Biology subjects

Fath, M. A.

Publications and source records attributed to Fath, M. A..

3 recordsLinked to original sources

bioRxiv2024

Targeting CXCR4 with -Pentixather Significantly Increases Overall Survival in Small Cell Lung Cancer

IntroductionSmall cell lung cancer (SCLC) has a 7% 5-year overall survival. C-X-C chemokine receptor 4 (CXCR4), an attractive target for theranostic agents, is highly expressed in SCLCs, and can be targeted with pentixather using the theranostic pair 212Pb/203Pb. The hypothesis that [212Pb/203Pb]-pentixather can be used safely and effectively for imaging and therapy in SCLC in xenograft models was tested. ResultsSPECT/CT imaging and biodistribution studies of tumor bearing mice injected with [203Pb]-pentixather demonstrated CXCR4-dependent uptake in tumors and accumulation of radioligand in kidneys and livers. Dosimetry calculations estimated [212Pb]-pentixather uptake in tumor and normal tissue. [212Pb]-pentixather treatment (37-111 kBq/g) of SCLC xenografts (DMS273 and H69AR) significantly prolonged survival and delayed tumor growth. When NSG mice grafted with human hCD34+ bone marrow were treated with [212Pb]-pentixather (37-111 kBq/g), significant cytopenias were observed in peripheral blood complete blood counts (CBCs) at 13-18 days post treatment which resolved by day 28-31. Flow cytometry of bone marrow hematopeotic stem cells in these animals at day 28-31 demonstrated a significantly reduced frequency of the human hematopoietic marker CD45 (hCD45+) and reconstitution of the bone marrow with murine CD45+ (mCD45+) lineages. Conclusions[203Pb]-pentixather can be used to image CXCR4 expressing SCLC xenografts and treatment with alpha emitter [212Pb]-pentixather significantly prolongs SCLC xenograft median overall survival. Significantly greater mCD45+ bone marrow repopulation was detected in NSG mice engrafted with human bone marrow 28-31 days following [212Pb]-pentixather treatment, relative to hCD45+ bone marrow.

cancer biology↗

bioRxiv2023

Day and night posture of the bluegill sunfish (Lepomis macrochirus)

Many animals assume characteristic postures when resting or sleeping. These postures are often stable and can be maintained passively, thus reducing the energy cost for maintaining an unstable posture. For example, many tetrapods lay prone on the ground and some negatively buoyant fishes are also able to rest on the substrate. Other fishes rest suspended in the water column. Counterintuitively, hovering this way can be of similar energetic cost to swimming. Even if the fish is perfectly neutrally buoyant, any displacement between its center of mass and center of buoyancy will produce destabilizing pitching torques that the fish must constantly work to counteract if they wish to maintain that posture. We hypothesized that a neutrally buoyant fish could rest at an equilibrium - a posture at which no destabilizing torques are produced by the body --to minimize the metabolic costs associated with hovering. Specifically, we studied the bluegill sunfish (Lepomis macrochirus), which is unstable in a horizontal posture. However, by pitching their bodies up or down they may be able to attain a less costly equilibrium posture, one which vertically aligns their center of mass and center of buoyancy. To test this hypothesis, we measured pitch angle of bluegill over the course of 24 hours. We also measured the pitch angles of the body that correspond to stable and unstable equilibria. We found that the stable equilibrium was a belly-up posture, and the unstable equilibrium is a dorsal side up posture pitched 53{+/-}26{degrees} head-down. The fish rested at a head-down pitch of -10.7{+/-}0.4{degrees} degrees, which is significantly steeper than the average pitch during the day of -3.4{+/-}0.8{degrees} degrees head down. These results show that bluegill do not rest at unstable or stable equilibrium. However, they do rest closer to unstable equilibrium at night than during the day. This may allow them to decrease destabilizing torques generated from the relative locations of the COM and COB while maintaining maneuverability.

biophysics↗

bioRxiv2022

Static Stability and Swim Bladder Volume in the Bluegill Sunfish (Lepomis macrochirus)

The static stability of a fish in the water is determined by the relative locations of its center of mass and center of buoyancy. These locations may not be constant, but may depend on the volume of the swim bladder. Changes in swim bladder volume affect both the distribution of mass and the overall volume of the fish, thus affecting the location of the center of mass and center of buoyancy, respectively. To determine the static stability and to examine the influence of the swim bladder on static stability, we used micro-computed tomography to estimate the locations of the center of mass and center of buoyancy in bluegill sunfish (Lepomis macrochrius). In fish oriented head up in the scanner, we found that the center of buoyancy is located 0.441 body lengths from the snout and 0.19 body lengths above the ventral surface of the pelvic girdle, and that the center of mass is 0.0012 BL posterior to and 0.00045 BL ventral to the center of buoyancy. Swim bladders from our specimens ranged in size from 1.9% to 7.6% total body volume, and we found no correlation between swim bladder volume and the distance between the center of mass and center of buoyancy. However, in fish scanned in a head-down orientation, the center of mass is anterior and dorsal to the center of buoyancy--the opposite configuration of that found in fish oriented head up. This change in center of mass and center of buoyancy seems to be caused by changes in the location of the swim bladder in the body: the centroid of the swim bladder is located more posteriorly in fish oriented head-down. The air in the bladder "rises" while heavier tissues "sink," driving a change in tissue distribution and changing the location of the center of mass relative to the center of buoyancy. We conclude that while static stability does not change with swim bladder volume, pitch angle could have a marked effect on static stability.

biophysics↗