Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?

This article summarizes the immune mediated effect of chemotherapies, the biological and clinical features of new immunotherapies like checkpoint blockers and the rational to use these treatment in combinatio

La importancia del inglés en Educación Infantil. La vuelta al mundo como estrategia didáctica para desarrollar el aprendizaje de la lengua inglesa

El lenguaje es una virtud que nos permite estructurar nuestra mente y comunicarnos con el entorno, sin embargo, no existe un idioma universal, son muchas las lenguas y dialectos que habitan con nosotros. Para ello, debemos afrontar esta concurrencia y adentrarnos en el aprendizaje de otras lenguas además de la materna. ¿Por qué no hacerlo simultáneamente desde que somos pequeños? Por ello, considerando importante fomentar la curiosidad e interés en nuestros alumnos, desarrollo una estrategia de carácter innovador que permita llevar a las aulas un tema amplio para desarrollar en lengua inglesa.Grado en Educación Infanti

Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

<p>Abstract</p> <p>Background</p> <p>The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.</p> <p>Methods</p> <p>Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured <it>in vivo </it>(tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and <it>in vitro </it>(cytotoxicity on human ovarian cancer cells).</p> <p>Results</p> <p><it>In vitro</it>, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. <it>In vivo</it>, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.</p> <p>Conclusion</p> <p>Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.</p

High-pressure intrapleural chemotherapy: feasibility in the pig model.

International audienceABSTRACT: BACKGROUND: The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. METHODS: Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. RESULTS: The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. CONCLUSIONS: High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura

Carcinomatous Meningitis from Unknown Primary Carcinoma

Carcinomatous meningitis (CM) occurs in 3 to 8% of cancer patients. Patients present with a focal symptom, and multifocal signs are often found following neurological examination. The gold standard for diagnosis remains the demonstration of carcinomatous cells in the cerebrospinal fluid on cytopathological examination. Despite the poor prognosis, palliative treatment could improve quality of life and, in some cases, overall survival. We report on a patient who presented with vertigo, tinnitus and left-sided hearing loss followed by progressive diffuse facial nerve paralysis. Lumbar cerebrospinal fluid confirmed the diagnosis of CM. However, no primary tumor was discovered, even after multiple invasive investigations. This is the first reported case in the English-language medical literature of CM resulting from a carcinoma of unknown primary origin

Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?

Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their clinical relevance, the biological and clinical features of immune checkpoint blockers and finally, the preclinical and clinical rationale for novel therapeutic strategies combining anticancer agents and immune checkpoint blockers

Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer

Background: Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC). Methods and Findings: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. Conclusions: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression

Patterns of Bone Failure in Localized Prostate Cancer Previously Irradiated: The Preventive Role of External Radiotherapy on Pelvic Bone Metastases

Introduction: External beam radiation therapy (EBRT) can cure localized prostate cancer (PCa) by sterilizing cancer cells in the prostate gland and surrounding tissues at risk of microscopic dissemination. We hypothesized that pelvic EBRT for localized PCa might have an unexpected prophylactic impact on the occurrence of pelvic bone metastases.Material and Methods: We reviewed the data of 332 metastatic PCa patients. We examined associations between the number (≤5 vs. &gt;5) and the location of bone metastases (in-field vs. out-of-field), which occurred at first relapse, and a previous history of EBRT for PCa (EBRT vs. No-EBRT).Results: One hundred and ten patients M0 at baseline were eligible. Fifty-six patients (51%) were in the No-EBRT group, and 54 patients (49%) in the EBRT group. The proportion of patients who developed &gt;5 bone metastases in the bony pelvis was higher in the No-EBRT group vs. the EBRT group: 10 patients (18%) vs. 2 patients (4%), respectively (p = 0.02). By multivariate analysis EBRT was associated with a lesser occurrence of patients who had &gt;5 bone metastases in the bony pelvis (OR = 0.17 [95%CI, 0.04–0.87], p = 0.03). Time to occurrence of bone metastases ≥5 years (OR = 0.10 [95%CI, 0.05–0.19], p &lt; 0.01), prior curative prostate treatment (OR = 0.58 [95%CI, 0.36–0.91], p = 0.02), &gt;5 bone metastases in bony pelvis (OR = 2.61 [95%CI, 1.28–5.31], p &lt; 0.01), &gt;5 bone metastases out of bony pelvis (OR = 1.73 [95%CI, 1.09–2.76], p = 0.02) were all predictive of overall survival.Conclusion: Previous pelvic EBRT for PCa is associated with a lower number of pelvic bone metastases, which is associated with better overall survival