RESUMEN
Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a unilateral microinjection of CoCl2 into the ventral hippocampus (vHPC) induced hypoxic insult and led to anxiety-related behaviors and deficit sociability in mice. NRG1 treatment significantly alleviated the CoCl2-induced increase of hypoxic-related molecules and behavioral abnormalities. Furthermore, NRG1 reduced the CoCl2-induced neuroinflammation and neuronal deficits in the vHPC or primary hippocampal neurons in mice. Collectively, these results suggest that NRG1 ameliorates hypoxia by alleviating synaptic deficits and behavioral abnormalities of the CoCl2-induced vHPC hypoxic model.
Asunto(s)
Neurregulina-1 , Enfermedades Neuroinflamatorias , Ratones , Animales , Neurregulina-1/metabolismo , Hipocampo/metabolismo , Conducta Social , Ansiedad/tratamiento farmacológicoRESUMEN
ABSTRACT: Despite anatomical proximity, prostatic adenocarcinoma with rectal invasion is rare. We describe a case of prostate cancer invading the anal sphincter, treated with radiation therapy (RT). A 78-year-old patient underwent definitive radiotherapy in 2018 because of poorly differentiated adenocarcinoma, Gleason 4 + 3 (7). The initial stage was mrT4N0 on magnetic resonance imaging (MRI) images. The pre-treatment prostate-specific antigen level was 142 ng/mL, and the patient was subjected to androgen deprivation therapy. RT was performed using volumetric modulated arc therapy (VMAT) and a dose of 76 Gy in 38 fractions. After 2 months, MRI showed a complete response. During RT, toxicity was limited to mild gastro-intestinal and urologic symptoms. This report is the first to describe prostate cancer invasion of the anal sphincter and to extend to that condition the use of RT - already regarded as a useful treatment option for inoperable locally advanced high-risk prostate cancer (PC). This study suggests that VMAT can be a safe and effective treatment option for locally advanced high-risk PC patients.
Asunto(s)
Adenocarcinoma , Canal Anal , Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Humanos , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Anciano , Canal Anal/patología , Canal Anal/efectos de la radiación , Radioterapia de Intensidad Modulada/métodos , Adenocarcinoma/radioterapia , Adenocarcinoma/patología , Recto/patología , Recto/efectos de la radiación , Recto/diagnóstico por imagen , Invasividad Neoplásica , Imagen por Resonancia Magnética , Resultado del TratamientoRESUMEN
ABSTRACT: Electron beams represent an important treatment modality for providing an accurate dose of therapy to superficial cancers. This case reports important findings of dermal invasion in patients with extramammary Paget's disease (EMPD) using microscopic measurements and electron beam coverage. EMPD is a rare cutaneous adenocarcinoma generally arising in the anogenital region. Surgery is still a curable treatment option for patients with EMPD, whereas radiation therapy (RT) is an alternative for inoperable cases and is necessary in cases where surgery is not performed. This case report describes our experience and reviews the relevant literature on the feasibility of electron RT according to the dermal invasion length. An 80-year-old patient was diagnosed with EMPD and presented for definite radiation treatment. We observed no grade 3 toxicities during electron RT, and at the last follow-up visit, no signs of relapse were observed. There are no reports of electron irradiation as a feasible treatment option for EMPD considering the epidermal invasion length.
