Hypermethylation of TMEM240 Involved in Expression Deficiency Predicts Poor Hormone Therapy Response and Disease Progression in Breast Cancer

Background:Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression.Methods:Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and relapse events. Illumina methylation arrays were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific real-time polymerase chain reaction (QMSP), quantitative real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation, mRNA and protein expression levels in 335 breast samples from Taiwanese and Korean patients. Kaplan–Meier curves, Cox proportional hazards regression and receiver operating characteristic curves were used to analyze 10-year survival and disease progression. The Cancer Genome Atlas (TCGA) dataset was used to investigate TMEM240 alterations in Western countries. Transient transfection and knockdown of TMEM240 were performed to determine its biological functions and its relationship to hormone drug treatment response in breast cancer cells.Results: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and cell migration. TMEM240 protein expression was observed in normal breast tissues, but not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. Almost all triple-negative breast cancer patients (95.7%, 22/23) had deficient TMEM240 protein expression. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least 2-fold higher in tumor tissues than in the matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy, better than the currently used biomarkers CEA and CA-153.Conclusions: Circulating methylated TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.

Optical Coherence Tomography Angiography in Herpetic Leucoma

Background: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. This study instends to investigate the potential of Optical Coherence Tomography Angiography (OCTA) device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology. Methods: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and Optical Coherence Tomography Angiography (OCT) with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6x6 mm in a depth of 800 μm. Results: Patients included had a mean age 53.267±21.542 (years±SD). The mean total vessel area was 50.907±3.435%. VD was higher in the nasal quadrant (51.156±4.276) but there were no significant differences between the three analyzed areas (p=0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings. Conclusions: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.

Review: Radionuclide Molecular Imaging Targeting HER2 in Breast Cancer with a Focus on Molecular Probes into Clinical Trials and Small Peptides

As the most frequently occurring cancer worldwide, breast cancer (BC) is the leading cause of cancer-related death in women. The overexpression of HER2 (human epidermal growth factor receptor 2) is found in about 15% of BC patients, and it is often associated with a poor prognosis due to the effect on cell proliferation, migration, invasion, and survival. As a result of the heterogeneity of BC, molecular imaging with HER2 probes can non-invasively, in real time, and quantitatively reflect the expression status of HER2 in tumors. This will provide a new approach for patients to choose treatment options and monitor treatment response. Furthermore, radionuclide molecular imaging has the potential of repetitive measurements, and it can help solve the problem of heterogeneous expression and conversion of HER2 status during disease progression or treatment. Different imaging probes of targeting proteins, such as monoclonal antibodies, antibody fragments, nanobodies, and affibodies, are currently in preclinical and clinical development. Moreover, in recent years, HER2-specific peptides have been widely developed for molecular imaging techniques for HER2-positive cancers. This article summarized different types of molecular probes targeting HER2 used in current clinical applications and the developmental trend of some HER2-specific peptides.

Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response

External validation in different cohorts is a key step in the translational development of new biomarkers. We previously described three host mRNA whose expression in peripheral blood is significantly higher (NPC2) or lower (DOCK9 and EPHA4) in individuals with TB compared to latent TB infection (LTBI) and controls. We have now conducted an independent validation of these genes by re-analyzing publicly available transcriptomic datasets from Brazil, China, Haiti, India, South Africa, and the United Kingdom. Comparisons between TB and control/LTBI showed significant differential expression of all three genes (NPC2high p < 0.01, DOCK9low p < 0.01, and EPHA4low p < 0.05). NPC2high had the highest mean area under the ROC curve (AUROC) for the differentiation of TB vs. controls (0.95) and LTBI (0.94). In addition, NPC2 accurately distinguished TB from the clinically similar conditions pneumonia (AUROC, 0.88), non-active sarcoidosis (0.87), and lung cancer (0.86), but not from active sarcoidosis (0.66). Interestingly, individuals progressing from LTBI to TB showed a constant increase in NPC2 expression with time when compared to non-progressors (p < 0.05), with a significant change closer to manifestation of active disease (≤3 months, p = 0.003). Moreover, NPC2 expression normalized with completion of anti-TB treatment. Taken together, these results validate NPC2 mRNA as a diagnostic host biomarker for active TB independent of host genetic background. Moreover, they reveal its potential to predict progression from latent to active infection and to indicate a response to anti-TB treatment.

Biochemical and haematological parameters predicting severity of Covid 19 infection: Lessons from first wave of pandemic

Corona virus disease 2019 (COVID-19) was declared as pandemic by WHO on March 10, 2020. Several countries around the globe have seen a two-wave pattern of reported cases. India is witnessing unprecedented spike in COVID-19 cases again since March 2021 especially in Maharashtra. Newer insights in pathogenesis of diseases, diagnosis and treatment modalities continue to evolve in case of novel infection. To study and compare laboratory parameters in COVID cases in first wave in 2020. Retrospective cross-sectional observational study. Total 400 cases; 354 RTPCR and 46 RAT confirmed cases of COVID-19 done at dedicated COVID Hospital. Comparison of laboratory parameters was done between 72 Severe and 328 Non-Severe cases by unpaired t-test. Statistically significant differences were seen in severe cases as compared to non severe cases in Lymphocyte count, Eosinophil count, Neutrophil Lymphocyte Ratio, CRP, D-dimer, Ferritin levels. WBC count, Platelet count and ALT did not show significant difference between severe and non severe cases. Lymphopenia, raised N/L ratio, Eosinopenia, increased D-dimer, Ferritin, CRP are associated with severe COVID disease. The routine laboratory tests can diagnose the disease, predict prognosis and complications and monitor treatment response.

