Clinicopathological Conditions Research Articles

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Brain Evaluation by Dual PET/CT with [18F] FDOPA and [18F] FDG in Differential Diagnosis of Parkinsonian Syndromes.

Parkinsonian syndromes are considered clinicopathological conditions that are challenging to diagnose. Molecular imaging with [18F]-FDOPA and [18F]-FDG contributes to a more accurate clinical diagnosis by evaluating presynaptic dopaminergic pathways and glucose metabolism, respectively. The aim of this study was to correlate diagnoses made from dual PET/CT with the initial clinical diagnoses, as well as during follow-ups in patients with Parkinsonian syndromes. A secondary objective was to describe the imaging findings. Methods: A total of 150 patients with a clinical diagnosis of neurodegenerative Parkinsonism were evaluated using dual PET/CT. Clinically, 82% were diagnosed with PD, while the remaining 18% had an atypical Parkinsonism. Results: Using dual PET/CT, the most frequent diagnosis was PD in 67% of the patients, with the rest being diagnosed with an atypical Parkinsonism. In an agreement analysis between the initial clinical diagnosis and the imaging diagnosis by dual PET/CT, a concordance of 94.1% (n = 95) was observed for PD. In the remaining patients, the clinical diagnosis differed from that suggested by dual PET/CT, with atypical Parkinsonian syndromes being diagnosed as DLB in 40% (n = 4), PSP in 46.7% (n = 7), MSA-C in 75% (n = 6), MSA-P in 70% (n = 7), and CBD in 66.7% (n = 4). A total of 38.66% (n = 58) of patients were followed up (median follow-up of 27 months), with a Kappa coefficient of 0.591 (p < 0.001), suggesting substantial agreement. Conclusions: Dual FDOPA-FDG PET/CT demonstrated moderate agreement with the initial clinical diagnosis of Parkinsonism and moderate to substantial agreement during follow-up. This dual technique, therefore, stands out in differentiating between types of Parkinsonisms.

Exploring contemporary breakthroughs in utilizing vesicular nanocarriers for breast cancer therapy.

Breast cancer (BC) is a heterogeneous disease with various morphological features, clinicopathological conditions and responses to different therapeutic options, which is responsible for high mortality and morbidity in women. The heterogeneity of BC necessitates new strategies for diagnosis and treatment, which is possible only by cautious harmonization of the advanced nanomaterials. Recent developments in vesicular nanocarrier therapy indicate a paradigm shift in breast cancer treatment by providing an integrated approach to address current issues. This review provides a detailed classification of various nanovesicles in the treatment of BC with a special emphasis on recent advances, challenges in translating nanomaterialsand future potentials.

Clinical Profile and Outcomes of Nephrotic Syndrome With Acute Kidney Injury in Adults: A Prospective Cohort Study.

Nephrotic syndrome (NS) is characterized by various clinicopathological conditions like proteinuria, hypoalbuminemia, and anasarca. Patients with NS are prone to experience associated problems like acute kidney injury (AKI). The present study aimed to investigate the clinical profile and outcomes of NS with AKI in adults. This prospective, observational study was conducted over a period of one year. Adult patients with NS diagnosed with AKI were enrolled in the study. Data were collected at baseline and patients were followed up for at least three months. A total of 60 patients were enrolled. The majority of the patients (78.3%) were aged between 18 and 30 years. Anemia was observed among 96.7% of the patients. A significant improvement was observed in the mean levels of proteinuria (5.80 vs. 1.70 gm/dL; P < 0.001), total cholesterol (270.00 mg/dL vs. 160.00 mg/dL), serum creatinine (2.18 mg/dL vs. 1.68 mg/dL; P < 0.001), and serum albumin (1.86 gm/dL vs. 3.29 gm/dL; P < 0.001) at baseline to three months. Pre-renal AKI was diagnosed in 95% of patients. According to histological classification, 19 patients had minimal change disease, whereas focal segmental glomerulosclerosis was observed in 23 patients. It was observed that 96.7% of the patients did not necessitate the need for renal replacement therapy. The present study successfully examined the clinical profile and outcomes of adults with NS and AKI. The findings provide valuable insights into the characteristics and prognosis of this patient population, contributing to a better understanding of NS with AKI in adults.

Analysis of clinicopathological features of 18 cases of hepatic angiosarcoma

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.

Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas

BackgroundComprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses.MethodsWe analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence.ResultsThe frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment.ConclusionsThis study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.

Evaluation of insertion methods and the anatomic region preference by the intensivists in central venous catheterization during COVID-19 pandemic: a survey-based study from Turkey

Background &amp; Objective: COVID-19 pandemic caused several clinicopathological conditions. The majority of the patients required intensive care. Even in the intensive care unit (ICU) setting, invasive procedures were challenging for healthcare workers due to the highly infectious nature of the disease and the need to work in cumbersome personal protective equipment. Peripheral and central venous catheterisation (CVC) were the most performed invasive procedures. We evaluated the preferred anatomical region and the preferred insertion method of CVC by the intensive care physicians.&#x0D; Methodology: The study was conducted between July 2020 and October 2020, after obtaining institutional ethics committee approval. Physicians working in ICUs across Turkey were included in the survey. A specialy prepared questionnaire was delivered online to the study sample via email invitation or social media applications. A total of 314 people received the questionnaire, 4 of the respondents did not allow the use of the survey data and 53 did not complete the questionnaire, so 57 records were excluded from the study and statistical data analysis was performed on 247 responses.&#x0D; Results: Participants were aged between 25 and 60 y. Regarding academic status, 97 of the participants were assistants, 112 were specialists, 25 were assistant professors, 5 were associate professors and 8 were professors. The number of catheters inserted by the physicians participating in the study showed statistically significant decrease during the pandemic period but controversially total number of catheters inserted in the ICUs showed no difference. Femoral vein was the most preferred anatomic region during pandemic period in both intubated patients, and patients using other ventilation support devices. Physician’s preferred method of catheter insertion remains the same.&#x0D; Conclusion: Central venous catheterisation is one of the vital invasive procedures performed on patients admitted to intensive care. The vital nature of the procedure, the proximity of the insertion site to the airway and the cumbersome personal protective equipment worn by healthcare workers made it a challenging intervention. we concluded that intensive care physicians in our country are reluctant to use central venous catheters because of concerns about contracting infection, and as a result of these concerns, they increase the use of personal protective equipment and protect themselves by changing anatomical site for catheterization.&#x0D; Key words: COVID-19; Central Venous Access; Central Venous Cannulation; Ultrasound-Guided; ICU&#x0D; Citation: Civraz AZT. Evaluation of insertion methods and the anatomic region preference by the intensivists in central venous catheterization during COVID-19 pandemic: a survey-based study from Turkey. Anaesth. pain intensive care 2023;27(5):619−624; DOI: 10.35975/apic.v27i5.2294&#x0D; Received: August 29, 2023; Reviewed: September 12, 2023; Accepted: September 19, 2023

Clinicopathological features and short outcomes of oliguric acute tubular injury.

To explore the clinicopathological features and analyze the relevant risk factors and short-term renal outcomes of acute tubular injury (ATI) patients. A total of 83 patients with biopsy-proven ATI were included in this retrospective cohort study. Clinical characteristic and histological feature data were collected, and renal recovery at 1 month postbiopsy was recorded. The severity of renal dysfunction, percentage of acute tubular lesions, interstitial inflammation and fibrosis of oliguric ATI patients were all significantly higher than those of nonoliguric patients. In the subgroup analysis of the oliguric patients, the serum creatinine and urinary microalbumin levels, severity of epithelial cell degeneration and cast formation of patients in the polyuric phase at biopsy were significantly lower than those of patients in the oliguric phase. A total of 59 patients had 1-month follow-up records, and complete renal recovery was observed in 42 patients. In the multivariate analysis, the total acute tubular injury area at biopsy was the most important independent risk factor for poor renal outcomes. Oliguric ATI patients had severe clinicopathological conditions. The severity of tubular lesions seriously influenced renal function recovery, demonstrating the importance of renal biopsy in assessing the prognosis of patients with kidney disease.

Novel Insights into miR-944 in Cancer.

Simple SummarymiR-944 is localized in intron 4 of TP63. ΔNp63 in intron 3 of TP63 recruits the transcription factor AP-2 to promote miR-944 gene expression, which mediates epidermal differentiation induction by ΔNp63. miR-944 is dysregulated in various cancers. In squamous cell carcinoma. miR-944 can target and inhibit 27 protein-coding genes, thereby regulating cell cycle, proliferation, apoptosis, epithelial mesenchymal transition, cancer cell invasion and migration, and other cell behaviors. The genes targeted by miR-944 are involved in three signaling pathways, including the Wnt/β-catenin pathway, Jak/STAT3 pathway, and PI3K/AKT pathway. miR-944 was regulated by a total of 11 competing endogenous RNAs, including 6 circular RNAs and 5 long non-coding RNAs. Abnormally expressed miR-944 can act as an independent prognostic factor and is closely related to tumor invasion, lymph node metastasis, TNM staging, and drug resistance. miR-944 is expected to become a critical biomarker with great clinical application value in cancer.miRNA is a class of endogenous short-chain non-coding RNAs consisting of about 22 nucleotides. miR-944 is located in the fourth intron of the TP63 gene in the 3q28 region. miR-944 is abnormally expressed in cancers in multiple systems including neural, endocrine, respiratory, reproductive, and digestive systems. miR-944 can target at least 27 protein-coding genes. miR-944 can regulate a series of cell behaviors, such as cell cycle, proliferation, invasion and migration, EMT, apoptosis, etc. miR-944 participates in the networks of 11 ceRNAs, including six circRNAs and five lncRNAs. miR-944 is involved in three signaling pathways. The abnormal expression of miR-944 is closely related to the clinicopathological conditions of various cancer patients. Deregulated expression of miR-944 is significantly associated with clinicopathology and prognosis in cancer patients. In addition, miR-944 is also associated with the development of DDP, RAPA, DOX, and PTX resistance in cancer cells. miR-944 is involved in the anticancer molecular mechanisms of matrine and Rhenium-liposome drugs. In conclusion, this work systematically summarizes the related findings of miR-944, which will provide potential hints for follow-up research on miR-944.

Sebaceous carcinoma of the lip: a case report and review of the literature

BackgroundSebaceous carcinoma is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. Sebaceous carcinoma in the oral cavity is extremely rare, with only 14 cases reported in literature. We reported the fourth case of sebaceous carcinoma involving the lipCase presentationA 71-year-old Caucasian male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extraoral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation, and salivary gland neoplasms. Operation was performed under local anesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascular stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein and epithelial membrane antigen, but negative for carcinoembryonic antigen. Based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered.ConclusionThe histogenesis, differential diagnosis, and clinicopathological conditions of this disease according to literature are reviewed. Sebaceous carcinoma should be distinguished from other tumors full of vacuolated clear cells. A periodic acid-Schiff stain and immunohistochemical stain for Ki-67, P53, cytokeratin, S-100, epithelial membrane antigen, and androgen receptor can be useful for the diagnosis.

Abstract 6179: Increased circulating PD-L1 expressing CD14 high CD16 negative classical monocytes correlate with poor prognosis in cancer patients treated with PD-1 blockade therapies

Abstract Background: Immune checkpoint inhibitors (ICIs), like PD-1 and PD-L1 blockade therapies, are currently considered as one of the most significant breakthroughs in potent cancer immunotherapy. However, many patients are non-responders or develop resistance following an initial response to ICIs. ICIs have no accurate predictive biomarkers. Previously, we showed that increased expression of PD-L1 molecules on CD14+ monocytes was significantly correlated with shorter overall survival (OS) for patients with several cancer types on PD-1 blockade therapies. As monocytes can be further classified into subsets (classical, intermediate, non-classical), we herein investigated the prognostic factors in peripheral blood mononuclear cell (PBMC) subsets and assessed the clinical significance for the PD-L1-expressing subsets of each of these cells including classical, intermediate and non-classical monocyte subsets in patients with various cancer types, along with their clinical implications in PD-1 blockade therapies. Material and Methods: We evaluated 44 patients (20 with gastric cancer, 17 with non-small cell lung carcinoma, and 7 with esophageal cancer) undergoing PD-L1 blockade therapy (pembrolizumab or nivolumab) for PD-L1 expression levels in classical (CD14high, CD16-), intermediate (CD14high, CD16+), and non-classical (CD14low, CD16+) monocytes measured via flow cytometry before ICI treatment. The percentages of PD-L1+ cells in respective monocyte subsets were compared with respect to different clinicopathological conditions and the association with survival time was assessed. Results: The number of PD-1 positive cells in CD14+ monocytes was very low (almost &amp;lt;1%). Also, the monocyte subset expressing PD-L1 had a high percentage of classical monocytes, whereas non-classical monocytes expressed less PD-L1. Higher levels of classical monocytes were correlated with shorter OS (P = 0.044), whereas higher levels of non-classical monocytes were correlated with longer OS (P = 0.027). Focusing on non-small cell lung cancer population (N = 17), higher levels of PD-L1-expressing CD14+ monocytes were statistically correlated with shorter OS (P = 0.025). Furthermore, analysis of a subset of monocytes showed that the higher PD-L1-expressing classical monocytes correlated with the shorter OS, suggesting that they predict poor prognosis (P = 0.0095). Conclusion: Circulating PD-L1-expressing classical monocytes in the peripheral bloods were associated with poor prognosis in patients treated with PD-1 blockade therapies. Among the monocyte subsets, classical monocyte, especially PD-L1-expressing classical monocytes can be a potential biomarker for prognosis in these patients. Citation Format: Ryotaro Ohkuma, Katsuaki Ieguchi, Makoto Watanabe, Tsubasa Goshima, Rie Onoue, Kazuyuki Hamada, Yutaro Kubota, Atsushi Horiike, Toshiaki Tsurui, Risako Suzuki, Nana Iriguchi, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Kiyoshi Yoshimura, Mayumi Tsuji, Yuji Kiuchi, Shinichi Kobayashi, Takuya Tsunoda, Satoshi Wada. Increased circulating PD-L1 expressing CD14 high CD16 negative classical monocytes correlate with poor prognosis in cancer patients treated with PD-1 blockade therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6179.

A Comprehensive Review of Yoga Research in 2020.

Objectives: Accumulated evidence garnered in the last few decades has highlighted the role of yoga in health and disease. The overwhelming mortality and morbidity mediated by noncommunicable epidemics such as heart disease and cancer have fostered a search for mechanisms to attenuate them. Despite overwhelming success in acute care, the efficacy of modern medicines has been limited on this front. Yoga is one of the integrative therapies that has come to light as having a substantial role in preventing and mitigating such disorders. It thus seems trite to analyze and discuss the research advancements in yoga for 2020. The present review attempts to distill recent research highlights from voluminous literature generated in 2020. Methods: This review was conducted on the articles published or assigned to an issue in 2020. The authors searched the PubMed database for clinical studies published in the English language, using yoga (including meditation) as the intervention, and having an adequate description of the intervention. Then, they extracted data from each study into a standardized Google sheet. Results: A total of 1149 citations were retrieved in the initial search. Of these, 46 studies met eligibility criteria and were finally included. The studies were predominantly on mental health and neuropsychology, addressing various issues such as anxiety, postural balance, migraine, academic performance, and childhood neglect. Anxiety, stress, and depression were other common denominators. Eight studies were on cardiorespiratory systems, including exercise capacity, cardiac rehabilitation, myocardial infarction, and hypertension. Three studies were on diabetes, evaluating the effect of yoga. Five studies focused on cognition, health status, and autonomic regulation and few others included cancers, infertility, ulcerative colitis, urinary incontinence, restless leg syndrome, rheumatoid arthritis, chronic pain, and metabolic syndrome. Finally, most studies were on noncommunicable diseases with one exception, human immunodeficiency virus; two randomized controlled trials were dedicated to it. Conclusions: Yoga has been studied under a wide variety of clinicopathological conditions in the year 2020. This landscape review intends to provide an idea of the role of yoga in various clinical conditions and its future therapeutic implications.

