Tumor-like Disease Research Articles

Abstract 157: Atherosclerosis Is A Smooth Muscle Cell-driven Tumor-like Disease

Background: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (e.g., macrophages, T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as “phenotypic switching,” plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. Methods: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches to investigate the features of SMC-derived cells in atherosclerosis. Results: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of oncogenic mutant, Kras G12D , in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide a proof of concept that niraparib, an anti-cancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. Conclusions: Our findings demonstrate that atherosclerosis is a SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant KrasG12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

Research on the potential mechanism of Deapioplatycodin D against pulmonary fibrosis based on bioinformatics and experimental verification

BackgroundPulmonary fibrosis (PF) is a group of respiratory diseases that are extremely complex and challenging to treat. Due to its high mortality rate and short survival, it's often referred to as a “tumor-like disease” that poses a serious threat to human health. ObjectiveWe aimed validate the potential of Deapioplatycodin D (DPD) to against PF and clarify the underlying mechanism of action of DPD for the treatment of PF based on bioinformatics and experimental verification. This finding provides a basis for the development of safe and effective therapeutic PF drugs based on DPD. MethodsWe used LPS-induced early PF rats as a PF model to test the overall efficacy of DPD in vivo. Then, A variety of bioinformatics methods, such as WGCNA, LASSO algorithm and immune cell infiltration (ICI), were applied to analyze the gene microarray related to PF obtained from Gene Expression Omnibus (GEO) to obtained key targets of PF. Finally, an in vitro PF model was constructed based on BEAS-2B cells while incorporating rat lung tissues to validate the regulatory effects of DPD on critical genes. ResultsDPD can effectively alleviate inflammatory and fibrotic markers in rat lungs. WGCNA analysis resulted in a total of six expression modules, with the brown module having the highest correlation with PF. Subsequently, seven genes were acquired by intersecting the genes in the brown module with DEGs. Five key genes were identified as potential biomarkers of PF by LASSO algorithm and validation dataset verification analysis. In the ICI analysis, infiltration of activated B cell, immature B cell and natural killer cells were found to be more crucial in PF. Ultimately, it was observed that DPD could modulate key genes to achieve anti-PF effects. ConclusionIn short, these comprehensive analysis methods were employed to identify critical biomarkers closely related to PF, which helps to elucidate the pathogenesis and potential immunotherapy targets of PF. It also provides essential support for the potential of DPD against PF.

Langerhans cell histiocytosis involving the temporal bone with destruction and subsequent reossification of the bony labyrinth boundaries.

With an incidence between 1-9/100 000 per year, Langerhans cell histiocytosis (LCH) is a rather rare disease from the hemato-oncologic disease spectrum (Hayes et al. 2009). The tumorlike disease with proliferation of histiocytic cells may manifest as localized to one organ or disseminated with infiltration of a wide variety of organs. Approximately 25-30 % of these cases show involvement of the temporal bone (Ni et al. 2017). With vertigo persisting for three years, chronic mastoiditis, and acute progressive hearing loss bilaterally (r > l) for three weeks, a 41-year-old woman presented at an emergency department. The DVT showed extensive bony destruction of large parts of the temporal bone on both sides, involving the vestibular organ, the cochlea, and the internal auditory canal. To confirm the suspicion of a systemic inflammatory process, a PE was performed from the mastoid with bioptic confirmation of an LCH. Systemic therapy was initiated. Post-therapeutic imaging showed almost complete remission with reossification of the preexisting defect zones and the internal auditory canal and labyrinth structures again showed bony margins. Clinically, there was an improvement of the vegetative symptoms with remaining bilateral sensorineural hearing loss. LCH of the temporal bone is a rare and often misdiagnosed disease due to its nonspecific clinical presentation. Awareness of temporal bone LCH and its occurrence in adults is essential for accurate and consistent diagnosis. · LCH is a rather rare disease from the hemato-oncological spectrum. · Affection of the temporal bone, especially such an extensive one (as in this case report), is rather atypical in adulthood. · Use of systemic therapy resulted in remission. · There was complete reossification of the osseous structures post-therapy. · A cochlear implant was able to be implanted to compensate for hearing loss.

