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Background: The relationship between paraspinal muscle degeneration and low back pain (LBP), disability, and structural changes has been investigated in the literature, but it is still a matter of debate. We differentiated paraspinal muscle magnetic resonance imaging by quality and quantity, focusing on fatty infiltration (FI) and paraspinal muscles cross-sectional area (CSA) from T12 to S1 in patients with and without chronic LBP. We aimed to determine whether paraspinal muscle quantity (CSA) and quality (FI) are positively associated with LBP or degenerative/spinopelvic changes in the spine., Methods: Between 2018 and 2021, we prospectively enrolled 205 patients aged between 18 to 65 years, of whom 153 patients had chronic back pain (back pain group) and 52 patients did not have chronic back pain (no back pain group), and collected clinicodemographic, structural, and spinopelvic data. We correlated these data with paraspinal muscle FI and CSA from T12 to S1. Multivariate models were run to highlight associations between pain, disability, or degenerative and spinopelvic parameters., Results: Age was not associated with increased FI but consistently with decreased CSA values. After adjusting for age, sex, and body mass index, FI was associated with an increased risk of back pain (OR, 8.80; 95% CI, 1.9-39.79; P = 0.006) and high disability scores (OR, 3.41; 95% CI, 1.12-10.30; P = 0.030). Decreased CSA was associated with reduced disc height ( P < 0.001), while FI and CSA did not associate with abnormal spinopelvic parameters., Conclusions: FI on paraspinal muscle highly correlates with back pain and disability but was not found in structural and degenerative changes in the lower back., Clinical Relevance: Findings from this study are clinically relevant for patient counseling and rehabilitation strategies., Level of Evidence: 2b., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Different procedures have been used for the treatment of lumbar juxtafacet cysts (JFCs). Recently, full-endoscopic cyst excision has been suggested as a reasonable alternative. We performed a meta-analysis to assess the overall rates of favorable outcomes and adverse events for each available treatment and determine the outcome and complication rates concerning spine stability., Methods: Multiple databases were searched for English-language studies involving adult patients with lumbar JFCs who had been followed for more than 6 months. Outcomes included the proportion of patients with a satisfactory outcome. Adverse events included recurrence and revision rates as well as intraoperative complications. We further stratified the analysis based on the spine's condition (degenerative listhesis vs without degenerative listhesis)., Results: A total of 43 studies, including 2226 patients, were identified. Over 80% of patients experienced satisfactory improvement after surgical excision but only 66.2% after percutaneous cyst rupture and aspiration. Overall, recurrence and revision rates were almost double in patients with preoperative degenerative listhesis at the cyst level, especially in the minimally invasive group (2.1% vs 31.3% and 6.8% vs 13.1%, respectively). The rate of full-endoscopic satisfactory outcomes was approximately 90%, with low rates of adverse events (<2%)., Conclusion: We analyzed the outcome and adverse event rates for each kind of available treatment for JFC. Full endoscopy has outcomes and rates of adverse events that overlap with open and minimally invasive approaches., Level of Evidence: 2A., Competing Interests: Financial Disclosures and Conflicts of Interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2022 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Purulent intracranial infections are threatening conditions. Different surgical approaches have been described, respecting the rationale of evacuating the fluid component of the purulent collection. Emerging evidence supports the use of the endoscope for the treatment of cerebral abscesses and subdural empyemas; especially the peculiarities of flexible endoscopes could potentially offer a more effective and conclusive management as compared with the drainage through catheters. We describe our experience in the treatment of intracranial purulent collections with flexible endoscopy, comparing it with the most recent literature., Methods: Ten patients affected by intracranial suppuration were treated with endoscopy at our institution. The neurosurgical technique is thoroughly described. The related literature is reviewed, providing a comprehensive overview on the endoscopic treatment of intracranial suppuration so far., Results: All the patients had a good clinical outcome, with no peri-operative complications. The postoperative scans showed significant radiological improvement, with important reduction of the pus volume. In all cases, the microbiological cultures showed positivity., Conclusions: In our experience, the use of the flexible scope proved feasible and effective in the treatment of intracranial purulent collections. Visual awareness of the internal capsule is not limited to a direct inspection of the fluid pus; it rather allows an active removal of the more solid (and perhaps more microbiologically significant) fibrinoid component, and also assists in final bleeding control and in assessing the extent of the evacuation. The steering capabilities of the fiberscope are particularly suitable for such purposes, allowing sampling the solid internal layer of the pyogenic membrane, and potentially shedding light on the actual clinical significance of this component of the abscess.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Irene Troncon et al.)

Objective: Surgical management of spinal dysraphism often requires the use of dural substitutes. Amniotic membrane (AM) has drawn the interest of clinicians for its valuable concentration of cytokines and factors capable of promoting wound healing, re-epithelialization, inhibiting fibrosis and regulating angiogenesis. These beneficial qualities could make AM an interesting dural substitute for spina bifida repair. In this study, we describe the use of banked homologous AM as a dural substitute for the repair of spinal dysraphism in newborns. Our purpose is to test the mechanical characteristics, as well as the safety and effectiveness of AM in preventing postoperative complications and re-tethering., Methods: The AM patch was carefully detached from the chorion of donors undergoing caesarean section, rinsed in saline solution, and cryopreserved in liquid nitrogen. Five newborns were treated using AM: three affected by open spinal dysraphism and two by spina bifida occulta. The AM patch was used as a dural substitute with two different positions and purposes: the amnion-side down covering the placode to prevent adhesions or placed extradurally facing the dura to avoid scarring and facilitating the sliding of the dural sac itself under the extradural tissue layers., Results: No adverse events occurred, and the surgical wounds healed without complications. MRI scans taken at 3 and 6 months after surgery showed a satisfying de-tethering of the spinal cord with no obvious evidence of new adherence formation., Conclusions: We present a multimodal interposition technique using AM as a reconstructive and anti-adhesive tissue for the treatment of open myelomeningocele (MMC) and lipomeningocele (LMC) treatment. In our experience, AM proved its efficacy in restoring the dural sac integrity without complications. We support the use of AM as a promising dural substitute, speculating on how the use of AM could potentially change reconstructive strategies for spinal dysraphism.

Osteoblastomas are rare, benign bone tumors mainly arising from the long bones and the posterior vertebral arches. Skull localizations account for approximately 15% of cases. A total amount of thirty cases involving the temporal bone are reported in the literature. Clinical presentation of temporal osteoblastomas often includes local pain and swelling, while 7 th and 8 th cranial nerve impairment is rare. We report the novel finding of increase intracranial pressure syndrome secondary to dominant transverse-sigmoid sinus junction compression caused by a small temporal bone osteoblastoma. Excision of the tumor with the restoration of venous flow in the sigmoid sinus was followed by a prompt clinical improvement. In the management of patients with a venous sinus compression, restoration of venous drainage should be a priority., Competing Interests: There are no conflicts of interest.

Background: Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis., Methods: Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used., Results: We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001)., Conclusion: Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions., Trial Registration: The study was approved by the institutional review board (545/2010 on 6th of May 2014) of the Medical University of Vienna ( http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/alle&#95;2010.pdf ).

Background: Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression., Methods: CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed., Results: We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003)., Conclusions: Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

Background: Small soft ventricular tumors are good candidates for complete removal by a purely endoscopic technique. This approach is particularly interesting for lesions located in the posterior third ventricle and aqueductal lumen., Methods: We present our method of endoscospic aspiration through direct contact between the tumor and the working channel of a flexible scope., Results: Aspiration without the intermediate use of cannulas is safe and has proved to be effective in the apparently total or partial removal of three soft tumors of different pathologies located in the third ventricle or aqueductal lumen. In one case, a second neuroendoscopy a few months later to repeat endoscopic third ventriculostomy (ETV) offered a unique opportunity to observe the absence of the tumor and the restored anatomy., Conclusions: Neuroendoscopy provides a safe, effective way to radically resect small soft tumors in these troublesome locations and can be a valuable alternative to microsurgery.

The L10P single nucleotide polymorphism (SNP) is located in the signal sequence of the transforming growth factor β1 (TGFβ1) gene. The proline-encoding (Pro-) allele of this SNP has been associated with an increased breast cancer risk, which has been attributed to the elevated secretion of this TGFβ1 variant observed in vitro and in male subjects. Here we investigated the association of the L10P SNP with serum levels of TGFβ1 in female breast cancer patients and controls. We genotyped the L10P SNP in 276 breast cancer patients and 255 controls. Serum TGFβ1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of the study population (n = 211). We found no evidence for an association of the L10P SNP with breast cancer risk (per-allele odds ratio: 0.91; 95% confidence interval: 0.71-1.16). However, patients with the Pro/Pro genotype exhibited a significantly younger age at breast cancer onset (55.2 ± 14.3 years) than Leu/Leu patients (60.6 ± 13.6 years; p = 0.04), which may reflect the ability of TGFβ to promote tumor progression. Mean TGFβ1 serum levels of Pro-allele carriers were 39.4 ± 7.4 ng/mL, whereas those of Leu/Leu subjects were 37.6 ± 6.0 ng/mL (p = 0.07). Thus, compared to a previous study of male subjects, we observed only a modest increase, if any, in TGFβ1 levels of female Pro-allele carriers.

Object: Massive intraventricular hemorrhages (IVHs) require aggressive and rapid management to decrease intracranial hypertension, because the amount of intraventricular blood is a strong negative prognostic predictor on outcome. Neuroendoscopy may offer some advantages over more traditional surgical approaches on outcome and may decrease the number of shunt procedures that need to be performed., Methods: The authors retrospectively reviewed the clinical and radiological data in 96 patients treated for massive IVH who were admitted between January 1996 and June 2008 to the neurosurgery unit after undergoing emergency CT scanning. Forty-eight patients (Group A) were treated with endoscopic aspiration surgery using a flexible endoscope with a "freehand" technique. A historical group of 48 patients (Group B) treated using external ventricular drain (EVD) placement alone was used as a comparison. The authors compared the radiological results with the clinical outcomes at 1 year according to the modified Rankin Scale and the need for internal CSF shunt treatment in the 2 groups., Results: Endoscopic aspiration did not significantly affect the outcome at 1 year as determined using the modified Rankin Scale. Patients who underwent endoscopy had an EVD in place for 0.18 days fewer than patients treated with an EVD alone. Patients undergoing external ventricular drainage alone had a 5 times greater chance of requiring a shunting procedure than those treated using neuroendoscopy and external ventricular drainage. Neuroendoscopy plus external drainage reduces shunting rates by 34% when compared with external drainage alone., Conclusions: The reduction in internal shunt surgery encourages the adoption of neuroendoscopic aspiration of severe IVH as a therapeutic tool to decrease shunt dependency.

Background: The TP53 Arg72Pro polymorphism encodes two p53 variants with different biochemical properties. Here we investigated the impact of this polymorphism on the expression of key p53 target genes in a panel of human breast carcinomas, breast cancer risk, and age at onset., Methodology/principal Findings: The Arg72Pro polymorphism was genotyped in 270 breast cancer patients and 221 control subjects. In addition, the Arg72Pro genotype of 116 breast tumors was determined, and correlated with intratumoral mRNA expression of TP53 and its key target genes MDM2, p21, BAX, and PERP, as quantified by qRT-PCR. We found a significantly increased breast cancer risk associated with the Pro-allele (per-allele odds ratio, 1.46; 95% confidence interval, 1.08-1.99), and a significantly later mean age at breast cancer onset for Pro/Pro patients (63.2±18 years) compared to Arg/Arg patients (58.2±15 years). The frequency of somatic TP53 inactivation was 25.4% in Arg/Arg, 20.9% in Arg/Pro, and 16.7% in Pro/Pro patients, which may reflect a higher selective pressure to mutate the Arg-allele. The median mRNA levels of p21 and BAX in the tumors of Pro-allele carriers were significantly reduced to 55.7% and 76.9% compared to Arg/Arg patients, whereas p53, MDM2 and PERP expression were hardly altered., Conclusions/significance: The p53(72Arg) variant appears to be a more potent in vivo transcription factor and tumor suppressor in human breast cancer than the p53(72Pro) variant. The Arg72Pro genotype has no significant effects in patients with TP53 mutated tumors, in which p53 is non-functional.

