Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an ...antibody–drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020.
We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2−) HR+/HER2− mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.
Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% 95% confidence interval (CI), 19.5%–45.6%; 17 partial responses; median DOR was 8.7 months (95% CI 3.7–12.7), median PFS was 5.5 months (95% CI 3.6–7.6), and median OS was 12 months (95% CI 9.0–18.2).
SG shows encouraging activity in patients with pretreated HR+/HER2− mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).
ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552
•Safety and efficacy of sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, were evaluated in patients with hormone receptor-positive/epidermal growth factor receptor 2-negative metastatic breast cancer (mBC).•Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%).•In 54 patients who received SG (10 mg/kg) and at least two prior lines of therapy for mBC, the objective response rate was 31.5%.•Responses achieved with SG were durable, with a median duration of response of 8.7 months and a median progression-free survival of 5.5 months.•Clinical activity seen is encouraging in relation to current standard-of-care chemotherapies in this setting.
Microwave drying works on the volumetric heating concept promoted by electromagnetic radiation at 0.915 or 2.450 GHz. In this study, banana (Musa Cavendish) was taken as the sample and treated under ...microwave drying. The effect of two process variables, namely slice thickness (2, 3.5, and 5 mm) and microwave power (180 W, 360 W, and 540 W), were studied on drying kinetics and color kinetics. It was observed that the inverse variation relationship exists between drying time and microwave power level while drying time and slice thickness exhibited a direct variation relationship. A Computer Vision System (CVS) was developed to measure the color values of banana in CIELab space using an algorithm written in MATLAB software. Once the color parameters were obtained, they were fitted in First and Zero-order kinetic models. Both models were found to describe the color values adequately. This study concludes that microwave drying is a promising dehydration technique for banana drying that reduces the significant time of drying. Application of CVS is an excellent approach to measure the surface color of banana.
Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter ...trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously.
Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer.
In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR).
SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.
•Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate with a hydrolyzable linker and an SN-38 payload.•The most frequent treatment-related adverse events (TRAEs) were nausea, diarrhea, neutropenia, alopecia, and fatigue.•Grade ≥3 TRAEs were infrequent except for treatment-related grade ≥3 neutropenia; discontinuation due to AEs was 8.3%.•AEs with SG parallel those of chemotherapy and can be managed with proactive intervention per established guidelines.•Objective response rates, coupled with disease control, are apparent across small disease cohorts, warranting further study.
This work uses numerical simulations of a thulium-doped optical fiber amplifier to predict various performance characteristics such as peak temperatures, expected output powers and efficiencies, ...presence of amplified spontaneous emission (ASE), and transverse mode instability (TMI) onset power thresholds. Single- and two-tone configurations are studied. In the latter case, the two laser sources are separated in frequency by the amount that corresponds to the peak Raman gain, and a few seed ratios at various total seed powers are examined. The goal is to provide the field with pertinent information on what is feasible for this type of amplifier.
The main focus of this study was to develop and calibrate a computerized image analysis system in order to measure the color of banana (
Musa Cavendish
) under microwave treatment. Bananas were cut ...into 2 mm slice thickness and dried at two different microwave power level; 540 W and 180 W. An algorithmic was developed which converted RGB color value from a color image into CIE L*a*b* values very well (Error
L*
= 2.163%, Error
a*
= 4.458%, Error
b*
= 5.224%). Once the calibration is completed, it was applied to measure the color change in the banana slice during drying. The value of L* decreased from 89.01 to 71.17 and from 82.60 to 72.53 for both microwave treated samples suggesting browning is taking place during the drying operation. The value of a* increased from − 0.80 to 11.50 and from − 3.90 to 5.18 for 540 and 180 W microwave treated banana slices respectively suggesting tendency of redness increased. The same type of increment was observed for b* value. It changed from 36.46 to 60.51 and 34.02 to 72.82 for 540 and 180 W microwave treated banana slices, respectively. Artificial Neural Network (ANN) modeling was used for prediction of the developed CVS’s values.
The dimension of biomolecules is of few nanometers, so the biomolecular devices ought to be of that range so a better understanding about the performance of the electronic biomolecular devices can be ...obtained at nanoscale. Development of optical biomolecular device is a new move towards revolution of nano-bioelectronics. Optical biosensor is one of such nano-biomolecular devices that has a potential to pave a new dimension of research and device fabrication in the field of optical and biomedical fields. This paper is a very small report about optical biosensor and its development and importance in various fields.
Cellular therapies, including chimeric antigen receptor T cell therapies (CAR-T), while generally successful in hematologic malignancies, face substantial challenges against solid tumors such as ...glioblastoma (GBM) due to rapid growth, antigen heterogeneity, and inadequate depth of response to cytoreductive and immune therapies, We have previously shown that GBM constitutively express stress associated NKG2D ligands (NKG2DL) recognized by gamma delta (γδ) T cells, a minor lymphocyte subset that innately recognize target molecules via the γδ T cell receptor (TCR), NKG2D, and multiple other mechanisms. Given that NKG2DL expression is often insufficient on GBM cells to elicit a meaningful response to γδ T cell immunotherapy, we then demonstrated that NKG2DL expression can be transiently upregulated by activation of the DNA damage response (DDR) pathway using alkylating agents such as Temozolomide (TMZ). TMZ, however, is also toxic to γδ T cells. Using a p140K/MGMT lentivector, which confers resistance to TMZ by expression of O(6)-methylguanine-DNA-methyltransferase (MGMT), we genetically engineered γδ T cells that maintain full effector function in the presence of therapeutic doses of TMZ. We then validated a therapeutic system that we termed Drug Resistance Immunotherapy (DRI) that combines a standard regimen of TMZ concomitantly with simultaneous intracranial infusion of TMZ-resistant γδ T cells in a first-in-human Phase I clinical trial (NCT04165941). This manuscript will discuss DRI as a rational therapeutic approach to newly diagnosed GBM and the importance of repeated administration of DRI in combination with the standard-of-care Stupp regimen in patients with stable minimal residual disease.
Electromagnetic wave propagation in optical fiber amplifiers obeys Maxwell equations. Using coupled mode theory, the full Maxwell system within an optical fiber amplifier is reduced to a simpler ...model. The simpler model is made more efficient through a new scale model, referred to as an equivalent short fiber, which captures some of the essential characteristics of a longer fiber. The equivalent short fiber can be viewed as a fiber made using artificial (unphysical) material properties that in some sense compensates for its reduced length. The computations can be accelerated by a factor approximately equal to the ratio of the original length to the reduced length of the equivalent fiber. Computations using models of two commercially available fibers – one doped with ytterbium, and the other with thulium – show the practical utility of the concept. Extensive numerical studies are conducted to assess when the equivalent short fiber model is useful and when it is not.
•Equivalent short fibers with artificial parameters can mimic longer real fibers.•Simulation of fiber amplifier gain is accelerated by equivalent short fibers.•Gain computations of Yb and Tm doped fibers completed hundred times faster.
The suitability of a grinder based on their performance, fenugreek and black pepper seeds were ground under ambient and cryogenic grinding condition with the help of rotor, ball, hammer and pin ...mills. Rotor, hammer and pin mills were found to be good for small scale grinding at a feed rate of 22.5gmin−1 under ambient conditions and at 24.5gmin−1 for cryogenic grinding (continuous process) whereas the ball mill could be used for a lower feed rate of 1.56gmin−1 under ambient grinding; and 2.08gmin−1 under cryogenic grinding (batch processes). Time taken in grinding an equal amount of sample to a definite size in various grinders was found to be in the order: ball mill>rotor mill>pin mill>hammer mill; order of feed rate: hammer mill>rotor mill>pin mill>ball mill; order of power consumptions: pin mill>hammer mill>rotor mill>ball mill; and order of surface area created: rotor mill>hammer mill>pin mill>ball mill. Out of the above selected grinders, the rotor mill was found to be the most suitable for grinding fenugreek and black pepper spices. Power consumption was found to be increasing with an increasing specific surface area. This study will be useful for food process industries while considering spice-grinding applications; and also in academic field to understand suitability of grinders, their grinding mechanism.
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•Parameters were determined for selection of better grinder for spices grinding.•Highlights the grinding mechanism of Rotor, Hammer, Ball and Pin mills.•Ambient and cryogenic grinding of fenugreek and pepper suggests a suitable grinder.•This comparative evaluation pin point the drawbacks of ambient grinding.
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