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Organizational identification has gained popularity in the organizational sciences and has important implications for the experiences of new undergraduate business students. Researchers have focused largely on how characteristics of organizations influence organizational identification, but limited work has explored how characteristics of the environment and the individual work together. In the present study, relationships between the dimensions of organizational socialization of undergraduate business students and university identification are investigated. Further, students' core self-evaluations are explored as a moderator of the relationship between socialization dimensions and organizational identification. The data for the study was collected from 209 entering-college first-year undergraduates in an introductory business course in the United States. We found that two socialization dimensions, people and organizational goals and values, are positively related to university identification. Furthermore, core self-evaluations interact with the history dimension to influence university identification, such that history socialization has a positive effect on university identification for students with high core self-evaluations but not for those with low core self-evaluations. Discussion, implications, and future research areas are included.

Olga Sergeeva,1 Yifan Zhang,1 Songqi Gao,2 E Ricky Chan,3 Maxim Sergeev,4 Renuka Iyer,5 Sandra Sexton,5 Norbert Avril,4 Zheng-Rong Lu,2 Zhenghong Lee1 1Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; 2Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; 3Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; 4Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 5Medical Oncology and Laboratory Animal Shared Resources, Roswell Park Cancer Institute, Buffalo, NY, USACorrespondence: Zhenghong Lee, Nuclear Medicine, Radiology, Case Western Reserve University, Bolwell S107, 11100 Euclid Avenue, Cleveland, OH, 44106, USA, Tel +1216-844-7920, Email zxl11@case.edu Zheng-Rong Lu, Biomedical Engineering, Case Western Reserve University, Wickenden 427, Mail Stop 7207, 10900 Euclid Ave, Cleveland, OH, 44106, USA, Tel +1 216-368-0187, Email zxl125@case.eduPurpose: We tested a recently developed short peptide radioligand for PET imaging of hepatocellular carcinoma (HCC) by targeting an oncoprotein, extra-domain B fibronectin (EDB-FN) in the tumor microenvironment.Methods: The radioligand consists of a small linear peptide ZD2 with 68Ga-NOTA chelator, and specifically binds to EDB-FN. PET images were acquired dynamically for 1 hour after intravenously (i.v.) injecting 37 MBq (1.0 mCi) of the radioligand into the woodchuck model of naturally occurring HCC. Woodchuck HCC originated from chronic viral hepatitis infection, which recapitulates the corresponding human primary liver cancer. The animals were euthanized post-imaging for tissue collection and validation.Results: For ZD2 avid liver tumors, the radioligand accumulation plateaued a few minutes after injection, while the liver background uptake stabilized 20 min post-injection. The status of EDB-FN in woodchuck HCC was confirmed by histology and validated by PCR and western blocking.Conclusion: We have showed the viability of using the ZD2 short peptide radioligand targeting EDB-FN in liver tumor tissue for PET imaging of HCC, which can potentially impact the clinical care for HCC patients.Keywords: peptide ligand, EDB fibronectin, positron emission tomography, woodchuck model

Talcum powder is recognized as the leading drug for pleurodesis, a treatment of choice for malignant pleural effusions. Recently, it was shown that hydrogel foam delivery systems significantly enhanced the number of adhesions between the chest wall and the lung in a New Zealand rabbit model due to the sol-gel transition. However, many questions still remain regarding the cause of improved efficacy, such as: (1) Would only hydrogel foams improve the efficacy of talc pleurodesis? (2) Is it possible to achieve the same efficacy of hydrogels using non-hydrogel foams? 3) What are the physicochemical properties that can be correlated to the efficacy of talc pleurodesis? In this study, we use non-hydrogel foam formulations to determine the efficacy of pleurodesis. Foam stability and rheology of the formulations were correlated to adhesion formation. The results clearly suggest a correlation of pleurodesis efficacy to the viscosity and modulus of the foam delivery system. [ABSTRACT FROM AUTHOR]

Protected areas such as national parks constitute an increasing land mass globally, but these areas are under increasing threat from climate change events such as drought, flooding, and bushfires. The recent Yosemite National Park fires in California provide an example of this issue. After any such disaster, authorities will need to restore those protected areas to their former state at significant costs within any public funding cycle. To corroborate that request, clear economic assessments of total costs and benefits will be required. However, in previous studies of these issues a complete set of government cost and/or benefit data may not be provided, skewing assessment results accordingly. Using South Australia's Kangaroo Island protected areas-which were significantly destroyed by bushfire in 2019-20-as a case study with a unique set of State government cost data we calculate a set of analyses via economic methods. Despite significant restoration costs the study found the discounted net present value of returning tourists to the Island is 3.15 over ten years for park tourism and regional economic impacts, providing an internal rate of return of 22%. The rebuild work is also expected to support around 430 full time equivalent (FTE) jobs during construction, with a return to full tourism supporting another 744 FTEs across relevant sectors (e.g. accommodation, retail) of the Kangaroo Island economy. This robust assessment makes it far easier for protected area managers to argue their funding case., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adam Loch reports financial support was provided by South Australian Department for Environment and Water. Thanks is also extended to Associate Professor Patrick O'Connor for his support and guidance on this project., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

An increasingly popular form of collaboration involves forming partnerships among researchers, educators, and community members to improve or transform education systems through research inquiry. However, not all partnerships are successful. The field needs valid, reliable, and useful measures to help with assessing progress toward partnership goals. In this community case study, we present a participatory, mixed-methods approach for creating measures to assess the progress of education research-practice partnerships (RPPs). The case illustrates a novel approach to measurement design, driven by perspectives and feedback of over 300 members of 80 partnerships. As a result, the measures align with the values and practices of the very collaborations the measures were intended to assess., Competing Interests: EH is employed by Partner to Improve and SS is employed by SageFox Consulting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Farrell, Penuel, Arce-Trigatti, Soland, Singleton, Resnick, Stamatis, Riedy, Henrick, Sexton, Wellberg and Schmidt.)

Photobac is a near infrared photosensitizer (PS) derived from naturally occurring bacteriochlorophyll- a, with a potential for treating a variety of cancer types (U87, F98 and C6 tumor cells in vitro). The main objective of the studies presented herein was to evaluate the efficacy, toxicity and pharmacokinetic profile of Photobac in animals (mice, rats and dogs) and submit these results to the United States Food and Drug Administration (US FDA) for its approval to initiate Phase I human clinical trials of glioblastoma, a deadly cancer disease with no long term cure. The photodynamic therapy (PDT) efficacy of Photobac was evaluated in mice subcutaneously implanted with U87 tumors, and in rats bearing C6 tumors implanted in brain. In both tumor types, the Photobac-PDT was quite effective. The long-term cure in rats was monitored by magnetic resonance imaging (MRI) and histopathology analysis. A detailed pharmacology, pharmacokinetics and toxicokinetic study of Photobac was investigated in both non-GLP and GLP facilities at variable doses following the US FDA parameters. Safety Pharmacology studies suggest that there is no phototoxicity, cerebral or retinal toxicity with Photobac. No metabolites of Photobac were observed following incubation in rat, dog, mini-pig and human hepatocytes. Based on current biological data, Photobac-IND received the approval for Phase-I human clinical trials to treat Glioblastoma (brain cancer), which is currently underway at our institute. Photobac has also received an orphan drug status from the US FDA, because of its potential for treating Glioblastoma as no effective treatment is currently available for this deadly disease., Competing Interests: Declaration of Competing Interest Except Dr. Pandey, the Founder and CSO of Photolitec, LLC, none of the authors have any financial interest in the technology related to Photobac., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Although melanoma accounts for only 5.3% of skin cancer, it results in >75% of skin-cancer-related deaths. To avoid disfiguring surgeries on the head and neck associated with surgical excision, there is a clear unmet need for other strategies to selectively remove cutaneous melanoma lesions. Mohs surgery is the current treatment for cutaneous melanoma lesions and squamous and basal cell carcinoma. While Mohs surgery is an effective way to remove melanomas in situ, normal tissue is also excised to achieve histologically negative margins. This paper describes a novel combination therapy of nonthermal plasma (NTP) which emits a multitude of reactive oxygen species (ROS) and the injection of a pharmaceutical agent. We have shown that the effects of NTP are augmented by the DNA-damaging prodrug, tirapazamine (TPZ), which becomes a free radical only in conditions of hypoxemia, which is often enhanced in the tumor microenvironment. In this study, we demonstrate the efficacy of the combination therapy through experiments with B16-F10 and 1205 Lu metastatic melanoma cells both in vitro and in vivo. We also show the safety parameters of the therapy with no significant effects of the therapy when applied to porcine skin. We show the need for the intratumor delivery of TPZ in combination with the surface treatment of NTP and present a model of a medical device to deliver this combination therapy. The importance of functional gap junctions is indicated as a mechanism to promote the therapeutic effect. Collectively, the data support a novel therapeutic combination to treat melanoma and the development of a medical device to deliver the treatment in situ.