Introduction: Somatosensory evoked potential (SEP) recordings and continuous electroencephalography (EEG) are important tools with which to predict Glasgow Outcome Scale (GOS) scores. Their combined use may potentially allow for early detection of neurological impairment and more effective treatment of clinical deterioration., Methods: We followed up 68 selected comatose patients between 2007 and 2009 who had been admitted to the Neurosurgical Intensive Care Unit of Treviso Hospital after being diagnosed with subarachnoid haemorrhage (51 cases) or intracerebral haemorrhage (17 cases). Quantitative brain function monitoring was carried out using a remote EEG-SEP recording system connected to a small amplification head box with 28 channels and a multimodal stimulator (NEMO; EBNeuro, Italy NeMus 2; EBNeuro S.p.A., Via P. Fanfani 97/A - 50127 Firenze, Italy). For statistical analysis, we fit a binary logistic regression model to estimate the effect of brain function monitoring on the probability of GOS scores equal to 1. We also designed a proportional odds model for GOS scores, depending on amplitude and changes in both SEPs and EEG as well as on the joint effect of other related variables. Both families of models, logistic regression analysis and proportional odds ratios, were fit by using a maximum likelihood test and the partial effect of each variable was assessed by using a likelihood ratio test., Results: Using the logistic regression model, we observed that progressive deterioration on the basis of EEG was associated with an increased risk of dying by almost 24% compared to patients whose condition did not worsen according to EEG. SEP decreases were also significant; for patients with worsening SEPs, the odds of dying increased to approximately 32%. In the proportional odds model, only modifications of Modified Glasgow Coma Scale scores and SEPs during hospitalisation statistically significantly predicted GOS scores. Patients whose SEPs worsened during the last time interval had an approximately 17 times greater probability of a poor GOS score compared to the other patients., Conclusions: The combined use of SEPs and continuous EEG monitoring is a unique example of dynamic brain monitoring. The temporal variation of these two parameters evaluated by continuous monitoring can establish whether the treatments used for patients receiving neurocritical care are properly tailored to the neurological changes induced by the lesions responsible for secondary damage.

Background: This study aims to assess the diagnostic value of multivoxel 2D chemical-shift imaging (CSI) proton magnetic resonance (MR) spectroscopy combined with perfusion magnetic resonance imaging (MRI) in the differential diagnosis and grading of brain tumors by comparing neuroimaging data with histopathological findings obtained after resection or biopsy., Methods: A total of 159 patients with a previous brain tumor diagnosis underwent multivoxel 2D CSI proton MR spectroscopy and perfusion MRI. MR spectroscopy multivoxel 2D CSI was performed with an echo time of 30, TR 1,500, FOV 160 mm, acquisition time 7 min 34 s. rCBV maps were evaluated during postprocessing. Statistical analysis was performed on the examination of distributive normality, with logarithmic transformations, Fisher's test, and Bonferroni's test. We used the Pearson's test to compare percentages., Results: In the differential diagnosis between GBM and metastases, MR spectroscopy multivoxel 2D CSI, combined with dynamic contrast enhanced MRI (DCE-MRI) perfusion, reached high sensibility and specificity (p < 0.000001). In brain tumor grading, the same method reached high sensibility and specificity (p < 0.000001) in distinguishing grade III-IV gliomas but encountered difficulty in determining grades within the two main groups of primary brain tumors, especially where mixed gliomas were involved., Conclusions: The systematic use of CSI spectroscopy and perfusion imaging has shown a high potential in the differential diagnosis and grading of brain tumors. Further exploration into diagnostic procedures that can significantly distinguish between grade III-IV and grade II tumors is needed.

Since children may not be able to complain of progressive reduction in optic acuity, visual assessment in infancy may present practical difficulties. The authors report a case of craniopharyngioma, which led a young child to early blindness before the correct diagnosis could be made. Similar to other reported cases, the authors found that surgery did not substantially modify the preoperative visual deficit. They conclude that minimal improvement in visual acuity can be expected despite successful microsurgical removal of the tumor.

Recently, amniotic fluid was suggested as a new source for stem-cell research and tissue engineering approaches. In order to enable isolation of stem cells and establishment of lines of such cells with an undifferentiated phenotype we have introduced green fluorescent protein regulated by the promoters of the stem cell-specific genes, Oct-4 or Rex-1, into human amniotic fluid cells. For the introduction of DNA into human amniotic fluid cells, we have optimized a specific transfection protocol. We found that human amniotic fluid contains cell populations which are able to activate these promoters. These undifferentiated cells expressing green fluorescent protein can be analysed on a flow cytometer. In addition, we have introduced a plasmid harboring a neomycin-resistance gene under the control of the Oct-4 promoter. G418 selection allowed the isolation of undifferentiated stem cells expressing Oct-4 protein out of human amniotic fluid samples. Our findings confirm the existence of stem cells within amniotic fluid. In addition, the ability to transfect human amniotic fluid cells and to isolate stem-cell marker-positive cells will provide the means to study and manipulate these cells for the purpose of basic and applied research.