Engineering Ferroptosis Inhibitors as Inhalable Nanomedicines for the Highly Efficient Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) refers to chronic progressive fibrotic interstitial pneumonia. It is called a "tumor-like disease" and cannot be cured using existing clinical drugs. Therefore, new treatment options are urgently needed. Studies have proven that ferroptosis is closely related to the development of IPF, and ferroptosis inhibitors can slow down the occurrence of IPF by chelating iron or reducing lipid peroxidation. For example, the ferroptosis inhibitor deferoxamine (DFO) was used to treat a mouse model of pulmonary fibrosis, and DFO successfully reversed the IPF phenotype and increased the survival rate of mice from 50% to 90%. Given this, we perceive that the treatment of IPF by delivering ferroptosis inhibitors is a promising option. However, the delivery of ferroptosis inhibitors faces two bottlenecks: low solubility and targeting. For one thing, we consider preparing ferroptosis inhibitors into nanomedicines to improve solubility. For another thing, we propose to deliver nanomedicines through pulmonary drug-delivery system (PDDS) to improve targeting. Compared with oral or injection administration, PDDS can achieve better delivery and accumulation in the lung, while reducing the systemic exposure of the drug, and is an efficient and safe drug-delivery method. In this paper, three possible nanomedicines for PDDS and the preparation methods thereof are proposed to deliver ferroptosis inhibitors for the treatment of IPF. Proper administration devices and challenges in future applications are also discussed. In general, this perspective proposes a promising strategy for the treatment of IPF based on inhalable nanomedicines carrying ferroptosis inhibitors, which can inspire new ideas in the field of drug development and therapy of IPF.

Upregulation of LAG3 modulates the immune imbalance of CD4+ T-cell subsets and exacerbates disease progression in patients with alveolar echinococcosis and a mouse model.

Infection with the cestode Echinococcus multilocularis (E. multilocularis) causes alveolar echinococcosis (AE), a tumor-like disease predominantly affecting the liver but able to spread to any organ. T cells develop functional defects during chronic E. multilocularis infection, mostly due to upregulation of inhibitory receptors such as T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and programmed death-1 (PD-1). However, the role of lymphocyte activation gene-3 (LAG3), an inhibitory receptor, in AE infection remains to be determined. Here, we discovered that high expression of LAG3 was mainly found in CD4+ T cells and induced regulatory T cells (iTregs) in close liver tissue (CLT) from AE patients. In a mouse model of E. multilocularis infection, LAG3 expression was predominantly found in T helper 2 (Th2) and Treg subsets, which secreted significantly more IL-4 and IL-10, resulting in host immune tolerance and disease progression at a late stage. Furthermore, LAG3 deficiency was found to drive the development of effector memory CD4+ T cells and enhance the type 1 CD4+ T-cell immune response, thus inhibiting metacestode growth in vivo. In addition, CD4+ T cells from LAG3-deficient mice produced more IFN-γ and less IL-4 when stimulated by E. multilocularis protoscoleces (EmP) antigen in vitro. Finally, adoptive transfer experiments showed that LAG3-knockout (KO) CD4+ T cells were more likely to develop into Th1 cells and less likely to develop into Tregs in recipient mice. Our work reveals that high expression of LAG3 accelerates AE disease progression by modulating the immune imbalance of CD4+ T-cell subsets. These findings may provide a novel immunotherapeutic strategy against E. multilocularis infection.

Endometriosis-targeted MRI imaging using bevacizumab-modified nanoparticles aimed at vascular endothelial growth factor.

Endometriosis is a tumor-like disease with high recurrence. In this case, the accurate imaging-based diagnosis of endometriosis can help clinicians eradicate it by improving their surgical plan. However, although contrast agents can improve the visibility of the tissue of interest in vivo via magnetic resonance imaging (MRI), the lack of biomarkers in endometriosis hinders the development of agents for its targeted imaging and diagnosis. Herein, aiming at the enriched vascular endothelial growth factor (VEGF) in endometriosis, we developed a targeting MRI contrast agent modified with bevacizumab, i.e., NaGdF4@PEG@bevacizumab-Cy5.5 nanoparticles (NPBCNs), to detect endometriosis. NPBCNs showed negligible cytotoxicity and high affinity towards VEGF in endometrial cells in vitro. Furthermore, NPBCNs generated a strong signal enhancement in vivo in endometriosis lesions in rats in T1-weighted images via MRI at 3 days post-injection, as confirmed by the histopathological staining results and fluorescence imaging on the same day. Our approach can enable NPBCNs to target endometriosis effectively, thus avoiding missed diagnoses.

Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in Echinococcus multilocularis-infected mice.

The cestode Echinococcus multilocularis larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood. Dendritic cells (DCs) are key cellular components in facilitating immune tolerance in chronic diseases, including AE. Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1-/-) mice display less severe AE as compared to wild-type (WT) mice during the infection. Mechanistically, IDO1 prevents optimal T cells responses by programming DCs into a tolerogenic state. Specifically, IDO1 prevents the maturation and migration potential of DCs, as shown by the significantly enhanced expression of the antigen-presenting molecule (MHC II), costimulatory molecules (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1-/- mice as compared to infected wild-type mice. More importantly, the tolerogenic phenotype of DCs is partly reverted in IDO1-/- mice, as indicated by enhanced activation, proliferation, and differentiation of both CD4+ and CD8+ - T cells upon infection with Echinococcus multilocularis, in comparison with WT mice. Interestingly, in absence of IDO1, CD4+ T cells are prone to differentiate to effector memory cells (CD44+CD62L-); in contrast, CD8+ T cells are highly biased to the central memory phenotype (CD44+CD62L+). Overall, these data are the first to demonstrate the essential role of IDO1 signaling in inducing immunosuppression in mice infected with Echinococcus multilocularis.

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.

Влияние пандемии COVID-19 на заболеваемость гортани

Among the symptoms of COVID-19, scientists pay the most attention to damage to the lower respiratory tract, neurological and cardiovascular systems, gastrointestinal tract, psychoemotional disorders and anosmia. Less common are articles about the state of auditory and vestibular as well as voice disorders. Inflammatory changes of the larynx, trauma due to intubation and severe coughing, neuropathy of the recurrent laryngeal nerve, consequences of the pathology of the bronchopulmonary system, psychogenic factors are indicated as the cause of dysphonia. The purpose of our study is to determine the structure of laryngeal morbidity in voice professionals during the COVID-19 pandemic. The analysis of case histories of 2,438 patients of voice professions who applied to the phoniatric department of the Saint Petersburg Institute of Ear, Throat, Nose, and Speech was performed. The diagnosis, a history of COVID-19, dysphonia directly during COVID-19 were considered. The number of patients compared to the period before the COVID-19 decreased by 39,8% due to anti-epidemic measures. The leading causes were functional dysphonia (29,3%), acute and chronic laryngitis (27,8%). Tumor-like disease are in third place (19,1%). Paresis of the larynx (8,5%) was diagnosed less frequently compared to the period before the pandemic, which is associated with a reduction in the number of elective operations on the organs of the head and neck. The frequency of laryngeal neoplasms (4,1%) has remained at the same level, almost half of them are malignant. Congenital malformations of the larynx were found in 2,9% of patients. Vascular pathology of the vocal folds was detected in 1.1%, scar stenosis, in 0,5%, rare diseases of the larynx, in 0,6% of patients. Appeals on the other occasions accounted for 6,1% of cases. 43,7% of patient have had COVID-19. The direct connection of dysphonia with COVID-19 was revealed in 18,0% of them. The most common cause of impaired vocal function against the background of coronavirus infection were functional dysphonia (39,1%) and inflammatory diseases of the larynx (34,9%). Tumor-like disease became the next most common (17,2%). Vascular pathology of the vocal folds was found less frequently (5,2%). Unilateral vocal fold paresis was detected in 3,1% of patients. One patient suffered from chondroperichondritis with granuloma formation in the area of the arytenoid cartilage of the larynx (0,5%). In relation to the total number of examined patients, COVID-19 as the cause of dysphonia was 7,9% of cases.

