The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC.

Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations.

Hepatic Vasculopathy and Regenerative Responses of the Liver in Fatal Cases of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects the nasopharynx and lungs and causes coronavirus disease-2019 (COVID-19). It may impact the heart, brain, kidney, and liver.1 Although functional impairment of the liver has been correlated with worse clinical outcomes, little is known about the pathophysiology of hepatic injury and repair in COVID-19.2,3 Histologic evaluation has been limited to small numbers of COVID-19 cases with no control subjects2,4 and demonstrated largely heterogeneous patterns of pathology.2,3.

Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA.

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.

A standardized suprapubic bottom-to-up approach in robotic right colectomy: technical and oncological advances for complete mesocolic excision (CME).

BACKROUND: Several studies have demonstrated a direct correlation between lymph node yield and survival after colectomy for cancer. Complete mesocolic excision (CME) in right colectomy (RC) reduces local recurrence but is technically demanding. Here we report our early single center experience with robotic right colectomy comparing our standardized bottom-to-up (BTU) approach of robotic RC with CME and central vessel ligation (CVL) facilitated by a suprapubic access with the "classical" medial-to-lateral (MTL) strategy. METHODS: A 4-step BTU approach of robotic RC guided by embryonal planes in the process of retrocolic mobilization with suprapubic port placement was performed in the BTU-group (n = 24; all with intention to treat cancer). In step 1 CME was initiated with caudolateral mobilization of the right colon guided by the fascia of Toldt across the duodenum and up to the Trunk of Henle. Subsequently, dissection was performed BTU right of the middle supramesenteric vessels with central ileocolic vessel ligation in step 2. Subsequent to separation of the transverse retromesenteric space and completion of mobilization the hepatic flexure in step 3, the transverse mesocolon was then transected right of the middle colic vessels in step 4. An extracorporeal side to side anastomosis was performed. We compared the outcome of the BTU-group with a MTL-group (n = 7). RESULTS: Patient characteristics like age, gender, BMI, comorbidity (ASA) and M-status were comparable among groups. There was no conversion. Overall complication rate was 35.5%. We experienced no anastomoses insufficiency, grade Dindo/Clavien III/IV complication or mortality in this study. Type I and II complications and surgical characteristics incl. OR-time, ICU- and hospital-stay were comparable between the two groups. However, the lymph node yield was superior in the BTU-group (mean 40.2 ± 17.1) when compared with the MTL-group (16,3 nodes ±8.5; p <  0,001). CONCLUSIONS: Compared to the classical MTL approach, robotic suprapubic BTU RC changes from a search of the layers bordering the oncological dissection to a consequent utilization of the planes as a retro-mesocolic guide during CME. The BTU strategy could bear the potential to increase the lymph node yield. Robotic systems may provide the technical requirements to combine advantages of both open and minimally invasive RC.

Understanding Client Vulnerability in the Disciplining of Legal Professionals in New South Wales.

Despite the increasing use of "vulnerability" in policy and legal documents, and the emerging scholarly literature about vulnerability and the law, there is little research focused on vulnerability from clients' perspectives. To address this gap, we analysed the New South Wales Civil and Administrative Tribunal (NCAT) and appellate court cases involving vulnerable clients and disciplined lawyers in NSW from 1 January 2011 to 30 January 2019. Our analysis of the cases draws from the "vulnerability theory" literature. We identified the following characteristics of clients for analysis: older age, gender, health impairment, and immigrant status. Twenty-eight tribunal cases and two appellate court cases involved vulnerable clients. Overall, the cases revealed that the relationship between public protection and vulnerability is not expressly discussed by NCAT. To optimise the legislative intent to safeguard the public, the NSW legislation should explicitly include vulnerability as a relevant feature of the disciplinary regime.

Identification of a novel gammaherpesvirus associated with (muco)cutaneous lesions in harbour porpoises (Phocoena phocoena).

Herpesviruses infect a wide range of vertebrates, including toothed whales of the order Cetacea. One of the smallest toothed whales is the harbour porpoise (Phocoena phocoena), which is widespread in the coastal waters of the northern hemisphere, including the North Sea. Here, we describe the detection and phylogenetic analysis of a novel gammaherpesvirus associated with mucocutaneous and skin lesions in stranded harbour porpoises along the Dutch coast, tentatively designated phocoenid herpesvirus 1 (PhoHV1). Phylogenetically, PhoHV1 forms a monophyletic clade with all other gammaherpesviruses described in toothed whales (Odontoceti) to date, suggesting a common evolutionary origin.

Compensating for the harms of family violence: statutory barriers in Australian victims of crime compensation schemes.

This article considers the compensative capacity of the victims of crime statutory schemes that are present in all eight Australian jurisdictions for primary victims of family violence. It argues that the recommendations of the Final Report on Family Violence conducted jointly by the Australian Law Reform Commission and the New South Wales Law Reform Commission in 2010, although a positive step, are insufficient to facilitate meaningful compensation to victims of family violence. In addition to the primary limitations identified by the Commissions--a requirement to report the crime to the police within a reasonable time and a requirement for multiple acts of violence to be reduced to a single act if they are related--there are other statutory barriers that disproportionately disadvantage victims of family violence. These include time limitation provisions, a requirement to report the crime to police, the restriction of compensation to prescribed categories of loss which exclude many of the social, vocational, emotional and psychological harms suffered by victims of family violence, and significant cut-backs on the non-economic component of the schemes. This article further argues that the statutory barriers cumulatively contribute to the perception of a crime as an isolated event perpetrated by a deviant individual. The article recommends that specific provisions for family violence victims should be introduced into all schemes including three categories of compensation not tied to criminal offences but rather the different forms of family violence, with a generous compensation range, and no requirement for proof of injury.

Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

Reinforcing historic distinctions between mental and physical injury: the impact of the civil liability reforms.

Mental injury has been differentiated from physical injury since its entry into Australian tort law, with mental injury consistently subject to the most onerous regime. In 2002 in its Review of the Law of Negligence, the Ipp Panel supported the historic distinction between physical and mental injury and recommended further (restrictive) changes to the common law rules in relation to mental injury. This article considers and evaluates the reforms which were introduced into six Australian jurisdictions in relation to mental injury in the tort of negligence in response to the Ipp Panel's recommendations arguing that the rationale for differentiating pure mental injury from physical injury and consequential mental injury is nebulous. It argues that the reforms operate to reinforce and magnify historic distinctions between physical and mental harm despite increasing recognition in the medical literature of the interrelationship between physical and psychiatric injury; despite the recognition of the professional ability of psychiatrists and psychologists to accurately pinpoint and diagnose mental injury; despite extensive documentation of the far-reaching and devastating impact that psychiatric injury has on victims, families and the community; and despite evidence that early and adequate treatment of mental injury can prevent a raft of damaging and costly personal and societal consequences.

Low Copper Diet-A Therapeutic Option for Wilson Disease?

Wilson's disease (WD) is an autosomal recessive inherited disease in which a pathological storage of copper in various organs is the mean pathophysiological mechanism. The therapy consists of drug therapy with chelating agents or zinc. For patients, nutrition is always an important issue. The aim of this review was to determine whether there are clear recommendations for a low copper diet for WD patients, or whether the essential trace element zinc plays a role? We were able to show that some of the foods with high copper content would have to be consumed in such large quantities that this is regularly not the case. Furthermore, there are also different absorption rates depending on the copper content. A lower copper intake only prevents the re-accumulation of copper. In summary, consistent adherence to drug therapy is more important than a strict diet. Only two foods should be consistently avoided: Liver and Shellfish.

Correlation of PET-MRI, Pathology, LOH, and Surgical Success in a Case of CHI With Atypical Large Pancreatic Focus.

Congenital hyperinsulinism (CHI) is a rare cause of severe hypoglycemia in newborns. In focal CHI, usually one activity peak in fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography-magnetic resonance imaging (PET-MRI) indicates one focal lesion and its resection results in cure of the child. We present the case of a 5-month-old girl with CHI. Mutational screening of genes involved in CHI revealed a heterozygous pathogenic variant in the ABCC8 gene, which was not detectable in the parents. 18F-DOPA PET-MRI revealed 2 distinct activity peaks nearby in the pancreatic body and neck. Surgical resection of the tissue areas representing both activity peaks resulted in long-lasting normoglycemia that was proven by a fasting test. Molecular analysis of tissue samples from various sites provided evidence that a single second genetic hit in a pancreatic precursor cell was responsible for the atypical extended pancreatic lesion. There was a close correlation in the resected areas of PET-MRI activity with focal histopathology and frequency of the mutant allele (loss of heterozygosity) in the tissue. Focal lesions can be very heterogenous. The resection of the most affected areas as indicated by imaging, histopathology, and genetics could result in complete cure.

Technical aspects of paediatric robotic pancreatic enucleation based on a case of an insulinoma.

BACKGROUND: Insulinomas are rare insulin-producing pancreatic neuroendocrine tumours leading to severe episodes of hypoglycaemia. Surgery is the predominant curative therapy. METHODS: We report here the first paediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10-year-old male with multiple endocrine neoplasia type 1. The port set-up was adapted for the narrowed dimensions of the paediatric peritoneal space. We comment on technical key steps for the organ-preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted. RESULTS: Following an uneventful post-operative course, the boy was discharged on day 11 with normalised glucose-metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting. CONCLUSIONS: The applicability of a robotic surgical system in limited space conditions such as found in the paediatric abdominal cavity is demonstrated here for pancreatic surgery.

Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies.

The liver as the largest organ in the human body is composed of a complex macroscopic and microscopic architecture that supports its indispensable function to maintain physiological homeostasis. Optical imaging of the human liver is particularly challenging because of the need to cover length scales across 7 orders of magnitude (from the centimeter scale to the nanometer scale) in order to fully assess the ultrastructure of the entire organ down to the subcellular scale and probe its physiological function. This task becomes even more challenging the deeper within the organ one hopes to image, because of the strong absorption and scattering of visible light by the liver. Here, we demonstrate how optical imaging methods utilizing highly specific fluorescent labels, as well as label-free optical methods can seamlessly cover this entire size range in excised, fixed human liver tissue and we exemplify this by reconstructing the biliary tree in three-dimensional space. Imaging of tissue beyond approximately 0.5 mm length requires optical clearing of the human liver. We present the successful use of optical projection tomography and light-sheet fluorescence microscopy to derive information about the liver architecture on the millimeter scale. The intermediate size range is covered using label-free structural and chemically sensitive methods, such as second harmonic generation and coherent anti-Stokes Raman scattering microscopy. Laser-scanning confocal microscopy extends the resolution to the nanoscale, allowing us to ultimately image individual liver sinusoidal endothelial cells and their fenestrations by super-resolution structured illumination microscopy. This allowed us to visualize the human hepatobiliary system in 3D down to the cellular level, which indicates that reticular biliary networks communicate with portal bile ducts via single or a few ductuli. Non-linear optical microscopy enabled us to identify fibrotic regions extending from the portal field to the parenchyma, along with microvesicular steatosis in liver biopsies from an older patient. Lastly, super-resolution microscopy allowed us to visualize and determine the size distribution of fenestrations in human liver sinusoidal endothelial cells for the first time under aqueous conditions. Thus, this proof-of-concept study allows us to demonstrate, how, in combination, these techniques open up a new chapter in liver biopsy analysis.

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling.

There is growing evidence that cancer stem cells (CSCs), a small subpopulation of self-renewal cancer cells, are responsible for tumor growth, treatment resistance, and cancer relapse and are thus of enormous clinical interest. Here, we aimed to isolate new CSC-like cells derived from human primary non-small cell lung cancer (NSCLC) specimens and to analyze the influence of different inhibitors of NF-κB and MYC signaling on cell survival. CSC-like cells were established from three squamous cell carcinomas (SCC) and three adenocarcinomas (AC) of the lung and were shown to express common CSC markers such as Prominin-1, CD44-antigen, and Nestin. Further, cells gave rise to spherical cancer organoids. Inhibition of MYC and NF-κB signaling using KJ-Pyr-9, dexamethasone, and pyrrolidinedithiocarbamate resulted in significant reductions in cell survival for SCC- and AC-derived cells. However, inhibition of the protein-protein interaction of MYC/NMYC proto-oncogenes with Myc-associated factor X (MAX) using KJ-Pyr-9 revealed the most promising survival-decreasing effects. Next to the establishment of six novel in vitro models for studying NSCLC-derived CSC-like populations, the presented investigations might provide new insights into potential novel therapies targeting NF-κB/MYC to improve clinical outcomes in NSCLC patients. Nevertheless, the full picture of downstream signaling still remains elusive.

Young migrant and refugee people's views on unintended pregnancy and abortion in Sydney.

Although abortion rates appear to be declining in high-income nations, there is still a need for accessible, safe abortion services. However, limited attention has been paid to understanding the social contexts which shape access to abortion information and services for communities who are less engaged with sexual and reproductive health care more generally. This paper explores the views and experiences of 27 migrant and refugee young people (16-24 years old) living in Sydney, Australia, regarding unintended pregnancy and abortion. Pregnancy outside marriage was described by all participants as a shameful prospect as it revealed pre-marital sexual activity. Even when abortion was described as culturally and/or religiously unacceptable, it was believed many families would find an abortion preferable to continuing an unintended pregnancy outside marriage. However, a pervasive culture of silence regarding sexual and reproductive health may limit access to quality information and support in this area. To better meet the needs of these young people, greater attention must be paid to strengthening youth and community awareness of the availability of contraception including emergency contraception, pregnancy options, and access to abortion information and services.

