Search Results (33)

Background: A micropapillary pattern (MP) and solid pattern (SP) in lung adenocarcinoma (LUAD), a major subtype of non-small-cell lung cancer (NSCLC), are associated with a poor prognosis and necessitate accurate preoperative identification. This study aimed to develop and validate a predictive model combining clinical and radiomics features for differentiating a high-risk MP/SP in LUAD. Methods: This retrospective study analyzed 180 surgically confirmed NSCLC patients (Stages I–IIIA), randomly divided into training (70%, n = 126) and validation (30%, n = 54) cohorts. Three prediction models were constructed: (1) a clinical model based on independent clinical and CT morphological features (e.g., nodule size, lobulation, spiculation, pleural indentation, and vascular abnormalities), (2) a radiomics model utilizing LASSO-selected features extracted using 3D Slicer, and (3) a comprehensive model integrating both clinical and radiomics data. Results: The clinical model yielded AUCs of 0.7975 (training) and 0.8462 (validation). The radiomics model showed superior performance with AUCs of 0.8896 and 0.8901, respectively. The comprehensive model achieved the highest diagnostic accuracy, with training and validation AUCs of 0.9186 and 0.9396, respectively (DeLong test, p < 0.05). Decision curve analysis demonstrated the enhanced clinical utility of the combined approach. Conclusions: Integrating clinical and radiomics features significantly improves the preoperative identification of aggressive NSCLC patterns. The comprehensive model offers a promising tool for guiding surgical and adjuvant therapy decisions. Full article

Cancerization of lobules (COL) is defined as the involvement of lobular acini by ductal carcinoma in situ (DCIS). Whether it represents a morphological variation in DCIS or a secondary extension of DCIS into lobules is debatable. The relation between COL and the probability of invasion is conflicting among different studies. We assessed if COL is a predictor of adverse pathological outcomes in mastectomy specimens. We reviewed the clinicopathological data of patients who underwent partial or total mastectomy for DCIS during a 3-year period (January 2015 until December 2017). Pathological parameters and follow-up data were collected. Whole-tissue hematoxylin and eosin (H&E) slides were reviewed and re-evaluated for COL. Cases with COL were stained immunohistochemically for E-cadherin and p120 to confirm the ductal phenotype of the neoplasms. In total, 171 mastectomies were identified including 65 specimens with pure DCIS and 106 specimens with DCIS with invasive carcinoma. COL was identified in 73 specimens. COL was significantly associated with adverse pathological outcomes including higher DCIS nuclear grade (p-value = 0.006), central (expansive “comedo”) necrosis (p-value = 0.008), presence of DCIS within or less than 2 mm from the surgical resection margin(s) (p-value = 0.004), higher percentage of blocks/slides with DCIS (p-value < 0.001), and extensive intraductal component (EIC) (applicable in cases with invasion) (p-value < 0.001). Invasion was seen in approximately two-thirds of the cases regardless of the presence of COL, with no statistical significance. Ninety-eight patients achieved 60 months of follow-up, of which only one patient developed local DCIS recurrence and had COL and EIC. Four other patients developed metastatic disease related to the invasive component. While other studies have previously hypothesized that COL may be associated with a worse pathological outcome at mastectomy, our results show that it may indeed be a measure of a higher disease burden representing EIC; however, it is not associated with an increased risk of detecting invasive carcinoma. Full article

Background: Breast cancer, the most prevalent cancer among women globally, develops primarily in the breast’s ducts or lobules. Drug resistance is a significant challenge in treating advanced cases, contributing to over 685,000 breast cancer-related deaths annually, and identifying novel compounds that inhibit key proteins is crucial for developing effective therapies. Methods: In this study, five transferase proteins with PDB IDs were selected due to their involvement in breast cancer: 1A52, 3PP0, 4EJN, 4I23, and 7R9V. Multitargeted docking studies were conducted using three different docking strategies and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) to calculate the binding affinities against the ZINC Natural compound library. Isoetin (ZINC000006523948), found mainly in Isoetaceae, was identified, and the results were compared with the Food and Drug Administration (FDA)-approved drug Tucatinib. In addition, molecular interaction fingerprints and pharmacokinetic profiling were evaluated. We also performed 5 ns WaterMap simulations to identify hydration sites and interactions, followed by 100 ns molecular dynamics (MD) simulations and MM/GBSA to assess the stability of the Isoetin–protein complexes. Results: The docking results indicated that Isoetin demonstrated superior binding and docking scores ranging from −9.901 to −13.903 kcal/mol compared to Tucatinib, which showed values between −4.875 and −10.948 kcal/mol, suggesting Isoetin’s potential efficacy as a therapeutic agent for breast cancer. Interaction fingerprints revealed significant interactions between Isoetin and key residues, including 28LEU, 12MET, 9PHE, 7ASP, 6ASN, and 6THR. The pharmacokinetics and DFT analysis of Isoetin supported its potential as a viable drug candidate. Furthermore, the 5 ns WaterMap simulations identified various hydration sites, and the 100 ns MD simulations showed that the Isoetin–protein complexes exhibited minimal deviations and fluctuations, indicating better stability than Tucatinib, and MM/GBSA confirmed Isoetin’s superior binding stability. Conclusions: Isoetin, a natural compound identified through in silico screening, demonstrates significant promise as a potential therapeutic agent for breast cancer as it outperforms the FDA-approved drug Tucatinib, the respective native and FDA-approved drug. However, experimental validation is necessary before considering Isoetin for clinical use. Full article

Background: Lymphedema represents a frequent cause of disability for patients undergoing oncological treatments and, being a chronic, non-reversible pathology, requires targeted and continuous rehabilitation treatments. To date, the studies available on the use of ultrasound in patients with lymphedema mainly report descriptive data; therefore, with this study, we wanted to describe in a more objective way the typical ultrasound alterations found in these patients, measuring the thickness of the different superficial structures, and defining subcutis echogenicity. Methods: 14 patients affected by secondary lymphedema of the upper limbs were enrolled in this cross-sectional observational study (12 had breast cancer and 2 with melanoma as their primary diagnosis). All patients were classified as stage II according to the ISL classification. Patients were examined between March and July 2023 with a clinical and an ultrasound evaluation. Ultrasound evaluation was performed following a protocol and took into consideration thickness of the cutis, subcutis, superficial and deep fascia, and subcutis echogenicity. Results: The cutis of the affected limbs was thicker in the distal anterior region of the arm and throughout the anterior region of the forearm. The subcutaneous tissue was thicker in the posterior region of the distal arm and throughout the forearm, including the dorsum of the hand and excluding only the proximal posterior region of the forearm. Fascial structures did not demonstrate statistically significant differences in thickness between pathological and healthy limbs, despite undergoing significant changes from a qualitative point of view (loss of the trilaminar skin appearance and the development of anechoic areas due to fluid accumulation around the hyperechoic adipose lobule). A statistically significant difference in the echogenicity of subcutaneous tissue was found at the distal anterior region of the arm and at the entire anterior forearm. Conclusions: High-resolution ultrasound has been confirmed to be a tool capable of supporting the diagnosis of lymphedema and identifying the most compromised regions of the limb. A tailored rehabilitation plan can be developed based on the non-uniform alterations in subcutaneous tissue, where some areas are affected earlier than others. This compartmentalization should be considered in lymphedema staging and management. Ultrasound may provide early detection of these changes, guiding a more precise therapeutic approach. Full article

Akatsuki disease (also known as pomade crust) is characterized by skin lesions resulting from inadequate skin hygiene. It is sometimes influenced by underlying psychological factors. Akatsuki disease sometimes mimics cutaneous horn or skin cancer. However, there are no previous reports of skin cancer accompanied with Akatsuki disease. Herein, we report a 79-year-old woman who was referred to our department with a tumor on her left cheek. Before performing a biopsy, we recommended that her family assist with regular facial cleansing. Two months later, the scales and crusts on her entire face had disappeared and the tumor on the left cheek had reduced. Skin biopsy was performed, and histological examination revealed ulcerative basaloid lobules consisting of cells with a small cytoplasm and large hyperchromatic nuclei. Peripheral palisading and tumor-stroma clefting were observed. A diagnosis of basal cell carcinoma was made. Full article

