Antibody-drug conjugates: beyond current approvals and potential future strategies.

The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in recent years have fuelled the ongoing development of this class of drugs. These novel agents combine the benefits of high specific targeting of oncogenic cell surface antigens with the additional cell kill from high potency cytotoxic payloads, thus achieving wider therapeutic windows. This review will summarise the clinical activity of ADCs in tumour types not covered elsewhere in this issue, such as gastrointestinal (GI) and genitourinary (GU) cancers and glioblastoma (GBM).

Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells.

The tendon enthesis plays a critical role in facilitating movement and reducing stress within joints. Partial enthesis injuries heal in a mechanically inferior manner and never achieve healthy tissue function. The cells responsible for tendon-to-bone healing remain incompletely characterized and their origin is unknown.

Harnessing a Feasible and Versatile Calvarial Suture 2-D Culture System to Study Suture Biology.

As a basic science, craniofacial research embraces multiple facets spanning from molecular regulation of craniofacial development, cell biology/signaling and ultimately translational craniofacial biology. Calvarial sutures coordinate development of the skull, and the premature fusion of one or more, leads to craniosynostosis. Animal models provide significant contributions toward craniofacial biology and clinical/surgical treatments of patients with craniofacial disorders.

An Evolutionary Conserved Signaling Network Between Mouse and Human Underlies the Differential Osteoskeletal Potential of Frontal and Parietal Calvarial Bones.

The mammalian calvarial vault is an ancient and highly conserved structure among species, however, the mechanisms governing osteogenesis of the calvarial vault and how they might be conserved across mammalian species remain unclear. The aim of this study was to determine if regional differences in osteogenic potential of the calvarial vault, first described in mice, extend to humans. We derived human frontal and parietal osteoblasts from fetal calvarial tissue, demonstrating enhanced osteogenic potential both and of human frontal derived osteoblasts compared to parietal derived osteoblasts.

Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis.

Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures.

Recruitment, outcomes, and toxicity trends in phase I oncology trials: Six-year experience in a large institution.

Background: With the rapid influx of novel anti-cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real-world data in this setting.

-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-Derived Parietal Bone Through Downregulation of .

Craniofacial development is a program exquisitely orchestrated by tissue contributions and regulation of genes expression. The basic helix-loop-helix (bHLH) transcription factor Twist1 expressed in the skeletal mesenchyme is a key regulator of craniofacial development playing an important role during osteoskeletogenesis. This study investigates the postnatal impact of haploinsufficiency on the osteoskeletal ability and regeneration on two calvarial bones arising from tissues of different embryonic origin: the neural crest-derived frontal and the mesoderm-derived parietal bones.

Expansion and Hepatic Differentiation of Adult Blood-Derived CD34+ Progenitor Cells and Promotion of Liver Regeneration After Acute Injury.

Unlabelled: The low availability of functional hepatocytes has been an unmet demand for basic scientific research, new drug development, and cell-based clinical applications for decades. Because of the inability to expand hepatocytes in vitro, alternative sources of hepatocytes are a focus of liver regenerative medicine. We report a new group of blood-derived CD34(+) progenitor cells (BDPCs) that have the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration.

An Overview of Direct Somatic Reprogramming: The Ins and Outs of iPSCs.

Stem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine.

Surveillance of Stem Cell Fate and Function: A System for Assessing Cell Survival and Collagen Expression In Situ.

Cell-based therapy is an emerging paradigm in skeletal regenerative medicine. However, the primary means by which transplanted cells contribute to bone repair and regeneration remain controversial. To gain an insight into the mechanisms of how both transplanted and endogenous cells mediate skeletal healing, we used a transgenic mouse strain expressing both the topaz variant of green fluorescent protein under the control of the collagen, type I, alpha 1 promoter/enhancer sequence (Col1a1(GFP)) and membrane-bound tomato red fluorescent protein constitutively in all cell types (R26(mTmG)).

High sensitivity troponin: Does the 50% delta change alter clinical outcomes in chest pain presentations to the emergency room?

Background: The National Heart Foundation (NHF) and Cardiac Society of Australia and New Zealand (CSANZ) Acute Coronary Syndrome (ACS) guidelines recommend the use of a high sensitivity troponin assay (hsTrop) in the assessment of patients presenting with ACS. A troponin delta of 50% compared with the previously recommended 20% is advocated by the guidelines to aid in the clinical diagnosis of ACS. We sought to determine the clinical impact of the updated recommendation to use 50% troponin delta for patients presenting with chest pain to the emergency department.

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens.