Chemically Modified Natural Polymer-Based Theranostic Nanomedicines: Are They the Golden Gate toward a de Novo Clinical Approach against Cancer?

Abstract Over-expression of P53-related protein detected by immunohistochemistry (IHC) and absence of p21waf1— expression, the main downstream target following P53 activation, are useful surrogate markers in identifying diffuse large B-cell lymphoma (DLBCL) patients with mutated P53-gene. Following recent studies on gene expression, tissue micro-array technology has been shown to represent a reliable technique in discriminating DLBCL with germinal center B-cell like (GC), or post- germinal center (non-GC) origin. We analyzed 80 consecutive patients with de-novo DLBCL, homogeneously treated with cure-intent (CHOP-like regimens +/− Rituximab) in a single Institution, for expression of p53/p21waf1—, with regard to the expression of GC (CD10+, bcl-6+/mum-1−/CD138−), and post-germinal center (CD10−, mum-1+, CD138+) IHC markers. Cases with 50% or more p53-positive neoplastic cells were defined as p53+++. All patients were provided with complete clinical information. Median age of our patients was 50 years, AAS was III or IV in half of patients, IPI was high or int/high in 36%. Median follow-up for survivors was 77 months. A p53+++/p21waf1— phenotype (corresponding to loss of function of the P53-gene) was detected in 19 of 80 patients (23%), while a GC phenotype characterized 42 patients (52%). Patients with P53+++/p21waf1— phenotype were more frequently resistant to induction therapies (p<0.0001) and had a significantly lower 5-year Progression Free Survival (PFS, 27% vs 48%, p=0.01). Patients with GC phenotype were associated with a better 5-year PFS than non-GC patients (57% vs 26%, p=0.02). When analysis was restricted to the 42 patients with GC phenotype, p53+++/p21waf1— phenotype could discriminate 28% of patients with PFS of 26% vs 68% of patients with GC pattern and other p53/p21waf1— phenotypes (p=0.005). In contrast, the outcome of patients with a non-GC phenotype was not modified by p53/ p21waf1— expression. At multivariate analysis, p53+++/p21waf1— phenotype, non-GC phenotype, and high IPI resulted the strongest independent factors in worsening PFS of our patients. Combining such adverse prognostic factors we could identify 60% of patients with an extremely poor prognosis (5-year PFS of 28%). Our results strongly point to the usefulness of a combined molecular and clinical approach for prognostic considerations in DLBCL, and should be validated in larger series.

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Corrigendum to “De novo synthesis of the complete genome of coxsackievirus A10 based on Golden Gate cloning combined with promoter reconstruction” [Plasmid 103 (2019) 17–24]

Plasmid ◽

10.1016/j.plasmid.2019.102439 ◽

2020 ◽

Vol 107 ◽

pp. 102439

Author(s):

Meng Li ◽

Jing Chen

Keyword(s):

Complete Genome ◽

De Novo ◽

Golden Gate ◽

De Novo Synthesis ◽

Golden Gate Cloning

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Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production

Pharmaceutics ◽

10.3390/pharmaceutics12060584 ◽

2020 ◽

Vol 12 (6) ◽

pp. 584 ◽

Cited By ~ 2

Author(s):

Mónica Vicente-Pascual ◽

Itziar Gómez-Aguado ◽

Julen Rodríguez-Castejón ◽

Alicia Rodríguez-Gascón ◽

Elisabetta Muntoni ◽

...

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

De Novo ◽

Topical Administration ◽

Interleukin 10 ◽

Viral Gene ◽

Clinical Approach ◽

Eye Drops ◽

Knock Out ◽

Corneal Inflammation

One of the main challenges in gene therapy is the issue of delivery, and it is especially relevant for the success of gene therapy in the cornea. In the present work, eye drops containing biocompatible non-viral vectors based on solid lipid nanoparticles (SLNs) as gene delivery systems to induce the expression of interleukin 10 (IL-10) were designed to address the treatment of corneal inflammation. Two kinds of SLNs combined with different ligands (protamine, dextran, or hyaluronic acid (HA)) and formulated with polyvinyl alcohol (PVA) were prepared. SLN-based vectors were characterized in terms of size, adhesiveness, viscosity, and pH, before topical administration to wild type and IL-10 knock out (KO) mice. The formulations showed a homogenous particle size below 400 nm and a positive surface charge to favor bioadhesion; the incorporation of PVA improved the corneal penetration. After three days of treatment by topical instillation, SLN-based vectors mainly transfected corneal epithelial cells, HA-formulations being the most effective ones. IL-10 was capable of reaching even the endothelial layer. Corneal sections showed no histological change and formulations seemed to be well tolerated after repeated topical administration. These promising results highlight the possible contribution of non-viral gene augmentation therapy to the future clinical approach of corneal gene therapy.

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CARDIAC ARRHYTHMIAS DURING PREGNANCY: A CLINICAL APPROACH

Fetal and Maternal Medicine Review ◽

10.1017/s0965539511000076 ◽

2011 ◽

Vol 22 (2) ◽

pp. 123-143 ◽

Cited By ~ 7

Author(s):

ZACHARY LAKSMAN ◽

LOUISE HARRIS ◽

CANDICE K SILVERSIDES

Keyword(s):

Heart Disease ◽

Pregnant Women ◽

Cardiac Disease ◽

Cardiac Arrhythmias ◽

De Novo ◽

Structural Heart Disease ◽

Clinical Approach ◽

History Of ◽

In Pregnancy

Physiologic changes in maternal haemodynamics, hormones and autonomic properties contribute to arrhythmias in pregnancy. While arrhythmias most commonly occur in pregnant women with structural heart disease or those with a history of cardiac arrhythmias, they can also occur de novo in women with no documented cardiac disease.

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The Marburg Collection: A Golden Gate DNA Assembly Framework for Synthetic Biology Applications in Vibrio natriegens

10.1101/2021.03.26.437105 ◽

2021 ◽

Author(s):

Daniel Stukenberg ◽

Tobias Hensel ◽

Josef Hoff ◽

Benjamin Daniel ◽

René Inckemann ◽

...

Keyword(s):

Replication Origin ◽

Doubling Time ◽

De Novo ◽

Plasmid Replication ◽

Growth Speed ◽

Dna Assembly ◽

Golden Gate ◽

E Coli ◽

Plasmid Construction ◽

Microplate Reader

Vibrio natriegens is known as the world's fastest growing organism with a doubling time of less than 10 minutes. This incredible growth speed empowers V. natriegens as a chassis for synthetic and molecular biology, potentially replacing E. coli in many applications. While first genetic parts have been built and tested for V. natriegens, a comprehensive toolkit containing well-characterized and standardized parts did not exist. To close this gap, we created the Marburg Collection - a highly flexible Golden Gate Assembly-based cloning toolbox optimized for the emerging chassis organism V. natriegens. The Marburg Collection overcomes the paradigm of plasmid construction - integrating inserts into a backbone - by enabling the de novo assembly of plasmids from basic genetic parts. This allows users to select the plasmid replication origin and resistance part independently, which is highly advantageous when limited knowledge about the behavior of those parts in the target organism is available. Additional design highlights of the Marburg Collection are novel connector parts, which facilitate modular circuit assembly and, optionally, the inversion of individual transcription units to reduce transcriptional crosstalk in multigene constructs. To quantitatively characterize the genetic parts contained in the Marburg Collection in V. natriegens, we developed a reliable microplate reader measurement workflow for reporter experiments and overcame organism-specific challenges. We think the Marburg Collection with its thoroughly characterized parts will provide a valuable resource for the growing V. natriegens community.

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Follicular Lymphoma Grade 3A Is Different from Grade 1/2 in the Real World

Blood ◽

10.1182/blood-2021-148271 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4524-4524

Author(s):

Chunyuan Li ◽

Ping Yang ◽

Wei Wan ◽

Shuozi Liu ◽

Hongmei Jing

Keyword(s):

Follicular Lymphoma ◽

De Novo ◽

Conflicts Of Interest ◽

Bone Marrow Involvement ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Time Frame ◽

Clinical Approach ◽

Ki 67 ◽

The Difference

Abstract Background: follicular lymphoma (FL) is histologically subdivided into grades 1/2(FL1/2), 3A(FL3A), and 3B(FL3B). FL3B is more like diffuse large B-cell lymphoma (DLBCL), while the clinical approach to FL1/2 and FL3A has been debated. We aim to explore the clinical, biological characteristics and outcomes between them. Methods: A retrospective analysis of 195 de novo FL patients within the same time frame (1999 to 2020) was identified. 141 patients were FL1/2, and 54 patients were FL3A. Results: Comparing with FL1/2, FL3A patients tend to present ECOG≥1, B symptoms, bone marrow involvement, digestive tract involvement, elevated LDH, Ki-67≥30%, CD10 negative, and multiple myeloma oncogene-1(MUM1) positive, while Ann Arbor stage I or II was usually seen in FL1/2. After received CHOP±R (cyclophosphamide, doxorubicin, vincristine and prednisone ±rituximab), the 5-year overall survival (OS) was 89.5% for FL1/2 and 61.1% for FL3A [ HR =3.742(95%CI:1.838-7.620),P <0.0001], the 5-year progression-free survival (PFS) was 62.5 for FL1/2 and 47.6% for FL3A [ HR =2.113(95%CI:1.297-3.443),P =0.003]. Conclusion: FL3A is more aggressive both clinically and biologically compared with FL1/2, and more attention should be paid to the difference of treatment between them. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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