Combined Analyses of GWAS, RNA-Sequence and Hi-C—A Novel Approach to Dissect Keloid Genetic Mechanism

Keloid is a tumor-like disease with infiltrating growth and high recurrence rate. Genetic contribution is expected due to the presence of autosomal dominant inheritance. However, GWAS failed to reveal functional mutation in exon regions but single nucleotide polymorphisms in non-coding region at loci 1q41, 3q22.3 and 15p21.3, suggesting the necessity of innovative genetic investigation. This study employed GWAS, RNA-sequence and Hi-C analysis to dissect keloid genetic mechanism using paired keloids and adjacent normal skins. Differentially expressed (DE) genes (DEGs), miRNAs and lncRNAs mined by epigenetics and transcriptome sequencing were identified to construct an DEmiRNA-DEG-DElncRNA network. From which, significant pathways involved in keloid pathogenesis including PPAR, axon guidance, insulin, ECM receptor, ERK and Wnt were enriched and verified. Furthermore, topologically associated domains at susceptible loci were located via Hi-C database in fibroblast IMR90 and six DERNAs (RAB27A, PYGO1, LINC02275, TEX9, NDAAF4-CCPG1, hsa-miR-335-5p) were identified and verified using immunohistochemistry assay, western blot and RT-qPCR. Their functions for cell cycle and apoptosis were confirmed by overexpressing and knocking-down assays. This study firstly revealed key biomarkers and pathways using RNA-sequence and previously reported locus mutation, indicating a feasible approach to reveal genetic contribution of keloid and other diseases failed by GWAS alone. Funding Statement: This research was supported by the National Natural Science Foundation (81671921 to WL). Declaration of Interests: The authors have declared no conflicting interests. Ethics Approval Statement: The study was approved by the Ethics Committee of Shanghai Ninth People's Hospital.

Active Components from Traditional Herbal Medicine for the Potential Therapeutics of Idiopathic Pulmonary Fibrosis: A Systemic Review.

Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of the lung parenchyma, excessive matrix accumulation, and decline in lung function. IPF still remains a great burden to the universe. At the moment, the available therapeutic regimens utilized for IPF such as non-pharmacological therapies (lung transplantation) and pharmacological therapies (drugs, nintedanib, pirfenidone, etc.) are normally accompanied by significant limitations, such as adverse reactions, low bioavailability, poor selectivity, low-tissue distribution, in vivo instability, systemic toxicity, inconveniency and unsafe usage. There is a need for the exploration and discovery of new novel remedies by researchers and scientists globally. Recent numerous preliminary studies have laid significant emphasis and demonstrated the antifibrotic importance, good curative actions (little or no adverse reactions), and multiple target sites of the active components from traditional herbal medicine (THM) against IPF, which could serve as a modern, alternative and potential therapeutics or drug candidates in treating IPF. This paper extensively summarizes the pharmacological actions and signaling pathways or mechanisms of active components obtained from THM for treating IPF. Moreover, the sources and modernization, markets, relevant FDA and CFDA studies (the USA and China), preclinical analysis, and various compositions of THM currently under clinical trials are also highlighted. Additionally, this present analytical data would be instrumental towards further drug progression or advancement of active components from THM for the potential therapeutics of IPF in the future.

Osteopontin Regulates Endometrial Stromal Cell Migration in Endometriosis through the PI3K Pathway

Endometriosis is generally characterized as a tumor-like disease because of its potential for distant metastasis and local tissue invasion, while whether osteopontin (OPN) plays a role in the pathogenesis of endometriosis has not been thoroughly investigated. We investigated the expression of OPN, urokinase plasminogen activator (uPA), phosphatidylinositol 3 kinase (PI3K), and phospho-PI3 kinase (p-PI3K) in endometrial stromal cells (ESCs). The serum concentration of OPN was determined by enzyme-linked immunosorbent assays (ELISA). OPN was downregulated to explore the corresponding change of uPA, p-PI3K, F-actin, and α-tubulin. The expression of OPN, uPA, PI3K, and p-PI3K was evaluated by western blot and quantitative real-time PCR (RT-qPCR) and the expression of F-actin and α-tubulin was confirmed by immunofluorescence assay. The proliferation and migration abilities of ESCs were investigated by CCK8, transwell, and wound scratch assays. Endometrial OPN, p-PI3K, and uPA expressions and serum OPN levels were increased in patients with endometriosis compared with the control. The expressions of p-PI3K, uPA, and α-tubulin were decreased by siRNA-OPN interference in ectopic ESCs. Activation and inhibition of the PI3K pathway apparently upregulate and downregulate uPA expression. Knockdown of OPN and inhibition of the PI3K pathway remarkably inhibited cell migration in ectopic ESCs. Meanwhile, activation of the PI3K pathway promoted the migration ability of ectopic ESCs. OPN may regulate the expression of uPA through the PI3K signal pathway to affect the migration ability of ESCs, indicating that OPN, uPA, and the PI3K pathway may be potential targets for interrupting development of endometriosis.

