Astha Bhatia

BACKGROUND: Different plant parts of Roylea cinerea (D. Don) Baill. (Lamiaceae), Clematis grata Wall. (Ranunculaceae), Cornus capitata Wall. (Cornaceae) are traditionally used in the management of diabetes and various other diseases. METHOD: The air-dried plant parts from different plants were coarsely powdered and macerated in methanol to obtain their crude extracts. The crude extracts were evaluated for their α-glucosidase inhibitory activity. On the basis of results obtained, the methanolic crude extract of Cornus capitata Wall. was further sequentially fractionated in hexane, diethyl ether, ethyl acetate, n-butanol. Fractions obtained were also evaluated for their α-glucosidase inhibitory potential. The kinetic study was performed using Lineweaver Burk plot to evaluate the type of inhibition. Furthermore, in silico analysis was also carried with active sites of the enzyme (PDB ID: 3WY1) using Autodock4. RESULTS: 50 μg/mL). Kinetic analysis indicated that Vmax and Km were increased indicating a competitive type of inhibition. In docking studies, among different constituents known in this plant, betulinic acid showed minimum binding energy (- 10.21 kcal/mol). The kinetic and docking studies have strengthened the observation made in the present study regarding the α-glucosidase inhibitory activity of Cornus capitata. CONCLUSION: The study provided partial evidence for pharmacological basis regarding clinical applications of Cornus capitata in the treatment of diabetes suggesting it to be a suitable candidate for the treatment of postprandial hyperglycemia.

PURPOSE: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3. METHODS: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety. RESULTS: Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%). CONCLUSION: SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

434 Background: Checkpoint inhibitors (CPIs) are standard therapy for pts with mUC after PLT-based regimens, with limited long-term disease control. SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) via a proprietary hydrolyzable linker. In the TROPHY-U-01 registrational phase 2 trial, SG monotherapy demonstrated significant activity and manageable safety in pts with mUC who progressed after prior PLT-based chemotherapy and CPI, with 27% objective response rate (ORR) and median overall survival of 11 months (Tagawa, et al. J Clin Oncol. 2021). Here, we present interim efficacy and safety results of combining SG with Pembro as 2nd-line therapy in CPI-naive pts with mUC who progressed after PLT-based chemotherapy (cohort 3). Methods: TROPHY-U-01 is a multicohort, open-label, global phase 2 trial. Eligible pts had measurable disease, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and creatinine clearance ≥30 mL/min. The recommended phase 2 dose (RP2D) was determined during a 10-pt safety lead-in, and additional pts were enrolled at the RP2D in a Simon 2-stage design. Primary endpoint: ORR by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Key secondary endpoints: investigator-assessed ORR, clinical benefit rate [CBR; complete response (CR) + partial response (PR) + stable disease], progression-free survival (PFS), and safety. Results: At the time of data cutoff, 41 pts received at least a dose of SG at the RP2D (10 mg/kg). Of these 41 pts, median (range) age was 67y (46–86), 83% men, 61% ECOG PS 1, 76% had ≥1 Bellmunt risk factor, and median (range) number of prior anticancer regimens was 1 (1–3). At a median follow-up of 5.8 mo, the investigator-assessed ORR was 34% (95% CI, 20.1–50.6; 1 CR; 13 PR); CBR was 44% (95% CI, 28.5–60.3); 6-mo PFS rate was 47%. Median time to response was 2.0 mo (95% CI, 1.3–2.8). Most common treatment-emergent adverse events (TEAEs) were diarrhea (76%), nausea (59%), anemia (56%), neutropenia (44%), and asthenia (41%). Treatment-related grade ≥3 AEs occurred in 59% of pts. Key grade ≥3 TEAEs of any cause included diarrhea (24%), anemia (20%), febrile neutropenia (10%), fatigue (7%), and asthenia (5%). Two pts discontinued treatment due to treatment-related AEs. No treatment-related death occurred. Conclusions: SG in combination with Pembro demonstrated encouraging ORR and CBR, with an overall manageable safety profile with no new safety signal in CPI-naive pts who progressed after prior PLT-based chemotherapy. The data support further evaluation of SG plus CPI in mUC. Limitations: small sample size, short follow-up, and lack of randomization. Biomarker evaluation is ongoing. Clinical trial information: NCT03547973.

Plants are valuable source of polysaccharides that make a large portion of our daily diet. These are natural polymers that are essential to sustain life. They provide high-value nutrition and positively help the immune system and improve the digestive properties. They also help in the elimination of toxic by-products from the human body. Polysaccharides and human health are inextricably linked and intertwined. These are also important components of the cell wall that provides its strength and integrity. Due to their indispensable role in human health, it is very important to know the different modifications and loss of nutritional value during the processing of plant material. Nowadays, these plant-based polysaccharides are used for diverse applications including wound dressing, drug delivery, laxative, cosmetic and pharmaceutical preparations. As an emerging area of plant-based medicines to reduce the side effects of synthetic sources, these polysaccharides are used to enhance the immunogenic response against a specific antigen. This review envisages some important polysaccharides (e.g. mucilages and gums, glycosamine glycans and chitin/chitosan) and their medical, cosmetic, and pharmaceutical applications, with emphasis on the relationship between their structure and function.Keywords: Polysaccharides; Nutrition; Health Functions; Cosmetics; Vaccine; Nutraceuticals