Purpose: Insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells in vitro, and elevated IGF-I serum levels are a risk factor for breast malignancies. This study evaluated IGF-I and IGF-II serum levels in healthy women and in patients with benign and malignant breast lesions and correlated them with tumor size., Experimental Design: Serum levels of the total and unbound fractions of IGF-I and IGF-II were analyzed in 65 patients with benign and malignant breast lesions and in 38 women without breast disease. ELISAs were used to detect serum IGF levels, with (total IGF) or without (free IGF) prior acid-ethanol extraction., Results: Total IGF-I serum concentrations were lower in healthy women than in breast cancer patients (P < 0.001) or patients with benign breast lesions (P = 0.010), but no differences were observed in free IGF-I levels. Conversely, healthy women had higher serum levels of free IGF-II than women with breast lesions (P = 0.003), and the free/total IGF-II ratio was significantly reduced in patients with breast disease (P = 0.001). Although IGF-I or IGF-II serum concentrations of breast cancer patients were similar to those of patients with benign lesions, the size of a malignant tumor was correlated to the ratio free/total IGF-II (P = 0.002)., Conclusions: Malignant breast tumors cannot be distinguished from benign breast lesions by systemic IGF serum levels. However, women with breast lesions have decreased IGF-II concentrations, and free IGF-II levels are clearly correlated to the size of a breast cancer, indicating an involvement in tumor growth.

Purpose: The interleukin 1 (IL-1) system plays an important role in human pathology and is involved in the local control of malignant disease. However, little is known about its expression in breast cancer and its correlation with prognostic parameters such as receptor status and grading., Experimental Design: The expression of IL-1alpha and other IL-1 family members was analyzed by reverse transcription-PCR, ELISA, and immunohistochemistry in breast cancer cell lines, tumor-derived fibroblasts, and breast cancer tissue biopsies and compared with sex steroid receptor status and grading., Results: In breast cancer cell lines, IL-1alpha and -beta gene expression was present in the phenotypically most malignant cell lines, whereas estrogen receptor (ER) alpha and progesterone receptor mRNA expression was confined to lines that exhibit a rather benign phenotype. Only the highly malignant receptor-negative tumor cell line MDA MB 231 expressed IL-1alpha protein, and none of the cell lines secreted IL-1beta. Biopsies from breast cancer tissue expressed various amounts of IL-1alpha, IL-1beta, and IL-1 receptor antagonist mRNA, but consistently high levels of IL-1tIR. IL-1alpha protein expression was detected in tumor cells and/or adjacent stroma in 88%, and epithelial protein expression was correlated with both poor differentiation (P = 0.002; r = 0.469) and decreasing epithelial ERalpha expression (P = 0.004; r = -0.387). Furthermore, stromal IL-1alpha was predominant in areas with low or absent ERalpha protein expression in neighboring tumor epithelium (P = 0.001; r = -0.457)., Conclusion: We have demonstrated the presence of a functional IL-1 system in breast cancer and found that IL-1alpha is inversely correlated with local sex steroid receptor expression. We hypothesize that the unphysiological expression of IL-1alpha in less differentiated and ERalpha-negative tumors might contribute to their local invasiveness and malignant behavior.

Background: It is the hope of investigators and patients alike that in future the isolation of pluripotent human stem cells will allow the establishment of therapeutic concepts for a wide variety of diseases. A major aim in this respect is the identification of new sources for pluripotent stem cells. Oct-4 is a marker for pluripotent human stem cells so far known to be expressed in embryonal carcinoma cells, embryonic stem cells and embryonic germ cells., Methods: Cells from human amniotic fluid samples were analysed for mRNA expression of Oct-4, stem cell factor, vimentin and alkaline phosphatase via RT-PCR. Oct-4 protein expression was investigated by Western blot analysis and immunocytochemistry. Oct-4-positive cells were also analysed for the expression of cyclin A protein via double immunostaining., Results: Performing RT-PCR, Western blot and immunocytochemical analyses revealed that in human amniotic fluid in the background of Oct-4-negative cells a distinct population of cells can be found, which express Oct-4 in the nucleus. Oct-4-positive amniotic fluid cell samples also express stem cell factor, vimentin and alkaline phosphatase mRNA. The Oct-4-positive amniotic fluid cells are actively dividing, proven by the detection of cyclin A expression., Conclusions: The results presented here suggest that human amniotic fluid may represent a new source for the isolation of human Oct-4-positive stem cells without raising the ethical concerns associated with human embryonic research.