Normal Spleen Research Articles

Induction of apoptosis by Fe(salen)Cl through caspase-dependent pathway specifically in tumor cells

Iron-based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salen)Cl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti-tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salen)Cl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T-cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salen)Cl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC) remain largely unaffected by Fe(salen)Cl. Fe(salen)Cl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salen)Cl treatment suggests that Fe(salen)Cl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salen)Cl-treated tumor cells is mediated through caspase-dependent pathway. This is the first report demonstrating that Fe(salen)Cl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next-generation anti-tumor drug.

You Are Never Too Old: A Case of Glycogen Storage Disease Type 1 in an Adult: 2017 Presidential Poster Award

Glycogen storage disease (GSD) type 1a, also known as Von Gierke's disease, is caused by the absence of glucose-6-dephosphatase. This disease usually manifests in infancy with hypoglycemia, hepatomegaly, and poor growth. In rare cases, adults have been diagnosed with GSD type 1a usually by the presence of hepatocellular adenomas. A 40-year-old Hispanic man presented initially after motor vehicle accident due to a seizure. CT abdomen was performed with an incidental finding of a liver mass, which was biopsied multiple times and showed hepatic adenoma. For two years after this initial presentation, he had multiple hospitalizations for abdominal pain due to ruptured hepatic adenomas, with resultant bleeding requiring embolization. He was diagnosed with GSD type 1 based on clinical features including hepatomegaly, seizures, stunted growth, and normal spleen size. This diagnosis was confirmed, prior to his sixth embolization for ruptured adenoma, with genetic testing which showed 2 copies of pathogenic variant G6PC gene detected (c. 113A>T). On physical exam, he was found to have a protuberant abdomen with hepatomegaly, short stature, thin limbs, and subcutaneous nodules consistent with tophi. CT abdomen showed multiple adenomas, the largest measuring 7 x 7 cm in the caudate lobe. Liver tests showed ALT 46 U/L, AST 43 U/L, ALP 456 U/L, bilirubin 0.3 mg/dL. He has undergone serial imaging to evaluate for change in liver lesion size as adenoma transformation to hepatocellular carcinoma has been described. Nutrition consult was obtained as dietary modification to promote optimal metabolic control has been described in younger patients with smaller lesions. Liver transplantation was discussed as patient had large, multiple adenomas with bleeding. GSD type 1a, usually a pediatric diagnosis, can uncommonly be seen in adults. To date, there are only two reported cases of patients with a later diagnosis in adulthood, typically found in patients with mild disease. A presentation of adenomatosis without previous known GSD type 1a can occur and should prompt further evaluation for this genetic mutation even in adults, especially if other features are suggestive of this genetic disorder.Figure: Multiple adenomas seen on sagittal view of CT abdomen.Figure: Hepatomegaly and multiple adenomas on coronal view of CT abdomen.

Splenic rupture following synchronised direct current cardioversion

Atraumatic rupture of the normal spleen is a rare entity. Often, a triggering factor or minor physical event can be ascribed as the aetiology for rupture, including coughing, vomiting or...

Optimal Use of Transient Elastography and Acoustic Radiation Force Impulse to Stage Liver Fibrosis in HIV/HCV‐Coinfected Patients in Clinical Practice

Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05-0.91) and high viral load (OR, 0.36; 95% CI, 0.17-0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21-9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.

Abstract CT017: First-in-human PET imaging with the PD-L1 antibody 89Zr-atezolizumab

Abstract Background: Programmed death-ligand 1 (PD-L1) expression has been associated with response to PD-1/PD-L1 inhibition, but responses are also seen in patients with PD-L1 negative tumors when assessed immunohistochemically (IHC) with various antibodies. To help understand these findings, we performed a first-in-human positron emission tomography (PET) imaging study with the anti-PD-L1 antibody atezolizumab labeled with zirconium-89 (89Zr) prior to treatment with atezolizumab to assess normal organ distribution and evaluate tumor tracer uptake in relation to PD-L1 IHC in archival and post-tracer tumor specimen and ultimately to treatment response. Methods: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), bladder cancer (BC) or triple-negative breast cancer (TNBC) received 10 mg unlabeled atezolizumab plus 37 MBq 89Zr-atezolizumab (~1 mg) followed by up to 4 PET scans (1 hour, days 2, 4 and 7 post-injection (pi)). Next, after obtaining a tumor biopsy for PD-L1 IHC 8-10 days after tracer injection, patients received atezolizumab (1200 mg) i.v. once every 3 weeks until disease progression (NCT02453984 and NCT02478099). Response was assessed every 6 weeks with RECIST1.1. Normal organ tracer uptake was calculated as percentage of the injected dose/kg (%ID/kg) 4 and 7 days pi, tumor tracer uptake as maximum standardized uptake value (SUVmax) and %ID/kg 7 days pi. Tumor biopsy PD-L1 expression was assessed in tumor cells (TC) and tumor infiltrating immune cells (IC) by HistoGeneX IHC with the SP142 assay (Ventana). Results: In this ongoing trial, 16/25 patients completed the PET series and received atezolizumab at least until the first response assessment. The median follow-up of these patients is 16 weeks (6-40+, NSCLC=6, BC=8, TNBC=2). The highest normal organ 89Zr-atezolizumab uptake was seen in the spleen (16.3±3.6 %ID/kg 4 days and 17.9±3.6 %ID/kg 7 days pi), and uptake in other lymphatic organs (single normal lymph nodes and tonsil) and sites of (chronic) inflammation (e.g. chronic sinusitis and bursitis) were detected. Uptake in liver, kidney and intestine was similar to other antibodies with 7.3±1.6, 5.5±2.0 and 4.7±2.4 %ID/kg, respectively, 7 days pi. Tumor SUVmax ranged between 1.6 and 46.0 (1.8-12.4 %ID/kg), with an up to 9-fold difference within patients, and 4-fold difference between patients. In 4 biopsied lesions with IC/TC 0, 89Zr-atezolizumab uptake calculated as SUVmax was 10.0±3.6 (7.1±1.6 %ID/kg). At this time only 4 biopsies had a IHC score of 2+ on either IC or TC, and there were no biopsies with a score of 3+, limiting the ability to determine correlation of PD-L1 IHC to imaging data. Conclusion: 89Zr-atezolizumab imaging showed high uptake in normal spleen, other normal lymphoid organs and regions of inflammation. Uptake in tumor lesions was heterogeneous within and between patients and even PD-L1 IHC 0 tumors showed clear tracer uptake. Citation Format: Frederike Bensch, Elly van der Veen, Annelies Jorritsma, Marjolijn Lub-de Hooge, Ronald Boellaard, Sjoukje Oosting, Carolien Schröder, Jeroen Hiltermann, Anthonie van der Wekken, Harry Groen, Bernard Fine, Nathan McKnight, Sandra Sanabria Bohorquez, Simon Williams, Luisa Veronese, Christoph Mancao, Adrienne H. Brouwers, Elisabeth de Vries. First-in-human PET imaging with the PD-L1 antibody 89Zr-atezolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT017. doi:10.1158/1538-7445.AM2017-CT017

The spleen

The spleen

Absence of Oesophageal Varices in Children with Splenomegaly and Advanced Intestinal Failure Associated Liver Disease

Objectives of the study: Children with splenomegaly and portal hypertension due to primary liver disease demonstrate presence of gastro- oesophageal varices (GOV) on oesophago-gastroduodenoscopy (OGD). Intestinal failure – associated liver disease (IFALD) is a secondary liver disease developing in 40% to 60% of infants requiring long term parenteral nutrition for irreversible intestinal failure. A proportion of these children develop life threatening complications of cirrhosis and portal hypertension. Assessment of portal hypertension is important to determine the type of intestinal transplantation (ITx) offered as a life saving option. Intestinal transplantation is the only life saving option for these children. During intestinal transplant assessment within our programme, we assessed the children for the presence of GOV. Aim: To evaluate the incidence of GOV in children with IFALD referred for small bowel transplant assessment. Methods: Medical records of 122 patients who underwent assessment for small bowel transplant (SBtx) over the last 12 years (Sept 04 to Dec 16) were reviewed. Data detailing spleen size, splenomegaly, liver biopsy with staging of hepatic fibrosis and presence of GOV on oesophago-gastroduodenoscopy (OGD) was recorded. Results: 118/122 children assessed were included in the study as 4 children did not have ultrasound scan (USS). 98/118 (83 %) children had splenomegaly on USS. 54/98 (55.1%) children underwent OGD and oesophageal varices were present in 11 children (20.3%), of which only 10 had Grade 1 and one had Grade 3 varices. Of the 20 patients with a normal sized spleen, 15 underwent an OGD- no varices have been detected. 56 children had an OGD and a liver biopsy performed at the same time. 51/56 patients had fibrosis, 26/51 (50.9 %) were graded as mild fibrosis on liver biopsy, and 8/56 (14.2 %) of them had oesophageal varices (grade 1). Moderate to severe fibrosis was noted in 25/51 (49%) children and only 2/25 (8%) children had GOV, all Grade I. Summary and Conclusion: Children with IFALD, who have a normal size spleen did not have varices at OGD and therefore do not require endoscopy to stage their liver disease. In children with IFALD, splenomegaly is common and GOV are infrequent. Their presence does also not correlate with the degree of liver-fibrosis. In conclusion, USS evidence of splenomegaly alone is a poor predictor for GOV and additional tests such as platelet count, hepatic elastography may improve the assessment of portal hypertension in children with intestinal failure associated liver disease.

The case of the mysterious vanishing spleen: autosplenectomy complicating pneumococcal sepsis

A 57-year-old previously healthy fisherman was admitted in fulminant pneumococcal septic shock, with disseminated intravascular coagulation, requiring aggressive management including bilateral below-knee amputations for ischaemic necrosis. He began to recover...

Evaluation of Liver, Kidney, and Spleen Elasticity in Healthy Newborns and Infants Using Shear Wave Elastography

Elasticity measurements of tissues can be valuable in the diagnosis and management of various diseases. The aim of this study was to determine the elasticity values for normal liver, kidney, and spleen of healthy newborns and infants using shear wave elastography (SWE) imaging. A total of 50 healthy term newborns and infants (19 girls and 31 boys; mean age 20.1 days, range 1 to 70 days) were examined by an experienced pediatric radiologist using SWE. None of them had any liver, kidney or spleen disease, or any other systemic disease that could affect these organs secondarily. All newborns and infants had a normal abdominal ultrasound scan. Age, sex, weight, height, and body mass index had no significant effects on shear wave velocity (SWV) values of liver and spleen. The SWV values of both kidneys decreased with age, weight, height, and body mass index. The mean SWV values were 1.70 m/s (range: 1.23-2.43 m/s) for the liver, 1.69 m/s (range: 0.8-2.40 m/s) for the right kidney, 1.70 m/s (range: 0.9-2.49 m/s) for the left kidney, and 2.03 m/s (range: 1.28-2.48 m/s) for the spleen. Shear wave elastography can be used to measure liver, kidney, and spleen elasticity in newborns and infants. The standard values for abdominal organs allow differentiation of healthy versus pathological tissue. We measured the normal values of SWE in healthy newborns and infants as reference data.

Sustained Immunosuppression Alters Olfactory Function in the MRL Model of CNS Lupus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is frequently accompanied by diverse neuropsychiatric manifestations. An increased frequency of olfactory deficits has been recently reported as another marker of CNS involvement in SLE patients. Similarly, we observed that spontaneous development of lupus-like disease in MRL/lpr mice is accompanied by altered olfaction-related behaviors. However, it remained unclear whether the behavioral deficits are due to systemic autoimmunity, or the distinct genetic make-up. To address this question, we presently examine whether prolonged treatment with the immunosuppressive drug cyclophosphamide (CY) restores odor-guided behaviors in MRL/lpr mice. Over 12 weekends, MRL/lpr and control MRL +/+ males were given ad lib access to a sweetened CY solution or a vehicle. Their responsiveness to different scents was assessed at ages corresponding to mild, modest, and severe disease. Odor-guided exploratory behavior was further examined in the novel object test at 21weeks of age, shortly before terminal assessment of immunopathology. In comparison to control groups, MRL/lpr mice exposed to CY exhibited normal spleen size and antibody levels, as well as increased responsiveness to an attractant and a novel object. However, CY treatment also exacerbated their aberrant response to a repellent, suggesting a dual mode of action on brain olfactory systems. The present results reveal that generalized immunosuppression modulates odor-guided behaviors in lupus-prone animals. Although key pathogenic mechanisms are not clear, the findings strengthen the construct validity of the MRL model by supporting the hypothesis that onset of systemic autoimmunity alters the activity of olfactory circuits.

Symptomatic pancreatic sarcoidosis

Objective: Report the case of female patient with symptomatic pancreatic sarcoidosis. Methods: Case Report. Results: A 65-year-old female was referred for the evaluation of severe fatigability, poor appetite, weight loss over the past two months and abdominal pain. She denied smoking cigarettes or alcohol intake. A review of systems was unremarkable. Her physical exam revealed the abdomen was soft, non-distended and non-tender with normal liver and spleen span. She presented with leukopenia, hypercalcemia, elevated liver enzyme an elevated alkaline phosphatase and an elevated erythrocyte sedimentation rate. An abdominal CT scan demonstrated a pancreatic head mass with retroperitoneal lymph node enlargement Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) were not performed. A CT scan guided pancreatic mass biopsy was performed with uncertain results. Laparoscopic pancreatic biopsy demonstrated noncaseating granulomas with Langerhan giant cells and fibrosis. Both an acid fast bacilli stain and gram stain for a fungal infection were negative. The patient presented elevated Angiotensin converting enzyme levels. Oral prednisone 40 mg daily for 7 days followed by a 7 week tapering schedule was initiated. The patient's signs and symptoms improved abdominal CT scan 6 weeks after treatment revealed no change in the size of the pancreas and peripancreatic lymph nodes. After 8 week of prednisone she remains clinically stable without any abnormal laboratory parameters. Conclusion: Sarcoidosis is a chronic multiorgan disease that uncommonly involves the pancreas. Pancreatic involvement is usually asymptomatic and discovered on autopsy. However, doctors should be cognizant that sarcoidosis can present with symptomatic pancreatic mass, albeit rarely.

Morphometric Study of Spleen in Iranian Cadavers from Razavi-Khorasan Province

Anthropologic parameters of the spleen are important because many diseases present with reduction or enlargement of the spleen. No data exists about the standard dimensions of the normal spleen in Iranian population. Therefore, the objective of the study was to investigate anthropologic parameters of the spleen in Iranian cadavers. In 2014-2015, this cross sectional study was undertaken from the Razavi Khorasan Province of Iran. Iranian cadavers (n=693, 152 female/541 male) with no history of poisoning, drug or alcohol addiction, no gross abnormality and injury of the spleen were included in the study. The length, width and thickness of spleen were measured using a Vernier caliper. The mean values of the demographic data were age= 40.28 ± 20.97 years; weight = 63.68 ± 17.40 kg; height = 160.03 ± 28.45 cm and BMI = 25.03 ± 20.46 kg/m2. The mean values of the spleen length, width, thickness, notch, weight and index in the cadavers were 11.32 ± 3.10 cm, 8.05 ± 2.35 cm, 20.12 ± 9.21 mm, 0.84 ± 1.35, 123.87 ± 82.46 g, and 2.01 ± 1.40, respectively. Accessory spleen was found in five cadavers. The anthropologic parameters of the spleen showed significant difference between males and females except for index of the spleen. Having standard data on the spleen is useful for radiologists, surgeons, anatomists and anthropologists. The results of the study may provide valuable data in the standardization of the anthropologic parameters of the spleen in the Iranian population.

Supercritical anti-solvent technique assisted synthesis of thymoquinone liposomes for radioprotection: Formulation optimization, in-vitro and in-vivo studies

The aim of this study was to develop Thymoquinone (TQ) loaded PEGylated liposomes using supercritical anti-solvent (SAS) process for enhanced blood circulation, and greater radioprotection. The SAS process of PEGylated liposomes synthesis was optimized by Box-Behnken design. Spherical liposomes with a particle size of 195.6±5.56nm and entrapment efficiency (%EE) of 89.4±3.69% were obtained. Optimized SAS process parameters; temperature, pressure and solution flow rate were 35°C, 140bar and 0.18mL/min, respectively, while 7.5mmol phospholipid, 0.75mmol of cholesterol, and 1mmol TQ were optimized formulation ingredients. Incorporation of MPEG-2000-DSPE (5% w/w) provided the PEGylated liposomes (FV-17B; particle size=231.3±6.74nm, %EE=91.9±3.45%, maximum TQ release >70% in 24h). Pharmacokinetics of FV-17B in mice demonstrated distinctly superior systemic circulation time for TQ in plasma. Effectiveness of radioprotection by FV-17B in mice model was demonstrated by non-significant body weight change, normal vital blood components (WBCs, RBCs, and Platelets), micronuclei and spleen index and increased survival probability in post irradiation animal group as compared to controls (plain TQ and marketed formulation). Altogether, the results anticipated that the SAS process could serve as a single step environmental friendly technique for the development of stable long circulating TQ loaded liposomes for effective radioprotection.

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

PurposeIn phase I/II-studies radiolabelled ABY-025 Affibody molecules identified human epidermal growth factor receptor 2 (HER2) expression in breast cancer metastases using PET and SPECT imaging. Here, we wanted to investigate the utility of a simple intra-image normalization using tumour-to-reference tissue-ratio (T/R) as a HER2 status discrimination strategy to overcome potential issues related to cross-calibration of scanning devices.MethodsTwenty-three women with pre-diagnosed HER2-positive/negative metastasized breast cancer were scanned with [111In]-ABY-025 SPECT/CT (n = 7) or [68Ga]-ABY-025 PET/CT (n = 16). Uptake was measured in all metastases and in normal spleen, lung, liver, muscle, and blood pool. Normal tissue uptake variation and T/R-ratios were established for various time points and for two different doses of injected peptide from a total of 94 whole-body image acquisitions. Immunohistochemistry (IHC) was used to verify HER2 expression in 28 biopsied metastases. T/R-ratios were compared to IHC findings to establish the best reference tissue for each modality and each imaging time-point. The impact of shed HER2 in serum was investigated.ResultsSpleen was the best reference tissue across modalities, followed by blood pool and lung. Spleen-T/R was highly correlated to PET SUV in metastases after 2 h (r = 0.96, P < 0.001) and reached an accuracy of 100% for discriminating IHC HER2-positive and negative metastases at 4 h (PET) and 24 h (SPECT) after injection. In a single case, shed HER2 resulted in intense tracer retention in blood. In the remaining patients shed HER2 was elevated, but without significant impact on ABY-025 biodistribution.ConclusionT/R-ratios using spleen as reference tissue accurately quantify HER2 expression with radiolabelled ABY-025 imaging in breast cancer metastases with SPECT and PET. Tracer binding to shed HER2 in serum might affect quantification in the extreme case.

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

The diffuse reduction in spleen density: an indicator of severe acute pancreatitis?

We observed that acute pancreatitis (AP) was associated with diffuse reduction in spleen density (DROSD) in some patients. Furthermore, the condition of these patients was more serious, and the potential relationship between DROSD and structural and functional injury of the spleen remained unclear. Therefore, we performed a preliminary exploration of these factors. We analysed pertinent clinical data for AP patients with normal spleen density (control group) and for those with DROSD (reduction group) at the First Affiliated Hospital of Harbin Medical University (June 2013–June 2015). We measured the immunoglobulin M (IgM) B-cells of the AP patients and examined pancreatic and splenic tissues from AP rats with optical microscopy and TEM. The reduction group had a higher acute physiology and chronic health evaluation II (APACHE II) score, a longer length of stay (LOS) and lower serum calcium than the control group. The levels of triglycerides (TG) and total cholesterol (TC) did not differ significantly between the two groups. The percentage of IgM memory B-cells was significantly lower in the DROSD group than in the control group. TEM revealed that the spleen T-lymphocytes were normal in AP rats, but pyroptotic and necrotic spleen B-cells were observed in the severe AP rats. In AP, DROSD was an independent indicator of more severe conditions. Furthermore, spleen B-lymphocytes showed obvious damage at the cellular level, and the immunological function of the spleen was down-regulated when AP was associated with DROSD.

Does coronal oblique length of spleen on CT reflect splenic index?

Splenic dimension of >12cm on coronal plane on ultrasound is considered to represent splenomegaly. We sought to estimate the accuracy of similar coronal oblique length of spleen on CT in identifying splenomegaly by comparing it with CT splenic index. We also sought to establish the splenic width, craniocaudal dimension (CC), thickness, and coronal oblique length in both normal and splenomegaly groups. 319 consecutive patients undergoing CT abdomen were included in the study and measurements of width (W), CC, thickness (T), and coronal oblique length (L) made. Splenic index was calculated based on the formula CC × W × T. Diagnostic accuracy of coronal oblique length in identifying splenomegaly on the basis of splenic index was assessed. Patients with splenic trauma were excluded. Patients with perisplenic collection that precluded proper measurement of spleen were excluded. Of the 319 patients, 41 patients had splenomegaly with splenic index >480. 278 patients showed normal splenic index less than or equal to 480. Sensitivity and specificity of coronal oblique length as ≥12cm in identifying splenomegaly were 97.8% and 34.1%, respectively. Positive and negative predictive values for the same were 91% and 70%, respectively (p value-0.000). There is overlap of numerical values for thickness and coronal oblique length in the normal and splenomegaly groups for a 95% confidence interval, whereas there is no significant overlap between these groups with respect to the craniocaudal length and width. Hence, craniocaudal length of 9.5cm and width of 10.6cm may be used as upper cutoff limit for normal spleen. Coronal oblique dimension of spleen >12cm is highly sensitive and shows good positive predictive value in diagnosing splenomegaly but has poor specificity and negative predictive value. Ideally, splenic index calculated using the CC, width, and thickness is the most reliable measurement for diagnosing splenomegaly. But if single measurements are to be used for identifying splenomegaly, craniocaudal length >9.5cm, width of >10.6cm, and coronal oblique dimension >12cm may be used.

