Search

Radioligand therapy (RLT) is gaining traction as a safe and effective targeted approach for the treatment of many cancer types, reflected by a substantial and growing commercial market (valued at $7.78 billion in 2021, with a projected value of $13.07 billion by 2030). Beta-emitting RLTs have a long history of clinical success dating back to the approval of Zevalin and Bexxar in the early 2000s, later followed by Lutathera and Pluvicto. Alpha radioligand therapeutics (ARTs) offer the potential for even greater success. Driven by ground-breaking clinical results in early trials, improved isotope availability, and better understanding of isotope and disease characteristics, the global market for alpha emitters was estimated at $672.3 million for the year 2020, with projected growth to $5.2 billion by 2027. New company formations, promising clinical trial data, and progression for many radioligand therapy products, as well as an inflow of investor capital, are contributing to this expanding field. Future growth will be fueled by further efficacy and safety data from ART clinical trials and real-world results, but challenges remain. Radionuclide supply, manufacturing, and distribution are key obstacles for growth of the field. New models of delivery are needed, along with cross-disciplinary training of specialized practitioners, to ensure patient access and avoid challenges faced by early RLT candidates such as Zevalin and Bexxar. Understanding of the history of radiation medicine is critical to inform what may be important to the success of ART-most past projections were inaccurate and it is important to analyze the reasons for this. Practical considerations in how radiation medicine is delivered and administered are important to understand in order to inform future approaches., Competing Interests: EO was employed by ARTbio Inc. MT was employed by F-Prime Capital., (Copyright © 2023 Ostuni and Taylor.)

Aim: Distal pancreatectomies (DP) are associated with high risk of postoperative complications, and in many series higher morbidity rate than duodenopancreatectomies has been reported. To evaluate the role of a collagen sponge with human fibrinogen and thrombin film (TachoSil®) in limiting the incidence of complications after DP., Methods: From 1996 to 2013, 221 patients have been submitted to distal pancreatectomy (± splenectomy) in our Division. A retrospective analysis has been conducted in a group of 36 consecutive and prospectively collected DP treated with intraoperative placement of TachoSil® on pancreatic stump from 2010 to 2013 (group 1). A control series of 36 consecutive patients (group 2) was matched 1:1 from hystorical database. The variables considered in the analysis were: age, gender, ASA score, pancreatic texture (hard vs. soft), histology, operative time, postoperative mortality, morbility (postoperative pancreatic fistula - POPF, postoperative hemorrage - PPH, delayed gastric emptying - DGE) and hospital stay. Differences between POPF, PPH, DGE and hospital stays between grops were investigated with χ² and t-Student test. Univariate analysis was conducted to determine factors related to POPF development. Statistical analysis was performed using freeware Microsoft Excel based program., Results: Post operative mortality was 0% in both groups. POPF were registered in 36.1% (13/36) and 41.6 % (15/36) in groups 1 and 2, respectively (P=n.s.); in group 1 we didn't observe grade C POPF, while 4 patients in control group developed grade C POPF (P<0,05). No differences were found between two groups in terms of incidence of PPH and DGE. The median duration of postoperative hospital stay in group 1 was 21.8 (7-189) days compared with 31.13 (9-249) days in group 2 (P<0.001)., Conclusion: The use of TachoSil® seems to be associated with lower incidence of grade C POPF but larger controlled trials are needed to surely assess the usefulness of TachoSil® in pancreatic surgery in order to reduce pancreatic specific complications and their severity.

We present a method that uses microcontact printing of alkanethiols on gold to generate patterned substrates presenting "islands" of extracellular matrix (ECM) surrounded by nonadhesive regions such that single cells attach and spread only on the adhesive regions. We have used this micropatterning technology to demonstrate that mammalian cells can be switched between growth and apoptosis programs in the presence of saturating concentrations of growth factors by either promoting or preventing cell spreading (Science 276:1425-1428, 1997). From the perspective of fundamental cell biology, these results suggested that the local differentials in growth and viability that are critical for the formation of complex tissue patterns may be generated by local changes in cell-ECM interactions. In the context of cell culture technologies, such as bioreactors and cellular engineering applications, the regulation of cell function by cell shape indicates that the adhesive microenvironment around cells can be carefully optimized by patterning a substrate in addition to using soluble factors (Biotech. Prog. 14:356-363, 1998). Micropatterning technology is playing a central role both in our understanding how ECM and cell shape regulate cell physiology and in facilitating the development of cellular biosensor and tissue engineering applications (Science 264:696-698, 1994; J. Neurosci. Res. 13:213-20, 1985; Biotech. Bioeng. 43:792-800, 1994).

Cell spreading was controlled independently of the amount and density of immobilized integrin ligand by culturing cells on single adhesive islands of different sizes (100-2500 microm(2)) and shapes (squares, circles, and lines) or on many smaller (3-5 microm diameter) circular islands that were coated with a saturating density of fibronectin and separated by non-adhesive regions. The amount of focal adhesions (FAs) containing vinculin and phosphotyrosine increased in direct proportion to cell spreading under all conditions. FAs localized asymmetrically along the periphery of the small islands that experienced highest tensional stress, and FA staining increased when cytoskeletal tension was stimulated with thrombin, whereas inhibitors of contractility promoted FA disassembly. Thus, these findings demonstrate the existence of an "inside-out" mechanism whereby global cell distortion produces increases in cytoskeletal tension that feed back to drive local changes in FA assembly. This complex interplay between cell morphology, mechanics, and adhesion may be critical to how cells integrate from and function in living tissues.

There are many experiments in which it would be useful to treat a part of the surface or interior of a cell with a biochemical reagent. It is difficult, however, to achieve subcellular specificity, because small molecules diffuse distances equal to the extent of the cell in seconds. This paper demonstrates experimentally, and analyzes theoretically, the use of multiple laminar fluid streams in microfluidic channels to deliver reagents to, and remove them from, cells with subcellular spatial selectivity. The technique made it possible to label different subpopulations of mitochondria fluorescently, to disrupt selected regions of the cytoskeleton chemically, to dislodge limited areas of cell-substrate adhesions enzymatically, and to observe microcompartmental endocytosis within individual cells. This technique does not require microinjection or immobilization of reagents onto nondiffusive objects; it opens a new window into cell biology.

Directed cell migration is critical for tissue morphogenesis and wound healing, but the mechanism of directional control is poorly understood. Here we show that the direction in which cells extend their leading edge can be controlled by constraining cell shape using micrometer-sized extracellular matrix (ECM) islands. When cultured on square ECM islands in the presence of motility factors, cells preferentially extended lamellipodia, filopodia, and microspikes from their corners. Square cells reoriented their stress fibers and focal adhesions so that tractional forces were concentrated in these corner regions. When cell tension was dissipated, lamellipodia extension ceased. Mechanical interactions between cells and ECM that modulate cytoskeletal tension may therefore play a key role in the control of directional cell motility.

Here we describe a method for quantifying traction in cells that are physically constrained within micron-sized adhesive islands of defined shape and size on the surface of flexible polyacrylamide gels that contain fluorescent microbeads (0.2-microm diameter). Smooth muscle cells were plated onto square (50 x 50 microm) or circular (25- or 50-microm diameter) adhesive islands that were created on the surface of the gels by applying a collagen coating through microengineered holes in an elastomeric membrane that was later removed. Adherent cells spread to take on the size and shape of the islands and cell tractions were quantitated by mapping displacement fields of the fluorescent microbeads within the gel. Cells on round islands did not exhibit any preferential direction of force application, but they exerted their strongest traction at sites where they formed protrusions. When cells were confined to squares, traction was highest in the corners both in the absence and presence of the contractile agonist, histamine, and cell protrusions were also observed in these regions. Quantitation of the mean traction exerted by cells cultured on the different islands revealed that cell tension increased as cell spreading was promoted. These results provide a mechanical basis for past studies that demonstrated a similar correlation between spreading and growth within various anchorage-dependent cells. This new approach for analyzing the spatial distribution of mechanical forces beneath individual cells that are experimentally constrained to defined sizes and shapes may provide additional insight into the biophysical basis of cell regulation., (Copyright 2002 Wiley-Liss, Inc.)

Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in basrelief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (> or = 50 microns), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

This review describes the pattering of proteins and cells using a non-photolithographic microfabrication technology, which we call 'soft lithography' because it consists of a set of related techniques, each of which uses stamps or channels fabricated in an elastomeric ('soft') material for pattern transfer. The review covers three soft lithographic techniques: microcontact printing, patterning using microfluidic channels, and laminar flow patterning. These soft lithographic techniques are inexpensive, are procedurally simple, and can be used to pattern a variety of planar and non-planar substrates. Their successful application does not require stringent regulation of the laboratory environment, and they can be used to pattern surfaces with delicate ligands. They provide control over both the surface chemistry and the cellular environment. We discuss both the procedures for patterning based on these soft lithographic techniques, and their applications in biosensor technology, in tissue engineering, and for fundamental studies in cell biology.

This paper describes the use of laminar flow of liquids in capillary systems to pattern the cell culture substrate, to perform patterned cell deposition, and to pattern the cell culture media. We demonstrate the patterning of the cell culture substrate with different proteins, the patterning of different types of cells adjacent to each other, the patterned delivery of chemicals to adhered cells, and performing enzymatic reactions over select cells or over a portion of a cell. This method offers a way to simultaneously control the characteristics of the surface to which cells are attached, the type of cells that are in their vicinity, and the kind of media that cells or part of a cell are exposed to. The method is experimentally simple, highly adaptable, and requires no special equipment except for an elastomeric relief that can be readily prepared by rapid prototyping.

This paper describes the fabrication of large (up to 45 cm(2)) arrays of microwells, with volumes as small as ∼3 fL/well and densities as high as 10(7) wells/cm(2). These arrays of microwells are formed by casting an elastomer, poly(dimethylsiloxane) (PDMS), against "masters" prepared by photolithography; arrays of microwells in other polymers can be formed by using a master consisting of posts in PDMS. A straightforward technique, discontinuous dewetting, allows wells to be filled rapidly (typically on the order of 10(4) wells/s) and uniformly with a wide range of liquids. Several rudimentary strategies for addressing microwells are investigated, including electroosmotic pumping and gaseous diffusion.

This article alerts dental practitioners to the challenge of working with patients who have suffered a cerebrovascular accident. The stroke patient struggles with many physical, neurological and psychosocial problems and needs effective dentist-patient communication. Specific techniques are presented to help the dental team interact more productively.