A Whole-Slide Image Managing Library Based on Fastai for Deep Learning in the Context of Histopathology: Two Use-Cases Explained

Background: Processing whole-slide images (WSI) to train neural networks can be intricate and labor intensive. We developed an open-source library dealing with recurrent tasks in the processing of WSI and helping with the training and evaluation of neuronal networks for classification tasks. Methods: Two histopathology use-cases were selected and only hematoxylin and eosin (H&amp;E) stained slides were used. The first use case was a two-class classification problem. We trained a convolutional neuronal network (CNN) to distinguish between dysembryoplastic neuroepithelial tumor (DNET) and ganglioglioma (GG), two neuropathological low-grade epilepsy-associated tumor entities. Within the second use case, we included four clinicopathological disease conditions in a multilabel approach. Here we trained a CNN to predict the hormone expression profile of pituitary adenomas. In the same approach, we also predicted clinically silent corticotroph adenoma. Results: Our DNET-GG classifier achieved an AUC of 1.00 for the ROC curve. For the second use case, the best performing CNN achieved an area under the curve (AUC) of 0.97 for the receiver operating characteristic (ROC) for corticotroph adenoma, 0.86 for silent corticotroph adenoma, and 0.98 for gonadotroph adenoma. All scores were calculated with the help of our library on predictions on a case basis. Conclusions: Our comprehensive and fastai-compatible library is helpful to standardize the workflow and minimize the burden of training a CNN. Indeed, our trained CNNs extracted neuropathologically relevant information from the WSI. This approach will supplement the clinicopathological diagnosis of brain tumors, which is currently based on cost-intensive microscopic examination and variable panels of immunohistochemical stainings.

Mercury in the human thyroid gland: Potential implications for thyroid cancer, autoimmune thyroiditis, and hypothyroidism.

ObjectiveMercury and other toxic metals have been suggested to be involved in thyroid disorders, but the distribution and prevalence of mercury in the human thyroid gland is not known. We therefore used two elemental bio-imaging techniques to look at the distribution of mercury and other toxic metals in the thyroid glands of people over a wide range of ages.Materials and methodsFormalin-fixed paraffin-embedded thyroid tissue blocks were obtained from 115 people aged 1–104 years old, with varied clinicopathological conditions, who had thyroid samples removed during forensic/coronial autopsies. Seven-micron sections from these tissue blocks were used to detect intracellular inorganic mercury using autometallography. The presence of mercury was confirmed using laser ablation-inductively coupled plasma-mass spectrometry which can detect multiple elements.ResultsMercury was found on autometallography in the thyroid follicular cells of 4% of people aged 1–29 years, 9% aged 30–59 years, and 38% aged 60–104 years. Laser ablation-inductively coupled plasma-mass spectrometry confirmed the presence of mercury in samples staining with autometallography, and detected cadmium, lead, iron, nickel and silver in selected samples.ConclusionsThe proportion of people with mercury in their thyroid follicular cells increases with age, until it is present in over one-third of people aged 60 years and over. Other toxic metals in thyroid cells could enhance mercury toxicity. Mercury can trigger genotoxicity, autoimmune reactions, and oxidative damage, which raises the possibility that mercury could play a role in the pathogenesis of thyroid cancers, autoimmune thyroiditis, and hypothyroidism.

A high number of PD-L1+ CD14+ monocytes in peripheral blood is correlated with shorter survival in patients receiving immune checkpoint inhibitors.

Targeting of anti-programmed cell death protein-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) is a standard therapeutic strategy for various cancers. The aim of the present study was to investigate the prognostic effect of pretreatment PD-L1 expression levels in peripheral blood mononuclear cell (PBMC) subsets for patients with several cancer types receiving anti-PD-1 blockade therapies. Thirty-two patients undergoing anti-PD-L1 blockade therapy, including 15 with non-small cell lung cancer, 14 with gastric cancer, 1 with melanoma, 1 with parotid cancer, and 1 with bladder cancer, were recruited for the present study. PD-L1 expression levels in CD3+, CD4+, CD8+, CD45RA+ and CCR7+ T cells; CD20+ B cells; CD14+ and CD16+ monocytes were measured via flow cytometry before treatment. The percentages of PD-L1+ cells in respective PBMC subsets were compared with respect to different clinicopathological conditions and the association with overall survival (OS) was assessed. The percentages of PD-L1+ with CD3+, CD4+ and CD8+ T cells including naïve and memory T cell subsets, or CD20+ B cells during pretreatment were not markedly correlated with the OS of patients (p > 0.05); however, the percentage of the PD-L1+ CD14+ monocyte subset was significantly correlated with OS (p = 0.0426). Increase in pretreatment expression levels of PD-L1 on CD14+ monocytes is associated with the OS of patients treated with immune checkpoint inhibitors. Further evaluation of large sample size and each specific cancer type might clarify the predictive role of PBMC in patients.

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei.

ObjectiveInterference with the transmission of sensory signals along visual and auditory pathways has been implicated in the pathogenesis of hallucinations. The relay centres for vision (the lateral geniculate nucleus) and hearing (the medial geniculate nucleus) appear to be susceptible to the uptake of circulating mercury. We therefore investigated the distribution of mercury in cells of both these geniculate nuclei.Materials and methodsParaffin-embedded tissue sections containing the lateral geniculate nucleus were obtained from 50 adults (age range 20–104 years) who at autopsy had a variety of clinicopathological conditions, including neurological and psychiatric disorders. The medial geniculate nucleus was present in seven sections. Sections were stained for mercury using autometallography. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury.ResultsTen people had mercury in cells of the lateral geniculate nucleus, and in the medial geniculate nucleus of three of these. Medical diagnoses in these individuals were: none (3), Parkinson disease (3), and one each of depression, bipolar disorder, multiple sclerosis, and mercury self-injection. Mercury was distributed in different groups of geniculate capillary endothelial cells, neurons, oligodendrocytes, and astrocytes. Mass spectrometry confirmed the presence of mercury.ConclusionMercury is present in different combinations of cell types in the lateral and medial geniculate nuclei in a proportion of people from varied backgrounds. This raises the possibility that mercury-induced impairment of the function of the geniculate nuclei could play a part in the genesis of visual and auditory hallucinations. Although these findings do not provide a direct link between mercury in geniculate cells and hallucinations, they suggest that further investigations into the possibility of toxicant-induced hallucinations are warranted.

CD109 promotes the tumorigenic ability and metastatic motility of pancreatic ductal adenocarcinoma cells

BackgroundAccumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC). MethodsPDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined. ResultsSuppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis. ConclusionsCD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.

A systemic analysis reveals TRIM24-SMARCC1 dependent poor prognosis of hepatocellular carcinoma

The role of TRIM24 in HCC and the mechanisms underlying the dysregulated expression of TRIM24 is poorly understood. Here, we systematically analyzed TRIM24 expression and its prognostic role in HCC using various open databases. More precisely, we found an up-regulated gene expression profile of TRIM24 in hepatocellular carcinoma by using Oncomine, cBioPortal, TCGA, and the Human Protein Atlas. The higher expression of TRIM24 is allied with various clinicopathological conditions such as cancer stages, tumor grade, nodal metastasis status, histological subtypes, and also mutant TP53 status based on the TCGA database. In addition to the mRNA expression profile, the correlation between mRNA expression and TRIM24 promoter methylation is entrenched using TCGA datasets from the UALCAN web and subsequently, we examined the liaison of TRIM24 promoter methylation with different clinicopathological conditions in HCC patients. We also clarified a negative correlation of the TRIM2 4 mRNA expression with antioxidant responsive genes using the TCGA cBioPortal database. Data mining via Kaplan-Meier Plotter and the Human Protein Atlas symbolized a positive tie-up among the higher TRIM24 gene expression, protein expression, and poor survival of HCC patients. Besides, we also identified a highly co-expressed gene, SMARCC1 with TRIM24 in the most predominant correlation fashion in HCC using UALCAN, cBioPortal, UCSC Xena database. Finally, we identified the co-expressed genes with gene oncological features, signaling pathways, and ENCODE ChIP-seq coordination in HCC development. Altogether, this study establishes that elevated TRIM24 expression might accelerate the cancer progression and poor prognosis in HCC patients in a concerted fashion with SMARCC1 expression, which would allow them as a potential therapeutic biomarker in HCC cases.

Prognostic and clinico-pathological significance of BIN1 in breast cancer

Abstract Bridging integrator 1 (BIN1) is a potential tumor suppressor that behaves as silent or misplaced in breast, prostate, skin, lung, and colon cancers. Previous studies noted decreased BIN1 expression in breast cancer (BC). Despite this, BIN1's role in breast cancer is not well understood and remains to be elucidated. Here, we computationally analyzed BIN1 expression and its prognostic role in BC using various databases. Specifically, we found a down-regulated expression profile for the BIN1 gene in different BC subtypes using Oncomine, TCGA, and bcGenExMiner v4.2 web. The expression of BIN1 was found to be associated with various clinico-pathological conditions including estrogen receptor (ER), progesterone receptor (PR) basal-like subtype, and triple-negative breast cancer (TNBC) based on analysis of the bcGenExMiner v4.2 and TCGA databases. In addition to mRNA expression, the correlation between mRNA expression and BIN1 promoter methylation was established using TCGA datasets from UCSC Xena and ULCAN web, and we subsequently examined the relationship of BIN1 promoter methylation with different clinico-pathological conditions in BC patients. Data mining via Kaplan-Meier plotter indicated a positive association between lower BIN1 expression and low BC patient survival and various clinico-pathological conditions in BC patients. Furthermore, we identified a list of genes co-expressed with BIN1 in BC using TCGA data from the ULCAN web. Among the co-expressed genes, glycophorin C (GYPC) had the most predominant positive correlation. This correlation was further confirmed in BC using UCSC Xena and bcGenExMiner v4.2 webs. Overall, this study establishes that attenuated BIN1 expression might induce progression and poor prognosis in BC patients with GYPC association. This could be useful for clinical BC therapy.

Pediatric Eosinophilic Gastrointestinal Disease: Perspectives and Pearls from the Allergy Clinic

Eosinophilic Gastrointestinal Diseases (EGID) are uncommon to rare gastrointestinal eosinophilic infiltrated clinicopathological conditions, ranging from the esophagus to the sigmoid colon. Outside of the near immediate newborn period, associated with milk or soy protein colitis ( Food protein-induced allergic proctocolitis) 1 the presence of exaggerated gastrointestinal eosinophilia is clinically relevant and has long-term concerns. In this review the separate clinical EGID conditions will be briefly reviewed, with added clinical pearls, based on an extensive Pediatric Allergy-Immunology experience.