Tumor Receptor-Mediated In Vivo Modulation of the Morphology, Phototherapeutic Properties, and Pharmacokinetics of Smart Nanomaterials.

To be clinically efficacious, nanotherapeutic drugs need to reach disease tissues reliably and cause limited side effects to normal organs and tissues. Here, we report a proof-of-concept study on the development of a smart peptidic nanophototherapeutic agent in line with clinical requirements, which can transform its morphology from nanoparticles to nanofibrils at the tumor sites. This in vivo receptor-mediated transformation process resulted in the formation and prolonged tumor-retention of highly ordered (J-aggregate type of photosensitizer) photosensitive peptide nanofibrillar network with greatly enhanced photothermal and photodynamic properties.

Functionalization of MOF-5 with mono-substituents: effects on drug delivery behavior.

Metal organic frameworks (MOFs) are widely used in drug carrier research due to their tunability. The properties of MOFs can be adjusted through incorporation of mono-substituents to obtain pharmaceutical carriers with excellent properties. In this study, different functional groups of -NH, -CH, -Br, -OH and -CH[double bond, length as m-dash]CH are connected to MOF-5 to analyse the effect of mono-substituent incorporation on drug delivery properties.

Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells.

Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis.

Multiple Dynamics in Tumor Microenvironment Under Radiotherapy.

The tumor microenvironment (TME) is an evolutionally low-level and embryonically featured tissue comprising heterogenic populations of malignant and stromal cells as well as noncellular components. Under radiotherapy (RT), the major modality for the treatment of malignant diseases [1], TME shows an adaptive response in multiple aspects that affect the efficacy of RT. With the potential clinical benefits, interests in RT combined with immunotherapy (IT) are intensified with a large scale of clinical trials underway for an array of cancer types.

Mitigating Coronavirus-Induced Acute Respiratory Distress Syndrome by Radiotherapy.

The acute respiratory distress syndrome (ARDS) induced by SARS-CoV-2-mediated cytokine storm (CS) in lungs leads to the high mortality in COVID-19 patients. To reduce ARDS, an ideal approach is to diminish virus loading by activating immune cells for CS prevention or to suppress the overactive cytokine-releasing immune cells for CS inhibition. Here, a potential radiation-mediated CS regulation is raised by reevaluating the radiation-mediated pneumonia control in the 1920s, with the following latent advantages of lung radiotherapy (LR) in treatment of COVID-19: (1) radiation accesses poorly circulated tissue more efficiently than blood-delivered medications; (2) low-dose radiation (LDR)-mediated metabolic rewiring and immune cell activation inhibit virus loading; (3) pre-consumption of immune reserves by LDR decreases CS severity; (4) higherdose radiation (HDR) within lung-tolerable doses relieves CS by eliminating in situ overactive cytokine-releasing cells.

Author Correction: Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Size-Transformable Hyaluronan Stacked Self-Assembling Peptide Nanoparticles for Improved Transcellular Tumor Penetration and Photo-Chemo Combination Therapy.

Size-transformable nanomedicine has the potential to overcome systemic and local barriers, leading to efficient accumulation and penetration throughout the tumor tissue. However, the design of this type of nanomedicine was seldom based on active targeting and intracellular size transformation. Here, we report an intracellular size-transformable nanosystem, in which small and positively charged nanoparticles (<30 nm) prepared from the self-assembly of an amphiphilic hexadecapeptide derivative was coated by folic acid- and dopamine-decorated hyaluronan (HA) to form large and negatively charged nanoparticles (∼130 nm).

Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2 breast cancer.

Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.

Pancreatic adenocarcinoma presents as a spectrum of a highly aggressive disease in patients. The basis of this disease heterogeneity has proved difficult to resolve due to poor tumor cellularity and extensive genomic instability. To address this, a dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic tumors.

Peptide-based materials for cancer immunotherapy.

Peptide-based materials hold great promise as immunotherapeutic agents for the treatment of many malignant cancers. Extensive studies have focused on the development of peptide-based cancer vaccines and delivery systems by mimicking the functional domains of proteins with highly specific immuno-regulatory functions or tumor cells fate controls. However, a systemic understanding of the interactions between the different peptides and immune systems remains unknown.

Galectin-1 inhibition induces cell apoptosis through dual suppression of CXCR4 and Ras pathways in human malignant peripheral nerve sheath tumors.

Background: The Ras signaling pathway is commonly dysregulated in human malignant peripheral nerve sheath tumors (MPNSTs). It is well known that galectin-1 (Gal-1) is essential to stabilize membrane Ras and thereby induce the activation of Ras. However, the role of Gal-1 in MPNST progression remains unknown.

Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells.

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells.

Immune targets in the tumor microenvironment treated by radiotherapy.

Radiotherapy (RT), the major anti-cancer modality for more than half of cancer patients after diagnosis, has the advantage of local tumor control with relatively less systematic side effects comparing to chemotherapy. However, the efficacy of RT is limited by acquired tumor resistance leading to the risks of relapse and metastasis. To further enhance the efficacy of RT, with the renaissances of targeted immunotherapy (TIT), increasing interests are raised on RT combined with TIT including cancer vaccines, T-cell therapy, and antibody-based immune checkpoint blockers (ICB) such as anti-CTLA-4 and anti-PD1/PD-L1.