Asunto(s)
Enfermedad de Paget Extramamaria , Masculino , Humanos , Anciano de 80 o más Años , Enfermedad de Paget Extramamaria/diagnóstico , Escroto/patología , Electrones , Recurrencia Local de Neoplasia/patología , Pene/patologíaRESUMEN
Recently, several studies have demonstrated that low-dose radiation (LDR) therapy has positively impacts on the treatment of Alzheimer's disease (AD). LDR suppresses the production of pro-neuroinflammation molecules and improves cognitive function in AD. However, it is unclear whether direct exposure to LDR causes beneficial effects and what mechanism is involved in neuronal cells. In this study, we first determined the effect of high-dose radiation (HDR) alone on C6 cells and SH-SY5Y cells. We found that SH-SY5Y cells were more vulnerable than C6 cells to HDR. Moreover, in neuronal SH-SY5Y cells exposed to single or multiple LDR, N-type cells showed decreased cell viability with increasing radiation exposure time and frequency, but S-type cells were unaffected. Multiple LDR increased proapoptotic molecules such as p53, Bax and cleaved caspase-3, and decreased anti-apoptotic molecule (Bcl2). Multiple LDR also generated free radicals in neuronal SH-SY5Y cells. We detected a change in the expression of the neuronal cysteine transporter EAAC1. Pretreatment with N-acetylcysteine (NAC) rescued the increased in EAAC1 expression and the generation of ROS in neuronal SH-SY5Y cells after multiple LDR. Furthermore, we verified whether the increased in EAAC1 expression induces cell defense or cell death promotion signaling. We showed that transient overexpression of EAAC1 reduced the multiple LDR-induced p53 overexpression in neuronal SH-SY5Y cells. Our results indicate that neuronal cells can be injured by increased production of ROS not only by HDR but also by multiple LDR, which suggests that combination treatment with anti-free radical agents such as NAC may be useful in multiple LDR therapy.
Asunto(s)
Acetilcisteína , Neuroblastoma , Humanos , Acetilcisteína/farmacología , Acetilcisteína/metabolismo , Apoptosis , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , Neuroblastoma/radioterapia , Neuroblastoma/metabolismo , Estrés Oxidativo , Supervivencia CelularRESUMEN
Nasopharyngeal sarcomatoid carcinoma (SaCa) is extremely rare, and concurrent chemoradiation is the standard treatment for squamous cell-based nasopharyngeal cancer (NPC). This case report gives the first explanation of a nasopharyngeal SaCa patient treated with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB), which is an excellent treatment modality that leads to complete response for locally advanced NPC. A 70-year-old male presented with nasal obstruction, epistaxis, and right neck node enlargements. Examination revealed an extensive tumor of nasopharyngeal tumor extending into the nasal cavity and right parapharyngeal space with bilateral lymphadenopathy on positron emission tomography (PET)-computed tomography images of focal hypermetabolic bone lesion in C4 body (stage T3N2M1). An excisional biopsy of nasopharyngeal wall mass showed a SaCa. He received concurrent chemoradiation which was VMAT and systemic chemotherapy (cisplatin 60 mg). A dose of 70 Gy was delivered to the planning target volume (PTV70) (gross tumor volume plus margin 3-5 mm) and PTV59.4(a wider margin around high-risk clinical target volume, including the clivus and neck nodes) all given in 33 fractions. Radiological examination such as magnetic resonance imaging (MRI) and PET images at the completion of external beam therapy revealed questionable residual disease. Follow-up MRI scans 4 weeks after radiotherapy revealed a complete tumor response. VMAT with SIB can be an effective treatment option for SaCa of the advanced nasopharynx.
Asunto(s)
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Sarcoma/radioterapia , Anciano , Antineoplásicos/uso terapéutico , Quimioradioterapia , Cisplatino/uso terapéutico , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Inducción de Remisión , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Resultado del TratamientoRESUMEN
Kaposi's sarcoma (KS) is an uncommon neoplastic vascular disease. The standard treatment for localized classic KS lesions is surgical excision or radiation. Superficial skin lesions are generally treated with electrons or low-energy photon fields using boluses. Radiotherapy (RT) can be used for poor surgical candidates or when surgery is expected to result in a poor cosmetic or functional outcome. This study is the first to describe a case of KS of the toe and web treated with electron RT, which precisely targeted the irregular skin lesion with a markedly higher presided effective treatment. An electron field is often limited in its effectiveness to deliver a homogeneous dose in cases with irregular contours. Here, we report our successful experience using low-energy electron beam radiation to treat KS of the toe and web. The patient was a 78-year-old woman who was diagnosed with KS located on the first and second toe and web, based on radiology, pathology, and immunohistochemical examinations. KS was located on the left foot and measured more than 2.5 cm. No regional nodal or distant organ metastasis was observed. She was medically inoperable. RT was performed using a 6-MeV electron with a 0.5-cm bolus and a dose of 50 Gy delivered in 25 fractions. Follow-up computed tomography 2 months after RT revealed a complete tumor response. Toxicity was limited to mild skin desquamation during treatment. The patient remains alive and has shown no evidence of disease for 2 years. This study suggests that electron RT is a safe and effective treatment option for skin lesions located on the toe and web.
Asunto(s)
Electrones/uso terapéutico , Sarcoma de Kaposi/radioterapia , Neoplasias Cutáneas/radioterapia , Dedos del Pie/efectos de la radiación , Anciano , Femenino , Humanos , Inducción de Remisión , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Dedos del Pie/patología , Resultado del TratamientoRESUMEN
The purpose of this study was to establish intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans for synchronous bilateral breast cancer (SBBC) and to compare those plans with the previous treatment plans using 3D conformal radiation therapy (3DCRT). The differences among the treatments were also statistically compared regarding dosimetry distribution and treatment efficiency. The research was conducted with 10 SBBC patients. The study established IMRT (12 fields with a single isocenter) and VMAT (2 partial arcs with a single isocenter) treatment plans for SBBC patients and then compared those plans with 3DCRT (8 fields with multiple isocenters). The plans were evaluated based on a dose-volume histogram analysis. For planning target volumes (PTVs), the mean doses and the values of V95%, V105%, conformity index, and homogeneity index were reported. For the organs at risk, the analysis included the mean dose, maximum dose, and VXGy, depending on the organs (lungs, heart, and liver). To objectively evaluate the efficiency of the treatment plans, each plan's beam times, treatment times (including set-up time), and monitor units were compared. Tukey test and one-way analysis of variance were used to compare the PTV and organs at risk values of the 3 techniques. Additionally, the independent-samples t-test was used to compare the 2 techniques (IMRT and VMAT) based on the values of Rt. PTV and Lt. PTV (p < 0.05). For PTV dose distribution, IMRT showed increases of approximately 1.2% in Dmean and of approximately 5.7% in V95% dose distribution compared with 3DCRT. In comparison to VMAT, 3DCRT showed about 3.0% higher dose distribution in Dmean and V95%. IMRT was the best in terms of conformity index and homogeneity index (p < 0.05), whereas 3DCRT and VMAT did not significantly differ from each other. In terms of dose distribution on lungs, heart, and liver, the percentage of volume at high doses such as V30Gy and V40Gy was approximately 70% lower for IMRT and approximately 40% lower for VMAT than for 3DCRT. For distribution volumes of low doses such as V5% and V10%, that for 3DCRT was approximately 60% smaller than for IMRT and approximately 70% smaller than for VMAT. Comparison between IMRT and VMAT showed that the IMRT was superior in all distribution factors. VMAT showed better treatment efficiency than 3DCRT or IMRT. Among the SBBC radiotherapy treatment plans, IMRT was superior to 3DCRT and VMAT in terms of PTV dose distribution, whereas VMAT showed the most outstanding treatment efficiency.
Asunto(s)
Neoplasias de la Mama/radioterapia , Neoplasias Primarias Múltiples/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Femenino , Corazón/efectos de la radiación , Humanos , Hígado/efectos de la radiación , Pulmón/efectos de la radiación , Órganos en Riesgo , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversosRESUMEN
The purpose of this study was to analyze the dosimetric difference between intensity-modulated radiation therapy (IMRT) using 3 or 5 beams and multistatic field technique (MSF) in radiotherapy of the left breast. We made comparative analysis of two kinds of radiotherapy that can achieve improved dose homogeneity. First is a MSF that uses both major and small irradiation fields at the same time. The other is IMRT using 3 or 5 beams with an inverse planning system using multiple static multileaf collimators. We made treatment plans for 16 early left breast cancer patients who were randomly selected and had undergone breast conserving surgery and radiotherapy, and analyzed them in the dosimetric aspect. For the mean values of V(95) and dose homogeneity index, no statistically significant difference was observed among the three therapies. Extreme hot spots receiving >110% of prescribed dose were not found in any of the three methods. Using Tukey's test, IMRT showed a significantly larger increase in exposure dose to the ipsilateral lung and the heart than MSF in the low-dose area, but in the high-dose area, MSF showed a slight increase. To improve dose homogeneity, the application of MSF, which can be easily planned and applied more widely, is considered optimal as an alternative to IMRT for radiotherapy of early left breast cancer.