The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation.

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing (POPDC) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower POPDC1 and POPDC3 mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. POPDC1 and POPDC3 transcript levels were highly correlated with each other and inversely correlated with LGR5, OLFM4, CDX2, and several mucin transcripts. The association of POPDC1 and POPDC3 downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.

Morphological and Histological Changes in the Human Anterior Cruciate Ligament after Rupture.

BACKGROUND: Injuries to the anterior cruciate ligament (ACL) are common and complete tears often fail to heal. ACL reconstruction is considered the surgical gold standard of care for ACL injuries in young active patients. OBJECTIVES: To determine the corresponding morphological and histological features of the torn ACL in different time periods after injury. METHODS: The study included 28 remnant specimens of torn ACLs from patients who had ACL reconstruction surgery of the knee. The remnant pathology was evaluated by its morphology during arthroscopy and by histopathologic measurements. RESULTS: At surgery there were three progressive and distinct morphological tear patterns. The first pattern was noticed within the first 3 months from injury and showed no scar tissue. The second pattern appeared later and was characterized by the appearance of scar tissue with adhesion to the femoral wall. The third pattern was characterized by adhesion of the ACL remnant to the posterior cruciate ligament. The histological changes of the first morphological pattern showed abundance of blood vessels and lymphocytes at the torn femoral end with few irregular collagen fibers. The second and third tear patterns showed decrement in the number of blood vessels and lymphocytes with longitudinally oriented collagen fibers. CONCLUSIONS: The morphological features of the ACL remnant in the first 3 months after injury showed no scar tissue and its histological features had the characteristics of a reparative phase. This phase was followed by a prolonged remodeling phase that ended with attachment of the remnant to the posterior cruciate ligament.

Leiomyosarcoma of the inferior vena cava. Our experience and a review of the literature.

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignant tumor, accounting for 2% of all LMSs. Less than 400 cases have been reported in literature. Computed tomography (CT) is the most accurate imaging method in assessing the location of the tumor within the IVC and magnetic resonance imaging (MRI) accurately identifies its extent and the potential for surgical resection. We present the case of a patient with inferior vena cava leiomyosarcoma (IVCL), for whom the pathological diagnosis was different from the initially expected one, the tumor appearance on pre-operative imaging mimicking renal cell carcinoma. The intraoperative difficulty of approaching renal hilum and IVC was a factor suggesting the vascular origin of the tumor, which was confirmed at pathological analysis. The extensive defect in the IVC after tumor excision led to the decision of complete transverse suturing of IVC, as significant collateral venous circulation was already present. Because IVCL is a rare disease, there is scarce data regarding the prognosis and treatment options. Long-term survival depends on the extent of the surgery. The need of vascular reconstruction is not always mandatory. Despite high recurrence rates, no consensus regarding adjuvant treatment exists yet. A multidisciplinary approach including surgical oncologists and vascular surgeons is mandatory to achieve the best patient outcomes. Perioperative planning, coordination and adherence to oncological techniques are critical.

Biocompatibility of a Marine Collagen-Based Scaffold In Vitro and In Vivo.

Scaffold material is essential in providing mechanical support to tissue, allowing stem cells to improve their function in the healing and repair of trauma sites and tissue regeneration. The scaffold aids cell organization in the damaged tissue. It serves and allows bio mimicking the mechanical and biological properties of the target tissue and facilitates cell proliferation and differentiation at the regeneration site. In this study, the developed and assayed bio-composite made of unique collagen fibers and alginate hydrogel supports the function of cells around the implanted material. We used an in vivo rat model to study the scaffold effects when transplanted subcutaneously and as an augment for tendon repair. Animals' well-being was measured by their weight and daily activity post scaffold transplantation during their recovery. At the end of the experiment, the bio-composite was histologically examined, and the surrounding tissues around the implant were evaluated for inflammation reaction and scarring tissue. In the histology, the formation of granulation tissue and fibroblasts that were part of the inclusion process of the implanted material were noted. At the transplanted sites, inflammatory cells, such as plasma cells, macrophages, and giant cells, were also observed as expected at this time point post transplantation. This study demonstrated not only the collagen-alginate device biocompatibility, with no cytotoxic effects on the analyzed rats, but also that the 3D structure enables cell migration and new blood vessel formation needed for tissue repair. Overall, the results of the current study proved for the first time that the implantable scaffold for long-term confirms the well-being of these rats and is correspondence to biocompatibility ISO standards and can be further developed for medical devices application.

Modified Doppler-guided laser procedure for the treatment of second- and third-degree hemorrhoids.

BACKGROUND: Hemorrhoids are a common anorectal condition with a major medical and socioeconomic impact. Owing to the high incidence of symptomatic hemorrhoids in the adult population together with the risk of complications of traditional surgery, researchers are seeking less invasive methods of hemorrhoidal treatment.The aim of this study was to present our experience with the mini-invasive Doppler guided hemorrhoidal laser procedure (HeLP) in symptomatic 2nd and 3rd degree hemorrhoids with absent or minimal mucosal prolapse. METHODS: The cohort included 62 patients with symptomatic hemorrhoids who underwent the HeLP at a tertiary medical center in 2014-2016. Data were collected on clinical and perioperative characteristics and outcome. Findings were compared between patients with second- and third-degree hemorrhoids. RESULTS: The cohort included 41 male and 21 female patients of mean age 41.5 years. Fifty-one had bleeding and 11 had hemorrhoidal syndrome. Mean operative time was 16.6 ± 3.7 minutes. A total of 8-12 arterial branches were treated. Patients were discharged home within a mean of 91.95 ± 20.48 minutes and allowed to resume normal activities. Compared to patients with second-degree hemorrhoids, patients with third-degree hemorrhoids had a significantly higher rate of recto-anal repair (18.2% vs 0, p < 0.05), intraoperative bleeding (11.3% vs 5%, p < 0.05), and thrombus formation in the hemorrhoids (11.3 % vs 0, p < 0.01). At the six-month follow-up, no complications were reported, and there was significant improvement in symptoms.Using the visual analog scale, no pain was reported by 82.3% of patients at one week after surgery and 95.2% of patients at one month after surgery. CONCLUSION: Patients with hemorrhoids treated with Doppler-guided laser had an excellent outcome in terms of resolution of symptoms and postoperative pain. Only Minor short-term complications were noted. Doppler-guided laser seems to be an effective and painless technique for the treatment of symptomatic second- to third grade hemorrhoids with minimal mucosal prolapse.

Laparoscopic Total Mesorectal Excision Following Transanal Endoscopic Microsurgery for Rectal Cancer.

BACKGROUND: Patients' selection for transanal endoscopic microsurgery (TEM) depends on diagnostic modalities; however, there are still some limitations in the preoperative diagnosis of rectal lesions, and in some reports, up to third of the adenomas resected by TEM were found to be adenocarcinoma; therefore, salvage radical resection (RR) remains necessary for achieving oncological resection. Salvage RR may encounter some technical problems as the violation of the mesorectum and the scar formation. In this study, we aimed to report the outcome in patients undergoing salvage RR in terms of morbidity and oncological results. MATERIALS AND METHODS: Demographic and clinical data pertaining to patients undergoing RR following TEM between 2004 and 2014 were retrospectively collected. RESULTS: One hundred forty one TEM were performed in the study period, 53 (38%) for malignant rectal lesions. Indication for TEM: 15 (28%) benign adenoma, 25 (47%) early rectal cancer, and 13 (25%) had clinical complete response after neoadjuvant radiochemotherapy. Ten (19%) patients had no residual tumor in TEM specimen, 15 (28%) had T1, and 2 of them underwent salvage low anterior resection (LAR). Ten (19%) had T2, 4 had LAR, and 1 had abdominoperineal resection (APR). Five (9%) had a T3, 3 underwent LAR, and 2 had APR. Among the 13 (25%) after chemo-radiotherapy (CRT), 4 had salvage AR. The time from TEM to RR was 47 days (range32-70). Of 16 salvage surgeries, 8 (50%) were laparoscopic. The median operative time was 210 minutes (range165-360). Five patients had protective ileostomy. Rectal perforation occurred in 2 (12%) patients; both had a posterior location, one after CRT. Two (12%) postoperative small-bowl obstruction and three wound infections occurred. There was no perioperative mortality in any of the patients who underwent RR. The final pathology was no residual disease in 9, T3N1 in 1, T3N0 in 3, T2N1 in 1, and T2N0 in 2 patients. Eight (50%) had adjuvant chemotherapy. CONCLUSION: Laparoscopic total mesorectal excision following TEM seems to be safe, and with no negative impact of the completeness of the resection. The concern of intraoperative specimen perforation is real, and should be dealt with meticulous technique and careful dissection, particularly after CRT.