Organoid models for translational pancreatic cancer research.

Despite recent advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) still retains the worst survival rate of common malignancies. Late diagnosis and lack of curative therapeutic options are the most pressing clinical problems for this disease. Therefore, there is a need for patient models and biomarkers that can be applied in the clinic to identify the most effective therapy for a patient.

A Plug-and-Play, Drug-on-Pillar Platform for Combination Drug Screening Implemented by Microfluidic Adaptive Printing.

Traditional high-throughput drug combination screening requires automatic pipetting of drugs into high-density microtiter plates. Here, a drug-on-pillar platform is proposed for efficient combination drug screening. Using the proposed approach, combination drug screening can be carried out in a plug-and-play manner, allowing for high-throughput screening of large permutations of drug combinations at various concentrations, such that drug dispensing and cell-based screening can be temporally separated and therefore can potentially be performed at distant laboratories.

Unique Photochemo-Immuno-Nanoplatform against Orthotopic Xenograft Oral Cancer and Metastatic Syngeneic Breast Cancer.

Sophisticated self-assembly may endow materials with a variety of unique functions that are highly desirable for therapeutic nanoplatform. Herein, we report the coassembly of two structurally defined telodendrimers, each comprised of hydrophilic linear PEG and hydrophobic cholic acid cluster as a basic amphiphilic molecular subunit. One telodendrimer has four added indocyanine green derivatives, leading to excellent photothermal properties; the other telodendrimer has four sulfhydryl groups designed for efficient intersubunit cross-linking, contributing to superior stability during circulation.

Identification of integrin drug targets for 17 solid tumor types.

Integrins are contributors to remodeling of the extracellular matrix and cell migration. Integrins participate in the assembly of the actin cytoskeleton, regulate growth factor signaling pathways, cell proliferation, and control cell motility. In solid tumors, integrins are involved in promoting metastasis to distant sites, and angiogenesis.

Targeting Galectin-1 Impairs Castration-Resistant Prostate Cancer Progression and Invasion.

The majority of patients with prostate cancer who are treated with androgen-deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of galectin-1 (Gal-1) is associated with prostate cancer progression and poor clinical outcome.

Outcomes of Preoperative Versus Postoperative Radiation for Heterotopic Ossification Prevention in Children With Neuromuscular Hip Dysplasia Undergoing Proximal Femoral Resection.

Background: Few studies exist to inform the extrapolated practice of irradiating children for heterotopic ossification (HO) prevention. We report the incidence of HO formation following prophylactic preoperative compared with postoperative radiation therapy (RT) in children with neuromuscular hip dysplasia (NHD) following proximal femoral resection (PFR).

Methods: A retrospective, 2-institution chart review was performed.

MKP1 mediates resistance to therapy in HER2-positive breast tumors.

Mitogen-activated protein kinase phosphatase 1 (MKP1 or DUSP1) is an antiapoptotic phosphatase that is overexpressed in many cancers, including breast cancer. MKP1 expression is inducible in radiation-treated breast cancer cells, and correlates with human epidermal growth factor receptor 2 (ERBB2, HER2) expression. The role of MKP1 in therapy resistance suggests that targeting MKP1 in HER2-positive breast tumors may significantly enhance the efficacy of anti-HER2 and other anticancer therapies.

NQO1-Mediated Tumor-Selective Lethality and Radiosensitization for Head and Neck Cancer.

Unlabelled: Ionizing radiation (IR) is a key therapeutic regimen for many head and neck cancers (HNC). However, the 5-year overall survival rate for locally advanced HNCs is approximately 50% and better therapeutic efficacy is needed.

Nad(p)h: quinone oxidoreductase 1 (NQO1) is overexpressed in many cancers, and β-lapachone (β-lap), a unique NQO1 bioactivatable drug, exploits this enzyme to release massive reactive oxygen species (ROS) that synergize with IR to kill by programmed necrosis.

A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.

Radioimmunoassay technology was utilized in the discovery of somatostatin and was quickly brought into therapeutics; however, it took the development of somatostatin congeners to solve its limitations of a short half-life. Therapeutic medical control of hyperhormonal states such as acromegaly, carcinoid syndrome and VIPoma significantly advanced from a nonspecific approach to one that specifically and effectively targeted the underlying pathophysiology. Clinical care was transformed from nonspecific symptom control to one of a significant improvement in not only quality of life, but also quantity of life.

CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance.

Tumor adaptive resistance to therapeutic radiation remains a barrier for further improvement of local cancer control. SIRT3, a member of the sirtuin family of NAD(+)-dependent protein deacetylases in mitochondria, promotes metabolic homeostasis through regulation of mitochondrial protein deacetylation and plays a key role in prevention of cell aging. Here, we demonstrate that SIRT3 expression is induced in an array of radiation-treated human tumor cells and their corresponding xenograft tumors, including colon cancer HCT-116, glioblastoma U87, and breast cancer MDA-MB231 cells.

Novel MSH2 Mutation in the First Report of a Vietnamese-American Kindred with Lynch Syndrome.

•First report of Lynch syndrome in a Vietnamese kindred•A novel MSH2 mutation has been identified.•Culturally sensitive screening programs need to be developed in this growing population.