Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects.

During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones.

Neuroinflammation in animal models of traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells.

PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity.

PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic enzymatic activity of PRDM16.

[Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones].

Objective: To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes (MDS) with PNH clones.

Methods: 218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing.

[Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia].

Objective: To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).

Methods: The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count.

Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia.

MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs.

[The assessment of symptomatic burden among Ph/BCR- ABL negative myeloproliferative neoplasm patients].

Objective: To investigate the value of myeloproliferative neoplasms Symptom Assessment Form total symptom score (MPN-SAF-TSS)in assessing constitutional symptoms among Ph/BCR- ABL negative myeloproliferative neoplasm (MPN)patients.

Methods: A cohort of 628 MPN patients were evaluated by MPN- SAF- TSS.

Results: Fatigue was the most common symptom (76.

L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.

Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1.

Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer.

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC).

Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment.

Effect of vitamin D on the recurrence rate of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation affecting target tissues including the joints, bones, and synovial membrane. However, the etiology and pathogenesis of RA remains to be determined, and investigations into the treatment of RA are imperative. Vitamin D (Vit D) was previously found to be associated with the activity of RA and exerts therapeutic benefits.

[Long- term outcome of thalidomide and cyclosporine in patients with IPSS low/intermediate- 1 myelodysplastic syndromes].

Objective: To investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.

Methods: Seventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.

Isolation and identification of a novel peptide from zein with antioxidant and antihypertensive activities.

The aim of this study is to isolate and identify a novel corn peptide (CP) from zein with antioxidant and antihypertensive activities based on bioactive-guided isolation procedures. Zein was hydrolyzed by using double enzymes immobilized with calcium alginate-chitosan beads and then fractionated and purified. The antioxidant and antihypertensive activities of the CP fractions were screened by in vitro and in vivo assays.

Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A Multi-institutional Experience.

Purpose: The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC.

Methods: Patients who underwent extended surgery for GBC at Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University, University of Michigan, and University of Texas MD Anderson between 1985 and 2008 were reviewed.

Sun1 deficiency leads to cerebellar ataxia in mice.

Migration and organization of the nucleus are essential for the proliferation and differentiation of cells, including neurons. However, the relationship between the positioning of the nucleus and cellular morphogenesis remains poorly understood. Inherited recessive cerebellar ataxia has been attributed to mutations in SYNE1, a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex.

Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo.

Chromosomal translocations affecting mixed lineage leukemia gene (MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. Here we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia.

Comparison of locoregional versus extended locoregional radiation volumes for patients with nonmetastatic gastro-esophageal junction carcinomas.

Introduction: To delineate an optimal clinical target volume (CTV) for gastroesophageal junction (GEJ) cancers by comparing locoregional versus extended locoregional radiation (RT) volumes.

Materials: This retrospective analysis examined 222 patients (111 matched pairs treated with locoregional versus extended locoregional RT) with nonmetastatic GEJ carcinomas treated with concurrent chemoradiation ± surgery. The CTV for locoregional volumes was defined as gross tumor volume + elective coverage of first-echelon nodes and sometimes the celiac axis.

A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer.

Background: Pathologic complete response (pCR) to neoadjuvant chemoradiation for esophageal cancer is associated with improved outcomes. We evaluated whether a nomogram designed to predict who would have a pCR after trimodality therapy could also predict outcome after definitive chemoradiation.

Methods: Patients in this retrospective, single-institution analysis had received chemoradiation without surgery for esophageal cancer from 1998 through 2010; 333 such patients had complete information on all variables required for the pCR nomogram: sex; T status (by endoscopic sonography); tumor grade; tumor avidity on positron emission tomography (PET); and esophagogastroduodenoscopy (EGD)-directed biopsy results after chemoradiation.

Correlation of clinical stage and performance status with quality of life in patients seen in a pancreas multidisciplinary clinic.

Introduction: The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL.

Patients And Methods: Data from 77 patients were evaluated. At initial presentation, disease and performance status were assessed, as well as QoL, which was obtained with the European Organisation for Research and Treatment of Cancer QLQ-PAN26 questionnaire.

A systematic classification of megakaryocytic dysplasia and its impact on prognosis for patients with myelodysplastic syndromes.

Background: Dys-megakaryopoiesis is defined as ≥10 % of dysplastic megakaryocytes in bone marrow smears by the World Health Organization. However, concordance rates for dysplastic megakaryocytes between different observers is low and, consequently, evaluation of dysmegakaryopoiesis is also often discordant.

Results: We performed CD41 immune staining and proposed a systematic classification of dys-megakaryopoiesis on bone marrow films: (1) micro-megakaryocytes (<12 µm); (2) micro-megakaryocytes (12-40 µm) with 1 nucleus; (3) micro-megakaryocytes (12-40 µm) with 2 nuclei; (4) micro-megakaryocytes (12-40 um) with multiple (more than 2) nuclei; (5) dysplastic megakaryocytes (≥40 µm) with 1 nucleus; (6) dysplastic megakaryocytes (≥40 µm) with 2 nuclei; and (7) dysplastic megakaryocytes (≥40 µm) with multiple (more than 2) nuclei.

[A study of prognostic value of cytogenetics in patients with primary myelofibrosis].

Objective: To evaluate the prognostic value of cytogenetics in Chinese with primary myelofibrosis (PMF).

Methods: Four hundred and thirty-nine Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the COX proportional hazards regression model were used to evaluate the prognostic scoring systems.

Local recurrence map to guide target volume delineation after radical prostatectomy.

Purpose: To describe the various anatomic locations of recurrent disease, in a cohort of men with radiographically visualized, biopsy-proven recurrent prostate cancer after radical prostatectomy (RP), in order to help guide contouring of the prostatic fossa clinical target volume (PF-CTV) when no gross recurrence is visible or when magnetic resonance imaging (MRI) is not used.

Methods And Materials: Ten representative patients with MRI-detected, biopsy-proven local recurrences of prostate adenocarcinoma after RP were selected. Areas of recurrence were delineated on individual MRI images, and then mapped onto axial and sagittal "template" MRI images to compositely demonstrate the documented areas of recurrence.

Prognostic impact of splenomegaly on survival of Chinese with primary myelofibrosis.

Predicting survival in persons with primary myelofibrosis (PMF) is typically based on the International Prognostic Scoring System (IPSS), the Dynamic IPSS (DIPSS) or the DIPSS-Plus. These scoring systems use clinical and laboratory data developed predominately in persons of European descent. Splenomegaly is not a prognostic variable in any of these scoring systems.

Characterization of two truncated forms of xylanase recombinantly expressed by Lactobacillus reuteri with an introduced rumen fungal xylanase gene.

The xylanase R8 gene (xynR8) from uncultured rumen fungi was cloned and successfully expressed in Lactobacillus reuteri. A xylanase activity of 132.1 U/mL was found in the broth of L.

Re-evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma.

Background: The optimal radiation dose for treating esophageal squamous cell carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4 Gy delivered with modern techniques are beneficial in terms of tumor control, survival, and toxicity.

Calreticulin mutations in Chinese with primary myelofibrosis.

We tested 357 Chinese with primary myelofibrosis for mutations in CALR, JAK2 and MPL. CALR mutations were detected in 76 subjects (21%). There were 24 (32%) type-1 (L367fs*46) and 49 (64%) type-2 (K385fs*47) mutations.