Cancer Lesions Research Articles

R2* mapping and reduced field-of-view diffusion-weighted imaging for preoperative assessment of nonenlarged lymph node metastasis in rectal cancer.

The aim of the current study is to investigate the diagnostic value of R2* mapping versus reduced field-of-view diffusion-weighted imaging (rDWI) of the primary lesion of rectal cancer for preoperative prediction of nonenlarged lymph node metastasis (NLNM). Eighty-one patients with pathologically confirmed rectal cancer underwent preoperative R2* mapping and rDWI sequences before total mesorectal excisions and accompanying regional lymph node dissections. Two radiologists independently performed whole-tumor measurements of R2* and apparent diffusion coefficient (ADC) parameters on primary lesions of rectal cancer. Patients were divided into positive (NLNM+) and negative (NLNM-) groups based on their pathological analysis. The tumor location, maximum diameter of the tumor, and maximum short diameter of the lymph node were assessed. R2* and ADC, pT stage, tumor grade, status of mesorectal fascia, and extramural vascular invasion were also studied for their potential relationships with NLNM using multivariate logistic regression analysis. The NLNM+ group had significantly higher R2* (43.56 ± 8.43 vs. 33.87 ± 9.57, p < 0.001) and lower ADC (1.00 ± 0.13 vs. 1.06 ± 0.22, p = 0.036) than the NLNM- group. R2* and ADC were correlated to lymph node metastasis (r = 0.510, p < 0.001 for R2*; r = -0.235, p = 0.035 for ADC). R2* and ADC showed good and moderate diagnostic abilities in the assessment of NLNM status with corresponding area-under-the-curve values of 0.795 and 0.636. R2* provided a significantly better diagnostic performance compared with ADC for the prediction of NLNM status (z = 1.962, p = 0.0498). The multivariate logistic regression analysis demonstrated that R2* was a compelling factor of lymph node metastasis (odds ratio = 56.485, 95% confidence interval: 5.759-554.013; p = 0.001). R2* mapping had significantly higher diagnostic performance than rDWI from the primary tumor of rectal cancer in the prediction of NLNM status.

T2-weighted imaging-based deep-learning method for noninvasive prostate cancer detection and Gleason grade prediction: a multicenter study.

To noninvasively detect prostate cancer and predict the Gleason grade using single-modality T2-weighted imaging with a deep-learning approach. Patients with prostate cancer, confirmed by histopathology, who underwent magnetic resonance imaging examinations at our hospital during September 2015-June 2022 were retrospectively included in an internal dataset. An external dataset from another medical center and a public challenge dataset were used for external validation. A deep-learning approach was designed for prostate cancer detection and Gleason grade prediction. The area under the curve (AUC) was calculated to compare the model performance. For prostate cancer detection, the internal datasets comprised data from 195 healthy individuals (age: 57.27 ± 14.45 years) and 302 patients (age: 72.20 ± 8.34 years) diagnosed with prostate cancer. The AUC of our model for prostate cancer detection in the validation set (n = 96, 19.7%) was 0.918. For Gleason grade prediction, datasets comprising data from 283 of 302 patients with prostate cancer were used, with 227 (age: 72.06 ± 7.98 years) and 56 (age: 72.78 ± 9.49 years) patients being used for training and testing, respectively. The external and public challenge datasets comprised data from 48 (age: 72.19 ± 7.81 years) and 91 patients (unavailable information on age), respectively. The AUC of our model for Gleason grade prediction in the training set (n = 227) was 0.902, whereas those of the validation (n = 56), external validation (n = 48), and public challenge validation sets (n = 91) were 0.854, 0.776, and 0.838, respectively. Through multicenter dataset validation, our proposed deep-learning method could detect prostate cancer and predict the Gleason grade better than human experts. Precise prostate cancer detection and Gleason grade prediction have great significance for clinical treatment and decision making. Prostate segmentation is easier to annotate than prostate cancer lesions for radiologists. Our deep-learning method detected prostate cancer and predicted the Gleason grade, outperforming human experts. Non-invasive Gleason grade prediction can reduce the number of unnecessary biopsies.

Toward confident prostate cancer detection using ultrasound: a multi-center study.

Deep learning-based analysis of micro-ultrasound images to detect cancerous lesions is a promising tool for improving prostate cancer (PCa) diagnosis. An ideal model should confidently identify cancer while responding with appropriate uncertainty when presented with out-of-distribution inputs that arise during deployment due to imaging artifacts and the biological heterogeneity of patients and prostatic tissue. Using micro-ultrasound data from 693 patients across 5 clinical centers who underwent micro-ultrasound guided prostate biopsy, we train and evaluate convolutional neural network models for PCa detection. To improve robustness to out-of-distribution inputs, we employ and comprehensively benchmark several state-of-the-art uncertainty estimation methods. PCa detection models achieve performance scores up to average AUROC with a 10-fold cross validation setup. Models with uncertainty estimation obtain expected calibration error scores as low as , indicating that confident predictions are very likely to be correct. Visualizations of the model output demonstrate that the model correctly identifies healthy versus malignant tissue. Deep learning models have been developed to confidently detect PCa lesions from micro-ultrasound. The performance of these models, determined from a large and diverse dataset, is competitive with visual analysis of magnetic resonance imaging, the clinical benchmark to identify PCa lesions for targeted biopsy. Deep learning with micro-ultrasound should be further studied as an avenue for targeted prostate biopsy.

Overview of granular cell tumor general hospitals in Iraq over 11-years

Granular cell tumor are rare tumors from Schwann cells with clinicopathological feature results, which may be shown in both benign and malignant tumor. Several tumors commonly appear in the oral cavity, gastrointestinal tract and skin.  This must be appropriately treated to avoid repetition or metastatic cancer lesions. The aim study is to search clinicopathological aspects of granular cell tumor diagnosed at different general hospitals in Iraq and to compare these findings with epidemiological findings from different governorates positions. The data was collected from different Iraq governorates in the mouth and tongue area from 2010 to 2020 years. Different parameters were displayed like age group, gender, topography, morphology and distribution of annual patients of the tumor. According to the available information about these characteristics, the inclusion criteria. The factor's frequencies were calculated from descriptive analysis of the data. A total (101) cases of granular cell tumor in mouth and tongue locations were found. (17) cases was the maximum value in the 2015 year and it followed by (15) cases in 2019 year as compared to other years. Baghdad governorate (95) cases have a greater number of patients than other governorates.

LRFE: A NOVEL LOCAL RESPONSE FEATURE ELIMINATION PROCESS FOR IDENTIFICATION OF LUNG CANCER CELLS

One of the main causes of cancer-related mortality across the globe is lung cancer.  Early-stage lung cancer frequently exhibits no symptoms, which delays diagnosis until the illness has progressed. Before symptoms manifest, screening and early detection techniques can aid in the early diagnosis and treatment of lung cancer. Many olden research papers have implemented image processing and few latest papers have implemented computer vision techniques to detect lung cancer. Particularly when dealing with minor or subtle anomalies, image processing algorithms may not be able to detect lung cancer lesions with sufficient sensitivity and specificity. It is still difficult to increase the detection algorithms' accuracy and dependability, especially when dealing with early-stage lesions or situations where attributes overlap. It takes a lot of processing power, such as high-performance GPUs and enormous memory capacities, to train deep learning models, particularly large-scale convolutional neural networks (CNNs). In this proposed research, the model pre-processes the images using the ostu and sober filter mechanisms because Otsu's approach adjusts to the features of the input image, including noise, contrast, and lighting fluctuations. It is capable of handling images with varying dynamic ranges and intensity distributions without depending on pre-established threshold settings. When it comes to image noise, the Sobel filter is more resilient than other edge detection methods. It produces clearer edge maps and fewer false detections by determining the gradient magnitude, which amplifies edge information while suppressing noise. The features are extracted using the tuned AlexNet pre-trained model, in AlexNet there is a layer known as “Layer-wise Relevance Propagation”. By giving each pixel or feature in the input image a relevance score, the LRP layer offers fine-grained feature attribution. This makes it possible to analyze in great depth which particular elements or areas of the input image are most important for the network to forecast, which helps to clarify the underlying patterns that the network has learned. At last, the extracted features are further reduced using the enhanced feature elimination method. By iteratively selecting subsets of features based on their importance, RFE helps to identify the most relevant features for the classification task. Integrating RFE with SVM classifiers can lead to improved model performance by focusing on the subset of features that are most discriminative and informative for the classification problem.

Bioimpedance based biomarker for the detection of precancerous and cancerous lesions of the pancreas: feasibility animal study

BackgroundPancreatic cancer (PC) remains a significant healthcare challenge due to its aggressive nature and poor prognosis. The current gold standard that combines imaging modalities, endoscopy, and biopsies has limited diagnostic efficacy due to various shortcomings.MethodsWe propose a feasibility study for the use of a bioimpedance biomarker to detect PC. The biomarker was evaluated in a double blind study on ex vivo pancreata of mice: 15 LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre, 2 LSL-KrasG12D, and 9 wild type controls (Study 1). To determine if the biomarker can distinguish between PC and acute pancreatitis (AP), we challenged it with 18 cerulein-induced AP and 6 saline-injected controls (Study 2).ResultsThe results from Study 1 showed 100% specificity and 94% sensitivity against histopathology outcomes; for Study 2 all AP and saline-injected pancreases were diagnosed as non-cancerous. Regression analysis revealed a positive correlation between biomarker and pathologically analyzed cancer-induced fibrosis (r(24)= 0.73 (p<0.001)).ConclusionThese findings demonstrate the potential of this bioimpedance biomarker as a diagnostic tool for PC.

Abstract PO1-07-12: Inverse modeling with surface temperature accurately detects the presence of breast cancer

Abstract Breast cancer affects over 250,000 women in the United States every year. Patient outcomes including overall survival significantly decline with large sized tumors and nodal involvement on initial presentation. The introduction of mammogram screening has been instrumental in the early detection of cancer. However, it has lower sensitivity in dense breast tissue and limited specificity which leads to unnecessary additional invasive testing. Several methods such as magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound imaging are used as adjunctive methods. However, there is still a need for cost-effective techniques without additional radiation exposure for breast cancer screening for use with mammography. We propose an adjunctive screening method using surface temperature measurements and inverse breast modeling for early detection of breath cancer. Methods: We enrolled patients who presented with mammogram detected breast tumors that were confirmed to be cancerous lesions by biopsy. We used prone position steady state infrared imaging of bilateral breasts to measure surface temperatures and multi-view MRI images to create patient specific 3D breast models. The inverse technique applies Levenberg-Marquard algorithms (LMA) and utilizes commercial software for thermal transport modeling. The inverse technique predicts a heat generation map normalized for baseline surface temperatures to localize the presence of an underlying tumor. Results: A total of 25 breast tumors (diameter range from 5 to 27 mm) from 24 patients were included in the analysis with a median patient age of 67 years. One patient had bilateral breast tumors. Mammogram data showed inclusion of mixed breast tissue composition including dense and extremely dense breast tissue. LMA accurately detected the tumor in all 25 patients with maximum absolute errors of 7 mm in location of the tumor in the breast and 1.78 mm in diameter. The accuracy of detection was not affected by tumor histology which included invasive ductal and lobular carcinomas, ductal and lobular carcinoma in-situ and atypical ductal hyperplasia. No heat sensitive tumors were detected in the 23 contralateral breasts which acted as internal negative controls. Conclusion: Infrared temperature profiles and inverse modeling successfully detected malignant breast tumors with no missed tumors or false positive results and could be used as adjunctive screening along with mammography, especially in patients with dense breast tissue. Citation Format: Nithya Sritharan, Carlos Gutierrez, Isaac Perez-Raya, Jose-Luis Gonzalez-Hernandez, Alyssa Owens, Donnette Dabydeen, Lori Medeiros, Satish Kandlikar, Pradyumna Phatak. Inverse modeling with surface temperature accurately detects the presence of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-12.

Abstract PO2-04-14: Dual Inhibition of WEE1 and PKMYT1 Synergistically Overcomes CDK4/6 Inhibitor Resistance in Breast Cancer

Abstract Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are approved for the treatment of advanced estrogen receptor-positive, HER2-negative (ER+ve) breast cancer when combined with endocrine therapy. However, the emergence of resistance to CDK4/6 inhibitors poses a significant clinical challenge. This study investigates the mechanisms underlying CDK4/6 inhibitor resistance and identifies a common occurrence of high replication stress in triple-negative breast cancer (TNBC) and CDK4/6 inhibitor-resistant ER+ve breast cancers. While ER+ve breast cancer patients have benefited from targeted therapy, TNBC patients, particularly those without germline BRCA1/2 or PALB2 mutations, lack effective treatment options. TNBC and CDK4/6 inhibitor-resistant ER+ve breast cancer cells exhibit an increased dependence on cell cycle arrest to repair replication stress-induced DNA damage. Failure to exit the cell cycle results in excessive DNA damage, thereby limiting their proliferative potential. Based on these findings, we hypothesize that dual inhibition of WEE1 and PKMYT1, two kinases involved in G2/M cell cycle transition and crucial for cell cycle arrest and DNA damage repair, could synergistically inhibit tumor growth. Although WEE1 and PKMYT1 share a common function in promoting G2/M cell cycle transition through CDK1 phosphorylation, their functions are not entirely redundant, suggesting that targeting both kinases may elicit a synergistic response. Recent clinical trials have shown resistance to WEE1-targeted monotherapies, emphasizing the need for combining WEE1 inhibitors with other agents, such as PKMYT1 inhibitors. We demonstrate the synergistic effects of WEE1 inhibitor (MK1775/AZD1775) and PKMYT1 inhibitor (RP6306) in a panel of TNBC and ER+ve breast cancer cells with acquired palbociclib resistance (PalboR). Combination treatment with both inhibitors leads to excessive unrepaired DNA damage, as indicated by increased γH2AX foci following 48 hours of combination treatment, whereas single-agent treatments induce significantly lower levels of DNA damage. Furthermore, we observed the AZD1775/RP6306 combination decreases the expression of the DNA repair protein Rad51 in PalboR cells. To evaluate the clinical potential of dual WEE1 and PKMYT1 inhibition, we generated organoids from metastatic breast cancer lesions of patients who had progressed on CDK4/6 inhibitors for ex vivo studies. Our results demonstrate that dual inhibition of WEE1 and PKMYT1 is more effective than single-agent treatments in eliminating CDK4/6 inhibitor-resistant organoids. Additionally, using patient-derived xenograft mouse models from patients who had progressed on palbociclib and endocrine treatment, we show that the AZD1775/RP6306 combination exhibits superior tumor suppression effects compared to single agents. Overall, this study highlights the potential therapeutic benefits of dual inhibition of WEE1 and PKMYT1 in overcoming CDK4/6 inhibitor resistance in TNBC and ER+ve breast cancer patients. These findings provide a rationale for future clinical trials aimed at exploring the clinical utility of this combination therapy. Citation Format: Mei-Kuang Chen, Grace DeAlessandro, Tuyen Bui, Khandan Keyomarsi. Dual Inhibition of WEE1 and PKMYT1 Synergistically Overcomes CDK4/6 Inhibitor Resistance in Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-14.

Abstract GS03-11: Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity

Abstract Background: Somatic genomic aberrations are acquired within the context of germline genomes which differ across individuals at millions of polymorphic sites. However, the role of germline variation in somatic evolution remains poorly understood. The most compelling example is is that deleterious germline variants in BRCA1 and, to a lesser extent, BRCA2 are preferentially associated with the development of triple-negative breast cancer (BC). The variable frequency of BC subtypes across ancestral populations further suggests a role for germline contributions. On the other hand, various lines of evidence indicate that avoidance of the adaptive immune system is a strong determinant of which somatic mutations persist within a tumor. Whether and how germline differences influence immunoediting has not been studied. Building on these observations, we sought to investigate whether germline variation mediates somatic evolution through immunoediting. Specifically, we hypothesize inherited variation in oncogenes would be subject to varied immunoediting pressures during malignant transformation and progression. A high burden of germline-derived epitopes in recurrently amplified oncogenes is predicted to select against amplification of the cognate gene during malignant transformation because this would increase epitope availability, the likelihood of epitope presentation, and immune-mediated cell death. Instead, immune pressures may select for amplification of an alternate driver gene with a lower germline-mediated epitope burden. We evaluated this hypothesis in a collection of 3,855 BC, spanning ductal carcinoma in situ (DCIS) to invasive BC, and metastatic lesions. Methods: We analyzed paired tumor and normal sequencing data from 1,087 primary and 702 metastatic breast cancer patients as well as somatic genomic profiles from 341 patients with DCIS using a novel algorithm to estimate germline-derived epitope burden (GEB) based on an individual’s genotype and class 1 HLA alleles. The relationship between GEB and subtype commitment, defined by the acquisition of focal oncogenic amplifications in five prognostic subgroups of BC: HER2+ disease and four high-risk of relapse ER+/HER2 integrative subgroups/clusters (ICs) which we previously described (IC1: 17q23, IC2: 11q13, IC6: 8p12, and IC9: 8q24) was evaluated. Specifically, we evaluated the association between the GEB per gene and whether an individual developed the corresponding subtype via logistic regression, correcting for the first six genetic principal components and somatic mutation burden. Outcome associations were evaluated via Cox Proportional Hazards Models. Results: Interrogating 3,855 breast cancer lesions, we demonstrate that germline-derived epitopes in recurrently amplified genes influence somatic evolution by mediating immunoediting. Individuals with a high GEB in ERBB2/HER2 are significantly less likely to develop HER2-positive breast cancer compared to other subtypes. The same holds true for recurrent amplicons that define four aggressive, high-risk of relapse, ER-positive integrative subgroups. Thus, GEB selects against cognate oncogene amplification. Tumors that overcome such immune-mediated negative selection are more aggressive and exhibited microenvironments depleted of lymphocytes, consistent with “immune cold” tumors. Conclusions: We demonstrate that inherited variation sculpts breast cancer subtypes, aggressivity, and immune landscapes by mediating anti-tumor immune responses. The implications of these findings are severalfold. First, GEB is prognostic, complementing other molecular measurements. Second, immunoediting pressures differ across the disease course, with implications for the timing of therapeutic interventions. Third, these data illuminate a broad source of currently under-appreciated immunogenic antigens. Citation Format: Kathleen Houlahan, Aziz Khan, Noah Greenwald, Robert West, Michael Angelo, Christina Curtis. Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-11.

Abstract PO2-29-04: An AI-based safeguard process to reduce aggressive missed cancers in dense breasts at screening mammography

Abstract Background: Dense breast tissue makes cancerous lesions difficult to identify on mammograms, resulting in many cancers missed at screening in patients with dense breasts. These missed cancers are then only diagnosed once they have grown to the point they can be more easily distinguished from the surrounding dense tissue. Dense breast tissue is more common in younger women, for whom early detection and diagnosis could lead to fewer years of life lost. This challenge motivated the FDA’s decision this year to require breast density to be included in patient reports, but notification does not solve the problem that these cancers are still often missed. Missing aggressive, fast growing cancers is particularly worrisome given they are more likely to progress to a stage where they are difficult to treat by the time they are detected in the future. Methods: A prospective study was conducted at one group practice of 6 radiologists over the course of 12 months to test a safeguard process to detect missed cancers so they could be treated more readily. AI software (Saige, DeepHealth, Inc.) was used to flag the most suspicious screening mammography exams that had not been recalled for work-up by an initial interpreting radiologist. An expert breast imager performed a safeguard review of each exam flagged. If the expert decided a recall was warranted, she would consult with the initial interpreting radiologist to decide if the patient should be recalled for further (diagnostic) imaging. Data was collected for each breast cancer diagnosed during this period. Patient data included breast density, age, and race. Cancer follow up data included pathology classification, hormone status, grade, staging, and Ki67 score. Aggressive cancers were identified as those with high grade (Grade 3), high Ki67 ( &amp;gt;=20%) or clinical stage of IIA or greater. A comparison was performed between cancers detected by the original interpreting radiologist and those detected through the safeguard process. Results: During the study period, 40,532 mammograms were obtained and 2,296 were flagged for safeguard review. The safeguard review led to 130 additional patient recalls and 41 additional cancer diagnoses. In women with dense breast tissue, 103 cancers were detected by routine interpretation and an additional 18 cancers (17.5%) detected through the safeguard process. In women without dense breast tissue, 116 cancers were detected by routine interpretation and 23 additional cancers were detected through the safeguard process. The cancers detected through the safeguard process included a larger percent of aggressive cancers (34.1% vs 30.6%, p=0.66) and more than double the percent of triple-negative cancers (9.8% vs 4.1%, p=0.13), though these differences were not statistically significant. The cancers detected through the safeguard process were from patients with similar demographics (age and race) to those whose cancers were detected by the interpreting radiologist. Conclusion: The AI-driven safeguard process results in a significant increase in breast cancers that would have been missed in patients with dense breast tissue. Many of the additional cancers were aggressive with almost 10% being triple-negative cancers. Without the safeguard process those aggressive cancers would not likely have been diagnosed until the next screening cycle in 1-2 years when treatment would likely have been less effective and outcomes poorer. Citation Format: Bryan Haslam, Jiye Kim, A. Gregory Soresen. An AI-based safeguard process to reduce aggressive missed cancers in dense breasts at screening mammography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-29-04.

Non-coding RNAs in Precursor Lesions of Colorectal Cancer: Their Role in Cancer Initiation and Formation.

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

A non-invasive approach to skin cancer diagnosis via graphene electrical tattoos and electrical impedance tomography

Objective. Making up one of the largest shares of diagnosed cancers worldwide, skin cancer is also one of the most treatable. However, this is contingent upon early diagnosis and correct skin cancer-type differentiation. Currently, methods for early detection that are accurate, rapid, and non-invasive are limited. However, literature demonstrating the impedance differences between benign and malignant skin cancers, as well as between different types of skin cancer, show that methods based on impedance differentiation may be promising. Approach. In this work, we propose a novel approach to rapid and non-invasive skin cancer diagnosis that leverages the technologies of difference-based electrical impedance tomography (EIT) and graphene electronic tattoos (GETs). Main results. We demonstrate the feasibility of this first-of-its-kind system using both computational numerical and experimental skin phantom models. We considered variations in skin cancer lesion impedance, size, shape, and position relative to the electrodes and evaluated the impact of using individual and multi-electrode GET (mGET) arrays. The results demonstrate that this approach has the potential to differentiate based on lesion impedance, size, and position, but additional techniques are needed to determine shape. Significance. In this way, the system proposed in this work, which combines both EIT and GET technology, exhibits potential as an entirely non-invasive and rapid approach to skin cancer diagnosis.

Investigation of Genetic Markers for Predicting Oral Cancer Progression and Patient Outcomes

ABSTRACT Background: Genomic methylation being used as a sensitive indicator for identifying oral potentially malignant disorders (OPMDS) and oral cancer could be a viable option. DNA methylation is a potential approach for “cancer therapeutics” and can help researchers truly understand the genomic mechanism that leads to cancer. Aim: Investigation of genetic markers for predicting oral cancer progression and patient outcomes. Methods and Materials: One hundred and twelve patients having oral premalignant lesions and malignant lesions were included in this study. Saliva samples were obtained for analysis of the expression of genetic markers, such as p16, DAP-K, and MGMT. The Illumina Infinium HumanMethylation450 BeadChip (Illumina Inc., USA) would be used to assess genome-wide DNA methylation according to the manufacturer’s instructions. Results: Methylation of all the genes, that is, p16, DAP-K, and MGMT, was observed in 12.7% of oral cancer lesions. 41.94% of oral cancer lesions were found to have methylation of two genes. 13.23% cases were found to be associated with methylation of p16 and DAP-K, 12.12% cases were found to have methylation in the p16 and MGMT, and 15.27% cases of oral cancer lesions showed methylation of DAP-K and MGMT. Conclusion: Genetic markers, such as p53, DAP-K, and MGMT, can be used for predicting oral cancer progression and patient outcomes.

Ultrasound Shear Elastography With Expanded Bandwidth (USEWEB): A Novel Method for 2D Shear Phase Velocity Imaging of Soft Tissues.

Ultrasound shear wave elastography (SWE) is a noninvasive approach for evaluating mechanical properties of soft tissues. In SWE either group velocity measured in the time-domain or phase velocity measured in the frequency-domain can be reported. Frequency-domain methods have the advantage over time-domain methods in providing a response for a specific frequency, while time-domain methods average the wave velocity over the entire frequency band. Current frequency-domain approaches struggle to reconstruct SWE images over full frequency bandwidth. This is especially important in the case of viscoelastic tissues, where tissue viscoelasticity is often studied by analyzing the shear wave phase velocity dispersion. For characterizing cancerous lesions, it has been shown that considerable biases can occur with group velocity-based measurements. However, using phase velocities at higher frequencies can provide more accurate evaluations. In this paper, we propose a new method called Ultrasound Shear Elastography with Expanded Bandwidth (USEWEB) used for two-dimensional (2D) shear wave phase velocity imaging. We tested the USEWEB method on data from homogeneous tissue-mimicking liver fibrosis phantoms, custom-made viscoelastic phantom measurements, phantoms with cylindrical inclusions experiments, and in vivo renal transplants scanned with a clinical scanner. We compared results from the USEWEB method with a Local Phase Velocity Imaging (LPVI) approach over a wide frequency range, i.e., up to 200-2000 Hz. Tests carried out revealed that the USEWEB approach provides 2D phase velocity images with a coefficient of variation below 5% over a wider frequency band for smaller processing window size in comparison to LPVI, especially in viscoelastic materials. In addition, USEWEB can produce correct phase velocity images for much higher frequencies, up to 1800 Hz, compared to LPVI, which can be used to characterize viscoelastic materials and elastic inclusions.

Pathologic outcome of incidentally detected tracer-avid lesions in 68Ga-PSMA-11 PET/CT for prostate cancer

Abstract   Prostate specific membrane antigen (PSMA) PET is effective in identifying prostate cancer metastases. However, PSMA PET uptake has also been described in other lesions, including non-prostate malignancies and benign processes. Purpose To identify causes of unexpected radiopharmaceutical accumulation on PSMA PET. Methods 2,054 study reports representing 1,873 unique patients who had underwent 68Ga-PSMA-11 PET/CT scans at a single large academic center from December 2015—April 2022 were retrospectively reviewed for the mention of unexpected PSMA uptake not initially thought to represent metastatic prostate cancer. Scans with pathologic outcome were reviewed by two blinded readers for scan indication and lesion location and quantitative parameters. Results In 48 patients, the PSMA-ligand avid incidental lesions revealed 19 cases of second malignancies, 17 cases of prostate cancer, and 13 cases of benign lesions. The most common lesion locations were lung (14), thyroid (14), lymph nodes (8), and bowel (4). Benign lesions exhibited lower molecular imaging PSMA (miPSMA) scores (median: 1 IQR: 1.00–1.25, p = 0.017) than metastatic prostate lesions (median: 2, IQR: 1–3). Second malignancies were larger (median: 34 mm, IQR: 27–39 mm) than metastatic prostate cancer (median: 14 mm, IQR: 12–19 mm, p = 0.001) and benign lesions (median: 19 mm, IQR: 13.00—31.00 mm, p = 0.03). PSMA-ligand avid lesions in scans performed in the initial staging for prostate cancer were more commonly associated with a diagnosis of a secondary malignancy than with metastatic prostate cancer (0 vs 8 lesions, p = 0.008). Higher SUVmax was observed for metastatic prostate cancer and second malignancy when compared to benign outcome. Conclusions Features that influence the probability of an incidental lesion representing a malignancy include lesion location, reason for the PSMA PET/CT study, and associated imaging features (size, SUVmax, and miPSMA score).

Comparison of 68Ga-FAPI-04 PET/CT with 18F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

The objective of this study is to evaluate the effectiveness of 68Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18F-FDG PET/CT. Fifty-nine patients who underwent both 18F-FDG and 68Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUVmax), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUVmax/ascending aorta SUVmean), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUVmax/liver SUVmean) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t-test. The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68Ga-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68Ga-FAPI-04 PET/CT than with 18F-FDG PET/CT (all P < 0.05). The accuracy (92.2 vs. 70.3%, P = 0.002) and sensitivity of 68Ga-FAPI-04 were significantly higher than that of 18F-FDG (78.6 vs. 71.4%, P = 0.011) in determining the lymph node status. 68Ga-FAPI-04 has a higher accuracy in staging (P = 0.041), which is mainly due to the ability of distant metastases detection. 68Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

Selenium May Be Involved in Esophageal Squamous Cancer Prevention by Affecting GPx3 and FABP1 Expression: A Case-Control Study Based on Bioinformatic Analysis

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai’an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.

Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.

Brain metastasis, a leading cause of cancer death, is a clinical challenge. Recently, genetic characterization of brain metastatic lesions based on next generation sequencing-based advanced technologies, such as single-cell RNA sequencing, has been performed to develop novel efficient therapies. The present study aimed to investigate brain-metastasis-specific biomarkers as well as relevant prognostic factors. The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized. Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors. High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.

Differential expression of DNA fragmentation factor 45 in leukoplakia and oral squamous cell carcinoma and its correlation with TNF-α levels

BackgroundDNA fragmentation factor (DFF) - 45, a heterodimeric protein, involved in apoptotic processes is found to play important role in various human cancers. Its role in the development and progression of oral cavity squamous cell carcinoma (OSCC) is still unclear. Tumour necrosis factor-α (TNF-α) has been found to be higher in OSCC, yet, the mechanism of circumventing the antitumor effect of this cytokine is not understood. Thus, the aim of this study was to evaluate the expression of DFF-45 in samples of OSCC, leukoplakia, and healthy oral mucosa (control) and correlate it with salivary and serum TNF-α. Materials and methodsSurgically excised specimens from patients with primary OSCC (n = 20) leukoplakia (n = 30) and normal oral mucosa (n = 25) were immuno stained for DFF-45. The relationship of DFF-45expression with clinical parameters and histological grading was also evaluated. TNF-α levels were measured in serum and saliva collected from study subjects using cytokine ELISA technique. ResultsThe expression of DFF-45 in OSCC was either absent or mild, while a significantly up-regulated expression of this protein was observed in leukoplakia lesions. TNF-α levels in both saliva and serum were significantly higher in OSCC group compared to control and leukoplakia. We observed a negative correlation between TNF-α levels and DFF-45 expression in OSCC, similar observation was found with histological staging of OSCC. ConclusionThe absence of DFF-45 in oral cancer lesion suggests that this protein may suppress tumour progression. Down regulation of DFF-45 by tumor cells may be a mechanism to evade the anti-cancer effect of TNF-α and further investigations may unravel its role into malignant transition.