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1.
Cureus ; 16(6): e63353, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39077250

RESUMEN

Stevens-Johnson Syndrome (SJS) constitutes a rather uncommon, and rarely fatal hypersensitivity reaction that primarily impacts the skin and mucous membranes and in certain cases may be attributed to drug administration. The aim of this article is to present a case of etoricoxib-induced SJS in a 46-year-old, female patient. The patient presented herself, as a medical emergency, to the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, reporting pain, especially acute pain while eating certain foods, discomfort, dysphagia, and a wound in the left half of the hard palate. The clinical examination revealed a broad ulcer, in the left half of the hard palate as well as multiple ulcerations and erosions in the upper and lower lip. Her medical history was clear; however, the patient mentioned to have received etoricoxib, due to severe back pain, one day prior to our clinical examination. The patient received methylprednisolone 16 mg, twice per day, for two days, followed by methylprednisolone 8 mg, twice per day, for two more days. Her symptoms resigned and since the connection between etoricoxib and SJS was established, the patient was advised to avoid etoricoxib and be wary of adverse effects, when taking drugs especially non-steroidal anti-inflammatory medication. This is one of the first case reports in the literature, linking etoricoxib administration with the emergence of SJS, highlighting the importance of pharmacovigilance. The up-to-date registration of drug-induced adverse effects is of immense importance to protect future patients. SJS does not have a defined treatment strategy. Therefore, most patients are given supportive care and symptomatic treatment, which most commonly involves corticosteroids and antivirals such as acyclovir.

2.
Invest New Drugs ; 38(1): 181-193, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31650446

RESUMEN

Epithelial ovarian cancer (EOC) accounts for nearly 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery and neo (adjuvant) platinum-based chemotherapy. Relapse of advanced high grade serous ovarian cancer (HGSOC) is related to the development of drug resistance. A defective DNA damage response is a defining hallmark of HGSOC. Poly (ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in breast cancer gene (BRCA1 or BRCA2) mutation carriers. Apart from inducing synthetic lethality, PARP inhibitors have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes. This "PARP trapping" potentiates synergism between PARP inhibition and both alkylating agents and platinum-based chemotherapy. However, there are remarkable differences in the ability of PARP inhibitors to trap PARP, based on the size and structure of each separate molecule. Since monotherapy with PARP inhibitors is unlikely to induce cancer cell death in BRCA-proficient tumors, the efficacy of PARP inhibitors could be potentially optimized when combined with DNA-damaging agents, or with molecular targeted agents that also impair mechanisms of DNA repair. Olaparib, rucaparib, and niraparib have all obtained US Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approval in ovarian cancer in different settings. Veliparib does not yet have an approved label; nevertheless, there are currently promising results available in preclinical and early clinical settings. This comprehensive review summarizes the mechanism of action of veliparib and provides an overview of its early and ongoing clinical investigations.


Asunto(s)
Bencimidazoles/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Femenino , Humanos , Pronóstico
3.
Ann Transl Med ; 8(24): 1707, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33490219

RESUMEN

High-grade serous ovarian carcinoma (HGSOC) is a leading cause of mortality among women worldwide. Currently, there is no clear consensus over the regime these patients should receive. The main two options are upfront debulking surgery with adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval debulking surgery (IDS). The former approach is proposed to be accompanied by lower chemoresistance rates but could lead to severe surgical comorbidities and lower quality of life (QoL). Optimizing patient's selection for upfront debulking surgery might offer higher progression-free and overall survival rates. Further studies need to be conducted in order to elucidate the predictive factors, which are favorable for patients undergoing upfront debulking surgery in cases of high-grade serous ovarian cancer.

4.
Diagnostics (Basel) ; 9(2)2019 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-31109041

RESUMEN

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance.

5.
Crit Rev Oncol Hematol ; 134: 46-55, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30771873

RESUMEN

Ovarian carcinosarcoma (OCS) constitute uncommon malignancies accounting for only 1-4% of ovarian cancers. Patients more often present with advanced stage disease and symptoms similar to those of epithelial ovarian cancers (EOC). Optimal tumor cytoreduction appears to be an important determinant of survival. Platinum-based chemotherapy remains the most commonly employed adjuvant treatment. The uncertain origin and poor prognosis of OCS motivate determination of the molecular basis of carcinosarcomas aggressive behavior in the hope of developing novel and effective treatment modalities. The present review summarizes the current knowledge on the epidemiology, pathology, prognostic factors, clinical presentation, and therapeutic interventions including future potential therapeutic targets.


Asunto(s)
Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Femenino , Humanos , Pronóstico
6.
J Pers Med ; 9(1)2019 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-30736475

RESUMEN

Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments.

7.
Anticancer Res ; 38(10): 5589-5597, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30275176

RESUMEN

Ewing's sarcoma (ES) of the spine with cord or radicular compression as an initial sign is infrequent. It is unclear, in alleviating a neurological deficit, whether decompressive laminectomy is preferred over chemotherapy. Herein, a literature review of the treatment approaches to the primary or metastatic ES of the spine has been performed. Collected data included clinical features of the patients, treatment, and outcome. There are reported 69 cases with initial presentation of cord or radicular compression of spinal cord, arising from primary or metastatic ES, treated either with initial chemotherapy and/or radiotherapy (RT) (33.33%, n=23), or decompressive surgery (66.66%, n=46). The median age at diagnosis was 17.95 years old (range=0.06-60), and 38 patients (55.07%) were male. Eighteen (78.26%) were initially treated with chemotherapy combined with RT, whereas 3 (13.04%) were managed with RT alone. One patient (4.35%) received only corticosteroids, while there are not available data for the treatment of another one (4.35%). The remaining 46 patients (66.66%) were initially treated with decompressive surgery. Among them, 40 (57.97%) received postoperative chemotherapy, RT or combined modality therapy, whereas 6 patients (8.69%) were not treated adjuvantly. Sixteen out of 23 patients (69.6%) treated with systemic therapy, and 37 from 46 (80.43%) of those managed with decompressive laminectomy were still alive at a mean follow-up period of 2.11 years (range=0.16-6) and 3.45 years (range=0.16-26.08), respectively. To summarize, spinal resection and reconstruction followed by adjuvant treatment reduce the risk of local recurrence, and improve long-term survival. However, ES of the spine is not a distinct clinical entity and can be either managed with chemotherapy and/or RT, similarly to other localization.


Asunto(s)
Neoplasias Óseas/cirugía , Sarcoma de Ewing/cirugía , Neoplasias de la Columna Vertebral/cirugía , Neoplasias Óseas/terapia , Terapia Combinada , Humanos , Pronóstico , Sarcoma de Ewing/terapia , Compresión de la Médula Espinal , Neoplasias de la Columna Vertebral/terapia
8.
Anticancer Res ; 38(9): 4987-4997, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30194142

RESUMEN

Malignant spinal cord compression (MSCC) is one of the most devastating complications of cancer. Patients often present with a history of progressive pain, paralysis, sensory loss, progressive spinal deformity, and loss of sphincter control. It is an emergency that requires rapid decision making on the part of several specialists, given the risk of permanent spinal cord injury or death. The goals of treatment in spinal metastases are pain control and improvement of neurological function in order to achieve better quality of life (QoL). The standard of care in most cases is rapid initiation of corticosteroids in combination with either surgical decompression in case of an operable candidate, followed by radiation therapy (RT) or RT alone. Surgery is associated with improved outcomes, but is not appropriate for many patients presenting with advanced symptoms of MSCC, such as paralysis, or those with a poor performance status, or cachexic state, as well as altered mental conditions, co-morbidities, surgical risks, and limited life expectancy. On the other hand, aggressive surgical treatment and post-operative RT is advocated for those with more favorable prognosis, or who are expected to have higher neurological recovery potential. Many candidates may require for combined anterior and posterior approaches to effectively deal with the compressive pathology and stabilize the spine. Most patients are presently treated by primary RT, given with the aim of improving function and symptom management. However, there is still debate regarding the most appropriate RT schedule. Rehabilitation can serve to relieve symptoms, QoL, enhance functional independence, and prevent further complications. Ambulatory status has been found to be an important prognostic factor for patients with MSCC.


Asunto(s)
Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/terapia , Neoplasias de la Médula Espinal/secundario , Neoplasias de la Médula Espinal/terapia , Corticoesteroides/uso terapéutico , Anciano , Ensayos Clínicos como Asunto , Descompresión Quirúrgica , Humanos , Manejo del Dolor , Cuidados Paliativos , Calidad de Vida , Radioterapia , Compresión de la Médula Espinal/complicaciones , Compresión de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/diagnóstico por imagen , Nivel de Atención
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