Background and Objectives: Primary prostatic stromal sarcoma is an exceptionally rare urological malignancy, constituting less than 0.1% of all prostatic cancers. It poses a significant clinical challenge due to its aggressive behavior and poor prognosis. Materials and Methods: We report the case of a 34-year-old male who presented with nonspecific lower urinary tract symptoms, including dysuria and increased urinary frequency. The initial diagnostic workup, including digital rectal examination and Magnetic Resonance Imaging (MRI), revealed a lobulated lesion within the prostate. A transurethral resection (TUR) was performed for diagnostic purposes, and histopathological examination revealed a “malignant mesenchymal tumor”. The patient underwent a laparoscopic radical prostatectomy. The pathology report confirmed the diagnosis of prostatic stromal sarcoma. The postoperative follow-up, including systemic CT and MRI, showed no evidence of recurrence or metastasis thus far. Results: Multidisciplinary management is essential for optimizing treatment outcomes in all urologic malignancies; however, it becomes particularly challenging and crucial in rare cases such as primary prostatic stromal sarcoma. In our case, the patient benefited from a coordinated approach involving urology, pathology, and oncology, underscoring the importance of collaborative care for rare and aggressive tumors like this. This case highlights the importance of early detection, complete surgical excision, and consideration of adjuvant therapies, given the aggressive nature of the disease. The role of novel therapeutic strategies, including immunotherapy and targeted therapies, is also discussed in the context of metastatic sarcomas. Conclusions: This case underscores the critical need for a comprehensive, multidisciplinary approach to managing primary prostatic stromal sarcoma. Ongoing research on innovative therapies offers hope for improved outcomes in metastatic stages. Full article

Background: This study aims to delineate anatomical landmarks crucial for complete mesocolic excision, focusing on Gerota’s fascia, which guides surgical dissection in right-sided colon cancer, forming the posterior limit. Employing a multimodal approach, the research aims to understand the fascial anatomy and its variations under pathological conditions. Methods: Three methods were applied: a pilot dissection on an embalmed cadaver for clear anatomical presentation of prerenal fascia, Mimics segmentation of the fascia and its relationship with the colon, and a retrospective analysis of MDCTA scans from 196 patients (mean age 65.73 y, 118 F/78 M). Systematic measurements of fascial thickness were taken at key renal levels—upper pole, hilum, lower pole, and infra-renal. Covariates analyzed included Body Mass Index, age, and sex. Results: The pilot dissection revealed the renal fascia of Gerota as the only true retrocolic compact connective tissue and the fusion fascia of Toldt as a mesh of strands of loose connective tissue and fat lobules. MDCTA showed clearer visualization of Gerota’s fascia at the hilum and inferior renal pole, predominantly on the left. There were significant differences in fascial thickness between sides (1.30 mm on the right and 1.34 mm on the left) and a positive correlation with BMI, whereas age and sex showed no significant effects. Conclusion: Gerota’s fascia is a critical anatomical landmark in CME for right colon cancer. This study highlights the fascia’s structural integrity, unaffected by the tumor, underscoring its importance in surgical navigation. Full article

Accurate prognosis and diagnosis are crucial for selecting and planning lung cancer treatments. As a result of the rapid development of medical imaging technology, the use of computed tomography (CT) scans in pathology is becoming standard practice. An intricate interplay of requirements and obstacles characterizes computer-assisted diagnosis, which relies on the precise and effective analysis of pathology images. In recent years, pathology image analysis tasks such as tumor region identification, prognosis prediction, tumor microenvironment characterization, and metastasis detection have witnessed the considerable potential of artificial intelligence, especially deep learning techniques. In this context, an artificial intelligence (AI)-based methodology for lung cancer diagnosis is proposed in this research work. As a first processing step, filtering using the Butterworth smooth filter algorithm was applied to the input images from the LUNA 16 lung cancer dataset to remove noise without significantly degrading the image quality. Next, we performed the bi-level feature selection step using the Chaotic Crow Search Algorithm and Random Forest (CCSA-RF) approach to select features such as diameter, margin, spiculation, lobulation, subtlety, and malignancy. Next, the Feature Extraction step was performed using the Multi-space Image Reconstruction (MIR) method with Grey Level Co-occurrence Matrix (GLCM). Next, the Lung Tumor Severity Classification (LTSC) was implemented by using the Sparse Convolutional Neural Network (SCNN) approach with a Probabilistic Neural Network (PNN). The developed method can detect benign, normal, and malignant lung cancer images using the PNN algorithm, which reduces complexity and efficiently provides classification results. Performance parameters, namely accuracy, precision, F-score, sensitivity, and specificity, were determined to evaluate the effectiveness of the implemented hybrid method and compare it with other solutions already present in the literature. Full article

α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca²⁺ permeability and can be quickly activated and desensitized, and is closely related to Alzheimer’s disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson’s disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat α7 nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat α7 nAChRs expressed in Xenopus laevis oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC₅₀) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of α7 nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that α7 nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of α7 nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of α7 nAChRs in the rat brain. Full article

Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from −4.527 to −8.809 Kcal/mol and MM/GBSA scores between −49.09 and −61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA’s role. Full article

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term “invasive lobular carcinoma” implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial–mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype. Full article

3D cell culture models replicating the complexity of cell–cell interactions and biomimetic extracellular matrix (ECM) are novel approaches for studying liver cancer, including in vitro drug screening or disease mechanism investigation. Although there have been advancements in the production of 3D liver cancer models to serve as drug screening platforms, recreating the structural architecture and tumor-scale microenvironment of native liver tumors remains a challenge. Here, using the dot extrusion printing (DEP) technology reported in our previous work, we fabricated an endothelialized liver lobule-like construct by printing hepatocyte-laden methacryloyl gelatin (GelMA) hydrogel microbeads and HUVEC-laden gelatin microbeads. DEP technology enables hydrogel microbeads to be produced with precise positioning and adjustable scale, facilitating the construction of liver lobule-like structures. The vascular network was achieved by sacrificing the gelatin microbeads at 37 °C to allow HUVEC proliferation on the surface of the hepatocyte layer. Finally, we used the endothelialized liver lobule-like constructs for anti-cancer drug (Sorafenib) screening, and stronger drug resistance results were obtained when compared to either mono-cultured constructs or hepatocyte spheroids alone. The 3D liver cancer models presented here successfully recreate liver lobule-like morphology, and may have the potential to serve as a liver tumor-scale drug screening platform. Full article

Renal cell carcinoma represents about 2% of all malignant tumours in adults. Metastases of the primary tumour in the breast make up to about 0.5–2% of the cases. Renal cell carcinoma metastases in the breast are extremely rare and have been sporadically recorded in the literature. In this paper, we present the case of a patient with breast metastasis of renal cell carcinoma 11 years after primary treatment. Case presentation: An 82-year-old female who had right nephrectomy due to renal cancer in 2010 felt a lump in her right breast in August 2021, whereby a clinical examination revealed a tumour at the junction of the upper quadrants of her right breast, about 2 cm, movable toward the base, vaguely limited, and with a rough surface. The axillae were without palpable lymph nodes. Mammography showed a circular and relatively clearly contoured lesion in the right breast. Ultrasound showed an oval lobulated lesion of 19 × 18 mm at the upper quadrants, with strong vascularisation and without posterior acoustic phenomena. A core needle biopsy was performed, and the histopathological findings and obtained immunophenotype indicated a metastatic clear cell carcinoma of renal origin. A metastasectomy was performed. Histopathologically, the tumour was without desmoplastic stroma, comprising predominantly solid-type alveolar arrangements of large moderately polymorphic cells, bright and abundant cytoplasm, and round vesicular cores with focally prominent nuclei. Immunohistochemically, tumour cells were diffusely positive for CD10, EMA, and vimentin, and negative for CK7, TTF-1, renal cell antigen, and E-cadherin. With a normal postoperative course, the patient was discharged on the third postoperative day. After 17 months, there were no new signs of the underlying disease spreading at regular follow-ups. Conclusion: Metastatic involvement of the breast is relatively rare and should be suspected in patients with a prior history of other cancers. Core needle biopsy and pathohistological analysis are required for the diagnosis of breast tumours. Full article

Breast cancer (BC) is the world’s second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from terminal tubulobular units; when the tumor is present only in the ducts or lobules in situ, it is called ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS). The biggest risk factors are age, mutations in breast cancer genes 1 or 2 (BRCA1 or BRCA2), and dense breast tissue. Current treatments are associated with various side effects, recurrence, and poor quality of life. The critical role of the immune system in breast cancer progression/regression should always be considered. Several immunotherapy techniques for BC have been studied, including tumor-targeted antibodies (bispecific antibodies), adoptive T cell therapy, vaccinations, and immune checkpoint inhibition with anti-PD-1 antibodies. In the last decade, significant breakthroughs have been made in breast cancer immunotherapy. This advancement was principally prompted by cancer cells’ escape of immune regulation and the tumor’s subsequent resistance to traditional therapy. Photodynamic therapy (PDT) has shown potential as a cancer treatment. It is less intrusive, more focused, and less damaging to normal cells and tissues. It entails the employment of a photosensitizer (PS) and a specific wavelength of light to create reactive oxygen species. Recently, an increasing number of studies have shown that PDT combined with immunotherapy improves the effect of tumor drugs and reduces tumor immune escape, improving the prognosis of breast cancer patients. Therefore, we objectively evaluate strategies for their limitations and benefits, which are critical to improving outcomes for breast cancer patients. In conclusion, we offer many avenues for further study on tailored immunotherapy, such as oxygen-enhanced PDT and nanoparticles. Full article

Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF (male to female) patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone. Full article