Journal articles on the topic 'Subcutaneous heterogeneity'

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1

Xie, Yao, Yongli Ji, Yunrui Lu, Yuankun Ma, Hui Ni, Jian Shen, Hong Ma, et al. "Distinct Characteristics Between Perivascular and Subcutaneous Adipose-Derived Stem Cells." Diabetes 71, no. 2 (November 9, 2021): 321–28. http://dx.doi.org/10.2337/db20-1129.

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Adipose-derived stem cells (ADSCs) can differentiate into vascular lineages and participate in vascular remodeling. Perivascular ADSCs (PV-ADSCs) draw attention because of their unique location. The heterogeneity of subcutaneous (SUB) and abdominal ADSCs were well addressed, but PV-ADSCs’ heterogeneity has not been investigated. In this study, we applied single-cell analysis to compare SUB-ADSCs and PV-ADSCs regarding their subpopulations, functions, and cell fates. We uncovered four subpopulations of PV-ADSCs (Dpp4+, Col4a2+/Icam1+, Clec11a+/Cpe+, and Sult1e1+ cells), among which the Clec11a+ subpopulation potentially participated in and regulated PV-ADSC differentiation toward a smooth muscle cell (SMC) phenotype. Distinct characteristics between PV-ADSCs and SUB-ADSCs were revealed.
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Luong, Quyen, Jun Huang, and Kevin Y. Lee. "Deciphering White Adipose Tissue Heterogeneity." Biology 8, no. 2 (April 11, 2019): 23. http://dx.doi.org/10.3390/biology8020023.

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Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.
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Boulet, Nathalie, David Estève, Anne Bouloumié, and Jean Galitzky. "Cellular heterogeneity in superficial and deep subcutaneous adipose tissues in overweight patients." Journal of Physiology and Biochemistry 69, no. 3 (November 25, 2012): 575–83. http://dx.doi.org/10.1007/s13105-012-0225-4.

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4

Da, Yong, Ge Shen, Ming Zhou, Tao Wang, Dapeng Dong, Lina Bu, Yun Shao, Qiyun Sun, and Ruoying Yu. "Rapid subcutaneous progression after immunotherapy in pretreated patients with metastatic carcinoma: two case reports." Journal of International Medical Research 50, no. 4 (April 2022): 030006052210942. http://dx.doi.org/10.1177/03000605221094274.

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There is heterogeneity in cancer patients’ responses to immune checkpoint inhibitors (ICIs), including hyperprogression, which is very rapid tumor progression following immunotherapy, and pseudoprogression, which is an initial increase followed by a decrease in tumor burden or in the number of tumor lesions. This heterogeneity complicates clinical decisions because either premature withdrawal of the treatment or prolonged ineffective treatment harms patients. We presented two patients treated with ICIs with heterogeneous responses. One patient had Merkel cell carcinoma in the right thigh, and the other had nasopharyngeal squamous carcinoma. The first patient was treated with sintilimab and the second with sintilimab combined with abraxane. In the first patient, subcutaneous lesions grew substantially after the first cycle of treatment with sintilimab. In the second patient, subcutaneous lesions grew gradually after the second cycle of treatment with sintilimab combined with abraxane. In both cases, biopsy examination confirmed that newly emerged lesions were metastases of the primary tumor. These two cases remind clinicians that when subcutaneous nodules appear after treatment with ICIs, pathological biopsy is needed to determine the nature—pseudoprogression or rapid progression—of the disease course.
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Da, Yong, Ge Shen, Ming Zhou, Tao Wang, Dapeng Dong, Lina Bu, Yun Shao, Qiyun Sun, and Ruoying Yu. "Rapid subcutaneous progression after immunotherapy in pretreated patients with metastatic carcinoma: two case reports." Journal of International Medical Research 50, no. 4 (April 2022): 030006052210942. http://dx.doi.org/10.1177/03000605221094274.

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There is heterogeneity in cancer patients’ responses to immune checkpoint inhibitors (ICIs), including hyperprogression, which is very rapid tumor progression following immunotherapy, and pseudoprogression, which is an initial increase followed by a decrease in tumor burden or in the number of tumor lesions. This heterogeneity complicates clinical decisions because either premature withdrawal of the treatment or prolonged ineffective treatment harms patients. We presented two patients treated with ICIs with heterogeneous responses. One patient had Merkel cell carcinoma in the right thigh, and the other had nasopharyngeal squamous carcinoma. The first patient was treated with sintilimab and the second with sintilimab combined with abraxane. In the first patient, subcutaneous lesions grew substantially after the first cycle of treatment with sintilimab. In the second patient, subcutaneous lesions grew gradually after the second cycle of treatment with sintilimab combined with abraxane. In both cases, biopsy examination confirmed that newly emerged lesions were metastases of the primary tumor. These two cases remind clinicians that when subcutaneous nodules appear after treatment with ICIs, pathological biopsy is needed to determine the nature—pseudoprogression or rapid progression—of the disease course.
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6

Haac, Bryce E., Nathan N. O'Hara, C. Daniel Mullins, Deborah M. Stein, Theodore T. Manson, Herman Johal, Renan Castillo, Robert V. O'Toole, and Gerald P. Slobogean. "Patient preferences for venous thromboembolism prophylaxis after injury: a discrete choice experiment." BMJ Open 7, no. 8 (August 2017): e016676. http://dx.doi.org/10.1136/bmjopen-2017-016676.

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ObjectiveLimited evidence for the optimal venous thromboembolism (VTE) prophylaxis regimen in orthopaedic trauma leads to variability in regimens. We sought to delineate patient preferences towards cost, complication profile, and administration route (oral tablet vs. subcutaneous injection).DesignDiscrete choice experiment (DCE).SettingLevel 1 trauma center in Baltimore, USA.Participants232 adult trauma patients (mean age 47.9 years) with pelvic or acetabular fractures or operative extremity fractures.Primary and secondary outcome measuresRelative preferences and trade-off estimates for a 1% reduction in complications were estimated using multinomial logit modelling. Interaction terms were added to the model to assess heterogeneity in preferences.ResultsPatients preferred oral tablets over subcutaneous injections (marginal utility, 0.16; 95% CI: 0.11 - 0.21,P<0.0001). Preferences changed in favor of subcutaneous injections with an absolute risk reduction of 6.98% in bleeding, 4.53% in wound complications requiring reoperation, 1.27% in VTE, and 0.07% in death from pulmonary embolism (PE). Patient characteristics (sex, race, type of injury, time since injury) affected patient preferences (P<0.01).ConclusionsPatients preferred oral prophylaxis and were most concerned about risk of death from PE. Furthermore, the findings estimated the trade-offs acceptable to patients and heterogeneity in preferences for VTE prophylaxis.
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7

Raajendiran, Arthe, Christoph Krisp, David P. De Souza, Geraldine Ooi, Paul R. Burton, Renea A. Taylor, Mark P. Molloy, and Matthew J. Watt. "Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points." American Journal of Physiology-Endocrinology and Metabolism 320, no. 6 (June 1, 2021): E1068—E1084. http://dx.doi.org/10.1152/ajpendo.00473.2020.

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Adipocyte metabolism varies depending on anatomical location and the adipocyte protein composition may orchestrate this heterogeneity. We used SWATH proteomics in patient-matched human upper- (visceral and subcutaneous) and lower-body (glutealfemoral) adipocytes and detected 4,220 proteins and distinguishable regional proteomes. Upper-body adipocyte proteins were associated with glycolysis, de novo lipogenesis, mitochondrial dysfunction, and oxidative stress, whereas lower-body adipocyte proteins were associated with enhanced PPARα activation, fatty acid, and BCAA oxidation, TCA cycle flux, and oxidative phosphorylation.
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8

Patel, Pavankumar, and Nicola Abate. "Role of Subcutaneous Adipose Tissue in the Pathogenesis of Insulin Resistance." Journal of Obesity 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/489187.

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Burden of obesity has increased significantly in the United States over last few decades. Association of obesity with insulin resistance and related cardiometabolic problems is well established. Traditionally, adipose tissue in visceral fat depot has been considered a major culprit in development of insulin resistance. However, growing body of the literature has suggested that adipose tissue in subcutaneous fat depot, not only due to larger volume but also due to inherent functional characteristics, can have significant impact on development of insulin resistance. There are significant differences in functional characteristics of subcutaneous abdominal/truncal versus gluteofemoral depots. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger vicious cycle of inflammation in subcutaneous adipose tissue and subsequent ectopic fat deposition. It is important to shift focus from fat content to functional heterogeneity in adipose tissue depots to better understand the relative role of subcutaneous adipose tissue in metabolic complications of obesity. Therapeutic lifestyle change continues to be the most important intervention in clinical practice at any level of increased adiposity. Future pharmaceutical interventions aimed at improving adipose tissue function in various subcutaneous depots have potential to help maintain adequate insulin sensitivity and reduce risk for development of insulin resistance complications.
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Vargas, Gracie, Manisha Chandalia, Yongquan Jiang, Himara Davila, Massoud Motamedi, and Nicola Abate. "Heterogeneity in Subcutaneous Adipose Tissue Morphology and Metabolic Complications in Overweight and Obese Women." Metabolic Syndrome and Related Disorders 11, no. 4 (August 2013): 276–82. http://dx.doi.org/10.1089/met.2013.0024.

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10

Hadoke, Patrick W. F., Carol-Ann McIntyre, Gillian A. Gray, and Christine H. Buckley. "Functional heterogeneity of large and small resistance arteries isolated from biopsies of subcutaneous fat." General Pharmacology: The Vascular System 35, no. 3 (September 2000): 119–27. http://dx.doi.org/10.1016/s0306-3623(01)00085-4.

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11

Kengkoom, K., and S. Ampawong. "Staphylococcus sciuri associated to subcutaneous abscess and dermatitis in ICR mouse." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 69, no. 1 (February 2017): 117–22. http://dx.doi.org/10.1590/1678-4162-8563.

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ABSTRACT Subcutaneous mass was found in ICR mouse during daily health observation in the breeding colony of the National Laboratory Animal Center, Mahidol University, Thailand. The animal was subsequently culled and humanely sacrificed due to the institutional preventive medicine policy. Microbiological and histopathological studies were performed for definitive diagnosis. The results described that the case was subcutaneous abscess and chronic dermatitis in association with Staphylococcus sciuri infection without epizootic and mortality. This was determined as the first reported case in Thailand occurring in mouse. Reproductive stress and abrasion skin wound may be the predisposing factors. Although pathogenic staphylococci in laboratory animals are limited to S. aureus and S. xylosus, S. sciuri opportunistic properties, natural history, and heterogeneity should not be forgotten.
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12

Ong, Wee Kiat, Smarajit Chakraborty, and Shigeki Sugii. "Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine." Biomolecules 11, no. 7 (June 22, 2021): 918. http://dx.doi.org/10.3390/biom11070918.

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Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs.
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13

Gundarov, Igor Alekseevich, and Eleonora Igorevna Pilguy. "Heterogeneity of regional population morbidity in Russia – assessment and prognosis principals." Medical Technologies. Assessment and Choice (Медицинские технологии. Оценка и выбор), no. 3 (37) (November 20, 2019): 16–21. http://dx.doi.org/10.31556/2219-0678.2019.37.3.016-021.

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The aim of the study is to develop the assessment technology and forecasting heterogeneity of regional incidence for differentiated healthcare management. Material and methods. The incidence of skin and subcutaneous tissue diseases in children aged 0–14 years in 2009–2017 in Russia was used as a material. The sources of information were the data of state statistics. Generally accepted statistical methods were used for the analysis. Results. The expressed heterogeneity of regions of the Russian Federation on children’s dermatological morbidity with a coefficient of variation of 28% is revealed. The marked size of heterogeneity steadily persisted in the 8-year follow-up. The stable predisposition of subjects to a certain rank place is proved. The territories were ranked according to the total 9-year rank. The classification of territories into types of low, medium and high risk of morbidity is carried out. Long-term stability of regional trajectories allows extrapolating them for prediction. Conclusion. The complex of statistical calculations forming the standard “forecast of regional heterogeneity technology assessment” is carried out. Used methods is universal and it could be used in assessment of any sign heterogeneity: morbidity, mortality, fertility, crime, unemployment, etc.
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14

Jiang, Songling, Lingjuan Piao, Eun Bi Ma, Hunjoo Ha, and Joo Young Huh. "Associations of Circulating Irisin with FNDC5 Expression in Fat and Muscle in Type 1 and Type 2 Diabetic Mice." Biomolecules 11, no. 2 (February 20, 2021): 322. http://dx.doi.org/10.3390/biom11020322.

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Irisin is an exercise-induced myokine, suggested to exert beneficial effects on metabolism. However, the studies on the regulation of irisin secretion and the expression of its precursor FNDC5 have shown conflicting data. The discrepancies among previous correlation studies in humans are related to the heterogeneity of the study population. The fact that irisin is not only a myokine but also an adipokine leads to the further complexity of the role of irisin in metabolic regulation. In this study, we examined the regulation of FNDC5 expression and irisin in circulation in both type 1 and type 2 diabetic mice, and their potential relationships with metabolic parameters. In streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet (HFD)-induced obese mice and db/db mice, the circulating irisin as well as FNDC5 gene expression in subcutaneous fat was downregulated. Muscle FNDC5 expression was only significantly lower in STZ mice, and epididymal fat FNDC5 expression was unaltered. It is interesting to note that plasma irisin levels correlated positively with subcutaneous fat FNDC5 expression, but not epididymal fat or muscle. Moreover, both irisin levels and subcutaneous fat FNDC5 correlated negatively with markers of insulin resistance. These results suggest a regulatory role for subcutaneous fat-derived FNDC5/irisin in metabolic disease.
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15

Hou, Biyu, Yan Zhao, Ping He, Chunyang Xu, Peng Ma, Sin Man Lam, Bowen Li, et al. "Targeted lipidomics and transcriptomics profiling reveal the heterogeneity of visceral and subcutaneous white adipose tissue." Life Sciences 245 (March 2020): 117352. http://dx.doi.org/10.1016/j.lfs.2020.117352.

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16

Tordjman, Joan, Adeline Divoux, Edi Prifti, Christine Poitou, Veronique Pelloux, Danielle Hugol, Arnaud Basdevant, et al. "Structural and inflammatory heterogeneity in subcutaneous adipose tissue: Relation with liver histopathology in morbid obesity." Journal of Hepatology 56, no. 5 (May 2012): 1152–58. http://dx.doi.org/10.1016/j.jhep.2011.12.015.

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17

Ogawa, R., M. R. Baidillah, S. Akita, and M. Takei. "Investigation of physiological swelling on conductivity distribution in lower leg subcutaneous tissue by electrical impedance tomography." Journal of Electrical Bioimpedance 11, no. 1 (May 14, 2020): 19–25. http://dx.doi.org/10.2478/joeb-2020-0004.

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AbstractThere is a strong need for a non-invasive measurement technique that is capable of accurately identifying the physiological condition change or heterogeneity of subcutaneous adipose tissue (SAT) by localizing the abnormalities within the compartment. This paper aims to investigate the feasibility of Electrical Impedance Tomography (EIT) to assess the interstitial fluid in subcutaneous adipose tissue as an enhancement method of bioelectrical impedance spectroscopy (BIS). Here, we demonstrate the preliminary result of EIT with a wearable 16 electrodes sensor. The image-based reference EIT with fat weighted threshold method is proposed. In order to evaluate the performance of our novel method, a physiological swelling experiment is conducted, and Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is also applied as a comparison with EIT results. The experimental results showed that the proposed method was able to distinguish the physiological swelling condition and effectively to remove the unexpected background noise. Furthermore, the conductivity variation in the subcutaneous layer had a good correlation with extracellular water volume change from MFBIA data; the correlation coefficient R2 = 0.927. It is concluded that the proposed method provides a significant prospect for SAT assessment.
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von Depka Prondzinskl, M., U. von Stamm, and E. B. Brcker. "Heterogeneity of the T-cell and macrophage infiltrate in cutaneous and subcutaneous metastases of melanoma patients." Melanoma Research 3, no. 3 (June 1993): 203–8. http://dx.doi.org/10.1097/00008390-199306000-00009.

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19

Fitzgerald, Jessica E., Brook K. Byrd, Roshani A. Patil, Rendall R. Strawbridge, Scott C. Davis, Chiara Bellini, and Mark Niedre. "Heterogeneity of circulating tumor cell dissemination and lung metastases in a subcutaneous Lewis lung carcinoma model." Biomedical Optics Express 11, no. 7 (June 8, 2020): 3633. http://dx.doi.org/10.1364/boe.395289.

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20

Alkhouli, Nadia, Jessica Mansfield, Ellen Green, James Bell, Beatrice Knight, Neil Liversedge, Ji Chung Tham, et al. "The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix." American Journal of Physiology-Endocrinology and Metabolism 305, no. 12 (December 15, 2013): E1427—E1435. http://dx.doi.org/10.1152/ajpendo.00111.2013.

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Adipose tissue (AT) expansion in obesity is characterized by cellular growth and continuous extracellular matrix (ECM) remodeling with increased fibrillar collagen deposition. It is hypothesized that the matrix can inhibit cellular expansion and lipid storage. Therefore, it is important to fully characterize the ECM's biomechanical properties and its interactions with cells. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. AT was obtained from 44 subjects undergoing surgery. Force/extension and stress/relaxation data were obtained. The effects of osmotic challenge were measured to investigate the cellular contribution to tissue mechanics. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. AT showed nonlinear stress/strain characteristics of up to a 30% strain. Comparing paired subcutaneous and omental samples ( n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa ( P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa ( P < 0.001), respectively. The energy dissipation density was lower in subcutaneous AT ( n = 13): 0.1 ± 0.1 and 0.3 ± 0.2 kPa, respectively ( P = 0.006). Stress/relaxation followed a two-exponential time course. When the incubation medium was exchanged for deionized water in specimens held at 30% strain, force decreased by 31%, and the final modulus increased significantly. Nonlinear microscopy revealed collagen and elastin networks in close proximity to adipocytes and a larger-scale network of larger fiber bundles. There was considerable microscale heterogeneity in the response to strain in both cells and matrix fibers. These results suggest that subcutaneous AT has greater capacity for expansion and recovery from mechanical deformation than omental AT.
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Bai, Xue, Michelle S. Kim, Gyulnara Kasumova, Justine Vanessa Cohen, Donald P. Lawrence, Christine Freedman, Riley Fadden, et al. "Organ site-specific radiological responses in anti-PD-1 monotherapy treated advanced melanoma patients." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9552. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9552.

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9552 Background: Melanoma is notorious for its high degree of heterogeneity with the implication that metastases in different sites react differently to immunotherapy. We aimed to explore the site-specific response pattern in anti-PD-1 monotherapy treated advanced melanoma patients. Methods: Clinical data was collected retrospectively from advanced melanoma patients treated with anti-PD-1 monotherapy at Massachusetts General Hospital (MGH) from Sept 2009 to Dec 2017. Radiological evaluations were carried out by radiologists from the MGH Tumor Imaging Metrics Core using irRECIST 1.1. Statistical analysis was carried out using ANOVA test. Results: Among 61 evaluated patients, 56 (91.8%) had at least one measurable target lesion(s) at baseline, including 35 (57.4%) patients with measurable lymph nodes (LN)/subcutaneous lesion(s), 25 (50.0%) with lung lesion(s), and 21 (34.4%) with liver lesion(s). At week-12 radiological evaluation after anti-PD-1 monotherapy initiation, lesions at different sites responded differently at marginal statistical significance (P = 0.071), namely mean percent changes compared with baseline were 3.75%, 5.12%, and -30.95% for LN/subcutaneous, liver, and lung lesions, respectively. Among patients who had disease under control (CR/PR/SD) (n = 37, 60.7%) by week-12 evaluation, the mean tumor percentage change at week-24 compared with week-12 were -8.94%, -12.18%, and -5.91% for LN/subcutaneous, liver, and lung lesions, respectively (P = 0.479). Conclusions: Although our small sample size limits definitive discrimination in organ site-specific response differences, it appears that lung lesions respond more quickly and to a greater extent compared with LN/subcutaneous and liver lesions in advanced melanoma patients treated with anti-PD-1 monotherapy. We will explore this in a larger, multicenter cohort.
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Elolemy, Gehan, Abdulrahman Al Rashidi, Ahmed Dehrab, Ammar Almathkouri, Alex Varghese, Mustafa Chikhly, and Fatema Alkhawaja. "Successful treatment of refractory lupus erythematosus profundus with the interleukin-6 antagonist tocilizumab: a case report." Lupus 29, no. 7 (March 19, 2020): 791–94. http://dx.doi.org/10.1177/0961203320913944.

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Lupus erythematosus profundus (LEP) is an unusual form of cutaneous lupus erythematosus (CLE) characterized by multiple subcutaneous induration and associated with considerable physical and psychological morbidity. The heterogeneity of CLE makes it difficult to understand its underlying pathogenesis and represents a therapeutic challenge. Recently, new insight into the pathogenesis of CLE has implicated various cytokines, opening doors to targeted biologic agents. We report a case of a 23-year-old female who presented with refractory LEP ulcers as an initial presentation of systemic lupus erythematosus. The lesions were resistant to multiple conventional therapies and remarkably responded to tocilizumab.
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He, Ping, Biyu Hou, Yanliang Li, Chunyang Xu, Peng Ma, Sin Man Lam, Victoria Gil, et al. "Lipid Profiling Reveals Browning Heterogeneity of White Adipose Tissue by Β3-Adrenergic Stimulation." Biomolecules 9, no. 9 (September 3, 2019): 444. http://dx.doi.org/10.3390/biom9090444.

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Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of β3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.
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Tejeda, J. F., A. Hernández-Matamoros, J. M. García-Cascos, and E. González. "Variability in subcutaneous fat composition of Iberian pigs reared in free-range conditions in the southwest of the Iberian Peninsula." Canadian Journal of Animal Science 100, no. 4 (December 1, 2020): 665–73. http://dx.doi.org/10.1139/cjas-2019-0191.

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A total of 80 free-range Iberian pigs reared with acorns and grass in eight different free-range systems (n = 10) in the southwest of the Iberian Peninsula were used to determine the relationship between fatty acid, tocopherol, and neophytadiene subcutaneous fat composition. The pigs were fed extensively for 79.1 ± 9.5 d from 110.9 ± 11.9 kg live weight at the beginning of the final fattening phase to 175.0 ± 15.9 kg slaughtered weight. Quercus suber and Quercus rotundifolia acorns were characterised by a high content of C18:1n-9 (58.3 and 63.1%, respectively) and γ-tocopherol [43.7 and 43.0 mg kg−1 dry matter (DM), respectively], while grass exhibited a high content of C18:3n-3 (42.5%), α-tocopherol (366.5 mg kg−1 DM) and neophytadiene (136.2 relative area units). The C18:1n-9 (54.4%–57.7%) and γ-tocopherol (2.7–4.1 mg kg−1 DM) contents in subcutaneous fat from Iberian pigs differed (p < 0.001) between the free-range systems studied. Pasture intake had a significant effect (p < 0.01) on subcutaneous fat content of C18:3n-3 (0.5%–0.8%), α-tocopherol (7.8–13.1 mg kg−1 DM) and neophytadiene (2.6–6.3 relative area units). However, the results demonstrated no correlations between accumulated levels of these compounds throughout the free-range period. In conclusion, the absence of correlations corroborated the heterogeneity of extensive rearing systems, with variations between years and geographical areas where the Iberian pigs were reared.
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Wang, Haifeng, Jingjing Guan, Xiaohan Zhang, Xinxin Wang, Tianliang Ji, Dandan Hou, Guiru Wang, and Jiao Sun. "Effect of Cold Application on Pain and Bruising in Patients With Subcutaneous Injection of Low-Molecular-Weight Heparin: A Meta-Analysis." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602962090534. http://dx.doi.org/10.1177/1076029620905349.

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To evaluate the effect of cold application on pain and bruising after the subcutaneous injection of low-molecular-weight heparin, 8 electronic databases were searched for randomized controlled trials and quasiexperimental studies from the inception of the databases to June 2019. Review Manager 5.3 software was used for the heterogeneity test and meta-analysis. A total of 8 studies including 694 participants were analyzed. The cold application group assessed with the Verbal Descriptor Scale pain assessment tool showed significant reductions in pain intensity immediately after injection. Compared to the control group, the cold application group showed a reduction in the occurrence of bruises at 12 hours, 24 hours, and 48 hours after injection. There was no significant difference in the area of bruising in the cold application group at 48 hours after injection, but the area of bruising at 72 hours after injection was significantly reduced. These results show that cold application can reduce the incidence of pain and bruising after subcutaneous injection of low-molecular-weight heparin and reduce the area of bruising 72 hours after injection. Additional studies with larger sample sizes are needed to confirm these findings.
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Liew, F. Y., S. M. Millott, and J. A. Schmidt. "A repetitive peptide of Leishmania can activate T helper type 2 cells and enhance disease progression." Journal of Experimental Medicine 172, no. 5 (November 1, 1990): 1359–65. http://dx.doi.org/10.1084/jem.172.5.1359.

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Leishmaniasis provides a biologically relevant model to analyze the heterogeneity of CD4+ T cells and may lead to answering the major question of the mechanism for the preferential induction of T helper type 1 (Th1) and Th2 cells. Using synthetic peptides corresponding to the tandemly repeating regions of Leishmania proteins, we have identified an epitope that can preferentially induce the disease-exacerbating Th2 cells in susceptible BALB/c mice. Lymph node cells from BALB/c mice immunized subcutaneously with the octamer (p183) of the repeating 10-mer peptide EAEEAARLQA proliferated strongly against the peptide as well as the soluble antigen extract (SolAg) of Leishmania major. The proliferative T cells are CD4+, major histocompatibility complex class II restricted, and secrete interleukin 4 (IL-4) but little or no IL-2 and interferon gamma when stimulated with the peptide in vitro. T cells from BALB/c mice with progressive disease, but not from BALB/c mice cured of the infection, recognized this epitope. BALB/c mice injected subcutaneously with p183 developed significantly exacerbated disease when subsequently challenged with L. major. Furthermore, subcutaneous injection with p183 prevented the subsequent induction of resistance against L. major by intravenous immunization with soluble antigen. The T cell response to p183 is H-2d restricted. Immunization of the genetically resistant B10.D2 mice with p183 also produced strong T cell responses and exacerbated disease when challenged with L. major.
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Pan, Runzhou, Yan Zhang, Rongrong Wang, Yao Xu, Hong Ji, and Yongcai Zhao. "Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials." PLOS ONE 17, no. 12 (December 30, 2022): e0279889. http://dx.doi.org/10.1371/journal.pone.0279889.

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Objective Type 2 diabetes mellitus(T2DM) is closely related to sarcopenic obesity(SO). Body composition measurement including body weight, body mass index, waist circumference, percentage body fat, fat mass, muscle mass, visceral adipose tissue and subcutaneus adipose tissue, plays a key role in evaluating T2DM and SO. The weight reduction effect of sodium-glucose cotransporter 2(SGLT-2) inhibitors has been demonstrated. However, there are warnings that SGLT-2 inhibitors should be used with caution because they may increase the risk of sarcopenia. The effect of SGLT-2 inhibitors on body composition in T2DM is inconclusive. In this work, a meta-analysis of randomized controlled trials was conducted to evaluate the effect of SGLT-2 inhibitors on body composition in T2DM. Methods PubMed, the Cochrane Library, EMbase and Web of Science databases were searched by computer. All statistical analyses were carried out with Review Manager version 5. 3. Results were compared by weight mean difference(WMD), with 95% confidence intervals(CI) for continuous outcomes. A random effects model was applied regardless of heterogeneity. The I2 statistic was applied to evaluate the heterogeneity of studies. Publication bias was assessed using Funnel plots. Results 18 studies with 1430 participants were eligible for the meta-analysis. SGLT-2 inhibitors significantly reduced body weight(WMD:-2. 73kg, 95%CI: -3. 32 to -2. 13, p<0. 00001), body mass index(WMD:-1. 13kg/m2, 95%CI: -1. 77 to -0. 50, p = 0. 0005), waist circumference(WMD:-2. 20cm, 95%CI: -3. 81 to -0. 58, p = 0. 008), visceral fat area(MD:-14. 79cm2, 95%CI: -24. 65 to -4. 93, p = 0. 003), subcutaneous fat area(WMD:-23. 27cm2, 95% CI:-46. 44 to -0. 11, P = 0. 05), fat mass(WMD:-1. 16kg, 95%CI: -2. 01 to -0. 31, p = 0. 008), percentage body fat(WMD:-1. 50%, 95%CI:-2. 12 to -0. 87, P<0. 00001), lean mass(WMD:-0. 76kg, 95%CI:-1. 53 to 0. 01, P = 0. 05) and skeletal muscle mass(WMD:-1. 01kg, 95%CI:-1. 91 to -0. 11, P = 0. 03). Conclusion SGLT-2 inhibitors improve body composition in T2DM including body weight, body mass index, waist circumference, visceral fat area, subcutaneous fat area, percentage body fat and fat mass reduction, but cause adverse effects of reducing muscle mass. Therefore, until more evidence is obtained to support that SGLT-2 inhibitors increase the risk of sarcopenia, not only the benefit on body composition, but also the adverse effect of the reduction in muscle mass by SGLT-2 inhibitors in T2DM should be considered.
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Vaeteewoottacharn, Kulthida, Chawalit Pairojkul, Ryusho Kariya, Kanha Muisuk, Kanokwan Imtawil, Yaovalux Chamgramol, Vajarabhongsa Bhudhisawasdi, et al. "Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model." Cells 8, no. 5 (May 23, 2019): 496. http://dx.doi.org/10.3390/cells8050496.

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Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. Recent multi-omics studies revealed the promising targets for CCA treatment; however, limited models for drug discovery are available. This study aimed to develop a patient-derived xenograft (PDX) model as well as PDX-derived cell lines of CCA for future drug screening. From a total of 16 CCA frozen tissues, 75% (eight intrahepatic and four extrahepatic subtypes) were successfully grown and subpassaged in Balb/c Rag-2-/-/Jak3-/- mice. A shorter duration of PDX growth was observed during F0 to F2 transplantation; concomitantly, increased Oct-3/4 and Sox2 were evidenced in 50% and 33%, respectively, of serial PDXs. Only four cell lines were established. The cell lines exhibited either bile duct (KKK-D049 and KKK-D068) or combined hepatobiliary origin (KKK-D131 and KKK-D138). These cell lines acquired high transplantation efficiency in both subcutaneous (100%) and intrasplenic (88%) transplantation models. The subcutaneously transplanted xenograft retained the histological architecture as in the patient tissues. Our models of CCA PDX and PDX-derived cell lines would be a useful platform for CCA precision medicine.
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Nieto, Juan C., Claudia Arajol, Loreto Carmona, Carlos Marras, and Luis Cea-Calvo. "Adherence to subcutaneous biological therapies in patients with inflammatory rheumatic diseases and inflammatory bowel disease: a systematic review." Immunotherapy 13, no. 5 (April 2021): 433–58. http://dx.doi.org/10.2217/imt-2021-0011.

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Aim: To assess adherence to subcutaneous biologicals in adults with inflammatory rheumatic diseases or inflammatory bowel disease and evaluate factors possibly associated with adherence. Materials & methods: Systematic searches were conducted of main databases from January 2000 to June 2019. Results: 41 articles (32 full papers and nine abstracts) were included in the review. Among studies which used a medication possession ratio threshold of ≥80% as the end point, adherence varied from 28.8 to 89.4%. Possible predictors of adherence were older age, professional or family member support, belief in medication necessity, lower concerns about medication and monthly versus weekly administration. Conclusion: Considerable variability in adherence rates across published studies reflects study heterogeneity and the absence of a ‘gold standard’ to measure adherence.
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Pukhalskaya, Tatsiana, Bruce R. Smoller, David M. Menke, and Olayemi Sokumbi. "A Previously Unrecognized Granulomatous Variant of Gamma-Delta T-Cell Lymphoma." Dermatopathology 8, no. 2 (June 17, 2021): 221–28. http://dx.doi.org/10.3390/dermatopathology8020027.

