RESUMEN
BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the usual treatment choice, with data regarding pharmaceutical treatment being scarce. CASE REPORT A 74-year-old female patient was admitted to "Laikon" General Hospital of Athens, Greece presenting with acute kidney injury secondary to diarrhea. The ultrasound, CT, and abdominal MRI performed showed a 12×6×10 cm tumorous liver lesion. Biopsy of the lesion revealed loosely organized, mesenchymal tissue with spindle cells, and myxoid stroma. Immunochemistry was positive for SMA and b-catenin. Right hemicolectomy was performed with tumor-free surgical margins (R0 resection) and tamoxifen was initiated. Six months after the last MRI (3 months after the use of tamoxifen), a follow-up MRI was performed. The tumor had increased to 14.2×11×12.3 cm, and at the next follow-up it had grown to 20.3×19 cm maximal dimensions; no new metastases were found. The patient received sorafenib and pazopanib. Our patient had PFS with sorafenib for more than 2 years and remained in a good performance status (ECOG 1). For Pazopanid, the median PFS for this treatment option was 6.5 months. CONCLUSIONS The results were good and show a promising method for the treatment of this rare but severe malignancy.
Asunto(s)
Fibromatosis Agresiva , Neoplasias Hepáticas , Femenino , Humanos , Anciano , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/cirugía , Sorafenib , Tamoxifeno , Neoplasias Hepáticas/diagnóstico por imagenRESUMEN
Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.
Asunto(s)
Neoplasias Endometriales , Hipertermia Inducida , Neoplasias Peritoneales , Sarcoma , Neoplasias Uterinas , Femenino , Humanos , Terapia Combinada , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Endometriales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma/tratamiento farmacológico , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.
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Cannabinoides , Neoplasias Pancreáticas , Apoptosis , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Endocannabinoides/metabolismo , Endocannabinoides/farmacología , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Receptores de Cannabinoides/metabolismoRESUMEN
Cachexia is a major characteristic of multiple non-malignant diseases, advanced and metastatic cancers and it is highly prevalent in pancreatic cancer, affecting almost 70-80% of the patients. Cancer cachexia is a multifactorial condition accompanied by compromised appetite and changes in body composition, i.e., loss of fat. It is associated with lower effectiveness of treatment, compromised quality of life, and higher mortality. Understanding the complex pathways underlying the pathophysiology of cancer cachexia, new therapeutic targets will be unraveled. The interplay between tumor and host factors, such as cytokines, holds a central role in cachexia pathophysiology. Cytokines are possibly responsible for anorexia, hypermetabolism, muscle proteolysis, and apoptosis. In particular, cachexia in pancreatic cancer might be the result of the surgical removal of pancreas parts. In recent years, many studies have been carried out to identify an effective treatment algorithm for cachexia. Choosing the most appropriate treatment, the clinical effect and the risk of adverse effects should be taken under consideration. The purpose of this review is to highlight the pathophysiological mechanisms as well as the current ways of cachexia treatment in the pharmaceutical and the nutrition field.
Asunto(s)
Caquexia/metabolismo , Neoplasias Pancreáticas/metabolismo , Tejido Adiposo/metabolismo , Corticoesteroides/uso terapéutico , Animales , Anorexia , Antiinflamatorios/uso terapéutico , Apetito , Composición Corporal , Caquexia/tratamiento farmacológico , Citocinas/metabolismo , Metabolismo Energético , Humanos , Hipotálamo/fisiología , Inflamación , Insulina/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos , Estado Nutricional , Neoplasias Pancreáticas/tratamiento farmacológico , Progesterona/uso terapéutico , Calidad de Vida , Zinc/deficiencia , Neoplasias PancreáticasRESUMEN
Abstract Small molecules that inhibit angiogenesis are attractive drug candidates for cancer, retinopathies, and age-related macular degeneration. In vivo, phenotypic screening in zebrafish (Danio rerio) emerges as a powerful methodology to identify and optimize novel compounds with pharmacological activity. Zebrafish provides several advantages for in vivo phenotypic screens especially for angiogenesis, since it develops rapidly, externally, and does not rely on a functional cardiovascular system to survive for several days during development. In this study, we utilize a transgenic line that allows the noninvasive monitoring of angiogenesis at a cellular level. The inhibition of angiogenesis can be observed under a fluorescent stereoscope and quantified. To exemplify the versatility and robustness of the zebrafish screen, we have employed a series of 60 novel compounds that were designed based on a potent VEGFR2 inhibitor. Herein, we report their structure-based design, synthesis, and in vivo zebrafish screening for optimal activity, toxicity, and off-target effects, which revealed six reversible inhibitors of angiogenesis.