Background: Cardioprotective effects of N -acetyl-ser-asp-lys-pro (Ac-SDKP) have been reported in preclinical models of myocardial remodeling. However, the rapid degradation of this endogenous peptide in vivo limits its clinical use., Method: To prolong its bioavailability, Ac-SDKP was encapsulated by phosphocholine lipid bilayers (liposomes) similar to mammalian cell membranes. The physical properties of the liposome structures were assessed by dynamic light scattering and scanning electron microscopy. The uptake of Ac-SDKP by RAW 264.7 macrophages and human and murine primary cardiac fibroblasts was confirmed by fluorescence microscopy and flow cytometry. Spectrum computerized tomography and competitive enzyme-linked immunoassays were performed to measure the ex vivo cardiac biodistribution of Ac-SDKP. The biological effects of this novel synthetic compound were examined in cultured macrophages and cardiac fibroblasts and in a murine model of acute myocardial infarction induced by permanent coronary artery ligation., Results: A liposome formulation resulted in the greater uptake of Ac-SDKP than the naked peptide by cultured RAW 264.7 macrophages and cardiac fibroblasts. Liposome-delivered Ac-SDKP decreased fibroinflammatory genes in cultured cardiac fibroblasts co-treated with TGF-β1 and macrophages stimulated with LPS. Serial tissue and serum immunoassays showed the high bioavailability of Ac-SDKP in mouse myocardium and in circulation. Liposome-delivered Ac-SDKP improved cardiac function and reduced myocardial fibroinflammatory responses in mice with acute myocardial infarction., Conclusion: Encapsulation of Ac-SDKP in a cell membrane-like phospholipid bilayer enhances its plasma and tissue bioavailability and offers cardioprotection against ischemic myocardial injury. Future clinical trials can use this novel approach to test small protective endogenous peptides in myocardial remodeling.

Purpose: We tested a recently developed short peptide radioligand for PET imaging of hepatocellular carcinoma (HCC) by targeting an oncoprotein, extra-domain B fibronectin (EDB-FN) in the tumor microenvironment., Methods: The radioligand consists of a small linear peptide ZD2 with 68 Ga-NOTA chelator, and specifically binds to EDB-FN. PET images were acquired dynamically for 1 hour after intravenously (i.v.) injecting 37 MBq (1.0 mCi) of the radioligand into the woodchuck model of naturally occurring HCC. Woodchuck HCC originated from chronic viral hepatitis infection, which recapitulates the corresponding human primary liver cancer. The animals were euthanized post-imaging for tissue collection and validation., Results: For ZD2 avid liver tumors, the radioligand accumulation plateaued a few minutes after injection, while the liver background uptake stabilized 20 min post-injection. The status of EDB-FN in woodchuck HCC was confirmed by histology and validated by PCR and western blocking., Conclusion: We have showed the viability of using the ZD2 short peptide radioligand targeting EDB-FN in liver tumor tissue for PET imaging of HCC, which can potentially impact the clinical care for HCC patients., Competing Interests: Dr Songqi Gao reports a patent WO2020150617A8 licensed to CWRU. Dr Zheng-Rong Lu reports a patent US Patent App. 17/424,104 pending to Molecular Theranostics, LLC. The authors report no other conflicts of interest in this work., (© 2023 Sergeeva et al.)

Economic value from protected areas informs decisions for biodiversity conservation and visitor benefits. Calculating these benefits assists governments to allocate limited budget resources. This study estimated tourism ecosystem service expenditure values for a regional protected area network in South Australia (57 parks) using direct transactional data, travel costs and economic multipliers. The big dataset came from a comprehensive booking system, which helped overcome common limitations associated with survey data (e.g., key areas rather than full network and high zero-value observations). Protected areas returned AU$373.8 million in the 2018-19 base year to the South Australian economy. The results indicate that combined estimation methods coupled to big data sets provide information on baseline expenditure to engage with critical conservation and tourism sites (e.g., Kangaroo Island). In this case they offer a unique full area network expenditure estimate which is an improvement on typical survey approaches, highlighting the advantage of protected area managers investing in big data. Finally, as South Australian protected areas exceed that in many other contexts the study offers important inputs to funding narratives and protected area expansion in line with global assessment targets., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: People with avascular necrosis of the hip have very limited treatment options currently available to stop the progression of this disease; this often results in the need for a hip replacement. There is some weak evidence that a class of drugs called bisphosphonates may delay the course of the disease, and this trial was commissioned and set up to provide robust evidence regarding the use of bisphosphonates in adults aged ≥ 18 years with this condition., Objectives: The aim of the Managing Avascular Necrosis Treatments: an Interventional Study ( MANTIS ) trial was to evaluate the clinical effectiveness and cost-effectiveness of a 12-month course of alendronate in the treatment of avascular necrosis., Design: This was a 66-month, definitive, multisite, two-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial, with an internal pilot phase., Setting: Eight secondary care NHS hospitals across the UK., Participants: Planned trial size - 280 adult patients with avascular necrosis., Intervention: Participants in the intervention group received 70 mg of alendronate (an oral bisphosphonate) weekly for 12 months., Main Outcomes: The main outcomes were Oxford Hip Score at 12 months (short-term outcome) and the time to decision that a hip replacement is required at 36 months (long-term outcome)., Results: Twenty-one patients were recruited and randomised to receive either the intervention drug, alendronate, or a placebo-matched tablet., Limitations: This trial was principally limited by low disease prevalence. Other limitations included the late disease stage at which participants were identified and the rapid progression of the disease., Future Work: This trial was limited by a low recruitment rate. Avascular necrosis of the hip should be treated as a rare disease. Future trials would need to recruit many more sites and recruit over a longer time period, and, for this reason, a registry may provide a more effective means of collecting data pertaining to this disease., Conclusions: The MANTIS trial was terminated at the end of the pilot phase, because it did not meet its go/no-go criteria. The main issue was a poor recruitment rate, owing to a lower than expected disease prevalence and difficulties in identifying the condition at a sufficiently early stage. Those patients who were identified and screened either were too advanced in their disease progression or were already taking medication. We would not recommend that a short-term interventional study is conducted on this condition until its prevalence, geographic foci and natural history and better understood. The difficulty of acquiring this understanding is likely to be a barrier in most health-care markets. One means of developing this understanding would be the introduction of a database/registry for patients suffering from avascular necrosis of the hip., Trial Registration: The trial is registered as ISRCTN14015902., Funding: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 43. See the NIHR Journals Library website for further project information.

Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in many diseases and in older adults through unknown mechanisms. Hypoxic stress has been proposed as a potential mechanism. However, experimental models to investigate the link between increased RDW and reduced survival are lacking. Here, we show that lifelong hypobaric hypoxia (~10% O2) increased erythrocyte numbers, hemoglobin, and RDW, while reducing longevity in male mice. Compound heterozygous knockout (hKO) mutations in succinate dehydrogenase (Sdh; mitochondrial complex II) genes Sdhb, Sdhc, and Sdhd reduced Sdh subunit protein levels, reduced RDW, and increased healthy life span compared with WT mice in chronic hypoxia. RDW-SD, a direct measure of MCV variability, and the SD of MCV showed the most statistically significant reductions in Sdh hKO mice. Tissue metabolomic profiling of 147 common metabolites showed the largest increase in succinate with elevated succinate/fumarate and succinate/oxoglutarate (2-ketoglutarate) ratios in Sdh hKO mice. These results demonstrate that mitochondrial complex II level is an underlying determinant of both RDW and healthy life span in hypoxia and suggest that therapeutic targeting of Sdh might reduce high RDW-associated clinical mortality in hypoxic diseases.

