DNA variants detected in primary and metastatic lung adenocarcinoma: a case report and review of the literature.

Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.

Investigation of lacrimal sac space-occupying lesions using color doppler ultrasound, computed tomography, and computed tomography dacryocystography.

AIM: To observe the imaging features of color Doppler ultrasound (CDU) and computed tomography (CT) or computed tomography dacryocystography (CT-DCG) in different types of lacrimal sac space-occupying lesions (SOLs). METHODS: This retrospective case series study included 21 patients with lacrimal sac SOLs who underwent lacrimal sac surgery between January 2018 and March 2022. The imaging features of CDU and CT or CT-DCG in these patients were extracted from the examination cloud system. The images were observed and analyzed. RESULTS: The detection rate of lacrimal SOLs between CDU (21/21, 100%) and CT or CT-DCG (20/21, 95.2%) had no statistically significant difference (P=1.0). CDU could detect the blood flow signals in all SOLs except mucocele and mucopeptide concretion. Among them, polyps had characteristic imaging changes on CDU and CT-DCG. The mucoceles and mucopeptide concretions had characteristic imaging changes on CDU, which could provide more information for differential diagnosis. CONCLUSION: The morphology and internal blood flow signals of lacrimal sac SOLs can be observed using CDU. CT or CT-DCG has advantages in observing structural damage around the lacrimal sac mass. Therefore, CDU may be used as a routine examination to exclude lacrimal sac SOLs before dacryocystorhinostomy in the absence of preoperative CT or CT-DCG.

Variability of Clinical Presentation in Patients Heterozygous for the F508del Cystic Fibrosis Variant: A Series of Three Cases and a Review of the Literature.

Cystic fibrosis (CF) is a genetic disease that affects the lung, pancreas, and other organs caused by the presence of biallelic CF-causing variants in the cystic fibrosis conductance regular gene (CFTR). CFTR variants can also be found in CFTR-related disorders (CFTR-RD), which present milder symptoms. Increasing access to next-generation sequencing has demonstrated that both CF and CFTR-RD have a broader array of genotypes than formerly thought. Here we present three patients who carry the most common CFTR pathogenic variant - F508del - but express a wide array of phenotypes. These cases open discussion on the role of concurrent variants in CFTR, the importance of early diagnosis and treatment, and the contribution of lifestyle factors in CF and CFTR-RD presentation.

Homozygous Carriers of F2 c.20210G>A Variant: A Report of Two Cases and Literature Review.

Thromboembolism is known to be a multifactorial event that is impacted by various genetic and environmental factors. The genetics society's recommended name for this variant is c.*97G>A (this is the nomenclature we need to use in the patient report). However, people have been using legacy names c.20210G>A or G20210A (so these are common names). One of the most common genetic variants associated with inherited thrombophilias, F2 c.20210G>A is acknowledged to be a weak but significant risk factor for thromboembolism. However, its clinical presentation has been described as phenotypically heterogeneous. We present two rare cases with homozygous F2 c.20210G>A variant, one of which also carries a heterozygous variant in coagulation factor V gene F5, c.1601G>A (p.Arg534Gln; commonly known as factor V Leiden). We described the clinical courses of these two cases and discussed F2 c.20210G>A and factor V Leiden as genetic risk factors in thromboembolism, the role of provoking factors, such as surgery and malignancy, and the management of such patients.

Circulating Proteins and Metabolite Biomarkers in Gastric Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development. METHODS: A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio. RESULTS: A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, ß-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk. CONCLUSION: The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.

Primary splenic diffuse large B-cell lymphoma presenting as a splenic abscess.

Diffuse large B-cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS-DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS-DLBCL with CD30. The patient was a 62-year-old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8-cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki-67 proliferation rate was approximately 80% in large cells. Notably, this PS-DLBCL was positive for CD30, an unusual finding among non-Hodgkin B-cell lymphomas, which, coupled with the Reed-Sternberg-like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B-cell lymphoma, its abscess-like appearance, and its expression of CD30.

Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray.

BACKGROUND: Liver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature. CASE PRESENTATION: We present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features. CONCLUSIONS: Diagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.

Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese.

OBJECTIVES: High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function. METHODS: Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging. RESULTS: The average age of the participants was 55.70 ±â€Š11.30 years old. The mean urinary sodium of the participants was 172.01 ±â€Š80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling. CONCLUSIONS: Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.

A rare case of complex variant translocation of t(9;22;16)(q34;q11.2;q24) in a newly diagnosed patient with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm associated with the dysregulated production of myeloid cells. The Philadelphia chromosome (Ph), t(9;22)(q34;q11), is a hallmark of the disease and found in 90-95% of diagnosed CML patients. The balanced, reciprocal translocation places the genes BCR and ABL1, next to each other, resulting in an increase of kinase activity. Additional cases involve complex variants, including translocation events involving an additional chromosome with the creation of the Ph chromosome. A rare three-way Ph chromosome complex variant, t(9;22;16)(q34;q11.2;q24), was identified in a 40-year-old female who presented with visual changes and leukocytosis. Cytogenetic analysis by G-banding revealed the presence of a three-way translocation involving the long arms of chromosomes 9, 22, and 16. Fluorescence in situ hybridization with a dual-color fusion probe confirmed the presence of the BCR::ABL1 fusion.

Proposal of Diagnostic Approach of Periodontal Primary Non Hodgkin Lymphoma of Bone with Flow Cytometry as an Essential Diagnostic Component.

BACKGROUND: Primary bone lymphoma is a rare type of lymphoid neoplasm with favorable prognosis, where Primary Non Hodgkin Lymphoma of bone (PB-NHL) is most common with the subtype. Amongst PB-NHL, diffuse large Bcell lymphoma represents the majority of cases. The mandible is a very uncommon site of involvement, presenting as a painful bone mass with high suspicion of osteomyelitis. METHODS: We report the case of a 45-year-old male with no significant past medical history who was admitted to the hospital with a large right jaw mass and pain after recent tooth removal. The original tissue biopsy was not diagnostic, and cultures were found to be negative for microorganisms. Due to enlargement of the mass, a fine needle aspiration (FNA) was done. At the time of rapid onsite evaluation of the FNA, atypical lymphoid cells were seen, and material was obtained for flow cytometry (FC) evaluation. This revealed an aberrant clonal B-cell population. The consequent immunohistochemical evaluation of original material supported the diagnosis of PB-NHL. After chemotherapy patient improved. RESULTS: After an extensive English language literature review, we identified and summarized the clinical presentations, diagnostic procedures, histopathologic features, treatment methods, and outcomes of forty-two cases of periodontal PB-NHL. Based on our findings, we propose a set of clinical features at initial presentation to increase the clinical suspicion of periodontal PB-NHL for practitioners. CONCLUSION: Based on our institution's experience and the literature review conclusions, we propose the University of Texas Medical Branch diagnostic approach for PB-NHL and suggest that FNA and FC should be utilized as the essential diagnostic component. The fast and efficient diagnosis of PB-NHL can facilitate the correct treatment and sufficiently improve patient care.

Synchronous tonsillar tumors with differing histopathology: A case report and review of the literature.

