Antioxidant potential of crude extract, flavonoid-rich fractions, and a new compound from the seeds of Cordia dichotoma

The current study assessed the antioxidant activity of methanolic extract and different fractions of the seeds of Cordia dichotoma by 2,2-diphenyl-2-picrylhydrazyl hydrate method. Phytochemical screening of C. dichotoma seed extract was done using thin-layer chromatography technique and phytochemical methods. The percentage yield of secondary metabolites like alkaloids and saponins was also determined. The methanolic extract was subjected to isolation by Column Chromatography. Phytochemical screening revealed the presence of significant amounts of phenols and flavonoids in the extract. TLC analysis confirmed the presence of phytoconstituents with the application of derivatizing agents like aluminium chloride and anisaldehyde. Total phenolic and flavonoid contents obtained were 37.7 and 32.16% w/w, respectively. The crude seed extract of C. dichotoma showed inhibition at all concentrations in a dose-dependent manner. Maximum scavenging activity was exhibited by the methanolic extract with a low IC50 value. A new compound named Cordioside was also isolated from the same extract. The phytochemical screening of the seed extract showed the presence of rich amounts of phenolic compounds and flavonoids, which may be acting as the key factors responsible for the antioxidant activity. The results revealed that methanolic extract and the aqueous fraction of C. dichotoma seed possess a significant antioxidant activity

Antioxidant potential of crude extract, flavonoid-rich fractions, and a new compound from the seeds of Cordia dichotoma

437-44The current study assessed the antioxidant activity of methanolic extract and different fractions of the seeds of Cordia dichotoma by 2,2-diphenyl-2-picrylhydrazyl hydrate method. Phytochemical screening of C. dichotoma seed extract was done using thin-layer chromatography technique and phytochemical methods. The percentage yield of secondary metabolites like alkaloids and saponins was also determined. The methanolic extract was subjected to isolation by Column Chromatography. Phytochemical screening revealed the presence of significant amounts of phenols and flavonoids in the extract. TLC analysis confirmed the presence of phytoconstituents with the application of derivatizing agents like aluminium chloride and anisaldehyde. Total phenolic and flavonoid contents obtained were 37.7 and 32.16% w/w, respectively. The crude seed extract of C. dichotoma showed inhibition at all concentrations in a dose-dependent manner. Maximum scavenging activity was exhibited by the methanolic extract with a low IC50 value. A new compound named Cordioside was also isolated from the same extract. The phytochemical screening of the seed extract showed the presence of rich amounts of phenolic compounds and flavonoids, which may be acting as the key factors responsible for the antioxidant activity. The results revealed that methanolic extract and the aqueous fraction of C. dichotoma seed possess a significant antioxidant activity

Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.

OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes

Treg Depletion Inhibits Efficacy of Cancer Immunotherapy: Implications for Clinical Trials

Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients.Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs present in tumors, draining lymph nodes and spleen and improved long-term survival (50% of mice survived >150 days). No improvement in survival was observed when Tregs were depleted 24 days after tumor implantation, suggesting that tumor burden is an important factor for determining efficacy of Treg depletion in clinical trials. In a T cell dependent model of brain tumor regression elicited by intratumoral delivery of adenoviral vectors (Ad) expressing Fms-like Tyrosine Kinase 3 ligand (Flt3L) and Herpes Simplex Type 1-Thymidine Kinase (TK) with ganciclovir (GCV), we demonstrate that administration of PC61 24 days after tumor implantation (7 days after treatment) inhibited T cell dependent tumor regression and long term survival. Further, depletion with PC61 completely inhibited clonal expansion of tumor antigen-specific T lymphocytes in response to the treatment.Our data demonstrate for the first time, that although Treg depletion inhibits the progression/eliminates GBM tumors, its efficacy is dependent on tumor burden. We conclude that this approach will be useful in a setting of minimal residual disease. Further, we also demonstrate that Treg depletion, using PC61 in combination with immunotherapy, inhibits clonal expansion of tumor antigen-specific T cells, suggesting that new, more specific targets to block Tregs will be necessary when used in combination with therapies that activate anti-tumor immunity

Model for in vivo progression of tumors based on co-evolving cell population and vasculature

With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure

Prophylactic Cefazolin Dosing and Surgical Site Infections: Does the Dose Matter in Obese Patients?

Background Most surgical prophylaxis guidelines recommend a 3-g cefazolin intravenous dose in patients weighing ≥ 120 kg. However, this recommendation is primarily based on pharmacokinetic studies rather than robust clinical evidence. This study aimed to compare the prevalence of surgical site infections (SSIs) in obese and non-obese patients (body mass index ≥ 30 kg/m2 and < 30 kg/m2), and those weighing ≥ 120 kg and < 120 kg, who received 2- g cefazolin preoperatively. Methods A retrospective case-control study was conducted in adult elective surgical patients. Patients receiving 2- g cefazolin were grouped as obese and non-obese, and by weight (≥ 120 kg or < 120 kg). The 90-day prevalence of SSI and potential contributing factors were investigated. Results We identified 152 obese (median 134 kg) and 152 non-obese control (median 73 kg) patients. Baseline characteristics were similar between groups, except for an increased prevalence in the obese group of diabetes (35.5% vs 13.2%; p < 0.001) and an American Society of Anaesthesiologists Score of 3 (61.8% vs 17.1%; p < 0.001). While not statistically significant, the prevalence of SSI in the obese group was almost double that in the non-obese group (8.6% vs 4.6%; p = 0.25) and in patients weighing ≥ 120 kg (n = 102) compared to those weighing < 120 kg (n = 202) (9.8% vs 5.0%; p = 0.17). Conclusion The prevalence of SSI was not significantly increased in obese patients, or those weighing ≥ 120 kg, who received cefazolin 2- g prophylactically; however, trends toward an increase were evident. Large-scale randomised trials are needed to examine whether a 2-g or 3-g cefazolin is adequate to prevent SSI in obese (and ≥ 120 kg) individuals