Valorisation of raw mango pickle industry waste into antimicrobial agent against postharvest fungal pathogens.

In mango pickle industry, a significant quantity of mango seed kernels is discarded as solid wastes. These seed kernels can be an ideal source for obtaining extracts rich in bioactive polyphenolic compounds with good antioxidant properties. The potential of mango kernel phenolic extract (MKPE) was investigated as a natural and effective antimicrobial agent for controlling major postharvest fungal pathogen infections, a significant threat to global food supply chains. Fungal pathogens contribute to the deterioration of fruits, vegetables, and grains during storage and transportation, leading to economic losses and compromised food safety. MKPE was obtained from pickling variety 'Ramkela' raw mango kernels, and its phenolic composition was characterized using LC-MS. The in vitro antifungal activity of MKPE against Botrytis cinerea, Colletotrichum gloeosporoides, and Rhizopus stolonifer was evaluated in vitro. A concentration-dependent inhibition of fungal radial growth against all three pathogens was observed, exhibiting the potential of MKPE as a valuable natural resource for addressing postharvest losses caused by fungal pathogens. The extraction process yielded a total phenolic content of 2128 mg GAE/100 g. Major polyphenolic bioactive compounds present were mangiferin, quercetin, and rhamnetin. The in-vitro antimicrobial assay showed reduction in the radial growth and inhibition percent of the pathogens. EC50 values of MKPE for B. cineria, C. gloeosporoides, and R. stolonifer was found to 364.17, 963.8 and 926 ppm, respectively. Our results demonstrate an economical, sustainable, and eco-friendly approach to manage post-harvest diseases rendered by fungi using mango MKPE from pickling industry waste.

Clinical outcomes and staff satisfaction after adoption of digital chest drainage system for minimally invasive lung resections.

Background: Digital chest drainage systems (DCDS) provide reliable pleural drainage while quantifying fluid output and air leak. However, the benefits of DCDS in the contemporary era of minimally invasive thoracic surgery and enhanced recovery after surgery (ERAS) protocols have not been fully investigated. Additionally, hospital and resident staff experiences after implementation of a DCDS have not been fully explored. The objective of this study was to evaluate the clinical outcomes and hospital staff experience after adoption of a DCDS for minimally invasive lung resections. Methods: A single-center retrospective review of patients who underwent minimally invasive lung resection (lobectomy, segmentectomy, and wedge resection) and received a DCDS from 11/1/2021 to 11/1/2022. DCDS patients were compared to sequential historical controls (3/1/2019-6/30/2021) who received a analog chest drainage system. For the analog system, chest tubes were removed when no bubbles were observed in the water seal compartment with Valsalva, cough, and in variable positions. With a DCDS, chest tubes were removed when the air leak was less than 30 cc/min for 8 hours, with no spikes. All patients followed an institutional ERAS protocol. Primary outcomes were length of stay (LOS) and chest tube duration. Hospital staff and residents were surveyed regarding their experience. Results: One hundred and twenty-four patients received DCDS, and 248 received an analog chest drainage system. There was a reduction in mean LOS (3.6 vs. 4.4 days, P=0.01) and chest tube duration (2.7 vs. 3.6 days, P=0.03) in the DCDS group. Hospital staff (n=77, 46% response rate) reported the DCDS easier to use (60%, P<0.001) and easier to care for patients with (65%, P<0.001) compared to the analog system. Surgical residents (n=28, 56% response rate) reported increased confidence in interpretation of air leak (75%, P<0.001) and decision-making surrounding chest tube removal (79%, P<0.001). Conclusions: Using a DCDS can reduce LOS and chest tube duration in the contemporary setting of minimally invasive lung resections and ERAS protocols. Increased confidence of resident decision-making for chest tube removal may contribute to improved outcomes.

Predictors of prolonged hospital stay after segmentectomy.

OBJECTIVE: Segmentectomy is becoming the standard of care for small, peripheral non-small cell lung cancer. To improve perioperative management in this population, this study aims to identify factors influencing hospital length of stay after segmentectomy. METHODS: Patients who underwent segmentectomy for any indication between January 2018 and May 2023 were identified using a prospectively maintained institutional database. Multivariable logistic regression models were used to estimate associations between clinical features and prolonged (≥3 days) hospital stay. A nomogram was designed to understand better and possibly calculate the individual risk of prolonged hospital stays. RESULTS: In total, 533 cases were included; 337 (63%) were female. Median age was 66 years (interquartile range [IQR], 63-75). The median size of resected lesions was 1.6 cm (IQR, 1.3-2.1 cm). Median hospital stay was 3 days (IQR, 2-4 days). Major adverse events occurred in 31 (5.8%) cases. The 30-day readmission rate was 5.8% (n = 31). There was no 30-day mortality; 90-day mortality was <1%. Patients older than 75 years (odds ratio [OR], 2.01, 95% confidence interval [CI], 1.15-3.57, P = .02), those with forced expiratory volume in 1 second <88% predicted (OR, 1.99; 95% CI, 1.38-2.89, P < .001), or positive smoking history (OR, 1.72; 95% CI, 1.15-2.60, P = .01) were more likely to have prolonged hospital stays after segmentectomy. A nomogram accounting for age, sex, forced expiratory volume in 1 second, body mass index, smoking history, and comorbidities was created to predict the probability of prolonged hospital stay with an area under the receiver operating characteristic curve of 0.66. CONCLUSIONS: Older patients, those with reduced pulmonary function, and current and past smokers have elevated risk for prolonged hospital stays after segmentectomy. Validation of our nomogram could improve perioperative risk stratification in patients who undergo segmentectomy.

Complete anatomic segmentectomy shows improved oncologic outcomes compared to incomplete anatomic segmentectomy.

OBJECTIVES: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.

Liposomal bupivacaine intercostal block placed under direct vision reduces morphine use in thoracic surgery.

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.

Lung cancer outcomes in the elderly: potential disparity in screening.

OBJECTIVES: The aim of this study was to analyse outcomes of lung cancer in the elderly. METHODS: A retrospective analysis was performed of patients in the National Cancer Database with NSCLC from 2004 to 2017 grouped into 2 categories: 70-79 years (A) and 80-90 years (B). Patients with multiple malignancies were excluded. Kaplan-Meier curves estimated the overall survival for each age group based on stage. RESULTS: In total, 466 051 patients were included. Less-invasive techniques (imaging and cytology) diagnosed cancer as a function of age: 14.6% in A vs 21.3% in B [P < 0.001, standardized mean difference (SMD) 0.175]. Clinical stage IA was least common in B (15%) compared to 17.3% in A (P < 0.001, SMD 0.079). Approximately 83.0% in B did not receive surgery compared to 70.0% in A (P < 0.001, SMD 0.299). Of the 83.0%, 8.0% were considered poor surgical candidates because of age or comorbidities compared with 6.2% in A (P < 0.001, SMD 0.299) For 71.0% in B, surgery was not the first treatment plan compared to 62.0% in A (P < 0.001, SMD 0.299). Survival curves showed worse prognosis for each clinical and pathologic stage for B compared to A. CONCLUSIONS: Patients older than 80 years present less frequently as clinical stage IA, are less commonly offered surgical intervention and are more frequently diagnosed using less accurate measures. They also have worse outcomes for each stage compared to younger patients.

The jugular-subclavian junction and venous drainage of the brain.

Lung cancers and mediastinal masses can invade the veins in the upper mediastinum and neck. It can be challenging to determine management options and the feasibility of resection particularly when tumors involve the major venous junctions. Furthermore, impaired flow in these veins can have devastating complications such as Paget-Schroetter syndrome, which describes a constellation of symptoms (arm swelling, cyanosis, pain) due to stenosis of the subclavian vein. This section will provide an overview of venous drainage of the brain, which can be divided into two major systems-superficial medullary venous system and deep medullary venous system. The anatomy and function of the great veins of the neck and upper mediastinum, including the internal jugular vein, subclavian vein, and brachiocephalic (i.e., innominate) vein will be described. Also discussed will be principles of ligation of the venous structures and the importance of keeping the venous junctions intact to facilitate and maximize the development of collateral flow. This section will also discuss ensuing complications when blood flow is impaired, such as development of upper extremity deep venous thrombosis and cerebral venous thrombosis (CVT). CVT can result in a stroke and is an umbrella term that refers to problems in cerebral venous outflow due to numerous etiologies.

Thymic en-bloc resection with veins: case demonstrations and review of the literature.

Locally invasive thymic neoplasms are challenging clinical scenarios and typically require a multidisciplinary approach. The involvement of major mediastinal veins such as the superior vena cava (SVC) used to be a contraindication to surgery, but with improved surgical technique and outcomes, this paradigm has shifted. In some situations, complex resections and reconstructions may be indicated and required to improve the long-term outcome of these patients. We report two of our cases along with a current review of literature. We also describe the preoperative workup, operative techniques, postoperative management, complications, and outcomes of patients with invasive thymic neoplasms that involve the mediastinal veins. Our first case describes a patient who was diagnosed with a thymoma extending from the diaphragm to the base of the neck that was also encasing major vascular structures including the SVC and left innominate vein. Our second case describes a patient who was also diagnosed with a large anterior mediastinal mass encasing the great veins and invading the chest wall. We describe the management of these patients and then delve deeper into operative techniques including SVC resection and reconstruction. We describe the types of conduits that can be used and complications to be mindful of when clamping the great veins, such as the SVC. Improvements in conduit materials and neoadjuvant and adjuvant therapies over the years have made it more feasible for patients with invasive thymic neoplasms to undergo surgery.

What's new in thoracic oncology.

Many changes have occurred in the field of thoracic surgery over the last several years. In this review, we will discuss new diagnostic techniques for lung cancer, innovations in surgery, and major updates on latest treatment options including immunotherapy. All these have significantly started to change our approach toward the management of lung cancer and have great potential to improve the lives of our patients afflicted with this disease.

Development, validation and a GAPI greenness assessment for the determination of 103 pesticides in mango fruit drink using LC-MS/MS.

A robust method was developed using LC-ESI-MS/MS-based identification and quantification of 103 fortified pesticides in a mango fruit drink. Variations in QuEChERS extraction (without buffer, citrate, and/or acetate buffered) coupled with dispersive clean-up combinations were evaluated. Results showed 5 mL dilution and citrate buffered QuEChERS extraction with anhydrous (anhy) MgSO4 clean-up gave acceptable recovery for 100 pesticides @ 1 µg mL-1 fortification. The method was validated as per SANTE guidelines (SANTE/11813/2021). 95, 91, and 77 pesticides were satisfactorily recovered at 0.1, 0.05, and 0.01 µg mL-1 fortification with HorRat values ranging from 0.2-0.8 for the majority. The method showed matrix enhancement for 77 pesticides with a global uncertainty of 4.72%-23.89%. The reliability of the method was confirmed by real sample analysis of different brands of mango drinks available in the market. The greenness assessment by GAPI (Green Analytical Procedure Index) indicated the method was much greener than other contemporary methods.

Development of a multiplex assay to assess activated p300/CBP in circulating prostate tumor cells.

Reduced SIRT2 deacetylation and increased p300 acetylation activity leads to a concerted mechanism of hyperacetylation at specific histone lysine sites (H3K9, H3K14, and H3K18) in castration-resistant prostate cancer (CRPC). We examined whether circulating tumor cells (CTCs) identify patients with altered p300/CBP acetylation. CTCs were isolated from 13 advanced PC patients using Exclusion-based Sample Preparation (ESP) technology. Bound cells underwent immunofluorescent staining for histone modifying enzymes (HMEs) of interest and image capture with NIS-Elements software. Using the cBioPortal PCF/SU2C dataset, the response of CRPC to androgen receptor signaling inhibitors (ARSI) was analyzed in 50 subjects. Staining optimization and specificity revealed clear expression of acetyl-p300, acetyl-H3K18, and SIRT2 on CTCs (CK positive, CD45 negative cells). Exposure to A-485, a selective p300/CBP catalytic inhibitor, reduced p300 and H3K18 acetylation. In CRPC patients, a-p300 strongly correlated with its target acetylated H3k18 (Pearson's R = 0.61), and SIRT2 expression showed robust negative correlation with a-H3k18 (R = -0.60). A subgroup of CRPC patients (6/11; 55%) demonstrated consistent upregulation of acetylation based on these markers. To examine the clinical impact of upregulation of the CBP/p300 axis, CRPC patients with reduced deacetylase SIRT2 expression demonstrate shorter response times to ARSI therapy (5.9 vs. 12 mo; p = 0.03). A subset of CRPC patients demonstrate increased p300/CBP activity based on a novel CTC biomarker assay. With further development, this biomarker suite may be used to identify candidates for CBP/p300 acetylation inhibitors in clinical development.

Management of scalp arteriovenous malformations: a rising trend towards percutaneous direct puncture embolization technique-our experience.

BACKGROUND: Scalp arteriovenous malformations (AVMs), or cirsoid aneurysms of the scalp, usually present with troublesome symptoms and cosmetic disfigurement. Endovascular/percutaneous embolization has evolved as a sole treatment method or adjunct to surgical excision in the management of scalp AVMs with an excellent outcome. PURPOSE: To discuss minimally invasive techniques for treating scalp AVMs as well as to highlight the role of embolization before surgery. MATERIAL AND METHODS: This is a retrospective study of 50 patients with scalp AVM who underwent embolization (percutaneous/endovascular) during 2010-2019 at a tertiary care center. n-butyl cyanoacrylate (n-BCA) was used as an embolizing agent in all the cases and the patients were followed up at three- and six-month intervals with Doppler evaluation. RESULTS: A total of 50 patients were included in the study. The occipital region was the most common location; 82% were Schobinger class II lesions and 18% were class III lesions. Thirteen patients had small-sized AVMs and 37 patients had large-sized AVMs. Post-embolization surgery was performed in 36 patients. Of the patients, 28 underwent percutaneous embolization, 20 underwent endovascular embolization, and two underwent both to achieve complete embolization of the lesion. The number of percutaneous procedures increased in the latter half of the study period as the safety and efficacy of the technique were established. No major complications were seen in this study. CONCLUSION: Embolization of scalp AVMs is a safe and effective technique and can be used in isolation for small lesions and as an adjunct procedure to surgery for large-sized lesions.

Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer.

PURPOSE: Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody-drug conjugates (ADC). EXPERIMENTAL DESIGN: TROP-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EPCAM or TROP-2-positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (n = 15) and gene expression signatures of treatment resistance (n = 40). We assessed the efficacy of TROP-2-targeting agents in a mouse xenograft model generated from prostate cancer cell lines. RESULTS: We demonstrated that TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti-TROP-2 agents in vivo. CONCLUSIONS: These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.

Lymph node sampling-what are the numbers?

Lung cancer is a deadly disease. Lymph node staging is the most important prognostic factor, and lymphatic drainage of the lung is complex. Major advances have been made in this field over the last several decades, but there is much left to understand and improve upon. Herein, we review the history of the lymphatic system and the creation of lymph node maps, the evolution of tumor, node, and metastasis lung cancer classification, the importance of lung cancer staging, techniques for lymph node dissection, and our recommendations regarding a minimum number of nodes to sample during pulmonary resection.

Image-guided video-assisted thoracoscopic surgery (iVATS): a single center experience and review.

Lung cancer screening techniques using low-dose computed tomography (LDCT) scans have improved over the last decade. This means that there is an increased rate of detection of small, often non-palpable, nodules and ground-glass opacities. Obtaining a definitive diagnosis of these nodules using techniques such as percutaneous image-guided biopsy or intraoperative localization is challenging, and these nodules have traditionally undergone routine surveillance. Image-guided video-assisted thoracoscopic surgery (iVATS), which is performed in a hybrid operating room, has made it more feasible to biopsy and resect these nodules. The first thoracic surgery hybrid operative room was introduced at our institution at Brigham and Women's Hospital. Herein, we describe our experience implementing this technique including the methods we used to train key personnel such as radiologists, surgeons, and anesthesiologists to ensure that this technique successfully translated to a clinical setting. We review the benefits of iVATS, which includes decreased rate of fiducial dislodgement, real-time imaging which facilitates successful fiducial placement, and smaller sized resection of lung parenchyma. We will also describe the comparisons between traditional diagnostic methods and iVATS, patient selection criteria and important technical details. Some centers describe alternative techniques for several of the technical aspects, including patient positioning, which we also mention. Lastly, we describe adverse events after iVATS, which are comparable to those seen after a standard VATS.

Hexavalent-Chromium-Induced Oxidative Stress and the Protective Role of Antioxidants against Cellular Toxicity.

Hexavalent chromium is a highly soluble environmental contaminant. It is a widespread anthropogenic chromium species that is 100 times more toxic than trivalent chromium. Leather, chrome plating, coal mining and paint industries are the major sources of hexavalent chromium in water. Hexavalent chromium is widely recognised as a carcinogen and mutagen in humans and other animals. It is also responsible for multiorgan damage, such as kidney damage, liver failure, heart failure, skin disease and lung dysfunction. The fate of the toxicity of hexavalent chromium depends on its oxidation state. The reduction of Cr (VI) to Cr (III) is responsible for the generation of reactive oxygen species (ROS) and chromium intermediate species, such as Cr (V) and Cr (IV). Reactive oxygen species (ROS) are responsible for oxidative tissue damage and the disruption of cell organelles, such as mitochondria, DNA, RNA and protein molecules. Cr (VI)-induced oxidative stress can be neutralised by the antioxidant system in human and animal cells. In this review, the authors summarise the Cr (VI) source, toxicity and antioxidant defence mechanism against Cr (VI)-induced reactive oxygen species (ROS).

A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer.

BackgroundNeuroendocrine prostate cancer (NEPC) is an aggressive subtype, the presence of which changes the prognosis and management of metastatic prostate cancer.MethodsWe performed analytical validation of a Circulating Tumor Cell (CTC) multiplex RNA qPCR assay to identify the limit of quantification (LOQ) in cell lines, synthetic cDNA, and patient samples. We next profiled 116 longitudinal samples from a prospectively collected institutional cohort of 17 patients with metastatic prostate cancer (7 NEPC, 10 adenocarcinoma) as well as 265 samples from 139 patients enrolled in 3 adenocarcinoma phase II trials of androgen receptor signaling inhibitors (ARSIs). We assessed a NEPC liquid biomarker via the presence of neuroendocrine markers and the absence of androgen receptor (AR) target genes.ResultsUsing the analytical validation LOQ, liquid biomarker NEPC detection in the longitudinal cohort had a per-sample sensitivity of 51.35% and a specificity of 91.14%. However, when we incorporated the serial information from multiple liquid biopsies per patient, a unique aspect of this study, the per-patient predictions were 100% accurate, with a receiver-operating-curve (ROC) AUC of 1. In the adenocarcinoma ARSI trials, the presence of neuroendocrine markers, even while AR target gene expression was retained, was a strong negative prognostic factor.ConclusionOur analytically validated CTC biomarker can detect NEPC with high diagnostic accuracy when leveraging serial samples that are only feasible using liquid biopsies. Patients with expression of NE genes while retaining AR-target gene expression may indicate the transition to neuroendocrine differentiation, with clinical characteristics consistent with this phenotype.FundingNIH (DP2 OD030734, 1UH2CA260389, R01CA247479, and P30 CA014520), Department of Defense (PC190039 and PC200334), and Prostate Cancer Foundation (Movember Foundation - PCF Challenge Award).

Reversible epigenetic alterations regulate class I HLA loss in prostate cancer.

Downregulation of HLA class I (HLA-I) impairs immune recognition and surveillance in prostate cancer and may underlie the ineffectiveness of checkpoint blockade. However, the molecular mechanisms regulating HLA-I loss in prostate cancer have not been fully explored. Here, we conducted a comprehensive analysis of HLA-I genomic, epigenomic and gene expression alterations in primary and metastatic human prostate cancer. Loss of HLA-I gene expression was associated with repressive chromatin states including DNA methylation, histone H3 tri-methylation at lysine 27, and reduced chromatin accessibility. Pharmacological DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibition decreased DNA methylation and increased H3 lysine 27 acetylation and resulted in re-expression of HLA-I on the surface of tumor cells. Re-expression of HLA-I on LNCaP cells by DNMT and HDAC inhibition increased activation of co-cultured prostate specific membrane antigen (PSMA)27-38-specific CD8+ T-cells. HLA-I expression is epigenetically regulated by functionally reversible DNA methylation and chromatin modifications in human prostate cancer. Methylated HLA-I was detected in HLA-Ilow circulating tumor cells (CTCs), which may serve as a minimally invasive biomarker for identifying patients who would benefit from epigenetic targeted therapies.

Amelioration for oxidative stability and bioavailability of N-3 PUFA enriched microalgae oil: an overview.

Technological improvements in dietary supplements and nutraceuticals have highlighted the significance of bioactive molecules in a healthy lifestyle. Eicosapentaenoic acid and Cervonic acid (DHA), omega-3 polyunsaturated fatty acids seem to be famed for their ability to prevent diverse physiological abnormalities. Selection of appropriate pretreatments and extraction techniques for extraction of lipids from robust microalgae cell wall are very important to retain their stability and bioactivity. Therefore, extraction techniques with optimized extraction parameters offer an excellent approach for obtaining quality oil with a high yield. Oils enriched in omega-3 are particularly imperiled to oxidation which ultimately affects customer acceptance. Bio active encapsulation could be one of the effective approaches to overcome this dilemma. This review paper aims to give insight into the cultivation methods, and downstream processes, various lipid extraction approaches, techniques for retaining oxidative stability, bioavailability and food applications based on extracted or encapsulated omega-3.

Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma.

PURPOSE: Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach. METHODS: We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio). RESULTS: Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003). CONCLUSION: In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.