Synergistic effects of radiotherapy and targeted immunotherapy in improving tumor treatment efficacy: a review

Radiotherapy (RT), unlike chemotherapy, is one of the most routinely used and effective genotoxic and immune response inducing cancer therapies with an advantage of reduced side effects. However, cancer can relapse after RT owing to multiple factors, including acquired tumor resistance, immune suppressive microenvironment buildup, increased DNA repair, thus favoring tumor metastasis. Efforts to mitigate these undesirable effects have drawn interest in combining RT with immunotherapy, particularly the use of immune checkpoint inhibitors, to tilt the pre-existing tumor stromal microenvironment into long-lasting therapy-induced antitumor immunity at multiple metastatic sites (abscopal effects). This multimodal therapeutic strategy can alleviate the increased T cell priming and decrease tumor growth and metastasis, thus emerging as a significant approach to sustain as long-term antitumor immunity. To understand more about this synergism, a detailed cellular mechanism underlying the dynamic interaction between tumor and immune cells within the irradiated tumor microenvironment needs to be explored. Hence, in the present review, we have attempted to evaluate various RT-inducible immune factors, which can be targeted by immunotherapy and provide detailed explanation to optimally maximize their synergy with immunotherapy for long-lasting antitumor immunity. Moreover, we have critically assessed various combinatorial approaches along with their challenges and described strategies to modify them in addition to providing approaches for optimal synergistic effects of the combination (AU)

Study of pharmacological properties of the methanolic extract of Dichrostachys cinerea bark (L.) Wight et Arn (Leguminosae) in isolated myometrium from pregnant rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of medicinal plants in Gabon contributes widely to the primary health care of the people of this area of Central Africa. This paper investigates the pharmacological properties of Dichrostachys cinerea, the plant barks are traditionally used by Gabonese and Ivorian populations to treat bronchial asthma, rheumatism, and other various diseases. Although D. cinerea barks have been reported to be used by population to facilitate childbirth, to the best of our knowledge no scientific evidence has been published. AIM OF STUDY: In the present study, we investigated the pharmacological properties of D. cinerea methanolic extract, on isolated uterine smooth muscle and compared its effects to those of oxytocin, which is used by obstetricians to facilitate childbirth. We also explored the possible mechanism pathways of the in vitro uterine contraction induced by D. cinerea. MATERIALS AND METHODS: The effects of different concentrations (3.2µg/ml, 16µg/ml, 80µg/ml, 400µg/ml, and 2mg/ml) of the methanolic extract of D. cinerea on isolated strips of the uteri of pregnant rats were studied. These effects were compared to those of oxytocin (8.4×10(-5)µg/ml, 8.4×10(-4)µg/ml, 8.4×10(-3)µg/ml, 8.4×10(-2)µg/ml). The EC (50) and E (max) was determined graphically and statistically analysed using one-way ANOVA and Dunnett post hoc test. RESULTS: Cumulative concentrations of D. cinerea have caused rise in the contractile force of the uterine fragments that were isolated from the pregnant rats, as seen with oxytocin concentrations. We observed contractions amplitude of 30.41mN (12%) at 80µg/ml and amplitude of 39.68mN (14.17%) at 400µg/ml for D. cinerea. In parallel, oxytocin concentration of 8.4×10(-3)µg/ml induced contractions of 45.82mN with the highest concentration (8.4×10(-2)µg/ml) that induced contractions of 55.82mN. CONCLUSIONS: Our results revealed that D. cinerea increased the contractile force and the frequency of muscle contractions. These findings support the use of D. cinerea to facilitate childbirth, as it has been used in traditional medicine.

Phytochemical screening and cytotoxicity studies of Chrysophyllum pruniforme Pierre ex Engl. barks.

BACKGROUND: Chrysophyllum pruniforme of family sapotaceae is a plant used in traditional medicine in Gabon. MATERIALS AND METHODS: In this study, C. pruniforme barks were subjected to phytochemical screening and cytotoxicity investigations. Different concentrations of aqueous and total phenolic extract were tested on mice and on human erythrocytes. RESULTS: Phytochemical screening of C. pruniforme barks revealed the presence of flavonoids, saponins, and tannins, reducing sugars, polyphenols and traces of anthraquinones. When tested in vitro, aqueous and the phenolic extracts showed hemolytic activities on human erythrocytes with phenolic compounds being more cytotoxic than aqueous extracts. In vivo study of toxicity, allowed to determine the LD50 at 90 mg/kg for the doses of 50, 150 and 250 mg/kg of body weight. CONCLUSION: These data indicate in one hand that C. pruniforme is rich in phenolic compounds and that the aqueous and total phenolic extracts could be considered as toxic for mice and maybe potentially toxic to humans in the other hand.