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Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome.
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Costouros, Nick G., Dominique Lorang, Yantian Zhang, Marshall S. Miller, Felix E. Diehn, Stephen M. Hewitt, Michael V. Knopp, et al. "Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI." Molecular Imaging 1, no. 3 (July 1, 2002): 153535002002021. http://dx.doi.org/10.1162/15353500200202124.

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Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.
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Araújo-Vilar, David, Antía Fernández-Pombo, Berta Victoria, Adrián Mosquera-Orgueira, Silvia Cobelo-Gómez, Ana Castro-Pais, Álvaro Hermida-Ameijeiras, Lourdes Loidi, and Sofía Sánchez-Iglesias. "Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant." Journal of Clinical Medicine 10, no. 7 (April 3, 2021): 1497. http://dx.doi.org/10.3390/jcm10071497.

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Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromised.
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Wu, Ying, K. Alaine Broadaway, Chelsea K. Raulerson, Laura J. Scott, Calvin Pan, Arthur Ko, Aiqing He, et al. "Colocalization of GWAS and eQTL signals at loci with multiple signals identifies additional candidate genes for body fat distribution." Human Molecular Genetics 28, no. 24 (November 6, 2019): 4161–72. http://dx.doi.org/10.1093/hmg/ddz263.

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Abstract Integration of genome-wide association study (GWAS) signals with expression quantitative trait loci (eQTL) studies enables identification of candidate genes. However, evaluating whether nearby signals may share causal variants, termed colocalization, is affected by the presence of allelic heterogeneity, different variants at the same locus impacting the same phenotype. We previously identified eQTL in subcutaneous adipose tissue from 770 participants in the Metabolic Syndrome in Men (METSIM) study and detected 15 eQTL signals that colocalized with GWAS signals for waist–hip ratio adjusted for body mass index (WHRadjBMI) from the Genetic Investigation of Anthropometric Traits consortium. Here, we reevaluated evidence of colocalization using two approaches, conditional analysis and the Bayesian test COLOC, and show that providing COLOC with approximate conditional summary statistics at multi-signal GWAS loci can reconcile disagreements in colocalization classification between the two tests. Next, we performed conditional analysis on the METSIM subcutaneous adipose tissue data to identify conditionally distinct or secondary eQTL signals. We used the two approaches to test for colocalization with WHRadjBMI GWAS signals and evaluated the differences in colocalization classification between the two tests. Through these analyses, we identified four GWAS signals colocalized with secondary eQTL signals for FAM13A, SSR3, GRB14 and FMO1. Thus, at loci with multiple eQTL and/or GWAS signals, analyzing each signal independently enabled additional candidate genes to be identified.
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Hum, Nicholas R., Aimy Sebastian, Sean F. Gilmore, Wei He, Kelly A. Martin, Aubree Hinckley, Karen R. Dubbin, et al. "Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo." Cancers 12, no. 3 (March 14, 2020): 690. http://dx.doi.org/10.3390/cancers12030690.

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Current pre-clinical models of cancer fail to recapitulate the cancer cell behavior in primary tumors primarily because of the lack of a deeper understanding of the effects that the microenvironment has on cancer cell phenotype. Transcriptomic profiling of 4T1 murine mammary carcinoma cells from 2D and 3D cultures, subcutaneous or orthotopic allografts (from immunocompetent or immunodeficient mice), as well as ex vivo tumoroids, revealed differences in molecular signatures including altered expression of genes involved in cell cycle progression, cell signaling and extracellular matrix remodeling. The 3D culture platforms had more in vivo-like transcriptional profiles than 2D cultures. In vivo tumors had more cells undergoing epithelial-to-mesenchymal transition (EMT) while in vitro cultures had cells residing primarily in an epithelial or mesenchymal state. Ex vivo tumoroids incorporated aspects of in vivo and in vitro culturing, retaining higher abundance of cells undergoing EMT while shifting cancer cell fate towards a more mesenchymal state. Cellular heterogeneity surveyed by scRNA-seq revealed that ex vivo tumoroids, while rapidly expanding cancer and fibroblast populations, lose a significant proportion of immune components. This study emphasizes the need to improve in vitro culture systems and preserve syngeneic-like tumor composition by maintaining similar EMT heterogeneity as well as inclusion of stromal subpopulations.
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Barchetta, Ilaria, Francesco Angelico, Maria Del Ben, Michele Di Martino, Flavia Agata Cimini, Laura Bertoccini, Licia Polimeni, et al. "Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes." Clinical Science 130, no. 19 (August 31, 2016): 1753–62. http://dx.doi.org/10.1042/cs20160348.

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Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65–0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different risk profiles among T2D patients.
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Rahnemaei, Fatemeh Alsadat, Fatemeh Abdi, Reza Pakzad, Seyedeh Hajar Sharami, Fatemeh Mokhtari, and Elham Kazemian. "Association of body composition in early pregnancy with gestational diabetes mellitus: A meta-analysis." PLOS ONE 17, no. 8 (August 15, 2022): e0271068. http://dx.doi.org/10.1371/journal.pone.0271068.

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Introduction Body composition as dynamic indices constantly changes in pregnancy. The use of body composition indices in the early stages of pregnancy has recently been considered. Therefore, the current meta-analysis study was conducted to investigate the relationship between body composition in the early stages of pregnancy and gestational diabetes. Method Valid databases searched for papers published from 2010 to December 2021 were based on PRISMA guideline. Newcastle Ottawa was used to assess the quality of the studies. For all analyses, STATA 14.0 was used. Mean difference (MD) of anthropometric indices was calculated between the GDM and Non-GDM groups. Pooled MD was estimated by “Metan” command, and heterogeneity was defined using Cochran’s Q test of heterogeneity, and I 2 index was used to quantify heterogeneity. Results Finally, 29 studies with a sample size of 56438 met the criteria for entering the meta-analysis. Pooled MD of neck circumference, hip circumference, waist hip ratio, and visceral adipose tissue depth were, respectively, 1.00 cm (95% CI: 0.79 to 1.20) [N = 5; I^2: 0%; p: 0.709], 7.79 cm (95% CI: 2.27 to 13.31) [N = 5; I2: 84.3%; P<0.001], 0.03 (95% CI: 0.02 to 0.04) [N = 9; I2: 89.2%; P<0.001], and 7.74 cm (95% CI: 0.11 to 1.36) [N = 4; I^2: 95.8%; P<0.001]. Conclusion Increased neck circumference, waist circumference, hip circumference, arm circumference, waist to hip ratio, visceral fat depth, subcutaneous fat depth, and short stature increased the possibility of developing gestational diabetes. These indices can accurately, cost-effectively, and affordably assess the occurrence of gestational diabetes, thus preventing many consequences with early detection of gestational diabetes.
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Jiang, Changying, Shaojun Zhang, Shengjian Huang, Yang Liu, Rongjia Zhang, Angela Leeming, Joseph Mitchell McIntosh, et al. "Pdox Models Empower Preclinical Drug Evaluation and Mechanistic Studies Via Faithful Recapitulation of the Pathology, Complex Heterogeneity, Genetic-Transcriptomic Landscape, and Therapeutic Response of Mantle Cell Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 3974. http://dx.doi.org/10.1182/blood-2019-128810.

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Introduction: Mantle cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma with poor prognosis. MCL cells display complex inter- and intra-patient heterogeneity and various dissemination patterns involving nodal and extranodal sites across patients. Due to its microenvironment distinct from patients' microenvironments, heterotopic or subcutaneous patient-derived xenograft (PDX) models are not ideal for studying clinical disease pathology, tumor heterogeneity, and clinical therapeutic responses. In contrast, patient-derived orthotopic xenografts (PDOXs) have been shown in many cancer types to faithfully recapitulate the primary patient cancers. Although a few MCL PDOX models have reportedly been established, these models have not been clearly defined or applied in mechanistic studies or preclinical drug studies. Methods: We established multiple MCL PDOX models from primary patient samples via intravenous or intraosseous routes and characterized these models for the first time in multiple dimensions. We performed longitudinal pathological and histological characterization of PDOX cells involved in the spleen, liver, stomach, lymph nodes, bone marrow, and/or peripheral blood across generations and disease stages, whole exon sequencing across dissemination sites and generations, and single-cell RNA sequencing across dissemination sites. We evaluated in vivo response to ibrutinib and venetoclax in one PDOX model derived from an ibrutinib-venetoclax dual-resistant MCL patient. An in vivo drug efficacy screen was performed to search for potential therapies to overcome ibrutinib-venetoclax dual resistance. Results: Longitudinal pathological and histological characterization of the PDOX models revealed faithful recapitulation of the clinical disease of MCL patients, and the PDOX models can be stably passed on to a series of generations. In vivo drug treatments including ibrutinib and venetoclax recapitulated the clinical response to these therapies. Whole exon sequencing and single-cell RNA sequencing of one ibrutinib-venetoclax dual-resistant PDOX model and its parental primary patient cells reflected reliable recapitulation of primary patient disease in genetic, cellular, and transcriptomic profiles, providing insights into potential targets to overcome therapeutic resistance. Single-cell transcriptomic profiling also revealed increased cancer hallmark signaling in the PDOX model compared to the primary patient samples used to established the PDOX model. Based on this, we performed an in vivo drug screen for the PDOX model and identified promising drugs that dramatically inhibited tumor burden in the spleen, liver, bone marrow, and peripheral blood. Intriguingly, a subcutaneous model (scPDOX) was derived from this PDOX model via subcutaneous implantation of its G1 PDOX cells and was found to be ibrutinib-resistant but venetoclax-sensitive in vivo. To understand the differential response to venetoclax and differential microenvironment of the PDOX model and its derived scPDOX model, whole exon sequencing and single-cell RNA sequencing of the cells from these models is currently being pursued. Conclusions: Our MCL PDOX models faithfully resembled the original MCL disease in histopathology, disease progression, tumor heterogeneity, genetic-transcriptomic profiling, and therapeutic responses. Therefore, these models provide invaluable platforms for mechanistic studies and preclinical drug studies. Disclosures Wang: VelosBio: Research Funding; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria; Kite Pharma: Consultancy, Research Funding; Acerta Pharma: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding.
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Zhao, Qi, Maria del Pilar Molina-Portela, Asma Parveen, Alexander Adler, Christina Adler, Hock E, Wei Wang, et al. "Heterogeneity and chimerism of endothelial cells revealed by single-cell transcriptome in orthotopic liver tumors." Angiogenesis 23, no. 4 (May 21, 2020): 581–97. http://dx.doi.org/10.1007/s10456-020-09727-9.

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Abstract The liver is a common host organ for cancer, either through lesions that arise in liver epithelial cells [e.g., hepatocellular carcinoma (HCC)] or as a site of metastasis by tumors arising in other organs (e.g., colorectal cancer). However, the changes that occur in liver stromal cells in response to cancer have not been fully characterized, nor has it been determined whether the different sources of liver cancer induce distinct stromal changes. Here, we performed single-cell profiling of liver stromal cells from mouse models of induced spontaneous liver cancer or implanted colorectal liver metastases, with a focus on tumor endothelial cells (ECs). While ECs in liver tissue adjacent to cancerous lesions (so-called adjacent normal) corresponded to liver zonation phenotypes, their transcriptomes were also clearly altered by the presence of a tumor. In comparison, tumor EC transcriptomes show stronger similarities to venous than sinusoidal ECs. Further, tumor ECs, independent of tumor origin, formed distinct clusters displaying conserved “tip-like” or “stalk-like” characteristics, similar to ECs from subcutaneous tumors. However, they also carried liver-specific signatures found in normal liver ECs, suggesting an influence of the host organ on tumor ECs. Our results document gene expression signatures in ECs in liver cancer and show that the host organ, and not the site of tumor origin (liver versus colorectal), is a primary determinant of EC phenotype. In addition, primarily in tumors, we further defined a cluster of chimeric cells that expressed both myeloid and endothelial cell markers and might play a role in tumor angiogenesis.
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Demichell, Romano, Graziella Pratesi, Roberto Foroni, Maria Grazia Barbagini, and Monica Tortoreto. "Relative Role of Host and tumor in the Growth Pattern of Murine and Human Neoplasms following Subcutaneous Transplantation in Mice." Tumori Journal 75, no. 5 (October 1989): 429–34. http://dx.doi.org/10.1177/030089168907500506.

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The growth patterns of two murine and eight human tumors, bilaterally implanted into subcutaneous tissue of groups of recipient mice, were studied. A Gompertz equation was fitted to experimental data for each individual implant and the Gompertz parameters were utilized as quantitative growth characteristics. The relative roles of the tumor-implanted flank (right versus left), of the individual host and of the tumor were analyzed by the paired t-test, simple linear regression model, one-way and two-way analysis of variance. Sixty pairs of Gompertz curves were obtained in seventy animals. Heterogeneity was the main characteristic of the growth pattern in all tumors under study, with a wide variability among the Gompertz parameters. Statistical analysis of experimental data showed that only the tumor systematically influenced the growth characteristics, whereas neither the tumor-implanted flank nor the individual host played a significant role. These results have both theoretical and practical implications.
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Elias, E. George. "New approach to adjuvant therapy in high-risk melanoma patients." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13129-e13129. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13129.

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e13129 Background: Cutaneous melanoma is relatively chemoresistant, but it is an immunogenic tumor. However, it is very heterogenetic. As a result, the present adjuvant therapy has been met with limited success due to non-specifity of therapy. GM-CSF administration in cutaneous metastatic melanoma increases the number and activation of naive dendritic cells which are antigen presenting cells that can process tumor antigens, while IL-2 stimulates and activates mainly T cells. Hypothesis: The consequential administration of a single short course of both agents intradermally at the primary site, prior to its excision, can result in high tumor cell kill and forms a triad of autologous tumor cells, dendritic cells and and T lymphocytes. This triad can be capable of inducing cytotoxic cells that can be taken up by the lymphatics to regional lymph nodes (LN). Methods: Newly diagnosed high risk patients, each is to receive a single injection of GM-CSF: 500 microgram at the primary (biopsy) site on day # 1, followed by IL-2: 11 million IU/day injected at the same site on days 2 and 3, one week before the definitive surgery. Postoperatively, the patient is to receive low dose GM-CSF at 250 microgram twice/week, self-administered subcutaneously, to maintain the initial response. Results: In a pilot study, the pathological examination of rsected tissues from treated patient revealed complete tumor necrosis with massive histiocytosis at the primary site. Immunohistochemical studies showed overexpression of CD4+, CD8+, CD25+ and CD83+ both at the primary and LN. Conclusions: This non-toxic outpatient program is safe and well tolerated. It can initiate patient-specific and tumor-specific cytotoxic T cells that can overcome heterogeneity of the tumor and confers therapeutic specificity. It also establishes the lymphatic route of administration. Postoperative subcutaneous administration of GM-CSF is to systemically maintain the initial response. The beneficial effect of this approach on survival has to be evaluated in a prospective controlled randomized clinical trial.
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E. Davis II, Gerald, George Sarandev, Alexander T. Vaughan, Kamal Al-Eryani, and Reyes Enciso. "The Use of Biologic Agents in the Treatment of Oral Lesions due to Pemphigus and Behcet's Disease: A Systematic Review." Journal of Anesthesiology and Pain Therapy 1, no. 1 (April 30, 2020): 14–23. http://dx.doi.org/10.29245/2768-5365/2020/1.1105.