Lack of PD-1 suppressed the growth of E. multilocularis in mice

Abstract The cestode Echinococcus multilocularis (E. multilocularis) infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor-like disease predominantly located in the liver. Until now, there have been few studies to explore how PD-1 contributes to parasite’s escape from immune attack and how it might be reversed. In this study, we found that liver PD-1 expression was significantly enhanced in AE patients. Compared to E. multilocularis infected wild-type mice, we found lesion’s weights in the liver were significantly deceased (101.20±43.12mg vs 393.70±123.5 mg, P<0.05) and lesion’s volumes were significantly lower (82.17±28.43 mm3 vs 429.30±148.30 mm3, P<0.05) in E. multilocularis infected PD-1 knockdown mice. This study demonstrates blocking PD-1 may suppress the growth of E. multulocularis in mice, and represent a possible approach to E. multilocularis immunotherapy.

Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model.

The cestode Echinococcus multilocularis infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor-like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explore how T-cell exhaustion contributes to the parasite's escape from immune attack and how it might be reversed. In this study, we found that liver T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was significantly enhanced and positively correlated with lesion activity in AE patients. High TIGIT expression in both liver-infiltrating and blood T cells was associated with their functional exhaustion, and its ligand CD155 was highly expressed by hepatocytes surrounding the infiltrating lymphocytes. In co-culture experiments using human blood T cells and hepatic cell line HL-7702, CD155 induced functional impairment of TIGIT+ T cells, and in vitro blockade with TIGIT antibody restored the function of AE patients' T cells. Similar TIGIT-related functional exhaustion of hepatic T cells and an abundant CD155 expression on hepatocytes were observed in E. multilocularis-infected mice. Importantly, in vivo blocking TIGIT prevented T-cell exhaustion and inhibited disease progression in E. multilocularis-infected mice. Mechanistically, CD4+ T cells were totally and CD8+ T cells partially required for anti-TIGIT-induced regression of parasite growth in mice. This study demonstrates that E. multilocularis can induce T-cell exhaustion through inhibitory receptor TIGIT, and that blocking this checkpoint may reverse the functional impairment of T cells and represent a possible approach to immunotherapy against AE.

The association between autosomal dominant polycystic kidney disease and cancer.

Autosomal dominant polycystic kidney disease (ADPKD) is considered as a tumor-like disease because there are many biological similarities between ADPKD and cancer. However, the commonalities between them are provocative, particularly under the conditions of recent clinical studies. In this paper, we review clinical studies about the association between cancer and ADPKD, and compare the biological characteristics between them, with focusing on cell proliferation, differentiation, migration, apoptosis, and polarity. With detailed literature reviewing, we believe that ADPKD patients have a higher risk of tumorigenesis and thus highly recommend being aware of tumorigenesis during follow-up in patients with ADPKD.

Pancreatic hamartoma, a rare benign disease of the pancreas: A case report.

Pancreatic hamartoma is an extremely rare, non-neoplastic, mass-forming lesion that may be mistaken for malignancy, and the pre-operative diagnosis is particularly challenging. The published literature contains only 23 cases of pancreatic hamartoma. The majority of the cases reported patients with a single benign tumor-like disease that received a pancreatectomy. Immunohistochemical findings confirmed the diagnosis following surgery. The current study reports the case of a 53-year-old female who presented to the Department of Abdominal Surgery, Chinese Academy of Medical Sciences, Cancer Hospital (Beijing, China), due to abdominal pain. Abdominal magnetic resonance imaging revealed a 22×14-mm mass in the head of the pancreas. The patient was pre-operatively diagnosed with a pancreatic space-occupying lesion, and subsequently underwent a pancreaticoduodenectomy. The post-operative course was uneventful. Histological examination of the resected lesion resulted in a diagnosis of pancreatic hamartoma. There were no signs of recurrence at 55 months post-surgery.

Pulmonary Langerhans cell histiocytosis

Pulmonary Langerhans cell histiocytosis is regarded as a reactive proliferation of the dendritic Langerhans cell population stimulated by chronic tobacco-derived plant proteins due to incomplete combustion but can also occur in childhood as a tumor-like systemic disease. Currently, both these forms cannot be morphologically distinguished. In the lungs a nodular proliferation of Langerhans cells occurs in the bronchial mucosa and also peripherally in the alveolar septa with an accompanying infiltration by eosinophilic granulocytes and destruction of the bronchial wall. Langerhans cells can be selectively detected with antibodies against CD1a and langerin. In the reactive isolated pulmonary form, abstinence from tobacco smoking in most patients leads to regression of infiltration and improvement of symptoms. In high-resolution computed tomography (HRCT) the small star-like scars can still be detected even after complete cessation of tobacco smoking.

Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord.

Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea-tures of 36 cases of inflammatory demyelinating pseudotumor in the spinal cord were retrospec-tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensorimotor disorder. Among them, six cases were misdiagnosed as having intra-dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologi-cally confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were com-mon. Magnetic resonance imaging revealed edema and space-occupying lesions to varying grees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like forcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re-sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional pa-logical properties.

Reviewer’s comment concerning “Aneurysmal bone cysts of the spine” (doi:10.1007/s00586-012-2510-x by M. Zileli et al.)

This is an excellent report of 18 cases of aneurysmal bone cyst (ABC) treated in a major center by very experienced surgeons who applied the most technically demanding procedures to treat at best these lesions. The AA report a high recurrence rate (28 %) notwithstanding a very aggressive attitude. This figure should arise a question regarding the possibility to improve the outcome, maybe also trying to reduce the aggressiveness as a side target. A similar critical analysis was performed in my group in 2004 after some unsuccessful cases, particularly, after a case recurrent three times after very aggressive surgery and solved only by radiotherapy, eventually resulting in a secondary leukemia. The conclusion was a complete different approach to ABC, starting from the consideration that ABC is a benign condition, sometimes self limiting [1], mostly considered as a pseudoturmoral hyper/dysplastic disease rather then a neoplastic disease [2, 3], as also the AA of this article correctly remind at the beginning of the introduction. In this perspective, we started to treat ABC not like a tumor but as a dysplasia. According to a growing experience reported in the literature [4–17], all the following cases were therefore submitted only to selective arterial embolization (SAE), repeating the procedure after 6–8 weeks until the healing of the disease. Pathological fracture or cord symptomatic compression was considered a contra-indication, while crossover to surgery had to be considered in case of persistent pain and neurological deterioration. Since that time 20 cases have been till now included in the study (a report on the first seven treated from 2004 to 2009 has been recently submitted for publication). Eighteen of these evolved to complete healing, two are undergoing treatment, only one required fixation of a pathologic fracture. All cases were submitted to CT scan and MRI before all SAE and this allowed to follow the evolution: the ABC progressively shrinks, reducing its volume, while a thin sclerotic border arises and completely surrounds the mass and progressively becomes thicker. The double content disappears and is gradually followed by bone formation (Fig. 1). As a technical detail, embolization should be performed by particles till the deeper arteries feeding the ABC and not at the periphery. In all cases, pain, when present, disappeared or significantly reduces since the first SAE, and no complication occurred. However the number of SAE required (1–7) has to be considered, remarking the exposition to radiation for angiographies and for following the evolution to healing. This must be discussed with the patient in the decision making process versus the morbidity and the recurrence risks of surgery. Fig. 1 Typical evolution of ABC after repeated SAE. a D’E. G., 41 years., severe pain (VAS 8) as a belt around the chest and lower limbs weakness. T5 and T6 involvement by ABC, b 2 months after first SAE (by particles). Pain immediately reduced ... In my opinion SAE should be considered the standard of care of ABC (unless pathologic fracture of severely increasing neurological deterioration is detected) or at least the first option, while aggressive surgery should be abandoned as both morbidity and recurrence rate is higher. I would conclude remarking that this otherwise excellent paper is burdened by a contradiction: while defining ABC as a tumor-like disease, the AA propose a very aggressive surgery, the same as usually performed in the treatment of aggressive benign or malignant tumors. A better critical analysis of the unsatisfying results (28 % recurrence rate) should bring to the same attitude we selected in our center after the process of self-criticism of our own results, similarly unsatisfactory.