Comparison of 24-hour versus random urine samples for determination and quantification of Bence Jones protein in a South African population

Background: The International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy.Objective: This study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population.Methods: Sixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 – March 2018. Measured 24-h urine BJP was compared to two estimated 24-h BJP excretions calculated as follows: Estimation 1 (E1): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 10. Estimation 2 (E2): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 15 mg/kg for women or × 20 mg/kg for men.Results: Correlation of estimation equations E1 and E2 to the measured 24-h urine BJP was 0.893. Patients showed no difference in classification of treatment response using either the E1 or E2 estimation equations when compared to the measured 24-h urine BJP results.Conclusion: This study demonstrates that the estimated 24-h BJP shows a high degree of correlation with the measured 24-h BJP and can likely be used to monitor treatment response in South African patients with MM.

Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance

Colorectal cancer (CRC) is one of the most common cancers worldwide, being the third most diagnosed in the world and the second deadliest. Solid biopsy provides an essential guide for the clinical management of patients with colorectal cancer; however, this method presents several limitations, in particular invasiveness, and cannot be used repeatedly. Recently, clinical research directed toward the use of liquid biopsy, as an alternative tool to solid biopsy, showed significant promise in several CRC clinical applications, as (1) detect CRC patients at early stage, (2) make treatment decision, (3) monitor treatment response, (4) predict relapses and metastases, (5) unravel tumor heterogeneity, and (6) detect minimal residual disease. The purpose of this short review is to describe the concept, the characteristics, the genetic components, and the technologies used in liquid biopsy in the context of the management of colorectal cancer, and finally we reviewed gene alterations, recently described in the literature, as promising potential biomarkers that may be specifically used in liquid biopsy tests.

Clinical Use of Neurophysiological Biomarkers and Self-Assessment Scales to Predict and Monitor Treatment Response for Psychotic and Affective disorders

Psychoses and affective disorders are severe mental illnesses with a considerable negative effect on an individual and global scale. They are among the most damaging and socially significant diseases, which contribute to permanent disabilities for the patients. The aim of this review is to analyse the capacity of neuroscientific methods as tools to reform psychiatry into a biologically valid medical discipline. Furthermore, it will focus on the application of the translational approach towards the diagnostic and therapeutic processes, as well as monitoring of treatment response by using valid biomarkers and psychometric instruments. By combining translational neuroscience with the latest psychopharmacology advances clinicians might be able to provide better quality of precision and individualized medical care for their patients. We visualise a reality in which neuroimaging methods will modify standard clinical evaluation of neuropsychiatric disorders, leading to a biologically valid diagnosis, monitoring and treatment in everyday clinical practice.

Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia

Sickle cell anemia (SCA) is a hereditary hemoglobinopathy with a variable phenotype. There is no single biomarker that adequately predicts disease severity and can be used to monitor treatment response in patients in clinical trials and clinical care. The use of clinical outcomes, such as vaso-occlusive crises (VOC), requires long and expensive studies, sometimes with inconclusive results. To address these limitations, there are several biomarkers under study to improve the ability to predict complications and assess treatment response in both clinical and research settings. Oxygen gradient ektacytometry, also called as oxygenscan, is an assay that measures the effects of deoxygenation and reoxygenation on red blood cell (RBC) deformability and is gaining popularity in SCA research, because it captures the dynamic sickling capacity of a patient’s RBCs as they are subjected to an oxygen gradient under steady shear stress. We describe here the oxygenscan methodology and evaluate the correlation between oxygenscan parameters and more well-known biomarkers of SCA such as fetal hemoglobin (HbF), F-cells, and dense red blood cells (DRBCs). Our data indicate that the oxygenscan curve is affected by all these parameters and the result incorporates the effects of %HbF, %F-cells, RBC hydration, and RBC membrane deformability.

Co-Occurrence Conundrum: Brain Metastases from Lung Adenocarcinoma, Radiation Necrosis, and Gliosarcoma

Non-small cell lung cancer (NSCLC) commonly presents with metastasis to the brain. When brain metastases are treated with stereotactic radiosurgery (SRS), longitudinal imaging to monitor treatment response may identify radiation necrosis, metastasis progression, and/or another primary brain malignancy. A 60-year-old female with metastatic NSCLC involving the brain underwent treatment with systemic therapy and SRS. While some brain metastases resolved, two remaining sites evolved to resemble radiation necrosis on magnetic resonance imaging and spectroscopy. One of those sites was later confirmed to be radiation necrosis after receding with steroids and bevacizumab. The other lesion continued to enlarge and was then surgically resected, pathologically proven to be a gliosarcoma. When scan findings diverge among multiple treated disease sites, imaging should be cautiously interpreted in conjunction with clinical information as well as early surgical consultation for biopsy consideration, especially when there is suspicion of unusual or superimposed pathologies.