Impact of ASA-score, age and learning curve on early outcome in the initiation phase of an oncological robotic colorectal program.

The ASA score is known to be an independent predictor of complications and mortality following colorectal surgery. We evaluated early outcome in the initiation phase of a robotic oncological colorectal resection program in dependence of comorbidity and learning curve. 43 consecutive colorectal cancer patients (median age: 74 years) who underwent robotic surgery were firstly analysed defined by physical status (group A = ASA1 + 2; group B = ASA3). Secondly, outcome was evaluated relating to surgery date (group E: early phase; group L: late phase). There were no differences among groups A and B with regard to gender, BMI, skin-to-skin operative times (STS), N- and M-status, hospital-stay as well as overall rate of complications according to Dindo-Clavien and no one-year mortality. GroupA when compared to group B demonstrated significantly lower mean age (65.5 years ± 11.4 years vs 75.8 years ± 8.9 years), T-stage and ICU-stay. When separately analyzed for patients age ICU-stay was comparable (> 75 years vs. < 75 years). Group E and L demonstrated comparable characteristics and early outcome except more frequent lymphatic fistulas in group E. STS was reduced in group L compared to group E. Beyond learning curve aspects in our series, we could demonstrate that patient's physical condition according to ASA rather than age may have an impact on early outcome in the initial phase of a robotic oncological colorectal program.

Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.

Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial-mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (NMYC) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.

Defensive medicine in general practice: recent trends and the impact of the Civil Liability Act 2002 (NSW).

This article presents the results of a survey conducted among New South Wales medical practitioners to assess the extent to which the enactment of the Civil Liability Act 2002 (NSW) has reduced the practice of defensive medicine. The new legislation was intended in part to reduce the practice of defensive medicine, both "assurance-type" measures, such as performing additional tests to assure patients they have received all possible care, and "avoidance-type" measures, such as avoiding the treatment of patients who may be at a higher risk for adverse outcomes and therefore at higher risk for filing lawsuits. However, the results of the survey reveal that many medical practitioners in New South Wales remain unaware of the legal reforms and the consequent reduction in their legal liability and continue to practise defensive medicine. This article argues therefore that while the ultimate aim of reducing litigation has been achieved in New South Wales through the introduction of the Civil Liability Act, the underlying and arguably more important aim of providing medical practitioners with a more secure environment in which to practise their profession effectively has not been achieved. The apparent failure to disseminate the legal changes to the medical profession illustrates the limitations of law reform to effectively engender social change without the active use of educative and other implementation initiatives.

A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.

RATIONALE: Neuroendocrine tumors (NETs) of the lung account for 5% of all cases of lung cancer, which itself is the leading cause of cancer-related death worldwide. In accordance to its rarity, only few cell lines of NETs exist, which even often lack key characteristics of the primary tumor, making it difficult to study underlying molecular mechanisms. PATIENT CONCERNS: The patient reported in this case is a 71-year old woman, which never smoked but suffered under dry cough. DIAGNOSES: Chest CT-scan showed a paracardiac nodule of the lingula with 2 × 1.8 cm in diameter. INTERVENTIONS: The detected paracardiac nodule of the lingula was anatomically resected using video assisted thoracic surgery. OUTCOMES: Histopathological diagnostic of the removed tissue identified the tumor as a well-differentiated typical carcinoid (TC), which represents one of the four subgroups of pulmonary NETs. Next to the successful treatment of the patient, we were able to propagate cancer stem cells (CSCs) out of the resected tumor tissue. To the best of our knowledge, we firstly isolated CSCs of a typical carcinoid, which were positive for the prominent CSC markers CD44, CD133 and nestin, confirming their stem cell properties. Additionally, CSCs, further referred as BKZ1, expressed the neuroendocrine marker synaptophysin, verifying their neuroendocrine origin. However, nuclear synaptophysin protein was also present in other stem cell populations, suggesting a role as general stem cell marker. LESSON: In line with the importance of CSCs in cancer treatment and the lack of CSC-models for neuroendocrine neoplasms, the here described BKZ1 cancer stem cell line of a typical carcinoid represents a promising new model to study pulmonary carcinoids and particular NETs.

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells.

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.