A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies.

To examine the ability of a new specimen handling technique to improve histopathological yield of ureteroscopic biopsies, performed in patients with suspected upper tract urothelial carcinoma (UTUC). In a bi-center retrospective study we compared the results of the new tissue handling technique (group 1) with the standard technique (group 2). In the new technique, to achieve maximal tissue preservation, the specimen is mounted on filter paper prior to embedding in paraffin. Multivariate analysis was performed to determine which factors are associated with optimal histological results. We further compared the biopsies with the final specimen in a subgroup of patients who underwent nephroureterectomy (NU). Of 55 ureteroscopic biopsies, 1 biopsy from group 1 (new technique) and 3 biopsies from group 2 (standard technique) were inadequate for pathological examination. 51 UTUC specimens were analyzed. Tumor grade and stage were determined in 85% and 63% of the patients in group 1 and in 83% and 25% of group 2 (p=0.85 and p=0.007). Orientation was preserved in 82% of group 1 and 42% of group 2 (p=0.003). On multivariate analysis biopsy technique and biopsy diameter were found to predict stage determination (p=0.01 and p=0.007) and tissue orientation (p=0.005 and p=0.04). Among patients who underwent NU, stage concordance between the biopsy and final pathology was observed in 56% and 27% of the patients in group 1 and 2, respectively. The new processing technique for small UTUC forceps biopsies decreases the rate of biopsies with insufficient material and improves biopsy interpretation.

Molecular Predictors of Response to Neoadjuvant Chemoradiation for Rectal Cancer.

OBJECTIVES: To determine whether the expression of specific molecular markers in the rectal cancer biopsies prior to treatment, can correlate with complete tumor response to chemoradiotherapy (CRT) as determined by the pathology of the surgical specimen. METHODS: We retrospectively examined pretreatment rectal biopsies of patients aged 18 years or older with locally advanced rectal cancer who had been treated with neoadjuvant CRT and surgical resection in our tertiary-care, university-affiliated medical center, between January 2001 and December 2011. Samples were analyzed for expression of B-cell lymphoma 2, P53, Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor, and the tumor regression grade after CRT and radical surgery. RESULTS: Forty-seven patients were included in the final analysis. Main outcome measures were the correlation between the expression of the molecular markers tested in the pretreatment biopsy, and complete tumor response. Complete pathologic response after CRT was attained in 27% of the patients. Percentage of cells expressing EGFR in the pretreated biopsies of patients having complete pathologic response after CRT and surgery was 33.08±7.87% compared to 19±15.36% (P=0.38), 6.66±2.83% (P<0.003), and 12.5±4.93% (P=0.033) in patients with partial response and tumor regression grades of 2, 3, and 4, respectively. The other molecular markers tested in the pretreatment biopsy did not corresponded with complete pathologic response. CONCLUSIONS: EGFR expression pattern in the pretreatment biopsies of rectal tumors can assist in identifying patients who will benefit from neoadjuvant CRT.

Expression of Topoisomerase II-α protein in salivary gland tumors.

Salivary glands give rise to approximately 30 histological distinct tumor types, which results in a diagnostic challenge for the pathologist. The present retrospective, immunohistochemical study aimed to evaluate the expression of Topoisomerase II-α, a nuclear enzyme, as a diagnostic and prognostic marker in benign and malignant salivary gland tumors, including leomorphic adenoma, mucoepidermoid carcinoma, acinic cell carcinoma and carcinoma ex-pleomorphic adenoma. A total of 59 cases of benign and malignant salivary gland tumors were included in the present study. Representative paraffin-embedded sections were immunostained for Topoisomerase II-α (Topo II-α). The expression level was semi-quantified for each case and then correlated with the histological diagnosis using hematoxylin and eosin-stained slides, grade of tumor and total survival. Significant differences were revealed between the expression level of Topo II-α in pleomorphic adenoma and mucoepidermoid carcinoma (P<0.001), carcinoma ex-pleomorphic adenoma (P<0.001), acinic cell carcinoma (P=0.005) and a group composed of all the malignant tumors (P<0.001). Cancer-specific survival rates were insignificantly increased in tumors expressing low levels of Topo II-α (P=0.464). Thus, the present study demonstrated different expression levels of Topo II-α in benign and malignant salivary gland tumors. These differing expression levels may act as valuable biomarkers for the correct histological diagnosis. Further studies conducted on a larger scale may lead to even more conclusive results.

Morphological changes in peri-prostatic sympathetic ganglion cells in aging males.

A significant part of morbidity in elderly male patients involves the pelvic organs and their autonomic neural regulation. The aim of the current study was to report the histopathological changes in the peri-prostatic ganglia in elderly males. The sympathetic ganglia from 36 prostatectomy specimens, 26 due to carcinoma of the prostate and 10 prostates from total cystectomies for transitional cell carcinoma, were examined. The age range was 54-88 years. A total of 5,075 ganglion cells were counted in all the specimens. Pathological changes were identified in 1,696 neuron cells as follows: Neuronophagia in 746 neuron cells, neuron cell vacuolization (330 cells), satellite cells vacuolization (423 cells), cell pyknosis (148 cells) and nageotte nodules (49 cells). A number of these changes increased with age. All the changes were more marked in the peri-prostatic ganglion cells of patients with prostatic adenocarcinoma compared with those with benign prostate hyperplasia, which may be due to local environmental changes associated with the presence of malignancy.

Gastritis in patients undergoing sleeve gastrectomy: Prevalence, ethnic distribution, and impact on glycemic.

Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese patients. The aim of this study was to evaluate the presence of Helicobacter pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy specimens, and its association to other variables.One hundred six sleeve gastrectomy specimens were examined histopathologically for the presence of gastritis and its relation to other factors like ethnicity, glycemic control, and postoperative complications.Twelve patients had HP gastritis, 39 had non-HP gastritis, and 55 had normal mucosa. There was a statistical difference between the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population 6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic control was worse in the gastritis group with a mean HbA1c of 8.344% while in the normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control reverted to normal in most the diabetic patients. There were few postoperative complications however, they were not related to HP.There is a high incidence of gastritis in obese patients. The incidence of gastritis in the Arab population in our study was higher than that in the Jewish population. The glycemic control before surgery was worse in patients with gastritis than in the normal mucosa group. HP bares no risk for postoperative complications after LSG and does not affect weight loss. However a larger cohort of patients must be studied to arrive at conclusive results.

Removable sinus stent for endoscopic sinus surgery: An animal trial.