BACKGROUND: Tonsillar squamous cell carcinoma (TSCC) due to human papillomavirus (HPV) infection has seen a dramatic increase in recent years. Bilateral tonsillar squamous cell carcinoma (biTSCC) has a much lower incidence than unilateral TSCC and three main hypotheses of biTSCC pathogenesis prevail: field carcinogenesis, single-clone, and multiple HPV infections. CASE: A 49-year-old Male with a remote history of chewing tobacco presented with symptoms of spitting up tissue and occasional hemoptysis. Physical exam showed a sole left tonsillar mass which was confirmed to be TSCC on biopsy. The patient's computed tomographic (CT) scan was consistent with this finding; however, positron emission tomography (PET) scan indicated a second tumor in the contralateral right tonsil. Surgical resection of both masses and selective neck dissection was performed, and the specimens were sent for further pathological analysis. No complications of surgery were noted and the final diagnosis of synchronous biTSCC was made. The tumors were a T2N0M0 left poorly differentiated TSCC (p16+, EGFR+, bcl2+) with basaloid features, and a T1N0M0 right well to moderately differentiated TSCC (p16+, EGFR+, bcl2-). CONCLUSION: Our present case was notable for differing tumor pathology and karyotype analysis between the right and left masses, directly supporting the multiple HPV infections hypothesis of biTSCC pathogenesis. Further genetic characterization of tonsillar tumors is needed to better characterize TSCC and best guide medical/surgical therapy.

Breast T-Lymphoblastic Lymphoma Presenting as a Single Mass in a Young Female with Family History of Breast Cancer.

Breast involvement by lymphoma is rare, constituting ≤0.5% of all breast malignancies, with T-cell lymphomas, comprising 2.5 to 7.5% of all lymphomas involving breast. Several types of T-cell lymphomas have been reported in breast, including anaplastic large-cell lymphoma, breast implant associated anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, adult T-cell lymphoma/leukemia, NK/T-cell lymphoma, and T-lymphoblastic lymphoma. Breast involvement by T-lymphoblastic lymphoma is very unusual and when it is observed, it usually occurs as a secondary involvement by known lymphoma.We report the case of a 33-year-old woman with family history of breast cancer who presented with a single right breast mass which was diagnosed as T-lymphoblastic lymphoma. At presentation, the patient was feeling well and did not have any B symptoms or any other signs of lymphoma or leukemia. One month after diagnosis, the patient presented to the emergency room with chest pain and shortness of breath and was found to have a large mediastinal mass with both pleural and pericardial effusions. Subsequent evaluation of peripheral blood smear and bone marrow biopsy showed increased amount of blasts and involvement by T-lymphoblastic lymphoma. The patient was induced with cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone chemotherapy. After two-cycles of chemotherapy, a computed tomography of the thorax showed marked interval decrease in size of anterior mediastinal mass, suggestive of positive treatment response.Here, we report the first well documented case of T-lymphoblastic lymphoma presented as a single breast mass without history of B symptoms and perform an extensive English language literature review.

Impact of Using Median vs. Mean in Calculating ERBB2 FISH Results in Breast Cancer.

INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 (ERBB2) testing is used to measure the status of ERBB2 gene expression and DNA amplification. Test results have been reported with a discrepancy as high as 20%. The purpose of this study was to improve ERBB2 fluorescence in situ hybridization (FISH) sensitivity by evaluating results generated by median as well as mean calculations. METHODS: We retrospectively identified breast cancer cases at our institution in which ERBB2 FISH testing was performed in-house from June 2018 to May 2020. FISH results were classified using the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines: groups 1 and 5 are FISH positive and negative, respectively, and groups 2-4 are equivocal requiring additional work-up. FISH counting sheets were collected and regrouped by median ERBB2 copy number counts and median ERBB2/CEP17 ratio and compared with the mean ERBB2 and mean ERBB2/CEP17 ratio. Intra-tumor genetic heterogeneity and CEP17 copy number gain (CEP17 ≥3) were assessed to see if they affect the discrepancy between median and mean groups. RESULTS: Seventy-two breast cancer cases were collected and evaluated. Eleven cases (11 of 72 [15%]) had discrepant grouping by mean and median calculations. A significant number of discrepancies were found for CEP17 copy number gain (p = 0.027) but not for ERBB2 (p = 0.411), the ERBB2/CEP17 ratio (p = 0.445), FISH results (p = 0.194), or genetic heterogeneity (p = 0.465). Among the four cases regrouped to median group 1, 2 were from mean group 3 and underwent anti-ERBB2 targeted therapy and 2 were from mean groups 4 and 5 may have benefitted from targeted therapy with more than 30% amplified cells. The median may be better to reflect the monosomy subclone within tumor tissues for the case 387 moved from mean group 5 to median group 2. The 6 cases moved from mean group 5 to median group 4 with CEP17 copy number gain may have had a poor prognosis based on other study result. CONCLUSION: Including the median calculation may increase ERBB2 sensitivity and identification of CEP17 copy number gain. Further clinical studies are necessary to examine the outcome of including median in calculating ERBB2/CEP17 values.

Discordant ERBB2 Status and Genome Wide DNA Copy Number Alterations in Breast Cancer and Synchronous Lymph Node Metastasis: A Case Report and Literature Review.

Erb-b2 receptor tyrosine kinase 2 (ERBB2) is a biomarker in the management of breast cancer (BC). Changes of ERBB2 status in primary and synchronous metastasis have been reported in approximately 5% of BC. Here we describe a 55-years-old female with a history of left-side BC and again diagnosed in 2019 with right-side BC tested ER-, PR-, ERBB2+ in breast tissue and triple negative in right axillary lymph node. The right BC and lymph node metastasis samples were tested by chromosomal microarray (CMA); the BC sample harbored more DNA copy number alterations than the lymph node specimen, suggesting that the lymph node metastasis was not directly originating from a dominant tumor clone in the right BC. This case highlights discordant ERBB2 status that can benefit from assessment of ERBB2 in both primary and metastatic specimens. This case also demonstrates the value of using CMA to help understand the clonal evolution of breast cancer metastasis especially when there are discordant biomarker results between primary and metastatic lesions.

Enrichment of CD44 in Exosomes From Breast Cancer Cells Treated With Doxorubicin Promotes Chemoresistance.

Exosomes secreted from tumor cells can remodel the tumor environment by promoting tumor metastasis and multidrug resistance. The aim of this study was to analyze the proteome profile of the breast cancer line resistant to doxorubicin resistance (MCF-7/ADR) by liquid chromatography linked to tandem mass spectrometry assay (LC-MS/MS). Our results revealed that DOX increases the exosomes release from MCF-7/ADR cells and the exosome-mediated proteins intercellular transfer in breast cancer chemoresistance regulation. The expression of the candidate target exosomic CD44 in DOX-resistant cells (A/Exo) was higher than in parental breast cancer cells (S/Exo), and the increasing levels of exosomic CD44 (21.65-fold) were higher than those of cellular CD44 (6.55-fold) (all p < 0.05). Similar results were obtained in clinical samples; exosomal CD44 in the serum of nonresponders was significantly higher than that in the chemotherapy-responsive group (p < 0.05). Also, we modified the MCF-7-derived exosomes loaded with siRNA against CD44 to observe the effects of targeting reduced CD44 expression in luminal A breast cancer cells. Exosome-siRNA targeted CD44 (Exos-siCD44) could efficiently silence its expression. When cocultured on Exos-siCD44, breast cancer cells exhibited reduced cell proliferation and enhanced susceptibility to DOX. The same phenomenon was observed in mice. In conclusion, breast cancer cells could spread resistance capacity by the intercellular transfer of proteins, especially CD44, via exosomes.

ERBB2 FISH and Chromosome Microarray Testing of Gastroesophageal Adenocarcinomas at a Single Institution.

Overexpression/amplification of erb-b2 receptor tyrosine kinase 2 (ERBB2) is a major prognostic factor in gastroesophageal cancers; it is currently the only biomarker established for the selection of targeted therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). Current standard procedure for determining ERBB2 status in such patients is immunohistochemistry (IHC), followed by in situ hybridization (ISH), when IHC result is equivocal. Insufficient knowledge regarding the utilities of chromosomal microarray (CMA) has hindered its use as an adjunct tool in ERBB2 analysis. Here, we performed CMA on 7 formalin-fixed paraffin-embedded (FFPE) GEA specimens previously tested by ERBB2 fluorescence in situ hybridization (FISH) and evaluated the concordance and performance of CMA. CMA identified 4 (57.1%) samples with amplification of ERBB2, compared to 3 (42.9%) by FISH. CMA also detected several additional DNA copy number variants in these samples, which may have prognostic and therapeutic indications. Further case studies and clinical trials may provide evidence for the utility of CMA-based genomic studies in the management of patients with suspected ERBB2-positive gastroesophageal adenocarcinoma.

Iron Overload in an HFE Heterozygous Carrier: A Case Report and Literature Review.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and tissue deposition. Three loss-of-function mutations in the hemochromatosis gene (HFE), namely, C282Y (c.845G>A), H63D (c.187C>G), and S65C (c.193A>T), account for the vast majority of HH cases. These mutations cause alterations in HFE membrane expression, structure, and/or activity, leading to dysregulation of iron absorption. It is well established that the phenotypic expression of HFE mutations varies markedly. Herein, we describe a 64-year-old Caucasian woman with a reported history of hemochromatosis. The father of the patient had died of complications due to iron overload. Testing of HFE codon C282Y, H63D, and S65C mutations showed heterozygous C282Y. The patient had significantly elevated transferrin saturation (TS) and serum ferritin (SF) levels. Her liver function test results showed elevated alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. The patient has been treated with regular phlebotomy to prevent the clinical manifestations of hemochromatosis.

Upregulation of BAG3 with apoptotic and autophagic activities in maggot extract­promoted rat skin wound healing.

Maggot extract (ME) accelerates rat skin wound healing, however its effect on cell maintenance in wound tissues remains unclear. B­cell lymphoma (Bcl) 2­associated athanogene (BAG)3 inhibits apoptosis and promotes autophagy by associating with Bcl­2 or Beclin 1. Bcl­2, the downstream effector of signal transducer and activator of transcription 3 signaling, is enhanced in ME­treated wound tissues, which may reinforce the Bcl­2 anti­apoptotic activity and/or cooperate with Beclin 1 to regulate autophagy during wound healing. The present study investigated expression levels of BAG3, Bcl­2, Beclin 1 and light chain (LC)3 levels in rat skin wound tissues in the presence and absence of ME treatment. The results revealed frequent TUNEL­negative cell death in the wound tissues in the early three days following injury, irrespective to ME treatment. TUNEL­positive cells appeared in the wound tissues following 4 days of injury and 150 µg/ml ME efficiently reduced apoptotic rate and enhanced BAG3 and Bcl­2 expression. Elevated Beclin 1 and LC3 levels and an increased LC3 II ratio were revealed in the ME­treated tissues during the wound healing. The results of the present study demonstrate the anti­apoptotic effects of BAG3 and Bcl­2 in ME­promoted wound healing. Beclin 1/LC3 mediated autophagy may be favorable in maintaining cell survival in the damaged tissues and ME­upregulated BAG3 may enhance its activity.

Is it Beneficial to Reuse the Balloon in Percutaneous Kyphoplasty for the Treatment of Non-Neoplastic Vertebral Compression Fractures?

BACKGROUND Percutaneous kyphoplasty (PKP) has been widely used to treat vertebral compression fractures (VCFs). Bilateral percutaneous punctures are always performed to access the fractured vertebrae. However, the procedure has expensive clinical costs, especially the cost for the device, which creates a heavy financial burden for patients. MATERIAL AND METHODS Data from 49 patients who have single-level non-neoplastic vertebral compression fracture (VCF) were collected for 12 months after treated by PKP, including 21 cases that used bilateral puncture with single balloon (S group) and 28 cases that used bilateral puncture with double balloon (D group). We assessed the clinical (visual analogue scale, VAS) and radiological (vertebral height and kyphotic angle, KA) outcomes. Cost data (gross medical cost, cost for the device and cost for drugs) were obtained from the medical bill of each patient. RESULTS Baseline patient variables were similar between the two groups except the compensation (S group

SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling.

BACKGROUND: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. METHODS: Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 µM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. RESULTS: SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. CONCLUSION: Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells.