Potential of Liver Serum Enzymes and SUVmax in Primary Tumors as Predictive Biomarkers With Correlational Evidence.

Introduction Cancer exerts a substantial influence on the body's metabolism through varied mechanisms, instigating a metabolic reprogramming that maintains the unchecked growth and survival of cancer cells, consequently perturbing diverse metabolic parameters. The introduction of positron emission tomography-computed tomography (PET/CT), delivering detailed insights into both metabolic and morphological aspects, has brought about a revolutionary shift in modern cancer detection. Exploring the potential connection between PET-CT metabolic features and the metabolic parameters of liver enzymes in an individual can unveil novel avenues for cancer diagnosis and prognosis. Materials and methods This study conducted a retrospective analysis of patient records from our institution, covering the period from January 2021 to September 2023, focusing on individuals with various malignancies. The data included information on gender, age, clinical history, and liver serum parameters, which were compiled into tables. Additionally, inflammatory indicators such as ALT (alanine transaminase), ALP (alkaline phosphatase), total protein (TP), ALT/AST ratio, and SUVmax were collected and plotted. The study used Pearson correlation analysis to assess the relationship between each inflammatory variable and SUV (max) as determined by PET-CT. Results In breast cancer, there was a statistically significant positive correlation (R2=0.0651) between serum ALP levels and SUVmax as determined by regression analysis. Hodgkin lymphoma, on the other hand, showed a statistically significant negative correlation between the ALT-to-AST ratio (ALT/AST) and SUVmax (r = -0.45, R2 = 0.204). In non-Hodgkin lymphoma patients, total protein (TP) was negatively correlated with SUVmax (R2=-0.081, r= -0.28), while in lung cancer patients, there was a significant positive correlation with regression correlation coefficients (R2 = 0.026, 0.024, 0.024, and 0.018 for ALT/AST, TP, ALP, albumin, and ALT, respectively). Conclusion Aligning with these results, it can be a recent addition to acknowledge that both the tumor metabolic parameter (SUVmax) and the levels of liver serum enzymes exhibit a potential for predicting patient prognosis in various cancers.

The impact of ambient temperature and powertrains of SUVs on the environment in Slovakia during the use phase.

This study compares different powertrains of sport utility vehicles (SUVs) with respect to ambient temperature and energy mix in Slovakia using the well-to-wheel (WTW) Life Cycle Assessment (LCA) method. Battery electric vehicles (BEV), plug-in hybrid electric vehicles (PHEV), and petrol and diesel vehicles were assessed and compared. The WTW study was conducted in SimaPro software assessing electricity/petrol/diesel production, transport, and use (energy conversion in the vehicle), with impact categories being climate change, particulates, NOx emissions, ionizing radiation, and fossil resource scarcity depending on the season (summer and winter). The results indicate that for Slovak conditions, BEV generally had the lowest environmental impact in both seasons studied. The only exceptions were ionizing radiation, which is clearly caused by the high share of nuclear power in the Slovak energy mix, and NOx emissions, which are caused by the combustion of biomass for electricity generation. The other impact categories were dominated by vehicles with an internal combustion engine. The results of emissions from fuel production are also given for each impact category. The transportation of fuel did not exceed the value of 1% for any impact category or for any powertrain. The conclusions of the study support the global trend in favour of vehicle electrification as an important way to reduce the negative environmental impacts of internal combustion engine vehicles in Slovakia.

Histone Methyltransferase SUV39H2 Supports Nasopharyngeal Carcinoma Cell Metastasis by Regulation of SIRT1.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. However, the underlying mechanism of Suppressor of variegation 3-9 homolog 2 (SUV39H2) in NPC remains poorly understood. RT-qPCR was carried out to examine SUV39H2 and SIRT1 expression in NPC tissues and cells. Kaplan-Meier method was utilized to evaluate the association between SUV39H2 level and overall survival. The function of SUV39H2 and SIRT1 in NPC cell viability, metastasis, and apoptosis was tested through CCK-8, transwell, and flow cytometry experiments. Here, it was uncovered that SUV39H2 level was augmented in NPC tissues and cells. Moreover, SUV39H2 expedited NPC cell viability, metastasis, and inhibited apoptosis, while SIRT1 addition reversed these impacts. Besides, SUV39H2 induced H3K9me3 enhancement to repress SIRT1 transcription via binding to SIRT1 promoter. Collectively, our results demonstrated upregulated SUV39H2 aggravated NPC tumorigenesis through SIRT1, which may offer a potential therapeutic target for NPC.

Comparison of Measurement and Prognostic Power of SUV Between High-Definition and Standard PET Imaging in Non-Small Cell Lung Cancer Patients.

This study aimed to evaluate the measurement and prognostic ability of the SUVmax of whole-body tumors (SUVmaxwb) in non-small cell lung cancer (NSCLC) patients, comparing high-definition (HD) PET imaging with standard-definition (SD) PET imaging. Methods: The study included 242 consecutive NSCLC patients who underwent baseline 18F-FDG PET/CT from April 2018 to January 2021. Two imaging techniques were used: HD PET (using ordered-subsets expectation maximization with point-spread function modeling and time-of-flight techniques and smaller voxels) and SD PET (with ordered-subsets expectation maximization and time-of-flight techniques). SUVmaxwb was determined by measuring all the tumor lesions in the whole body, and tumor-to-background ratio (TBR) was calculated using the background SUVmean of various body parts. Results: The patient cohort had an average age of 68.3 y, with 59.1% being female. During a median follow-up of 29.6 mo, 83 deaths occurred. SUVmaxwb was significantly higher in HD PET than SD PET, with respective medians of 17.4 and 11.8. The TBR of 1,125 tumoral lesions was also higher in HD PET. Univariate Cox regression analysis showed that SUVmaxwb from both HD and SD PET were significantly associated with overall survival. However, after adjusting for TNM (tumor, node, metastasis) stage, only SUVmaxwb from SD PET remained significantly associated with survival. Conclusion: HD PET imaging in NSCLC patients yields higher SUVmaxwb and TBR, enhancing tumor visibility. Despite this, its prognostic value is less significant than SD PET after adjusting clinical TNM stage. Thus, consideration should be given to using HD PET reconstruction to increase tumor visibility, and SD PET is recommended for NSCLC patient prognostication and therapeutic evaluation, as well as for the classification of lung nodules.

Quantitative assessment of cardiac 123iodo-metaiodobenzylguanidine SPECT/CT in patients with arrhythmogenic right ventricular cardiomyopathy: Novel insight in disease monitoring.

BACKGROUND: The heart-to-mediastinum ratio (H/M-Ratio) of 123iodo-metaiodobenzylguanidine (123I-MIBG) represents state-of-the-art assessment for sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to evaluate quantitative reconstruction of 123I-MIBG uptake and to demonstrate its correlation with echocardiographic parameters. METHODS: Cardiac innervation was assessed in 23 patients diagnosed with definite ARVC or borderline ARVC and 12 patients with other cardiac disease presenting arrhythmia, using quantitative 123I-MIBG Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging. Tracer uptake was evaluated in the left (LV) and right ventricle (RV) based on a CT scan after quantitative image reconstruction. The relationship between tracer uptake and echocardiographic parameter data was examined. RESULTS: Absolute quantification of 123I-MIBG uptake in the LV and RV is feasible and correlates accurately with the gold standard H/M Ratio. When comparing sensitivity and specificity, the area under the curve (AUC) favors standardized uptake value (SUV) of the RV over the right-ventricle-to-mediastinum-ratio (RV/M-Ratio) for diagnosing ARVC. A reduced RV-SUV in patients with definite ARVC is associated with reduced RV function. RV polar maps revealed globally reduced 123I-MIBG uptake without segment-specific reduction in the RV. CONCLUSIONS: Quantitative 123I-MIBG SPECT in ARCV patients offers robust potential for clinical reporting and demonstrates a significant correlation with RV function. Segmental RV analysis needs to be evaluated in larger samples. In summary, cardiac 123I-MIBG imaging using SUV could facilitate image-guided therapy in patients diagnosed with ARVC.

The Association between the Body Mass Index, Chronic Obstructive Pulmonary Disease and SUV of the Non-Tumorous Lung in the Pretreatment [18F]FDG-PET/CT of Patients with Lung Cancer.

Background: A debate persists on the prognostic value of the pre-therapeutic standardized uptake value (SUV) of non-tumorous lung tissue for the risk assessment of therapy-related pneumonitis, with most studies lacking significant correlation. However, the influence of patient comorbidities on the pre-therapeutic lung SUV has not yet been systematically evaluated. Thus, we aimed to elucidate the association between comorbidities, biological variables and lung SUVs in pre-therapeutic [18F]FDG-PET/CT. Methods: In this retrospective study, the pre-therapeutic SUV in [18F]FDG-PET/CT was measured in non-tumorous areas of both lobes of the lung. SUVMEAN, SUVMAX and SUV95 were compared to a multitude of patient characteristics and comorbidities with Spearman's correlation analysis, followed by a Bonferroni correction and multilinear regression. Results: In total, 240 patients with lung cancer were analyzed. An elevated BMI was significantly associated with increased SUVMAX (ß = 0.037, p < 0.001), SUVMEAN (ß = 0.017, p < 0.001) and SUV95 (ß = 0.028, p < 0.001). Patients with chronic obstructive pulmonary disease (COPD) showed a significantly decreased SUVMAX (ß = -0.156, p = 0.001), SUVMEAN (ß = -0.107, p < 0.001) and SUV95 (ß = -0.134, p < 0.001). Multiple other comorbidities did not show a significant correlation with the SUV of the non-tumorous lung. Conclusions: Failure to consider the influence of BMI and COPD on the pre-therapeutic SUV measurements may lead to an erroneous interpretation of the pre-therapeutic SUV and subsequent treatment decisions in patients with lung cancer.

Evaluation of chest CT-scans following lung stereotactic ablative radiotherapy: Challenges and new insights.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called 'benign' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF's) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called 'actionable radiological features' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

A PET/MRI study on the effect of obesity and NAFLD on hepatic [18F]FDG uptake.

PURPOSE: The potential limitations of hepatic [18F]FDG-PET imaging for individuals with obesity and excessive liver fat (NAFLD) are being investigated. In this study, we aim to determine the reliability of standardized uptake values (SUVs) focusing on adjustment for liver fat content (LFC) derived from DIXON images and the effects of whole-body normalizations. METHODS: Lean and with obesity volunteers who underwent [18F]FDG-PET/MRI were reviewed retrospectively. DIXON fat images were used to determine LFC and for adjustment of SUVmean. The hepatic SUVs (mean, fat adjusted mean and max) were normalized to body weight, lean body mass and body surface area. Blood samples were analysed for glucose, serological liver enzymes and lipoproteins for further correlation of [18F]FDG uptake. RESULTS: Out of 11 volunteers with obesity (M:8, F:3, BMI:30-39 kg/m2), 9 confirmed the presence of NAFLD (>5.6 % fat). 22 age-matched lean volunteers (M:10, F:11, BMI:19-26 kg/m2) were used as control group. Both SUVmean, before and after adjustment to LFC, did not provide any difference between lean and with obesity groups under BW, LBM and BSA. SUVmax BW showed a difference between groups (p = 0.05). SUVs were independent of levels of GPT, GOT, gGT, insulin, HOMA-IR, triglycerides, cholesterol and LDL. Volunteers with low HDL were clustered with an increased hepatic [18F]FDG uptake. CONCLUSION: Our method for adjustment of hepatic [18F]FDG-PET with DIXON fat images allows to achieve accurate results for individuals with NAFLD and obesity. For homogenic results, raw SUVmean should be combined with adjustment for liver fat, appropriate normalization and consideration of HDL levels.

Patlak Slope versus Standardized Uptake Value Image Quality in an Oncologic PET/CT Population: A Prospective Cross-Sectional Study.

Patlak slope (PS) images have the potential to improve lesion conspicuity compared with standardized uptake value (SUV) images but may be more artifact-prone. This study compared PS versus SUV image quality and hepatic tumor-to-background ratios (TBRs) at matched time points. Early and late SUV and PS images were reconstructed from dynamic positron emission tomography (PET) data. Two independent, blinded readers scored image quality metrics (a four-point Likert scale) and counted tracer-avid lesions. Hepatic lesions and parenchyma were segmented and quantitatively analyzed. Differences were assessed via the Wilcoxon signed-rank test (alpha, 0.05). Forty-three subjects were included. For overall quality and lesion detection, early PS images were significantly inferior to other reconstructions. For overall quality, late PS images (reader 1 [R1]: 3.95, reader 2 [R2]: 3.95) were similar (p > 0.05) to early SUV images (R1: 3.88, R2: 3.84) but slightly superior (p ≤ 0.002) to late SUV images (R1: 2.97, R2: 3.44). For lesion detection, late PS images were slightly inferior to late SUV images (R1 only) but slightly superior to early SUV images (both readers). PS-based TBRs were significantly higher than SUV-based TBRs at the early time point, with opposite findings at the late time point. In conclusion, late PS images are similar to early/late SUV images in image quality and lesion detection; the superiority of SUV versus PS hepatic TBRs is time-dependent.

The Diagnostic Performance of 2-[18F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis.

Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5-93.3), a pooled specificity of 48.1% (95% CI: 27-69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4-92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17-0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3-2.4), and a pooled diagnostic odds ratio of 6.7 (3.5-12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.

RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.

In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.

Assessing the effectiveness of MRI, 18F-fluciclovine PET, SUVmax, and PSA in detecting local recurrence of prostate cancer after prostatectomy.

Purpose: The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy. Material and methods: Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics. Results: The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925. Conclusions: The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

Askin's Tumor in the Chest Wall-a Rare Clinical Entity and Review of Literature.

Askin tumors are the rare malignancy of neuroectodermal origin of the thoracic wall. Its prevalence is more in younger age group who present with vague symptoms leading to delayed diagnosis. We hereby present a case report of complex management of large chest wall tumor in a young boy and review the literature of this entity.

Value of Semi-Quantitative Parameters of 68Ga-FAPI-04 PET/CT in Primary Malignant and Benign Diseases: A Comparison with 18F-FDG.

Objectives: We aimed to compare the value of the semiquantitative parameters of 68Ga-labeled FAP inhibitor (68Ga-FAPI)-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) in diagnosing primary malignant and benign diseases. Materials and Methods: 18F-FDG and 68Ga-FAPI-04 PET/CT images of 80 patients were compared. Semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), peak SUV by lean body mass (SULpeak), metabolic tumor volume (or tumor volume of FAPI; FAPI-TV), and TLG (or total lesion activity of FAPI; FAPI-TLA), were automatically obtained using the IntelliSpace Portal image processing workstation with a threshold of 40% SUVmax. The liver blood pool was measured as the background, and the tumor-to-background ratio (TBRliver) was calculated. Results: In all malignant lesions, FAPI-TV and FAPI-TLA were higher in 68Ga-FAPI-04 PET/CT than in 18F-FDG. In the subgroup analysis, 68Ga-FAPI-04 had higher FAPI-TV and FAPI-TLA and lower SUVmax than 18F-FDG had in group A, including gynecological tumor, esophageal, and colorectal cancers. However, six semiquantitative parameters were higher in group B (the other malignant tumors). For the benign diseases, SUVmax, SUVmean, SUVpeak, and SULpeak were lower in 68Ga-FAPI-04 PET/CT than in 18F-FDG. 68Ga-FAPI-04 PET/CT showed a lower liver background and a higher TBRliver than 18F-FDG did. 68Ga-FAPI-04 PET/CT had higher accuracy, sensitivity, and specificity than 18F-FDG had. Conclusion: More accurate semiquantitative parameters and lower abdominal background in 68Ga-FAPI-04 PET/CT make it more competitive in the differential diagnosis of malignant and benign diseases than in 18F-FDG.

The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

OBJECTIVE: The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. METHODS: A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. CONCLUSIONS: This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

The Additional Role of F18-FDG PET/CT in Characterizing MRI-Diagnosed Tumor Deposits in Locally Advanced Rectal Cancer.

Rationale: F18-FDG PET/CT may be helpful in baseline staging of patients with high-risk LARC presenting with vascular tumor deposits (TDs), in addition to standard pelvic MRI and CT staging. Methods: All patients with locally advanced rectal cancer that had TDs on their baseline MRI of the pelvis and had a baseline F18-FDG PET/CT between May 2016 and December 2020 were included in this retrospective study. TDs as well as lymph nodes identified on pelvic MRI were correlated to the corresponding nodular structures on a standard F18-FDG PET/CT, including measurements of nodular SUVmax and SUVmean. In addition, the effects of partial volume and spill-in on SUV measurements were studied. Results: A total number of 62 patients were included, in which 198 TDs were identified as well as 106 lymph nodes (both normal and metastatic). After ruling out partial volume effects and spill-in, 23 nodular structures remained that allowed for reliable measurement of SUVmax: 19 TDs and 4 LNs. The median SUVmax between TDs and LNs was not significantly different (p = 0.096): 4.6 (range 0.8 to 11.3) versus 2.8 (range 1.9 to 3.9). For the median SUVmean, there was a trend towards a significant difference (p = 0.08): 3.9 (range 0.7 to 7.8) versus 2.3 (range 1.5 to 3.4). Most nodular structures showing either an SUVmax or SUVmean ≥ 4 were characterized as TDs on MRI, while only two were characterized as LNs. Conclusions: SUV measurements may help in separating TDs from lymph node metastases or normal lymph nodes in patients with high-risk LARC.

Inhibition of SUV39H1 reduces tumor angiogenesis via Notch1 in oral squamous cell carcinoma.

Targeting tumor angiogenesis is an important approach in advanced tumor therapy. Here we investigated the effect of the suppressor of variegation 3-9 homolog 1 (SUV39H1) on tumor angiogenesis in oral squamous cell carcinoma (OSCC). The GEPIA database was used to analyze the expression of SUV39H1 in various cancer tissues. The expression of SUV39H1 in OSCC was detected by immunohistochemistry, and the correlation between SUV39H1 and Notch1 and microvascular density (MVD) was analyzed. The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment. The migration and tube formation of vascular endothelial cells by conditioned culture-medium of different treatments of oral squamous cell cells were measured. The transcriptional level of SUV39H1 is elevated in various cancer tissues. The transcription level of SUV39H1 in head and neck squamous cell carcinoma was significantly higher than that in control. Immunohistochemistry result showed increased SUV39H1 expression in OSCC, which was significantly correlated with T staging. The expression of SUV39H1 was significantly correlated with Notch1 and CD31. In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression. The decreased expression of SUV39H1 in OSCC cells lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells. Inhibition of Notch1 further enhance this effect. Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.

FDG uptake in the cervical muscles after neck dissection: imaging features and postoperative natural course on 18F­FDG­PET/CT.

PURPOSE: This study aimed to assess the imaging features and postoperative natural course of 18F-fluorodeoxyglucose (FDG) uptake in the cervical muscles after neck dissection. MATERIALS AND METHODS: This study included 83 patients who underwent preoperative and postoperative 18F-FDG-PET/CT and were diagnosed with head and neck malignancy after neck dissection. Postoperative 18F-FDG-PET/CT was performed within 5 years after neck dissection. Preoperative and postoperative FDG uptake of the trapezius, sternocleidomastoid, scalene, pectoralis major, and deltoid muscles was visually assessed. Increased postoperative uptake was visually defined as higher postoperative FDG uptake than the preoperative one in the corresponding muscle. The maximum standardized uptake value (SUVmax) was measured in cases with increased postoperative uptakes. RESULTS: Increased postoperative uptakes were observed in 43 patients (52%). The trapezius (31/83, 37%), sternocleidomastoid (19/83, 23%), and scalene (12/83, 14%) muscles were involved, as opposed to the pectoralis major and deltoid muscles were not. Increased postoperative uptakes were observed on the dissected side in all 43 patients. Significant differences between SUVmax estimated from the mixed-effects model and postoperative months were observed in the trapezius muscle (Coefficient (ß) = -0.038; 95% confidence interval (CI): [-0.047, -0.028]; p < 0.001) and sternocleidomastoid muscle (ß = -0.015; 95% CI: [-0.029, -0.001]; p = 0.046). CONCLUSIONS: Increased postoperative uptakes in the cervical muscles were observed on the dissected side in approximately half of the patients after neck dissection. The SUVmax in the trapezius and sternocleidomastoid muscles decreased after surgery over time.

HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

Impact of 18F-FDG PET Intensity Normalization on Radiomic Features of Oropharyngeal Squamous Cell Carcinomas and Machine Learning-Generated Biomarkers.

We aimed to investigate the effects of 18F-FDG PET voxel intensity normalization on radiomic features of oropharyngeal squamous cell carcinoma (OPSCC) and machine learning-generated radiomic biomarkers. Methods: We extracted 1,037 18F-FDG PET radiomic features quantifying the shape, intensity, and texture of 430 OPSCC primary tumors. The reproducibility of individual features across 3 intensity-normalized images (body-weight SUV, reference tissue activity ratio to lentiform nucleus of brain and cerebellum) and the raw PET data was assessed using an intraclass correlation coefficient (ICC). We investigated the effects of intensity normalization on the features' utility in predicting the human papillomavirus (HPV) status of OPSCCs in univariate logistic regression, receiver-operating-characteristic analysis, and extreme-gradient-boosting (XGBoost) machine-learning classifiers. Results: Of 1,037 features, a high (ICC ≥ 0.90), medium (0.90 > ICC ≥ 0.75), and low (ICC < 0.75) degree of reproducibility across normalization methods was attained in 356 (34.3%), 608 (58.6%), and 73 (7%) features, respectively. In univariate analysis, features from the PET normalized to the lentiform nucleus had the strongest association with HPV status, with 865 of 1,037 (83.4%) significant features after multiple testing corrections and a median area under the receiver-operating-characteristic curve (AUC) of 0.65 (interquartile range, 0.62-0.68). Similar tendencies were observed in XGBoost models, with the lentiform nucleus-normalized model achieving the numerically highest average AUC of 0.72 (SD, 0.07) in the cross validation within the training cohort. The model generalized well to the validation cohorts, attaining an AUC of 0.73 (95% CI, 0.60-0.85) in independent validation and 0.76 (95% CI, 0.58-0.95) in external validation. The AUCs of the XGBoost models were not significantly different. Conclusion: Only one third of the features demonstrated a high degree of reproducibility across intensity-normalization techniques, making uniform normalization a prerequisite for interindividual comparability of radiomic markers. The choice of normalization technique may affect the radiomic features' predictive value with respect to HPV. Our results show trends that normalization to the lentiform nucleus may improve model performance, although more evidence is needed to draw a firm conclusion.