Calcitriol induces estrogen receptor alpha expression through direct transcriptional regulation and epigenetic modifications in estrogen receptor-negative breast cancer cells

xlomafota13 shared this article with you from Inoreader Calcitriol induces estrogen receptor alpha expression through direct transcriptional regulation and epigenetic modifications in estrogen receptor-negative breast cancer cells Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5951-5964. eCollection 2021. ABSTRACT Patients with estrogen receptor (ER) α-negative breast tumors have a poor prognosis and are not suitable for hormone therapy. Previously, we demonstrated that calcitriol, the active metabolite of vitamin D, induces ERα expression and re-establishes the response to antiestrogens in ER-negative breast cancer cells. However, the mechanisms involved in this process have not been elucidated. Therefore, the present study was undertaken to investigate the mechanisms implicated in the calcitriol-induced ERα expression in ER-negative breast cancer cells. Using EMSA and ChIP assays, we found that the calcitriol/vitamin D receptor (VDR)/retinoic X receptor (RXR) complex binds to putative vitamin D response elements (VDREs) in the ERα gene promoter region. In addition, we established by a fluorometric assay that calcitriol decreased DNA-methyltransferase and histone deac etylase activities. Flow cytometry and qPCR analyses showed that co-treatment of calcitriol with inhibitors of the histone deacetylase and DNA methyltransferase, and genistein significantly increased ERα expression, compared to that observed with the compounds alone. In conclusion, the calcitriol-dependent ERα induction in ER-negative breast cancer cells results from binding of the VDR-RXR complex to VDREs in the ERα gene promoter region, including the downregulation of enzymes with chromatin-remodeling activities. These results may bring forth novel mechanistic knowledge into the actions of calcitriol in ERα-negative breast cancer. PMID:35018235 | PMC:PMC8727803 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies

xlomafota13 shared this article with you from Inoreader Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6173-6187. eCollection 2021. ABSTRACT Combined immune checkpoint inhibitors (ICIs) along with tyrosine kinase inhibitors (TKIs) and locoregional therapies have been used increasingly to treat hepatocellular carcinoma (HCC). Biomarkers are required to predict the treatment efficacy of ICIs with or without combination therapies in patients with unresectable HCC. This study enrolled 95 consecutive patients with unresectable HCC from May 2017 to June 2021 from two hospitals retrospectively. Of the 95 patients, 15 and 80 had Barcelona Clinic Liver Cancer stages B and C, respectively. The median ICI treatment duration was 3.43 (1.87-7.87) months, and 77 patients received combination therapies. Radiological imaging was not performed in 13 patients. Objective response and disease control rates were 27.4% and 53.7%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 4. 07 (1.59-6.54) months and 14.53 (6.93-22.14) months, respectively. Alpha-fetoprotein (AFP) response was defined as a decline of >15% in the serum AFP level within the initial 3 months of ICI therapy according to Youden's index. AFP response was determined to be a predictor of disease control (odds ratio: 11.657, 95% confidence interval [CI]: 2.834-47.941, P=.001). Macrovascular invasion (MVI), AFP response (hazard ratio [HR]: 0.488, 95% CI: 0.255-0.934, P=.030), combination therapy, and disease control were predictors of PFS, and MVI, AFP response (HR: 0.344, 95% CI: 0.160-0.737, P=.006), and disease control were predictors of OS. AFP response was a predictor of disease control, PFS, and OS. These findings indicate that AFP response can serve as a biomarker to predict treatment outcomes in patients with unresectable HCC receiving ICIs with or without TKIs or locoregional therapies. PMID:35018250 | PMC:PMC8727811 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors associated with colorectal cancer screening intent and uptake among adult Non-Hispanic Black men

xlomafota13 shared this article with you from Inoreader Factors associated with colorectal cancer screening intent and uptake among adult Non-Hispanic Black men Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6200-6213. eCollection 2021. ABSTRACT Non-Hispanic (NH) Black men in the United States have the lowest five-year colorectal cancer (CRC) survival rate across all racial/ethnic and sex subgroups and are less likely than their NH White counterparts to complete CRC screening. We hypothesized that greater masculinity barriers to medical care (MBMC) would be negatively associated with CRC screening uptake. Employing a survey design, we examined the MBMC scale and other psychosocial factors influencing CRC screening intent and uptake in a sample of 319 NH Black men aged 45 to 75 years residing in Minnesota, Ohio, and Utah. A series of ordinary least squares and logistic regression models were run with intention and uptake as the outcome variable while controlling for various demographic characteristics. Independent variables in all models included average score on the MBMC; CRC screening knowledge, beliefs and values; and barriers to and social support for CRC screening. Social support, marital status, and age were positively associated with CRC screening intention. Increased CRC screening knowledge and older age were associated with a greater likelihood of completing a stool-based screening test for CRC. Fewer masculinity-related and CRC screening barriers were associated with a greater likelihood of undergoing a sigmoidoscopy or colonoscopy. Contrary to our primary hypothesis, lesser MBMC-related perceptions were associated with increased CRC screening uptake among NH Black men. Our findings inform future CRC promotion programs and emphasize the need for multilevel interventions tailored toward this marginalized population to reduce disparities in screening and survival. PMID:35018252 | PMC:PMC8727804 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Truncating CDKN1A mutations: an insight into the biology of urinary tract carcinomas?

xlomafota13 shared this article with you from Inoreader Truncating <em>CDKN1A</em> mutations: an insight into the biology of urinary tract carcinomas? Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6214-6217. eCollection 2021. ABSTRACT A recent in silico study by Arnoff and El-Deiry found that urothelial carcinomas of the bladder and upper tract as well as chromophobe renal cell carcinoma are more likely than other malignancies to harbor alterations in the CDKN1A gene, encoding for the cyclin-dependent kinase inhibitor p21Waf1, a major target of p53 regulatory pathways. Most of these mutations were truncating and thus presumably resulting in loss of p21Waf1 function. Herein, we discuss the prognostic and therapeutic implications of these findings. PMID:35018253 | PMC:PMC8727807 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring

xlomafota13 shared this article with you from Inoreader Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Keratinization and Cornification are not equivalent processes but keratinization in fish and amphibians evolved into cornification in terrestrial vertebrates

xlomafota13 shared this article with you from Inoreader Keratinization and Cornification are not equivalent processes but keratinization in fish and amphibians evolved into cornification in terrestrial vertebrates Via Experimental Dermatology Abstract The present account offers a generalized view of the evolution of process of terminal differentiation in keratinocytes of the epidermis in anamniotes, indicated as keratinization, into a further differentiating process of cornification in the skin and appendages of terrestrial vertebrates. Keratinization indicates the prevalent accumulation of intermediate filaments of keratins (IFKs) and is present in most fish and amphibian epidermis and inner epithelia of all vertebrates. During land adaptation terrestrial vertebrates evolved a process of cornification and keratinocytes became dead corneocytes by the addition of numerous others proteins to the IFKs framework, represented by keratin associated proteins (KAPs) and corneous proteins (CPs). Most of genes coding for these types of proteins are localized in chromosomal loci different and un-related from those of IFKs, and CPs originated from a gene cluster indicated as Epidermal Differentiation Complex (EDC). During the evolution of reptiles and birds the epidermis and corneous derivatives such as scales, claws, beaks, and feathers, mainly accumulate a type of CPs that overcome IFKs and containing a 34 amino acid beta-sheet core indicated as corneous beta-proteins (CBPs), formerly known as beta-keratins. Mammals did not evolve a beta-sheet core in their CPs and KAPs but instead produced numerous cysteine-rich IFKs in their epidermis and specialized KAPs in hairs, claws, nails, hooves and horns. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exercise-based dysphagia rehabilitation for adults with oesophageal cancer: a systematic review

xlomafota13 shared this article with you from Inoreader Exercise-based dysphagia rehabilitation for adults with oesophageal cancer: a systematic review Via swallowing exercises BMC Cancer. 2022 Jan 10;22(1):53. doi: 10.1186/s12885-021-09155-y. ABSTRACT BACKGROUND: Dysphagia is prevalent in oesophageal cancer with significant clinical and psychosocial complications. The purpose of this study was i) to examine the impact of exercise-based dysphagia rehabilitation on clinical and quality of life outcomes in this population and ii) to identify key rehabilitation components that may inform future research in this area. METHODS: Randomised control trials (RCT), non-RCTs, cohort studies and case series were included. 10 databases (CINAHL Complete, MEDLINE, EMBASE, Web of Science, CENTRAL, and ProQuest Dissertations and Theses, OpenGrey, PROSPERO, RIAN and SpeechBITE), 3 clinical trial registries, and relevant conference abstracts were searched in November 2020. Two independent authors assessed articles for eligibility before completing data extraction, quality assessment using ROBINS-I and Downs and Black Checklist, followed by descriptive data analysis. The primary outcomes included oral intake, respiratory status and quality of life. All comparable outcomes were combined and discussed throughout the manuscript as primary and secondary outcomes. RESULTS: Three single centre non-randomised control studies involving 311 participants were included. A meta-analysis could not be completed due to study heterogeneity. SLT-led post-operative dysphagia intervention led to significantly earlier start to oral intake and reduced length of post-operative hospital stay. No studies found a reduction in aspiration pneumonia rates, and no studies included patient reported or quality of life outcomes. Of the reported secondary outcomes, swallow prehabilitation resulted in significantly improved swallow efficiency following oesophageal surgery compared to the control group, and rehabilitation following surgery resulted in significantly reduced vallecular and pyriform sinus residue. The three studies were found to have 'serious' to 'critical' risk of bias. CONCLUSIONS: This systematic review highlights a low-volume of low-quality evidence to support exercise-based dysphagia rehabilitation in adults undergoing surgery for oesophageal cancer. As dysphagia is a common symptom impacting quality of life throughout survivorship, findings will guide future research to determine if swallowing rehabilitation should be included in enhanced recovery after surgery (ERAS) programmes. This review is limited by the inclusion of non- randomised control trials and the reliance on Japanese interpretation which may have resulted in bias. The reviewed studies were all of weak design with limited data reported. PMID:35012495 | DOI:10.1186/s12885-021-09155-y View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Patterns of pharyngeal manifestations of chronic indulgence in “Qat” consumption

xlomafota13 shared this article with you from Inoreader Patterns of pharyngeal manifestations of chronic indulgence in "Qat" consumption Via Clinical Otolaryngology Abstract The aim of this work is to report a series of cases of qat chewers with a pattern of pharyngeal complications and to illustrate the end result of damage to the mucosal lining of the oro- and hypo-pharynx. The commonest presentation is the end result of the acute inflammatory phase. The cases included in the study show variable degrees of narrowing of the pharynx as seen by videoendoscope for the nasopharynx, oropharynx and larynx. Results The observations of the study are collected from 25 cases with varying presentations extending from feeling of nasal obstruction to variable degrees of dysphagia. The end result of the scarring is illustrated by figures and a table showing the relative incidence of the site of maximum narrowing. Conclusion Qat chewing has a strong correlation with a pattern of pharyngeal complications which need to be further investigated in a wide sample case-control study. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Frontal Sinus Fractures

xlomafota13 shared this article with you from Inoreader Frontal Sinus Fractures Via leak of cerebrospinal fluid 2021 Dec 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. ABSTRACT Skull fractures are common injuries observed in the setting of both blunt and penetrating trauma. The frontal sinuses are located within the frontal bone, superior and medial to the orbits. The frontal sinuses begin developing around 5 to 6 years of age and become fully developed between the ages of 12 and 20. Sensation is provided by both the supraorbital and supratrochlear nerves, which are branches of the ophthalmic division of the trigeminal nerve (CN V1). The blood supply to the frontal sinuses comes from the supraorbital and supratrochlear arteries. The frontal sinuses consist of bony anterior and posterior tables (walls) and they drain inferiorly, medially, and posteriorly via the frontal recess into either the middle meatus or ethmoid infundibulum, depending on the attachment of the uncinate process of the ethmoid bone. If the un cinate process attaches to the lamina papyracea, the frontal sinus drains into the middle meatus via the semilunar hiatus. If the uncinate process attaches to the skull base or the middle turbinate, the frontal sinus drains into the ethmoid infundibulum before emptying into the middle meatus. The anterior border of the frontal recess is the posterior wall of the agger nasi air cell, while the posterior wall is formed by the ethmoid bulla. The medial wall of the frontal recess is the middle turbinate, and the lateral wall is the orbit. While the volume of the frontal sinus is extremely variable, the average size is approximately 10 mL; the sinus itself may be entirely absent in 0.8-7.4% of patients, unilaterally, and may be bilaterally absent in up to 5% of patients. Frontal cranial bones have a greater thickness than the more lateral temporal bones (6.15 cm in males, 7.13 cm in females compared to 4.33 cm and 4.41 cm, respectively). As a result, these fractures require a more forceful mechanism of injury than other facial bone fractures, occur less frequently than other forms of skull trauma, and often present with concurrent injuries. These other injuries include naso-orbito-ethmoid fractures, orbital injuries, cerebrospinal fluid (CSF) leak, intracranial hemorrhage, and cervical spine fractures, among others. The potential for other potentially devastating injuries to occur along with frontal sinus fractures makes a thorough evaluation of these patients imperative. Additionally, appropriate classification and indications for surgical repair of frontal sinus fractures remain controversial, resulting in a variety of management strategies. PMID:32491451 | Bookshelf:NBK557519 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Frequency-specific prediction model of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss

xlomafota13 shared this article with you from Inoreader Frequency-specific prediction model of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2022 Jan 11. doi: 10.1007/s00405-021-07246-x. Online ahead of print. ABSTRACT PURPOSE: The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL. METHODS: We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 14 days; 126 males/109 females; age range 17-87 years (average 61.0 years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000 Hz was measured at every octave before (HLpre) and after (HLpost) treatment. A multiple regression model was constructed for HLpost (dependent variable) using five explanatory variables (age, days from onset to treatment, presence of vertigo, HLpre, and hearing level of the contralateral ear). RESULTS: The multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000 Hz. The width of the 70% prediction interval was narrower for 4000/8000 Hz (± 18.2/16.3 dB) than for low to mid-frequencies. Among the five explanatory variables, HLpre showed the largest partial correlation coefficient for any frequency. The partial correlation coefficient for HLpre increased as the frequency increased, which may partially explain the high multiple correlation coefficients for high frequencies. CONCLUSION: The present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL. PMID:35015092 | DOI:10.1007/s00405-021-07246-x View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cerebral Spinal Fluid Leak Disorders

xlomafota13 shared this article with you from Inoreader Cerebral Spinal Fluid Leak Disorders Via leak of cerebrospinal fluid 2021 Nov 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. ABSTRACT The cerebrospinal fluid (CSF) acts as a nourishing and protective layer surrounding the central nervous system. This protective cushion circulates within the ventricular system and the subarachnoid space around the brain and the spinal cord, which helps to provide the buoyancy to counteract various shear and stress encountered during the movement of the skull and vertebral column. In various disorders that present with CSF leak, the loss of this protective nutrient-rich layer can injure the function of the brain and the spinal cord. Such conditions might be associated with fractures in the skull base, congenital bony defects, or might be associated with raised intracranial pressure (ICP). It also predisposes the brain and spinal cord to the external environment increasing the risk of meningitis, ventriculitis, and arachnoiditis. The traditional concept of CSF formation, distribution, and absorption was previously based on the bulk flow model. However, this model seems inadequate to explain the pathophysiological mechanisms of various CSF flow-related disorders based on recent literature. The currently accepted CSF flow system comprises pulsatile CSF flow, lymphatic system, capillary exchange, and the traditional ventricular-cisternal system. According to the current understanding, the production of CSF is from multiple sources, primarily from the choroid plexus of the lateral and fourth ventricles. Apart from this, interstitial space, ependyma, and dural sleeves of the spinal nerve roots also contribute to the total CSF turnover. Similarly, CSF is absorbed in multiple sites, with dural venous sinuses being the major drainage site via arachnoid granulations followed by choroid plexus and glymphatic system. PMID:35015396 | Bookshelf:NBK576371 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.