Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis

Background: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. Objective: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. Methods: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. Results: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. Conclusions and Significance: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment

Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect

Antagonistic Roles of SEPALLATA3, FT and FLC Genes as Targets of the Polycomb Group Gene CURLY LEAF

In Arabidopsis, mutations in the Pc-G gene CURLY LEAF (CLF) give early flowering plants with curled leaves. This phenotype is caused by mis-expression of the floral homeotic gene AGAMOUS (AG) in leaves, so that ag mutations largely suppress the clf phenotype. Here, we identify three mutations that suppress clf despite maintaining high AG expression. We show that the suppressors correspond to mutations in FPA and FT, two genes promoting flowering, and in SEPALLATA3 (SEP3) which encodes a co-factor for AG protein. The suppression of the clf phenotype is correlated with low SEP3 expression in all case and reveals that SEP3 has a role in promoting flowering in addition to its role in controlling floral organ identity. Genetic analysis of clf ft mutants indicates that CLF promotes flowering by reducing expression of FLC, a repressor of flowering. We conclude that SEP3 is the key target mediating the clf phenotype, and that the antagonistic effects of CLF target genes masks a role for CLF in promoting flowering

DEP and AFO Regulate Reproductive Habit in Rice

Sexual reproduction is essential for the life cycle of most angiosperms. However, pseudovivipary is an important reproductive strategy in some grasses. In this mode of reproduction, asexual propagules are produced in place of sexual reproductive structures. However, the molecular mechanism of pseudovivipary still remains a mystery. In this work, we found three naturally occurring mutants in rice, namely, phoenix (pho), degenerative palea (dep), and abnormal floral organs (afo). Genetic analysis of them indicated that the stable pseudovivipary mutant pho was a double mutant containing both a Mendelian mutation in DEP and a non-Mendelian mutation in AFO. Further map-based cloning and microarray analysis revealed that dep mutant was caused by a genetic alteration in OsMADS15 while afo was caused by an epigenetic mutation in OsMADS1. Thus, OsMADS1 and OsMADS15 are both required to ensure sexual reproduction in rice and mutations of them lead to the switch of reproductive habit from sexual to asexual in rice. For the first time, our results reveal two regulators for sexual and asexual reproduction modes in flowering plants. In addition, our findings also make it possible to manipulate the reproductive strategy of plants, at least in rice

Application of isothermal titration calorimetry in evaluation of protein–nanoparticle interactions

Nanoparticles (NPs) offer a number of advantages over small organic molecules for controlling protein behaviour inside the cell. Protein binding to the surface of NPs depends on their surface characteristics, composition and method of preparation (Mandal et al. in J Hazard Mater 248–249:238–245, 2013). It is important to understand the binding affinities, stoichiometries and thermodynamical parameters of NP–protein interactions in order to see which interaction will have toxic and hazardous consequences and thus to prevent it. On the other side, because proteins are on the brink of stability, they may experience interactions with some types of NPs that are strong enough to cause denaturation or significantly change their conformations with concomitant loss of their biological function. Structural changes in the protein may cause exposure of new antigenic sites, “cryptic” peptide epitopes, potentially triggering an immune response which can promote autoimmune disease (Treuel et al. in ACS Nano 8(1):503–513, 2014). Mechanistic details of protein structural changes at NP surface have still remained elusive. Understanding the formation and persistence of the protein corona is critical issue; however, there are no many analytical methods which could provide detailed information about the NP–protein interaction characteristics and about protein structural changes caused by interactions with nanoparticles. The article reviews recent studies in NP–protein interactions research and application of isothermal titration calorimetry (ITC) in this research. The study of protein structural changes upon adsorption on nanoparticle surface and application of ITC in these studies is emphasized. The data illustrate that ITC is a versatile tool for evaluation of interactions between NPs and proteins. When coupled with other analytical methods, it is important analytical tool for monitoring conformational changes in proteins

Generation of ESTs for Flowering Gene Discovery and SSR Marker Development in Upland Cotton

BACKGROUND: Upland cotton, Gossypium hirsutum L., is one of the world's most important economic crops. In the absence of the entire genomic sequence, a large number of expressed sequence tag (EST) resources of upland cotton have been generated and used in several studies. However, information about the flower development of this species is rare. METHODOLOGY/PRINCIPAL FINDINGS: To clarify the molecular mechanism of flower development in upland cotton, 22,915 high-quality ESTs were generated and assembled into 14,373 unique sequences consisting of 4,563 contigs and 9,810 singletons from a normalized and full-length cDNA library constructed from pooled RNA isolated from shoot apexes, squares, and flowers. Comparative analysis indicated that 5,352 unique sequences had no high-degree matches to the cotton public database. Functional annotation showed that several upland cotton homologs with flowering-related genes were identified in our library. The majority of these genes were specifically expressed in flowering-related tissues. Three GhSEP (G. hirsutum L. SEPALLATA) genes determining floral organ development were cloned, and quantitative real-time PCR (qRT-PCR) revealed that these genes were expressed preferentially in squares or flowers. Furthermore, 670 new putative microsatellites with flanking sequences sufficient for primer design were identified from the 645 unigenes. Twenty-five EST-simple sequence repeats were randomly selected for validation and transferability testing in 17 Gossypium species. Of these, 23 were identified as true-to-type simple sequence repeat loci and were highly transferable among Gossypium species. CONCLUSIONS/SIGNIFICANCE: A high-quality, normalized, full-length cDNA library with a total of 14,373 unique ESTs was generated to provide sequence information for gene discovery and marker development related to upland cotton flower development. These EST resources form a valuable foundation for gene expression profiling analysis, functional analysis of newly discovered genes, genetic linkage, and quantitative trait loci analysis

Functional Analysis of the Two Brassica AP3 Genes Involved in Apetalous and Stamen Carpelloid Phenotypes

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation

Gold nanoprisms as a hybrid in vivo cancer theranostic platform for in situ photoacoustic imaging, angiography, and localized hyperthermia

The development of high-resolution nanosized photoacoustic contrast agents is an exciting yet challenging technological advance. Herein, antibody (breast cancer-associated antigen 1 (Brcaa1) monoclonal antibody)- and peptide (RGD)-functionalized gold nanoprisms (AuNprs) were used as a combinatorial methodology for in situ photoacoustic imaging, angiography, and localized hyperthermia using orthotopic and subcutaneous murine gastric carcinoma models. RGD-conjugated PEGylated AuNprs are available for tumor angiography, and Brcaa1 monoclonal antibody-conjugated PEGylated AuNprs are used for targeting and for in situ imaging of gastric carcinoma in orthotopic tumor models. In situ photoacoustic imaging allowed for anatomical and functional imaging at the tumor site. In vivo tumor angiography imaging showed enhancement of the photoacoustic signal in a time-dependent manner. Furthermore, photoacoustic imaging demonstrated that tumor vessels were clearly damaged after localized hyperthermia. This is the first proof-of-concept using two AuNprs probes as highly sensitive contrasts and therapeutic agents for in situ tumor detection and inhibition. These smart antibody/peptide AuNprs can be used as an efficient nanotheranostic platform for in vivo tumor detection with high sensitivity, as well as for tumor targeting therapy, which, with a single-dose injection, results in tumor size reduction and increases mice survival after localized hyperthermia treatment.National Basic Research Program of China (No. 2015CB931802)National Natural Science Foundation (China) (Nos. 81225010, 81327002, 31170961, 20771075, and 20803040)National High-Tech R&D Plan of China (No. 2014AA020700)Shanghai Science and Technology Fund (Nos. 13NM1401500 and 15DZ2252000

Continuous-time modeling of cell fate determination in Arabidopsis flowers

<p>Abstract</p> <p>Background</p> <p>The genetic control of floral organ specification is currently being investigated by various approaches, both experimentally and through modeling. Models and simulations have mostly involved boolean or related methods, and so far a quantitative, continuous-time approach has not been explored.</p> <p>Results</p> <p>We propose an ordinary differential equation (ODE) model that describes the gene expression dynamics of a gene regulatory network that controls floral organ formation in the model plant <it>Arabidopsis thaliana</it>. In this model, the dimerization of MADS-box transcription factors is incorporated explicitly. The unknown parameters are estimated from (known) experimental expression data. The model is validated by simulation studies of known mutant plants.</p> <p>Conclusions</p> <p>The proposed model gives realistic predictions with respect to independent mutation data. A simulation study is carried out to predict the effects of a new type of mutation that has so far not been made in <it>Arabidopsis</it>, but that could be used as a severe test of the validity of the model. According to our predictions, the role of dimers is surprisingly important. Moreover, the functional loss of any dimer leads to one or more phenotypic alterations.</p