BACKGROUND: The goal of endoscopic sinus surgery in chronic sinusitis is to create good drainage of the paranasal sinuses. Metal stents used to prevent lateralization of the middle concha are associated with adverse effects. OBJECTIVE: The aim of this experimental study was to evaluate the feasibility and safety of a newly developed composite removable stent. METHODS: The composite removable stent was implanted in nine sheep (18 stents) in the ethmoid cavity after performing an ethmoidectomy and was examined for stability, ease of removal, and adverse effects. Histologic findings were compared between implantation and nonimplantation sites at several time points after stent deployment and removal. RESULTS: None of the stents migrated or fell out of the nose. After 4 weeks, there was no infection in the nose or around the stents, and there was no damage to the mucosa. An histologic study showed only mild-to-moderate inflammatory cell infiltration relative to control sites, with no damage to the mucosal epithelium and no necrosis at distant sites. At 2 weeks after stent removal, slight-to-moderate fibroplasia was noted in the deep nasal tissue, with slight-to-moderate osteocartilaginous metaplasia and bone remodeling but no necrotic or inflammatory changes in surrounding tissues. At 4 weeks after stent removal, the middle meatus remained open. CONCLUSION: The promising results of the composite removable stent in a sheep model justify further studies in patients undergoing endoscopic sinus surgery for chromic sinusitis.

Seminal Tract Amyloidosis: Synchronous Amyloidosis of the Seminal Vesicles, Deferent Ducts and Ejaculatory Ducts.

Senile Seminal Vesicle Amyloidosis (SSVA) increases with age. Involvement of the whole seminal tract, i.e. the seminal vesicles, ejaculatory and deferent ducts was first reported by us in the International Symposium on Amyloidosis 1998. Since then we encountered four more cases of SSVA. In all these cases the ejaculatory and deferent ducts were also involved by amyloid. The amyloid was located mostly sub-epithelially, stained positively with Congo red, gave green birefringence under polarized light and was permanganate sensitive, slightly positive for lactoferrin immunostaining and negative for all known amyloid types. In recent years the amyloid was found to be derived from Semenogelin I, a major constituent of the seminal fluid which is present in the epithelial cells of the seminal vesicle and vas deference. This would explain the deposition of amyloid not only in the seminal vesicles but also in the deferent an ejaculatory ducts which transport the seminal fluid. In a review of the literature we found three more articles on SSVA in which the amyloid was not limited to the seminal vesicles alone. We propose to designate this type of amyloid as "Senile seminal Tract Amyloidosis" (SSTA) instead of "Senile Seminal Vesicle Amyloidosis (SSVA)".

The predictive value of dendritic cells in early squamous cell carcinoma of the tongue.

OBJECTIVES: The aim of this study was to evaluate the relationship between dendritic cell density in early squamous cell carcinoma (SCC) of the tongue and patients' clinical outcome. METHODS: Representative samples of low-risk SCC of the tongue (T1-2,N0,M0) from a homogeneous group of 18 patients following local complete excision and elective selective neck dissection, were immunostained with antibodies against S100 and CD1a. Dendritic cell density was analyzed by outcome. RESULTS: Mean dendritic cell densities were 17 cells/HPF for tumoral S100 and CD1a counts, and 10 cells/HPF for peritumoral S100 and CD1a counts. Better disease-free survival was associated with low peritumoral S100- and CD1a- positive cell counts (p=0.006 and p=0.004, respectively), and with low tumoral S100- and CD1a- positive cell counts (p=0.037 and p=0.04, respectively). Lymphocytic response was decreased in tumors with high dendritic cell density (p=NS). There was no association of dendritic cell density with patient age, tumor size and depth of invasion. CONCLUSIONS: These results may suggest an association between dendritic cell accumulation and functional immunologic impairment.

A3 adenosine receptor agonist, CF102, protects against hepatic ischemia/reperfusion injury following partial hepatectomy.

Ischemia/reperfusion (IR) injury during clinical hepatic procedures is characterized by inflammatory conditions and the apoptosis of hepatocytes. Nuclear factor­κB (NF­κB), nitric oxide and the expression levels of inflammatory cytokines, tumor necrosis factor­α and interleukin­1 were observed to increase following IR and mediate the inflammatory response in the liver. CF102 is a highly selective A3 adenosine receptor (A3AR) agonist, and has been identified to induce an anti­inflammatory and protective effect on the liver via the downregulation of the NF­κB signaling pathway. The present study aimed to determine the effect of CF102 on protecting the liver against IR injury. The potential protective effect of CF102 (100 µg/kg) was assessed using an IR injury model on 70% of the liver of Wistar rats, which was induced by clamping the hepatic vasculature for 30 min. The regenerative effect of CF102 was assessed by the partial hepatectomy of 70% of the liver during 10 min of IR. CF102 reduced the levels of liver enzymes following IR injury. A higher regeneration rate in the CF102 treatment group was observed compared with the control group, suggesting that CF102 had a positive effect on the proliferation of hepatocytes following hepatectomy. CF102 had a protective effect on the liver of Wistar rats subsequent to IR injury during hepatectomy. This may be due to an anti­inflammatory and anti­apoptotic effect mediated by the A3AR.

Visualization of Grossly Undetectable Breast Tumors by Refixation in Lymph Node Revealing Solution.

Introduction Breast lesions might be missed by the traditional method of inspection, palpation, and sectioning of the specimen. Lymph node revealing solution (LNRS) was first introduced by us as a fixative that enhances the retrieval of lymph nodes in breast carcinoma and other malignancies. This is a preliminary report of our experience with the use of LNRS in order to visualize malignant breast tumors that were not detected by the traditional method. Material and Methods Eight post-chemoradiation-treated tumors, 6 relumpectomy specimens, and 1 post mammotome lumpectomy with no grossly detectable residual tumor and 2 mastectomy specimens with multifocal tumors which were missed by the first inspection were postfixed in LNRS for 24 hours and sectioned. Results In some of the cases, small tumors up to 0.5 cm were visualized as white gray lesions. Carcinoma has been confirmed by histopathologic examination and the final diagnosis had to be changed. Conclusion Postfixation in LNRS enhances the visualization of grossly undetectable breast lesions and it is worthwhile to use it in problematic cases in order to arrive at a more accurate diagnosis.

CD1a-positive dendritic cell density predicts disease-free survival in papillary thyroid carcinoma.

OBJECTIVES: Dendritic cells are common in inflammatory processes and in papillary thyroid carcinoma (PTC). Previous studies of the predictive value of S100-positive dendritic cell density for PTC outcome yielded inconsistent results. This study investigated the association of dendritic cell density and PTC recurrence based on CD1a expression. METHODS: Representative slides from 56 consecutive specimens of PTC were immunostained with anti-CD1a antibodies, and dendritic cell density was analyzed by disease-free survival. RESULTS: Dendritic cells were abundant in the tumoral tissue and sparse in the normal peritumoral tissue. Peritumoral dendritic cell density >1.1 cells/HPF was inversely associated with the risk of recurrence. Similar results were obtained with tumoral dendritic cell density (>12 cells/HPF), although the statistical significance was marginal. CONCLUSIONS: High CD1a-positive dendritic cell density is associated with improved disease-free survival in PTC. The specificity of anti-CD1a immunostain for activated dendritic cells may explain the better outcome prediction in this study than in studies using S100 protein.

Ablation of experimental colon cancer by intratumoral 224Radium-loaded wires is mediated by alpha particles released from atoms which spread in the tumor and can be augmented by chemotherapy.

PURPOSE: We developed (224)Ra-loaded wires, which release by recoil alpha emitting nuclei into solid tumors and cause tumor cell killing. This research examined if the major damage was inflicted by alpha particles emitted from these atoms or by direct gamma and beta emissions from the inserted wires. We also examined the efficacy of this treatment against colon cancer in combination with chemotherapy. MATERIALS AND METHODS: Mouse colon carcinomas (CT-26 xenografts), treated by intra-tumoral radioactive wires loaded with (224)Ra atoms were monitored for effects on tumor growth, intratumoral tissue damage and distribution of alpha emitting atoms. The effects were compared with those of (224)Ra-loaded wires coated with poly methyl methacrylate (PMMA), which blocks atom recoil. Similar experiments were performed with radioactive wires combined with systemic 5-FU. RESULTS: (224)Ra-loaded wires inhibited tumor growth and formed necrotic areas inside the tumor. PMMA coated wires did not inhibit tumor growth, and caused minor intratumoral damage. Autoradiography images of tumors treated with (224)Ra-loaded wires revealed a spread of alpha emitters over several mm, whereas PMMA-coated wires showed no such spread. Injection of 5-FU with (224)Ra-loaded wires augmented tumor growth retardation and cure. CONCLUSIONS: (224)Ra-loaded wires ablate solid tumors by the release of alpha-particle emitting atoms inside the tissue, an effect that can be enhanced by combining this method with chemotherapy.

Multifunctional activity of a small tellurium redox immunomodulator compound, AS101, on dextran sodium sulfate-induced murine colitis.

Inflammatory bowel diseases (IBDs) are a group of idiopathic, chronic immune-mediated diseases characterized by an aberrant immune response, including imbalances of inflammatory cytokine production and activated innate and adaptive immunity. Selective blockade of leukocyte migration into the gut is a promising strategy for the treatment of IBD. This study explored the effect of the immunomodulating tellurium compound ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) on dextran sodium sulfate (DSS)-induced murine colitis. Both oral and intraperitoneal administration of AS101 significantly reduced clinical manifestations of IBD. Colonic inflammatory cytokine levels (IL-17 and IL-1ß) were significantly down-regulated by AS101 treatment, whereas IFN-γ was not affected. Neutrophil and α4ß7(+) macrophage migration into the tissue was inhibited by AS101 treatment. Adhesion of mesenteric lymph node cells to mucosal addressin cell adhesion molecule (MAdCAM-1), the ligand for α4ß7 integrin, was blocked by AS101 treatment both in vitro and in vivo. DSS-induced destruction of colonic epithelial barrier/integrity was prevented by AS101, via up-regulation of colonic glial-derived neurotrophic factor, which was found previously to regulate the intestinal epithelial barrier through activation of the PI3K/AKT pathway. Indeed, the up-regulation of glial-derived neurotrophic factor by AS101 was associated with increased levels of colonic pAKT and BCL-2 and decreased levels of BAX. Furthermore, AS101 treatment reduced colonic permeability to Evans blue and decreased colonic TUNEL(+) cells. Our data revealed multifunctional activities of AS101 in the DSS-induced colitis model via anti-inflammatory and anti-apoptotic properties. We suggest that treatment with the small, nontoxic molecule AS101 may be an effective early therapeutic approach for controlling human IBD.

A new Ki-67 / E-cadherin cocktail reduces inter-observer variation of the calculated proliferative index.

The proliferative index in breast carcinoma is usually calculated by the percentage of the Ki-67 positive cells out of the total number of malignant cells. In order to reduce the inter-observer variability of the calculated proliferative index a cocktail of antibodies against E-Cadherin and Ki-67 (Ki/Cad Cocktail) is presented. The cocktail was applied on 59 cases of infiltrating duct carcinoma of breast and compared to the consecutive slides stained for Ki-67 alone. The Ki/Cad cocktail has the advantage that by adding the anti E-Cadherin antibody, all the malignant epithelial cells are highlighted and can be differentiated from other proliferating cells. Statistical analysis proved that the cocktail increases the inter-observer agreement from 89 % to 97 % as compared to the Ki-67 alone and also reduces the overlap between the cancer grades.