmacokinetic properties of these radiopharmaceuticals.


Asunto(s)
Ciclobutanos/química , Neoplasias/diagnóstico por imagen , Radiofármacos/química , Ciclobutanos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Tomografía de Emisión de Positrones , Radiofármacos/uso terapéutico
13.
Medicine (Baltimore) ; 100(21): e26143, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34032765

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , COVID-19/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , SARS-CoV-2/inmunología , Neoplasias Gástricas/tratamiento farmacológico , Adulto , COVID-19/complicaciones , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Ciclobutanos/uso terapéutico , Docetaxel/uso terapéutico , Quimioterapia Combinada/métodos , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/inmunología , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Sorafenib/uso terapéutico , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/inmunología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Tratamiento Farmacológico de COVID-19
14.
Rheumatology (Oxford) ; 60(11): 5089-5097, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33693494

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.


Asunto(s)
Ciclobutanos/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Transportadores de Anión Orgánico/antagonistas & inhibidores , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Quinolinas/uso terapéutico , Adolescente , Adulto , Anciano , Ciclobutanos/farmacología , Método Doble Ciego , Femenino , Humanos , Enfermedades Renales/inducido químicamente , Masculino , Persona de Mediana Edad , Quinolinas/farmacología , Resultado del Tratamiento , Adulto Joven
15.
Dermatol Ther ; 34(1): e14726, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33377267

RESUMEN

Squaric acid dibutyl ester (SADBE) as topical immunotherapy is a good alternative in patients with refractory alopecia areata. In this study, we aimed to evaluate the effectiveness of SADBE treatment in alopecia areata (AA) and alopecia totalis/alopecia universalis (AT/AU) patients and determine the prognostic factors affecting treatment response. Data obtained from 34 (AA/AT/AU) patients treated with SADBE were analyzed retrospectively. Of the 34 patients, 16 (47.1%) were female and 18 (52.9%) were male. Sufficient responses were obtained in 19 (55.9%) patients. About 9 of the 19 patients (47.4%) with sufficient response reached a cosmetically acceptable level. As the severity of disease subsided, response to treatment increased. A better response was obtained when the disease onset in the spring and winter. Patients with a disease duration between 1 and 5 years responded better to the SADBE treatment compared to those with a disease shorter than 1 year and longer than 5 years. Severity of the disease, onset season of the disease, number of flares, duration of disease, and low levels of vitamin D in adult patients were observed to affect the SADBE response negatively.


Asunto(s)
Alopecia Areata/tratamiento farmacológico , Ciclobutanos , Adulto , Alopecia/diagnóstico , Alopecia/tratamiento farmacológico , Alopecia Areata/diagnóstico , Ciclobutanos/uso terapéutico , Femenino , Humanos , Inmunoterapia , Masculino , Estudios Retrospectivos
16.
J BUON ; 25(3): 1490-1496, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32862595

RESUMEN

PURPOSE: To compare the efficacy and safety of etoposide combined with lobaplatin or cisplatin in the first-line treatment of extensive-stage small cell lung cancer (SCLC). METHODS: A total of 98 extensive-stage SCLC patients treated at the Oncology Department from March 2015 to March 2017 were enrolled and divided into etoposide + lobaplatin group (EL group, n=49) and etoposide + cisplatin group (EP group, n=49) using a random number table. The clinical data of all patients were collected, and the short-term effective rate, changes in the levels of serum tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and neurone specific enolase (NSE) before and after chemotherapy and adverse reactions were compared between the two groups. Moreover, the patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded. RESULTS: In EL group and EP group, the level of serum NSE significantly declined after treatment compared with that before treatment, but the levels of serum CEA and CYFRA21-1 were not significantly decreased after chemotherapy compared with those before chemotherapy. The incidence rate of leukopenia, erythropenia and thrombocytopenia was 71.4%, 44.9% and 40.8%, respectively, in EL group, and 85.7%, 30.6% and 24.5%, respectively, in EP group, and the degree I-II decline was more common in both groups. The proportion of gastrointestinal reactions was 14.3% and 59.2%, respectively, in EL group and EP group, with significant difference between the two groups. During follow-up, the 1-year OS was 59.2% (29/49) and 51.9% (25/49), respectively, and the 2-year OS was 26.5% (13/49) and 20.4% (10/49), respectively, in EL group and EP group. The survival curves of were plotted using the Kaplan-Meier method and log-rank test showed no statistically significant differences in the OS and PFS between the two groups. CONCLUSIONS: The short-term efficacy of EL and EP regimens is equivalent in the first-line treatment of extensive-stage SCLC, both OS and PFS are similar, and the adverse reactions can be tolerated. The EL regimen produced mild gastrointestinal reactions, and is worthy of clinical popularization.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Ciclobutanos/uso terapéutico , Etopósido/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Epirrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Pulmonar de Células Pequeñas/metabolismo
17.
Cell Mol Biol (Noisy-le-grand) ; 66(3): 48-51, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32538746

RESUMEN

Alpha-fetoprotein (AFP) is a protein encoded by the AFP gene and normally produced by the fetus. The purpose of this study is to investigate the efficacy of lobaplatin in combination with 5-fluorouracil (5-FU) and doxorubicin on AFP and treatment of primary carcinoma of the liver by transhepatic arterial chemotherapy and embolization (TACE). Patients with primary carcinoma of the liver who took the TACE for treatment were enrolled in this study and divided randomly into the research group and the control group. Patients in the research group adopted the TACE in combination with lobaplatin, while those in the control group took cisplatin instead in combination with TACE. We compared the baseline data, hepatic indicators before treatment and after 1 month of treatment, efficacy and the incidence rates of adverse events after TACE between two groups. Differences in the baseline data, including Child-pugh grade, type of liver cirrhosis, KPS scores and AFP showed no statistical significance (P >0.05). Before the treatment, we identified no significant differences in the comparison of ALT, AST, TBiL and ALB between two groups (P >0.05), while significant differences emerged after treatment (P <0.05). Also, efficacy comparison revealed the significant difference between the two groups (P <0.05). After TACE, patients in the research group reported 1 case of nausea, 1 of vomiting and 1 of necrotic absorption fever, and those in the control group reported 3 cases of nausea, 5 of vomiting and 4 of necrotic absorption fever, with a significant difference in comparison of the incidence rates (P <0.05). TACE is a promising strategy for the treatment of primary carcinoma of the liver, while lobaplatin, as the 3rd generation of anti-tumor platinum-based drugs, is less toxic than cisplatin, but excels in efficacy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioembolización Terapéutica , Ciclobutanos/uso terapéutico , Doxorrubicina/uso terapéutico , Fluorouracilo/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , alfa-Fetoproteínas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Quimioembolización Terapéutica/efectos adversos , Ciclobutanos/farmacología , Doxorrubicina/farmacología , Femenino , Fluorouracilo/farmacología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/farmacología , Resultado del Tratamiento
18.
Urol Oncol ; 38(7): 636.e1-636.e6, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32317221

RESUMEN

OBJECTIVES: To evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment. METHODS: We analyzed available records of men who underwent a 18F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized. RESULTS: A total of 115 men underwent imaging with 18F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38. CONCLUSION: This study constitutes an early single institution series evaluating the use of 18F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans.


Asunto(s)
Ácidos Carboxílicos/uso terapéutico , Ciclobutanos/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico , Ácidos Carboxílicos/farmacología , Ciclobutanos/farmacología , Humanos , Masculino , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/sangre , Estudios Retrospectivos
19.
J Appl Toxicol ; 40(7): 947-964, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32072669

RESUMEN

Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.


Asunto(s)
Ciclobutanos/toxicidad , Ciclobutanos/uso terapéutico , Obesidad/tratamiento farmacológico , Fenómenos Fisiológicos Reproductivos/efectos de los fármacos , Rosuvastatina Cálcica/toxicidad , Rosuvastatina Cálcica/uso terapéutico , Testículo/efectos de los fármacos , Adulto , Animales , Humanos , Masculino , Modelos Animales , Ratas , Ratas Wistar
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