3-(1'-Hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll a derivative currently undergoing human clinical trials, was conjugated with mono-, di-, and tri-Gd(III)tetraxetan (DOTA) moieties. The T 1 /T 2 relaxivity and in vitro PDT efficacy of these conjugates were determined. The tumor specificity of the most promising conjugate was also investigated at various time points in mice and rats bearing colon tumors, as well as rabbits bearing widespread metastases from VX2 systemic arterial disseminated metastases. All the conjugates showed significant T 1 and T 2 relaxivities. However, the conjugate containing 3-Gd(III)-aminoethylamido-DOTA at position 17 of HPPH demonstrated great potential for tumor imaging by both MR and fluorescence while maintaining its PDT efficacy. At an MR imaging dose (10 μmol/kg), HPPH-3Gd(III)DOTA did not cause any significant organ toxicity in mice, indicating its potential as a cancer imaging (MR and fluorescence) agent with an option to treat cancer by photodynamic therapy (PDT).

Background: Epidermal growth factor receptor (EGFR) inhibitors, including cetuximab and panitumumab, are valuable therapeutics for colorectal cancer (CRC), but resistance to these inhibitors is common. The reason for such resistance is not well understood, which hampers development of better therapeutic strategies. Although activating mutations in KRAS, BRAF and PIK3CA are considered major drivers of CRC resistance to EGFR inhibitors, therapeutic targeting of these drug resistance drivers has not produced substantial clinical benefit., Methods: We exploited cell lines and mouse tumor models (cell line xenografts and patient derived xenografts) for experiments of genetic and pharmacologic depletion of EGFR and/or its family member HER2, including EGFR mutants, inhibition of EGFR ligand shedding, and biochemical analysis of signaling proteins, to delineate the mechanism of CRC resistance to EGFR inhibitors and to assess the therapeutic activity of PEPD G278D , which is a recombinant human protein that induces the degradation of both EGFR and HER2., Results: The sensitivity of CRC cells to cetuximab and panitumumab correlates with the ability of these drugs to induce EGFR downregulation. PEPD G278D strongly inhibits oncogenic signaling and growth of CRC cells by causing profound depletion of EGFR and HER2, regardless of activating mutations of KRAS, BRAF and PIK3CA. siRNA knockdown of EGFR or HER2 also inhibits CRC cells resistant to EGFR inhibitors. Tumors harboring mutated KRAS, BRAF and/or PIK3CA also overexpress EGFR ligands, further suggesting that EGFR signaling remains important to the tumors. While excessive tumor-generated high-affinity EGFR ligands block target engagement by PEPD G278D , aderbasib, an inhibitor of ADAM10 and ADAM17, enables PEPD G278D to exert strong antitumor activity by inhibiting ligand shedding. Moreover, adding fluorouracil, which is commonly used in CRC treatment, to the combination of PEPD G278D and aderbasib further enhances tumor inhibition., Conclusions: Our study shows that CRC resistance to EGFR inhibitors results primarily from the inability of the inhibitors to downregulate their target and that a PEPD G278D -based combination treatment overcomes the resistance., (© 2022. The Author(s).)

Purpose: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture., Methods: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27., Results: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978)., Conclusion: Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture., (Copyright © 2021 Chinese Medical Association. All rights reserved.)

T H 2 cells and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment are unknown. Here, we show that oncogenic Kras G12D increases IL-33 expression in pancreatic ductal adenocarcinoma (PDAC) cells, which recruits and activates T H 2 and ILC2 cells. Correspondingly, cancer-cell-specific deletion of IL-33 reduces T H 2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, IL-33 secretion is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL-33 or anti-fungal treatment decreases T H 2 and ILC2 infiltration and increases survival. Consistently, high IL-33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identify therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL-33., Competing Interests: Declaration of interests P. Dey and A.A. have a patent pending on targeting IL-33 and mycobiome in cancer: US Provisional Patent Application Serial No. 63/238,531. R.A.D. is a co-founder, adviser, and/or director of Tvardi Therapeutics, Asylia Therapeutics, Stellanova Therapeutics, Nirogy Therapeutics, and Sporos Bioventures. Tvardi and Nirogy are developing STAT3 and MCT inhibitors, respectively. A.M. receives royalties from Cosmos Wisdom Biotechnology and Thrive Earlier Detection, an Exact Sciences Company. A.M. is also a consultant for Freenome and Tezcat Biotechnology. The other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mice are the most common animal used to study disease, but there are real concerns about the reproducibility of many of these experiments. This review discusses how several different sources of chronic stress can directly impact experimental outcomes. Mandated housing conditions induce an underappreciated level of chronic stress but are not usually considered or reported as part of the experimental design. Since chronic stress plays a critical role in the development and progression of many somatic diseases including cancer, obesity, and auto-immune diseases, this baseline stress can directly affect outcomes of such experiments. To study the role of stress in both physical and psychiatric diseases, there has been a proliferation of protocols for imposing chronic stress on mice. For somatic diseases, biomarkers can be used to compare the models with the disease in patients, but to evaluate the validity of psychiatric models, behavioral tests are carried out to assess changes in behavior and these tests may themselves cause an underappreciated degree of additional stress. Therefore, it is important for animal welfare to reduce baseline stress and select the most humane protocols for inducing and assessing chronic stress to obtain the most reliable outcomes.