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Background: Current treatments for pemphigus and Behcet's disease, such as corticosteroids, have long-term serious adverse effects. Objective: The objective of this systematic review was to evaluate the efficacy of biologic agents (biopharmaceuticals manufactured via a biological source) on the treatment of intraoral lesions associated with pemphigus and Behcet's disease compared to glucocorticoids or placebo. Methods: PubMed, Web of Science, Cochrane Library, and EMBASE were searched for randomized controlled studies up to January 2019. Bias was assessed with the risk of bias tool. Results: Out of 740 references retrieved, only four randomized controlled trials (RCTs) were included, comprised of a total of 158 subjects (138 pemphigus and 20 Behcet's disease). All studies were assessed at high risk of bias. Heterogeneity of data prevented the authors from performing a meta-analysis. Infliximab or rituximab with short-term prednisone showed higher safety and lowered cumulative prednisone dose than prednisone alone in the treatment of pemphigus. Subcutaneous injection of etanercept provided 45% of patients free of ulcers compared to 5% in the placebo group in one study with Behcet's disease; however, no difference was found in pemphigus patients. Conclusion: Though biological agents alone or in combination with prednisone showed favorable results in three RCTs compared to prednisone alone or placebo, a meta-analysis could not be undertaken due to high heterogeneity. Results are inconclusive, and larger, well-designed RCTs are needed.
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Yip, Connie, Amanda Weeks, Gary J. R. Cook, Karen Shaw, Muhammad Siddique, David B. Landau, and Vicky Goh. "Pathological heterogeneity after trastuzumab and combination chemotherapy in HER2+ gastroesophageal adenocarcinoma xenograft." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 42. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.42.

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42 Background: Trastuzumab (T) is the standard of care in advanced HER2+ gastroesophageal (GE) adenocarcinoma with response in 47% of patients. We evaluated its pathological effects in a HER2+ OE19 xenograft model aiming to improve future treatment intensification/response assessment. Methods: SCID mice (n = 23) bearing subcutaneous OE19 tumors were treated with intraperitoneal saline (control), Cisplatin 4mg/kg once a week (C), Trastuzumab 20mg/kg twice a week (T) or Cisplatin and Trastuzumab (CT) for 2 weeks. Volumetric tumor response was measured by MRI. Excised tumors were stained for IHC markers of hypoxia (Pimonidazole), proliferation (Ki-67) and angiogenesis (CD34). Hypoxic (HF) and proliferative fractions (PF) were defined as the ratios of tumor area positively stained for Pimonidazole/Ki-67 to area of whole tumor section. Microvessel density (MVD) was defined as the average number of blood vessels/endothelial cells identified within 0.01cm2field at x100 magnification. Pathological assessment was performed for whole tumor, centre and rim. Mean±SD are presented. Kruskal-Wallis test was used to compare HF, PR, MVD and volumetric change between groups; significance at < 0.05. Results: Tumor growth was reduced in CT (+83% from baseline MRI) compared to control (+600%), C (+275%) and T (+129%) groups (p= 0.015). Monotherapy treated tumors had lower HF (C 0.08±0.03, T 0.09±0.07) compared to CT (0.16±0.06) and control (0.15±0.04) (p= 0.039). T and CT treated animals had higher MVD (T 23.5±12.7, CT 37.3±10.3) compared to control (18.1±10.4) and C (18.1±7.5) (p= 0.014). Whole tumor PF was lower in the monotherapy groups but this was not significant (p =0.123). PF and MVD were higher in tumor centre compared to rim in T and CT groups compared to control but there was no spatial difference in hypoxia distribution. Conclusions: Tumor control was improved with combination treatment but no synergistic pathological effect was seen; CT treated tumors were more hypoxic/angiogenic compared to monotherapy with greater cellular density/angiogenesis within tumor centre. This could be due to predominant early cytostatic effect and ongoing angiogenic normalisation with CT therapy at 2 weeks.
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43

Tan, Peck S., Amanda L. Gavin, Nadine Barnes, Duane W. Sears, David Vremec, Ken Shortman, Sebastian Amigorena, Patricia L. Mottram, and P. Mark Hogarth. "Unique Monoclonal Antibodies Define Expression of FcγRI on Macrophages and Mast Cell Lines and Demonstrate Heterogeneity Among Subcutaneous and Other Dendritic Cells." Journal of Immunology 170, no. 5 (March 1, 2003): 2549–56. http://dx.doi.org/10.4049/jimmunol.170.5.2549.

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44

Ravindrakumar, Chandru, Saravanan Sanniyasi, Pervez Ahmed, and Surya Subramaniam. "Laparoendoscopic Approach in the Management of Abdominal Wall Hernia - Our Initial Experience from Chennai, India." Journal of Evolution of Medical and Dental Sciences 10, no. 31 (August 2, 2021): 2422–26. http://dx.doi.org/10.14260/jemds/2021/496.

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BACKGROUND Incisional hernias are a common occurrence following midline laparotomy. Numerous techniques have been employed in the management of this common condition. Randomized trials and evidence based medicine help us in deciding what the optimal treatment is in a particular condition. This is often not possible in case of hernia due to the heterogeneity of population. Laparoscopy is gaining popularity in the management of this condition as results are comparable to open surgery with lesser post-operative pain. The placement of mesh intraperitoneally as in laparoscopic intraperitoneal onlay mesh repair has its own disadvantage such as mesh erosion into viscera. Placement of mesh endoscopically as an onlay repair seems to be a good option, more so in the developing world, considering the prohibitive cost of composite mesh. The purpose of this study was to analyze the technical ease, reproducibility, outcome, postoperative pain and complications of laparoendoscopic hybrid technique in the management of abdominal wall hernia. METHODS This technique combines the benefits of minimal invasive surgery and ease of onlay mesh repair, while reducing wound related problems associated with open surgery. It involves first a laparoscopic approach in entry, reducing the contents, visualizing the sac followed by endoscopic dissection using the same trocar anterior to abdominal wall in the subcutaneous plane. This is followed by sac dissection, suturing the abdominal wall and placing an onlay mesh RESULTS Fifteen patients have been operated; no subcutaneous drains were placed. A polypropylene onlay mesh was used and fixation done with suturing. No major complications were seen. There was no subcutaneous emphysema. CONCLUSIONS The laparoendoscopic hybrid technique offers advantage of being minimally invasive and having lower wound related complications, with early ambulation and decreased hospital stay. It is also technically easier to suture the defect and allow complete excision of the sac. However a randomized trial is necessary and larger series are required to compare the results with other established techniques. KEY WORDS Incisional Hernia, Laparo - Endoscopic - Onlay Mesh, Surgical Techniques, SCOLA
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45

Chen, Xiaochen, Wu Depei, Aining Sun, Huiying Qiu, Xiaojin Wu, and Xiaolan Shi. "Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Study of 12 Cases." Blood 118, no. 21 (November 18, 2011): 5217. http://dx.doi.org/10.1182/blood.v118.21.5217.5217.

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Abstract Abstract 5217 Objective: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and distinct type of T-cell lymphoma. The objective of this study was to explore the clinical presentation, treatment, and prognosis of patients with SPTCL. Methods: Twelve cases of SCPTCL, treated in our hospital between June 2005 and June 2010, were included in this study. Their clinicopathological data were reviewed and analyzed retrospectively. Results: The median age at diagnosis was 41 years (range 25–69 years) and 7 (58%) were women. 9 cases had a CD3+, CD4-, CD8- phenotype; 2 cases, a CD3+, CD4-, CD8+ phenotype; and 1 case, a CD3+, CD4+, CD8- T-cell phenotype. In all cases, strong expression of cytotoxic proteins (granzyme B, TIA-1, perforin) was observed. CD56 was expressed in 8 of 12 cases. 4 patients had presented with solitary or localized skin lesions. Ulceration was observed in 3 patients. B symptoms, such as fever, chills, night sweats, and weight loss, had been recorded in 7 of 12 patients. Laboratory abnormalities, mainly anemia, leucopenia, thrombocytopenia or combined cytopenias, and elevated liver function tests and lactate dehydrogenase, were reported in 4 patients. Bone marrow examination showed histiocytic hyperplasia, hemophagocytosis, or decreased cellularity in 3 cases, but no evidence of lymphoma. A HPS was diagnosed in 4 of 12 patients (33%), and was fatal in 2 of them. Four patients presenting with solitary or localized skin lesions had been treated with radiotherapy (2 cases) or surgery (2 cases). All 4 patients reached complete remission and only 1 of them showed a skin relapse, which was treated successfully with radiotherapy again. Eight patients with diffused lesions were treated with chemotherapy (CHOP or CHOP-like courses). After initial treatment 5 (63%) of 8 patients had developed new skin lesions, and 2 of them had developed extracutaneous localizations. Then the 3 of the relapsed patients were treated with autologous stem cell transplantation, all of whom obtained complete remission. At the time of last follow-up (median follow-up: 34 months; range: 10–60 months), 5 patients are in complete remission, 4 patients have ongoing skin disease, while 3 patients have died, 2 of the complications of HPS or therapy-related side effects and 1 of unrelated disease. The 3-year OS and DSS of the patients were 75% and 42%, respectively. Patients without HPS had a significantly better 3-year OS (88%) than patients with HPS (50%; P <.001). Conclusion: SPTCL seems to be a kind of heterogeneity disease. The factors associated with an unfavorable disease course were: diffuse lesions, a low white blood cell count, elevated lactate dehydrogenase, and combine with HPS. Autologous stem cell transplantation may improve the overall survival of high risk patients. Disclosures: No relevant conflicts of interest to declare.
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46

Song, Xiuyue, Yali Yu, Yu Leng, Lei Ma, Jie Mu, Zihan Wang, Yalan Xu, et al. "Expanding tubular microvessels on stiff substrates with endothelial cells and pericytes from the same adult tissue." Journal of Tissue Engineering 13 (January 2022): 204173142211253. http://dx.doi.org/10.1177/20417314221125310.

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Endothelial cells (ECs) usually form a monolayer on two-dimensional (2D) stiff substrates and a tubular structure with soft hydrogels. The coculture models using ECs and pericytes derived from different adult tissues or pluripotent stem cells cannot mimic tissue-specific microvessels due to vascular heterogeneity. Our study established a method for expanding tubular microvessels on 2D stiff substrates with ECs and pericytes from the same adult tissue. We isolated microvessels from adult rat subcutaneous soft connective tissue and cultured them in the custom-made tubular microvascular growth medium on 2D stiff substrates (TGM2D). TGM2D promoted adult microvessel growth for at least 4 weeks and maintained a tubular morphology, contrary to the EC monolayer in the commercial medium EGM2MV. Transcriptomic analysis showed that TGM2D upregulated angiogenesis and vascular morphogenesis while suppressing oxidation and lipid metabolic pathways. Our method can be applied to other organs for expanding organ-specific microvessels for tissue engineering.
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47

Koibuchi, N., S. Matsuzaki, H. T. Ma, M. Sakai, and S. Yamaoka. "Induction of ornithine decarboxylase immunoreactivity in the male mouse kidney following testosterone treatment: an axial heterogeneity in the proximal tubule." Journal of Endocrinology 136, no. 1 (January 1993): 85—NP. http://dx.doi.org/10.1677/joe.0.1360085.

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ABSTRACT The effect of testosterone on the activity of ornithine decarboxylase (ODC), its protein level and immunocytochemical distribution were examined in the mouse kidney. Male BALB C mice at 8 weeks of age were used throughout. Fourteen hours before death, they received a subcutaneous injection of testosterone (1 mg/animal) or solvent to measure renal ODC activity or to detect the distribution of ODC immunoreactivity in the kidney. Renal ODC activity and the content of the enzyme were markedly increased after testosterone treatment. Histologically, few cells that were obviously immunoreactive to ODC were observed in the control animals and in the testosterone-treated animals a marked increase in ODC immunoreactivity was observed only in the cortex. ODC immunoreactive cells were located diffusely in the proximal tubule. In the pars recta, cells were stained weakly and homogeneously, while in the pars convoluta, the luminal surface of the cells showed stronger immunoreactivity. Moreover, many granule-like particles that were strongly ODC immunoreactive were observed inside the lumen of the pars convoluta. These results show that testosterone treatment induces an increase in ODC content in certain cells located in the proximal tubule of the cortex. Journal of Endocrinology (1993) 136, 85–89
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48

DuBuske, Lawrence. "Efficacy and safety of sublingual allergen immunotherapy." Allergy and Asthma Proceedings 43, no. 4 (July 1, 2022): 272–80. http://dx.doi.org/10.2500/aap.2022.43.220036.

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Sublingual immunotherapy (SLIT)-tablets represent a new allergen immunotherapy option for clinicians. In North America, there are five SLIT-tablets approved for the treatment of allergic rhinoconjunctivitis (ARC). No SLIT-drops products are currently approved in the United States or Canada. This work reviewed the efficacy of the timothy grass SLIT-tablet, five-grass SLIT-tablet, ragweed SLIT-tablet, house-dust mite SLIT-tablet, and tree SLIT-tablet in patients with ARC. All the SLIT-tablets showed consistent clinical efficacy for the treatment of ARC in large, double-blind, placebo-controlled trials, including for both patients who were monosensitized and those who were polysensitized. Treatment with house-dust mite SLIT-tablet has shown efficacy in patients who are pollen sensitized during their respective pollen seasons. In contrast to SLIT-tablets, efficacy studies of SLIT-drops show high heterogeneity of treatment effect. Although data are scarce, data that compared the efficacy of SLIT-tablets versus ARC pharmacotherapy generally indicated that SLIT-tablets had a greater benefit than pharmacotherapy when compared with placebo, particularly for perennial ARC. When compared with subcutaneous immunotherapy, analysis of these data indicated that SLIT-tablets had a benefit over subcutaneous immunotherapy in regard to safety but somewhat less benefit in regard to efficacy. The safety of SLIT-tablets has been well documented, and a U.S. Food and Drug Administration class label with safety considerations is present in the prescribing information for all SLIT-tablets. No new safety signals have been observed after reinitiating SLIT-tablets after a short treatment interruption.
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49

Russo, S. A., and O. Greengard. "gamma-Glutamyltranspeptidase activity in intact leukocytes: flow cytometric analysis and sorting." Journal of Histochemistry & Cytochemistry 37, no. 3 (March 1989): 323–30. http://dx.doi.org/10.1177/37.3.2563747.

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A fluorescent method developed for visualizing gamma-glutamyltranspeptidase (GGT) in intact liver cells was adapted to leukocytes and used in a multiparameter flow cytometric study of blood and bone marrow cells from rats with subcutaneous implants of mammary carcinoma 5A. The severe granulocytosis caused by this non-metastatic tumor was preceded by a progressive rise in the percentage of leukocytes with high GGT fluorescence. Both granulocytes and small, immature cells of bone marrow showed increased GGT expression, whereas in blood this increase was attributable entirely to mature granulocytes. At 28 days (but not yet at 14 days) after carcinoma implantation, 20-30% of blood or bone marrow granulocytes constituted a distinct subpopulation in that their GGT fluorescence intensity range was much higher and did not overlap with the range for the rest of the population. The results indicate that fluorescent GGT assay of intact leukocytes provides a useful probe for flow cytometric analysis of population heterogeneity in leukoproliferative disorders.
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50

Radu, Pompilia, Maryam Ebadi, Aldo J. Montano-Loza, and Jean Francois Dufour. "What Is the Role of Body Composition Assessment in HCC Management?" Cancers 14, no. 21 (October 27, 2022): 5290. http://dx.doi.org/10.3390/cancers14215290.

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In the last decade, body composition (BC) assessment has emerged as an innovative tool that can offer valuable data concerning nutritional status in addition to the information provided by the classical parameters (i.e., body mass index, albumin). Furthermore, published data have revealed that different types of body composition are associated with different outcomes. For example, abnormalities of skeletal muscle, a common finding in cirrhotic and oncologic patients, are associated with poor outcome (i.e., high morbidity and high mortality). The disposition (visceral/subcutaneous adipose tissue) and radiodensity of adipose tissue proved to also be determinant factors for HCC outcome. Despite all the advantages, BC assessment is not part of the standard pre-therapeutic workup. The main reasons are the high heterogeneity of data, the paucity of prospective studies, the lack of a standard assessment method, and the interpopulation variation of BC. This paper aims to review the available evidence regarding the role of BC as a prognostic tool in the HCC population undergoing various therapies.
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