Runx1 Orchestrates Sphingolipid Metabolism and Glucocorticoid Resistance in Lymphomagenesis.

ABSTRACTThe three‐membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumor suppressors and oncogenes. In mouse models, the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over‐expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the “sphingolipid rheostat” from ceramide to sphingosine‐1‐phosphate (S1P). Testing of this relationship in lymphoma cells was therefore a high priority. We find that ectopic expression of Runx1 in lymphoma cells consistently perturbs the sphingolipid rheostat, whereas an essential physiological role for Runx1 is revealed by reduced S1P levels in normal spleen after partial Cre‐mediated excision. Furthermore, we show that ectopic Runx1 expression confers increased resistance of lymphoma cells to glucocorticoid‐mediated apoptosis, and elucidate the mechanism of cross‐talk between glucocorticoid and sphingolipid metabolism through Sgpp1. Dexamethasone potently induces expression of Sgpp1 in T‐lymphoma cells and drives cell death which is reduced by partial knockdown of Sgpp1 with shRNA or direct transcriptional repression of Sgpp1 by ectopic Runx1. Together these data show that Runx1 plays a role in regulating the sphingolipid rheostat in normal development and that perturbation of this cell fate regulator contributes to Runx‐driven lymphomagenesis. J. Cell. Biochem. 118: 1432–1441, 2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

New bioactive peptide reduces the toxicity of chemotherapy drugs and increases drug sensitivity.

Anticancer bioactive peptide(ACBP) is extracted from normal goat spleens and exhibits antitumor activity alone and in combination with low cisplatin doses to achieve antitumor efficacy similar to higher cisplatin doses via sustained medication modes. In the present study, we investigated whether elevated levels of induced or normal ACBP in MKN‑45 gastric cancer(GC) cells may reduce their toxicity to oxaliplatin(L‑OHP) in a dose‑dependent manner. The growth inhibition rate(IR), morphological changes and gene expression were examined in MKN‑45 GC cells. Compared with normal ACBP, induced ACBP alone significantly enhanced the anticancer activity of L‑OHP‑mediated apoptosis and reduced the amount and side‑effects of L‑OHP (P<0.05). The inhibition of cancer cell growth at high concentrations of induced ACBP and L‑OHP was significantly more effective than at low concentrations. In addition, for the first time, we examined the potential of a combination of induced ACBP and L‑OHP to increase L‑OHP sensitivity in human gastric carcinoma xenograft tumors. Nude mice were implanted with human gastric carcinoma MKN‑45 cells and treated with an intraperitoneal injection of 0.5ml of normal saline, 30µg/ml ACBP, 20µg/ml L‑OHP or 30µg/ml ACBP+20µg/ml L‑OHP[combination of anticancer bioactive peptide and oxaliplatin(A+L)] via the tail vein twice a week. Invivo short‑term intermittent use of induced ACBP alone significantly inhibited MKN‑45 tumor growth. The combination of induced ACBP and L‑OHP also significantly improved the quality of life of the nude mice and reduced the toxicity of L‑OHP. Based on flow cytometry and gene expression analyses, A+L significantly increased the proportion of cells in the G2/M phase (P<0.05) relative to ACBP or L‑OHP alone, and short‑term intraperitoneal injection of ACBP increased the sensitizing effect of L‑OHP. Collectively, these results suggest that high levels of induced ACBP in combination with L‑OHP via a short‑term intermittent medication mode could be a useful clinical therapeutic strategy for GC.

Littoral-cell angioma of the spleen: a case report.

Littoral-cell angioma (LCA), a primary angioma which clinically belongs to splenic hemangioma, can be mostly found in normal spleen red sinus shore cells of reticuloendothelial cell system. The cells of LCA strongly express endothelial and tissue cell associated antigens that indicate a dual differentiation characteristic; whereas only endothelial cell markers are positive in normal spleen red sinus shore cells. Diagnosis of LCA relies on histopathology. Regular follow-up is needed to monitor recurrence and metastasis.