Interstitial photodynamic therapy (I-PDT) is a promising therapy considered for patients with locally advanced cancer. In I-PDT, laser fibers are inserted into the tumor for effective illumination and activation of the photosensitizer in a large tumor. The intratumoral light irradiance and fluence are critical parameters that affect the response to I-PDT. In vivo animal models are required to conduct light dose studies, to define optimal irradiance and fluence for I-PDT. Here we describe two animal models with locally advanced tumors that can be used to evaluate the response to I-PDT. One model is the C3H mouse bearing large subcutaneous SCCVII carcinoma (400-600 mm 3 ). Using this murine model, multiple light regimens with one or two optical fibers with cylindrical diffuser ends (cylindrical diffuser fiber, CDF) can be used to study tumor response to I-PDT. However, tissue heating may occur when 630 nm therapeutic light is delivered through CDF at an intensity ≥60 mW/cm and energy ≥100 J/cm. These thermal effects can impact tumor response while treating locally advanced mice tumors. Magnetic resonance imaging and thermometry can be used to study these thermal effects. A larger animal model, New Zealand White rabbit with VX2 carcinoma (~5000 mm 3 ) implanted in either the sternomastoid (neck implantation model) or the biceps femoris muscle (thigh implantation model), can be used to study I-PDT with image-based pretreatment planning using computed tomography. In the VX2 model, the light delivery can include the use of multiple laser fibers to test light dosimetry and delivery that are relevant for clinical use of I-PDT., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Radiolabeled short peptide ligands targeting prostate-specific membrane antigen (PSMA) were developed initially for imaging and treatment of prostate cancers. While many nonprostate solid tumors including hepatocellular carcinoma (HCC) express little PSMA, their neovasculature expresses a high level of PSMA, which is avid for Gallium-68-labeled PSMA-targeting radio-ligand ( 68 Ga-PSMA-11) for positron emission tomography (PET). However, the lack of a spontaneous animal model of tumor-associated vascular PSMA overexpression has hindered the development and assessment of PSMA-targeting radioligands for imaging and therapy of the nonprostatic cancers. We identified detectable indigenous PSMA expression on tumor neovascular endothelia in a naturally occurring woodchuck model of HCC., Methods: Molecular docking was performed with 3 bait PSMA ligands and compared between human and woodchuck PSMA. Initially, PET images were acquired dynamically after intravenously injecting 37 MBq (1.0 mCi) of 68 Ga-PSMA-11 into woodchuck models of HCC. Subsequently, 10-minute static PET scans were conducted for other animals 1-hour after injection due to HCC and liver background uptake stabilization at 30-45 minutes after injection. Liver tissue samples were harvested after imaging, fresh-frozen for quantitative reverse transcription polymerase chain reaction and western blot for validation, or fixed for histology for correlation., Results: Our preclinical studies confirmed the initial clinical findings of 68 Ga-PSMA-11 uptake in HCC. The agents (ligands and antibodies) developed against human PSMA were found to be reactive against the woodchuck PSMA., Conclusion: This animal model offers a unique opportunity for investigating the biogenesis of tumor-associated vascular PSMA, its functional role(s), and potentials for future treatment strategies targeting tumor vascular PSMA using already developed PSMA-targeting agents., Competing Interests: Conflicts of Interest: The authors disclose no conflicts.