Anatomical Description of Anterior Parametrium: A Probable Answer to Pelvic Recurrence Following Radical Hysterectomy.

A prospective analysis of a retrospective data of patients with cervix carcinoma treated by minimal invasive surgery at high-volume gynecology oncology center analyzing that minimal access surgery is an acceptable treatment modality in cervix carcinoma. The study included 423 patients who underwent laparoscopic/robotic radical hysterectomy after pre-operative evaluation after taking their consent and obtaining ethical approval from the IRB. Post-operatively, patients were followed up at regular intervals for clinical examination and ultrasonography for a median range of 36 months.

Swallowing: A delayed milestone post-surgery in tongue cancers.

Functional rehabilitation remains an important factor in the post-operative period following tongue cancer surgeries. Patients undergoing surgery for tongue cancers require intense rehabilitation in order to restore their swallowing function, and improve their nutritional status and quality of life. Various swallowing scales like the Functional Oral Intake Scale (FOIS), Performance status scale in head and neck cancer (PSSHNC) and 100 ml water swallow test are used to assess functionality in these patients.

Unraveling the Differentially Articulated Axes of the Century-Old Renin-Angiotensin-Aldosterone System: Potential Therapeutic Implications.

Among numerous choices in cardiovascular therapies used for the management of hypertension and heart failure, drugs affecting the renin-angiotensin-aldosterone system (RAAS) hold substantial therapeutic roles. Therapies aimed at modifying the RAAS and its overactivation are employed for the management of various insidious disorders. In the pharmacologic perspective, RAAS is one of the frequently manipulated systems for the management of hypertension, heart failure, myocardial infarction, and renal disease.

Retraction Note: Selective killing of cancer cells by a small molecule targeting the stress response to ROS.

This Letter is being retracted owing to issues with Fig. 1d and Supplementary Fig. 31b, and the unavailability of original data for these figures that raise concerns regarding the integrity of the figures.

Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing.

Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for the treatment of neurological disorders, such as Huntington's disease. Small, endogenous vesicles known as exosomes have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load into exosomes upon co-incubation, without altering vesicle size distribution or integrity.

YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression.

Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment.

Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress.

The Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of cellular activities, including those involved in tumour metastasis and apoptosis. Here we identify an indispensable function of ROCK1 in metabolic stress-induced autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal component of the phosphoinositide 3-kinase class III lipid-kinase complex that induces autophagy, as an interacting partner of ROCK1.

A network of transcription factors operates during early tooth morphogenesis.

Improving the knowledge of disease-causing genes is a unique challenge in human health. Although it is known that genes causing similar diseases tend to lie close to one another in a network of protein-protein or functional interactions, the identification of these protein-protein networks is difficult to unravel. Here, we show that Msx1, Snail, Lhx6, Lhx8, Sp3, and Lef1 interact in vitro and in vivo, revealing the existence of a novel context-specific protein network.

Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development.

Bmp4 expression is tightly regulated during embryonic tooth development, with early expression in the dental epithelial placode leading to later expression in the dental mesenchyme. Msx1 is among several transcription factors that are induced by epithelial Bmp4 and that, in turn, are necessary for the induction and maintenance of dental mesenchymal Bmp4 expression. Thus, Msx1(-/-) teeth arrest at early bud stage and show loss of Bmp4 expression in the mesenchyme.

Selective killing of cancer cells by a small molecule targeting the stress response to ROS.

Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells.

Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage.

Although apoptosis triggered by ultraviolet B (UVB)-mediated activation of the c-Jun N-terminal kinase (JNK) pathway is mediated by both intrinsic and extrinsic pathways, the mechanism of initiation of JNK activation remains obscure. Here, we report the characterization of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification. Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway.

Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation.

A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger (Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes.

Transcriptional targets of p53 that regulate cellular proliferation.

In response to various forms of cellular stress, including DNA damage, ribonucleotide depletion, and abnormal proliferative signals, p53 becomes activated as a transcription factor, targeted genes that induce cell-cycle arrest and apoptosis. Eliminating damaged, stressed, or abnormally proliferating cells from the replicating cell population prevents the propagation of potentially cancer-prone cells. Here we focus on the transcriptional targets of p53 that regulate the cell cycle.

An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed.